Editorial: Dermatologic Surgery 1997

Jeffrey A. Klein, M.D.

There are two standards of care for tumescent liposuction: true tumescent liposuction, which is totally by local anesthesia, and semi-tumescent liposuction, which requires general anesthesia or heavy IV sedation. Both techniques can be done safely. However, there is a greater risk and a definite tendency for a surgeon to exceed the limits of safety when using semi-tumescent liposuction. There have been no deaths associated with true tumescent liposuction.

The tumescent technique was developed to minimize surgical risk and optimize patient comfort. When a surgeon intentionally modifies the tumescent technique and increases the risks of surgical complications, then the technique cannot accurately be termed the true tumescent technique or true tumescent liposuction.

When liposuction by general anesthesia (IV or inhalational), and a modified tumescent technique results in a patient’s death from the effects of excessive volumes of fat removal, excessive IV fluids, hypothermia, or complications of general anesthesia such as anoxia, pulmonary embolus, or asystole, is it accurate to state that the death was associated with associated with tumescent liposuction?

Consider the following vignette. A group of specialists starts using a safe surgical technique not invented by them; then they modify the technique, making it more dangerous; then they experience serious complications and fatal outcomes; then they claim only they have the training and experience to perform such a dangerous procedure.

In order to assure the public that not all tumescence techniques are created equal, and to avoid confusion over terminology, the following definitions must be articulated. Because the tumescent technique for liposuction has evolved and greatly improved over the years, prior terminology is now antiquated and inaccurate. The following definitions are intended to provide some precision to one’s tumescent vocabulary.

The Tumescent Technique is a pharmacologic method of drug delivery that produces wide spread local, regional, or systemic effects by subcutaneous infiltration of very dilute solutions of the drug in physiologic saline or a similar solution. Any type of drug that can be injected subcutaneously is a potential candidate for
delivery by the tumescent technique.

Tumescent Hemostasis is achieved using the tumescent technique to produce widespread, profound, and prolonged vasoconstriction in subcutaneous fat by the infiltration of very dilute epinephrine, for example 1:1,000,000,(that is 1 g epinephrine per 1,000,000 mL of normal saline or Ringer’s lactate, which is equivalent to 1 mg/1,000 mL).

Tumescent Anesthesia is a technique for local anesthesia. It uses large volumes of dilute lidocaine and dilute epinephrine to permit liposuction totally by local anesthesia without general anesthesia, or IV sedation, and with virtually no significant blood loss. The actual formulation of the tumescent anesthetic solution varies as a function of clinical requirements. Typically the concentration of lidocaine varies between 500 and 1,500 mg/L, while epinephrine may vary between 0.5 and 1.5 mg/L.

True Tumescent Liposuction is a very specific method of doing liposuction totally and exclusively by local anesthesia. Tumescent liposuction incorporates tumescent anesthesia (dilute lidocaine and epinephrine) with the use of micro-cannulas, and small incisions that are not closed with sutures. Incisions that are not closed with sutures promote copious postoperative drainage, which in turn reduces systemic lidocaine absorption and dramatically reduces postoperative inflammation as well as bruising, soreness, tenderness, and swelling. To the best of my knowledge there have been no deaths associated with tumescent liposuction totally by local anesthesia without parenteral narcotic analgesia or general anesthesia.

Semi-tumescent Liposuction, or semi-tumescent technique, is the liposuction by general anesthesia (IV or inhalational) or heavy IV sedation. It is a forme fruste, on an incomplete version of tumescent liposuction. Semi-tumescent liposuction implies that the tumescent technique is used only for its ability to produce profound hemostasis, and postoperative anesthesia. Semi-tumescent liposuction has increased risks including the toxicity and dangerous side effects of general anesthesia. Semi-tumescent liposuction ignores the improved safety provided by local anesthesia compared with the risks associated with general anesthesia. Every death reported in association with liposuction has also been associated with general anesthesia, heavy IV sedation, or bupivacaine.

Meretricious (1)- Tumescent Liposuction is identical to the outmoded wet technique, with the exception that the patient has been falsely promised that the tumescent technique will be used. Unfortunately such deception is not uncommon. Having been educated by the media, most prospective patients demand the safety of the tumescent technique. It is meretricious to promise the tumescent technique of the surgeon has never performed or does not intend to perform liposuction totally by local anesthesia.

Licentious (2)- Tumescent Liposuction is dangerous liposuction associated with any one of the following: liposuction of an excessive volume of fat, excessive number of areas treated, excessive IV fluids infused, excessive blood loss, excessive quantities of local anesthetics, and the complications of general anesthesia. Licentious liposuction is dangerous liposuction that goes far beyond the limits of safety as defined by the empiric rules of normal human physiology.

Before the tumescent technique, the safe maximum volume of liposuction was limited by surgical blood loss. With the advent of tumescent vasoconstriction, safety limits for liposuction still exist, but they are now less obvious. Tumescent hemostasis seduces surgeons into a false sense of security. With liposuction totally by local anesthesia, an alert comfortable patient can communicate, and warn the surgeon about the onset of symptoms of excessive surgery such as hypothermia, hypo tension, or pulmonary congestion. However, with tumescent hemostasis surgeons see no blood loss, and with general anesthesia or heavy IV sedation they are more likely to miss early signs of impending shock. In this sense, general anesthesia predisposes to excessive liposuction and requires extra caution.

Licentious liposuction occurs most frequently in association with general anesthesia because Brobdingnagian volumes of fat are liposuctioned more easily general anesthesia. Consequently, the risk of an iatrogenic death is significantly greater with liposuction by general anesthesia or heavy IV sedation.

When tumescent liposuction crosses beyond the pale and into the domain of excessive surgical trauma, it metamorphoses from a benign cosmetic procedure into a malignant process. A cavalier surgical attitude, a naive sense of security, an avaricious motivation, or a foolish desire to satisfy a patient’s request to “do it all in one surgery” are dangerous ingredients; add general anesthesia to the recipe and the result is a prescription for disaster. There is no antidote for this poisonous combination. The only safe approach is prevention, which requires a knowledge of modern pharmacology and physiology, a careful surgical technique, and prudent limits to the amount and extent of surgery. Above all do no harm.

Ultimately, not even board certification significantly reduces the risk of death from liposuction. The only factor that significantly affects the safety of liposuction is the type of anesthesia that is used. The tumescent technique for liposuction totally by local anesthesia is safer than the semi-tumescent technique that uses general anesthesia or heavy IV sedation.

Open Drainage and Bimodal Compression

Jeffrey A. Klein, M.D.

The goals of postliposuction care must be to minimize edema, bruising and patient discomfort. The postoperative pain and edema resulting from sutured incisions and prolonged postliposuction compression is an irrational remnant from the days before the tumescent technique.

Antediluvian (before tumescent technique) liposuction resulted in such extensive blood loss that patients often had to donate and bank their own blood before surgery and receive an autotransfusion afterward. Prior to the advent of tumescent vasoconstriction, providing hemostasis and preventing hematomas or seromas were the primary goals of postliposuction external compression. Prolonged high-grade compression was thought necessary to prevent or diminish the size of hematomas and seromas. With the advent of the tumescent technique, and with its profound vasoconstriction and surgical hemostasis, imperatives of postliposuction care have changed. Some surgeons, however, are still unfamiliar with the technique of open-drainage and bimodal compression. The goal of postliposuction care is to optimize patient recovery, which in turn requires an objective comparison of available alternatives.

Liposuction Edema

Extracellular postliposuction edema occurs when there is excessive fluid postoperatively within the extracellular space. The two factors responsible for extracellular edema are impaired lymphatic drainage and excess capillary filtration. Lymphedema is distinctly different from venous capillary edema.[1] Treatments of these conditions are also distinctly different. If one’s perverse goal is to produce the maximum degree of postliposuction edema, one must prevent the egress of subcutaneous fluid (1) by trapping the maximum amount of bloody fluid within the subcutaneous space and (2) by simultaneously blocking all lymphatic drainage. This goal can be achieved by closing incisions with sutures and then applying a high degree of external compression to collapse lymphatic capillaries.

In contrast, open drainage with bimodal compression minimizes postliposuction edema. Open drainage refers to an expedited drainage of blood-tinged anesthetic solution via incisions not closed by sutures. Bimodal compression refers to two sequentially applied degrees of postoperative compression. The first degree is a relatively high-grade compression that accelerates the drainage via open incisions. The second is a low-grade compression, employed after drainage has ceased, that is mild enough not to collapse the lymphatic capillaries, but adequate to increase interstitial hydrostatic pressure.

Lymphatic Drainage

The surgical effect of liposuction upon the lymphatics is unique in several respects. First, liposuction disrupts or destroys most lymphatic capillaries within the targeted adipose tissue. Second, lymphatic damage from liposuction is not permanent. Lymphatic capillaries regenerate within a few weeks after being torn by a liposuction cannula. In contrast, after surgical lymph node dissection, damage to lymphatics is permanent.

Damaged lymphatics are not able to transport excess interstitial fluid back to the blood. Lymphatic insufficiency can cause especially severe swelling and edema. The persistence of extravasated plasma proteins increases the interstitial fluid osmotic pressure and draws even more fluid out of the capillaries.

Excess Capillary Filtration

Excessive capillary filtration or fluid shift from the intravascular to the interstitial space is influenced by increased capillary permeability, decreased plasma colloid osmotic pressure, and increased capillary hydrostatic pressure. Decreased plasma colloid osmotic pressure occurs after liposuction because of loss of plasma protein through ruptured capillaries, consumption of hemostatic procoagulant proteins, and iatrogenic hemodilution with unnecessary IV fluid crystalloids, and possibly hemorrhage. Increased capillary hydrostatic pressure may occur after liposuction as a result of general anesthesia, secondary immobilization of limbs, and loss of sympathetic vascular tone.

Lymphedema

Lymphedema is edema caused by inadequate lymphatic function resulting from agenesis, destruction or obstruction of lymph vessels or lymph nodes. On a molecular level, lymphedema is the result of a failure of the lymphatics to remove large molecular proteins from the interstitial space. Although both hematic and lymphatic capillaries reabsorb interstitial water, the lymphatic capillaries are responsible for reabsorbing large proteinaceous molecules.

Although lymph capillary injury is an inevitable consequence of liposuction, the extent and duration of liposuction lymphedema can be significantly reduced by rational postoperative care. Early and aggressive efforts to expel as much blood-tinged anesthetic fluid as possible give immediate results. Once the drainage fluid is allowed to become trapped within interstitial microloculations, the edema becomes persistent and will only resolve once the injured lymphatic capillaries have been regenerated.

Normal Lymphatic Function

Proteins and other large molecules are too large to be absorbed into the blood directly across capillary membrane. Lymphatic capillaries have large gaps between adjacent endothelial cells that permit passage of large-molecular-weight substances. Lymphatic endothelial cell edges overlap each other slightly, forming minute unidirectional endothelial valves into the lumen of the lymphatic capillary. In addition, some lymphatic capillary endothelial cells overlap to a much greater degree than usual endothelial cell overlap and form internal bivalve flaps that act as one-way valves inside the lymphatic capillary. This valve structure inhibits retrograde lymph flow.

Microscopic Structure of Lymphatics

The wall of a terminal lymphatic capillary has an interior layer formed by a single thin endothelial cell and an external basal lamina that is widely fenestrated. In many places there are wide gaps between adjacent endothelial cells. These holes in the lymphatic capillaries facilitate the uptake of macromolecules, proteins, bacteria, blood cells, and tumor cells.[2]

Effects of Edema and Compression on Lymphatics

There is an important distinction between the effects of increased interstitial pressure owing to edematous fluid overload compared to the effects of compression on the external surface of the body, which elevates interstitial hydrostatic pressure.

In the first instance, the expansion of the swollen interstitial tissue causes the inside diameter of the lymphatic capillary to dilate. From the perspective of mathematical topology, edema causes every point within the tissue compartment to move further apart from every other point. This includes the lymphatic endothelial cells. The expanded lymphatic capillary inside diameter increases lymph flow, which tends to reduce the edema.

In the second instance, external compression squeezes the interstitial tissue and can compress the capillary lumen. This constriction limits the lymph flow and ultimately impairs the lymphatic capillary ability to reduce edema.

The Lymphatic Pump Mechanism

The rate of lymphatic flow is determined  by the lymphatic pump mechanism and interstitial fluid pressure. The one-way lymphatic capillary valves allow a degree of lymphatic pumping when capillaries are compressed intermittently by an external force, such as by large muscles of a limb, movement of the body, arterial pulsations, and external massage. When larger lymphatic vessels become stretched with lymph fluid, the smooth muscle in the wall of the vessels contracts automatically and forces the lymph fluid through the proximal valve and into the next segment of the lymphatic vessel. This lymphatic pump mechanism generates the negative interstitial fluid pressure.

For the liposuction patient, excessive external pressure from compressive postoperative garments may be counterproductive. Continuous external compression, for example, from high-compression postoperative garments may cause the delicate lymphatic capillaries to collapse, impede lymph flow, and effectively block lymphatic drainage.

Lymph Flow and Interstitial Fluid Pressure

The normal interstitial fluid pressure is subatmospheric and ranges between -6 mm Hg to 0 mm Hg (atmospheric pressure). Experimental measurements in dogs show that the rate of lymph flow varies as a function of interstitial fluid pressure.[3] There is very little lymph flow below -6 mm Hg. Between -6 mm Hg and 0 mm Hg the rate of lymph flow increases exponentially until it reaches a maximum between 1 or 2 mm Hg. The rate of flow at 0 mm Hg is 20 times greater than at -6 mm Hg; however, when interstitial pressure exceeds 1 or 2 mm Hg, the lymph flow rate reaches a plateau. Lymph flow fails to increase with higher interstitial fluid pressures. One can conclude that a high compression postoperative garment is unlikely to increase the rate of lymph flow after liposuction.

Wound Fluid Osmolality

The clinical laboratory measurement of a serum osmolality requires that a serum sample be frozen as soon as possible after it is obtained. A long delay in freezing the sample exposes the serum proteins to temperature-dependent proteolysis. By effectively multiplying the number of solute particles in solution, proteolysis amplifies the osmolality of a sample. The trauma from tumescent liposuction allows plasma proteins to leak out of injured capillaries and into the subcutaneous wound space. Once a protein molecule has entered the subcutaneous wound space it can only re-enter the blood by way of lymphatic absorption.

Fresh wound fluid has an osmolality of approximately 10 mmol greater than serum.  This osmotic pressure gradient will tend to draw water from intravascular space, across the capillary wall and into the wound space. Incubating residual blood-tinged tumescent fluid at body temperature increases the osmolality of fluid over time. This exacerbates postliposuction edema by an osmotic amplification by incubation.

Iatrogenic hemodilution by infusion of IV crystalloid fluids will increase intravascular hydrostatic pressure and therefore augment edema. External compression will counteract the effects of intravascular hydrostatic pressure but hinder the lymphatic uptake of would fluid containing protein molecules.

Antique Postliposuction Care

Liposuction causes a certain amount of subcutaneous bleeding as well as damage to the subcutaneous lymphatic capillaries. The combination of subcutaneous bleeding and impaired lymphatic drainage entraps large osmotically active molecules and produces an osmotic edema. Any technique for postliposuction care that contributes to this osmotic edema will increase the degree of postliposuction edema, pain, and bruising.

The traditional liposuction and postliposuction techniques often consort to produce an unnecessary degree of prolonged healing and edema. Incomplete tumescent infiltration will lead to subcutaneous bleeding, encourage a postoperative subcutaneous inflammation, and augment postoperative edema. The super-wet technique is an example of suboptimal tumescent liposuction. Sutured liposuction incisions prevent percutaneous drainage of residual blood-tinged anesthetic solution and encourage subcutaneous edema. Long-term use of a high-compression postliposuction elastic garment will compress and impair subcutaneous lymphatic capillaries and further block lymphatic uptake of large osmotically active molecules. There is a more efficient and effective method for postliposuction care.

An ideal method for postliposuction care prevents problems before they occur. Prolonged edema, excessive bruising, and persistent inflammation are the most bothersome and most common undesirable sequella of liposuction. To a large extent these problems can be avoided with a rational and scientific approach to postliposuction care. One successful method of postliposuction care uses open drainage, special super-absorbent pads that provide distributive compression, and bimodal compression.

Open Drainage and Compression Sponges

Open drainage after tumescent liposuction refers to the technique for maximizing the drainage of blood-tinged anesthetic solution by using adits (1.5 mm or 2 mm punch excisions for microcannula access to subcutaneous fat) to facilitate postoperative drainage, locating adits in strategic locations in order to encourage gravity-assisted drainage, and allowing the adits to remain open instead of being closed with sutures. Open drainage demands the use of comfortable, high-capacity absorptive pads, also known as compression sponges.

Compression sponges are a functional combination of absorptive sponges and compression pads. Absorptive sponges are required for the containment of the objectionable postoperative blood-tinged drainage. Containing the drainage avoids alarming the patient and prevents staining of clothing and furniture. Complete absorption and containment of the drainage allows the patient to mobile and sociable. The copious drainage that occurs after tumescent liposuction demands absorptive pads with a special design.

Compression pads are postoperative cushions place over liposuctioned areas in order to distribute the compression provided by an elastic compression garment in a smooth and uniform manner. Uniform, gentle compression of subcutaneous tissue after liposuction collapses the gaps within the interstitial collagen of the dermis. Therefore, dermal compression prevents bruising by blocking the outward percolation of red blood cells up toward the epidermis.

An effective and practical way of applying the compression-absorption pads over the targeted areas is to use a combination of a few strips of paper tape and elastic tube netting, similar to the method of applying dressings over burn wounds. After the compression-absorption pads are well positioned, one can apply the elastic compression garment. The optimal garment in this regard must be able to accommodate the bulk of the pads, and the pads must be easy for the patient to take off and put on again without assistance.

Bimodal compression refers to the sequential use of two different degrees of postliposuction compression. First, a high degree of compression is maintained while drainage persists and for an additional 24 hours past the time when all the drainage has ceased. Twenty-four hours after all drainage has ceased only a relatively mild degree of compression is required.

In the Old Days Sutures were Necessary

In the days of antediluvian liposuction, surgeons were compelled to close liposuction incisions with sutures. Before the tumescent technique and microcannulas, liposuction cannulas were large and required large incisions, which required sutures for proper healing. With the modern tumescent technique (including the use of microcannulas and adits), postliposuction healing is better when incisions are not closed with sutures.

In the past, using sutures to close an incision was seen as necessary to prevent infections. In fact, with the advent of nearly bloodless tumescent liposuction, many of the problems that necessitated the closure of liposuction incisions with sutures no longer exist. Without tumescent vasoconstriction there was a relatively high incidence of hematomas and seromas. Hematomas and seromas provide an avascular medium for bacterial growth and infection. An open incision had the potential for being a port of entry for an infection.

With the tumescent technique, hematomas are rare, and the incidence of seromas is virtually eliminated by open drainage and good compression. Tumescent lidocaine further reduces the risks of infection, because residual interstitial lidocaine is bacteriocidal in the sense that it appears to prevent infections after tumescent liposuction. Therefore, the tumescent technique appears to have reduced the risk factors for infection, and open drainage probably reduces the risk of infection even further.

Adits

An adit is a technical engineering term that describes a horizontal opening by which a mine is entered or drained. A micro-adit used in tumescent liposuction is a small circular hole made by a tiny (1.5 mm or 2 mm) skin biopsy punch. Adits facilitate and promote the open drainage of residual blood-tinged anesthetic solution associated with tumescent liposuction.

It is common knowledge that 1.5-mm and 2-mm skin biopsy punches leave virtually no scars. Therefore, 1.5-mm or 2-mm punch excisions can be placed over a liposuction area with minimal risk of scarring. Adits are especially helpful areas, such as the thighs and the abdomen, where postoperative edema and bruising can be more pronounced and bothersome than in other areas.

A 16- or 14-gauge microcannula can easily pass through a 1.5 mm adit. These size microcannulas can enter through a 1.5-mm round hole with virtually no epidermal friction as the microcannula is pushed and pulled through the skin. A 12-gauge microcannula often requires a 2-mm adit. With a careful and skilled liposuction technique, especially in areas of the skin such as the inner thigh, a 1.5-mm adit can often accommodate a 12-gauge microcannula with minimal epidermal trauma.

For the outer thigh the best site for an adit is the most dependent margin of the targeted area. Insert a 16- or 14-gauge microcannula through the tiny hole and create multiple liposuction tunnels in order to funnel the postoperative drainage to the adit opening.

The most important advantage to using round adits is that round holes remain patent for a longer time than a slit incision. Round 1.5-mm and 2-mm adits allow better drainage than simple incisions. The edges of a microincision may close and heal before the blood-tinged anesthetic has been completely drained, therefore entrapping blood-tinged anesthetic solution in the subcutaneous space.

Several 2-mm punch excisions placed along the lower margin of the abdomen, above the pubic area, allow more drainage than tiny slit incisions. Adits placed along the lower abdomen plus firm, uniform compression will virtually eliminate postliposuction ecchymosis and seromas and dramatically reduce postoperative swelling and tenderness.

Even with the use of a large cannula and the closure of incisions with sutures, the judicious use of adits can provide all the advantages of open drainage. The strategic use of surgical adits significantly improves the rate of recovery by decreasing the duration of postoperative bruising, swelling, tenderness, and significantly reduces the incidence of seromas and hematomas.

Eliminating Sutures

The most significant advantage of placing adits or eliminating sutures is the dramatic acceleration of recovery and reduction of postliposuction edema. There is a striking contrast between closing incisions with sutures compared to allowing the adits or incisions to remain open. Sutures do not benefit from a 4-mm microincision. Some surgeons close incisions with sutures because of a concern that the profuse drainage will alarm the patient and necessitate increased nursing care[4]; however, with super-absorptive compression sponges, there is no longer any need for concerns about messy postliposuction drainage.

The advantages of not using sutures include (1) more complete drainage, leading to less edema, less tenderness, and less ecchymosis; (2) adits and microincisions (5 mm) heal better without sutures because there is no suture-induced inflammation, no foreign-body reactions, and no cross-hatch scars; (3) patients need not return for suture removal, therefore saving the patient time and avoiding inconvenience. Patients become less apprehensive about the disconcerting appearance of blood-tinged drainage once it has been explained that the greater the drainage the less the postliposuction bruising, swelling, and soreness.

Compression Sponges

Compression sponges or pads have two distinct functions. They completely absorb the copious tumescent drainage and therefore improve patient comfort and hygiene. Containing SAP and cellulose, a 25 cm x 50 cm (10 inch x 20 inch) compression sponge can absorb up to 1,000 mL of watery fluids. Secondly, these compression sponges or pads distribute the compressive force of an elastic garment over the treated area in a smooth, uniform fashion. By uniformly compressing the dermal interstitial collagen, the interstices between the dermal collagen bundles are narrowed and red blood cells are prevented from moving toward the skin surface. Therefore, bruising is prevented.

Super-absorbent compression sponges eliminate postoperative bruising in a fashion similar to adhesive-backed, closed-cell foam when applied postoperatively over an area of the body that has been treated by liposuction. Compression pads are superior to adhesive closed-cell foam for postliposuction care. Adhesive foam applied to the skin after liposuction can crimp and cut off dermal vascular dermal supply, and therefore cause focal avascular dermal bullae. Adhesive foam must remain on the skin for several days, which precludes the possibility of showering. In contrast, the compression sponges are replaced once or twice daily, permitting patients to shower. Whereas adhesive foam only reduces bruising, super-absorbent compression pads both reduce bruising by compression and reduce osmotic edema by facilitating open drainage.

History of Postliposuction Compression

The tradition of long-term use of high-compression garments after liposuction is a vestige of the earliest days of liposuction during the late 1970s and early 1980s. In the days before the tumescent technique, antediluvian liposuction created a proteinaceous melange of grumous clotted blood, inflammatory cytokines, prostoglandins, and fragmented adipose tissue. By closing incisions with sutures, this inflammatory detritus was trapped within the subcutaneous wound. The patient was required to endure weeks of being wrapped in special plastic adhesive “French” tape in the manner of a mummy. Taking a normal shower or bath was not an option. Removing the tape could be so dreadful that some patients required systemic narcotic analgesia. Eventually surgeons replaced the use of “French tape” with high-compression elastic postoperative garments. With either type of compression, there was a high rate of seroma formation, massive bruising, prolonged swelling and tenderness, and significantly delayed return to normal activity.

Chronic venous edema and acute postliposuction edema are distinctly different pathophysiologic processes. Leg edema owing to venous disease is best treated and prevented by providing graduated leg compression beginning at 15 mm Hg to more than 30 mm Hg distally, and decreasing proximally. In contrast, local edema owing to tumescent liposuction can be largely prevented by open drainage and uniform (non-graduated) bimodal compression. It is a misconception that the pathophysiology of acute postliposuction leg edema resembles chronic post-phlebitic venous disease. Chronic venous insufficiency is due to venous hypertension and a hydrostatic pressure gradient that favors chronic leakage of intravascular fluid into the interstitial tissues. Acute postliposuction edema is due to acute posttraumatic hemorrhage, inflammation, and an osmotic pressure gradient.

Excessive Compression

Prolonged high compression is only necessary when drainage is impeded by closing incisions with sutures. With old-fashioned liposuction, the subcutaneous voids and tunnels were filled with blood, clot, or hematoma. Constant compression applied externally to the skin has the tendency to squeeze the delicate subcutaneous lymphatic capillary, causing the lumen to collapse upon itself and preventing interstitial fluid from entering the lymphatic capillary lumen. Therefore, excessive continuous external compression may actually impede lymphatic drainage and exacerbate postoperative edema. Without open drainage, the compression delivered by traditional postliposuction garments may be detrimental.

Graduated Verses Bimodal Compression

Therapeutic compression after liposuction is qualitatively different from the type of compression used to treat leg vein disease. Varicose vein treatment requires compression to overcome venous hypertension, and prevention of perioperative deep vein thrombosis requires compression to prevent the venostasis associated with the general anesthesia-induced loss of sympathetic vascular tone. In contrast, compression after tumescent liposuction is intended to expel the subcutaneous fluid containing a melange of blood, fragmented adipocytes, and trauma-induced inflammatory exudates.

Lower extremity venous stasis is treated by a graduated compression garment. Graduated compression is necessary to counter the hydrostatic (gravitational) forces within veins having incompetent valves.[5] Because the hydrostatic force exerted by a vertical column of fluid increases as a function of the column’s length, venous pressure in leg veins with incompetent valves increases distally when the patient is in an upright posture. In this setting, graduated compression is necessary to counteract the progressive increase in physical forces exerted by fluid contained within the “closed” hydraulic system of the lower extremity.

Graduated compression is not necessary after tumescent liposuction. Open drainage and bimodal compression are more efficient and more comfortable, and the compression garments are easier to put on and take off compared to graduated compression garments.

Optimal Compression is Bimodal

Proper postoperative compression after tumescent liposuction requires two degrees of compression applied sequentially (i.e., the compression after tumescent liposuction is bimodal). Bimodal compression involves two distinct therapeutic phases: the drainage phase and the post-drainage phase.

During the drainage phase, high compression is applied immediately after liposuction to encourage drainage from adits and open microincisions. Uniform high compression will maximize the drainage out of the suctioned subcutaneous adipose tissue onto the absorptive dressings and minimize postliposuction edema. With open drainage and high compression, the tumescent drainage usually ceases in 24 to 72 hours. After liposuction of an unusually large abdomen or thighs, drainage may persist for several additional days. Once all the drainage has ceased, external compression is no longer essential. The ultimate cosmetic result does not depend on continued compression after all tumescent drainage has ceased.

During the post-drainage phase, after all the drainage of blood-tinged anesthetic solution has ceased, only a mild degree of compression is needed. Once external drainage has ceased, lymphatic uptake is the only means of clearing the subcutaneous tissue of protein-laden edema fluid. The function of mild compression is to augment the interstitial fluid hydrostatic pressure just enough to counterbalance the increased interstitial fluid osmotic pressure, and thereby slow the rate of transudation of intravascular water. Mild compression also provides a sense of security during physical activity and seems to provide a moderate degree of analgesia and comfort.

[1] Majino G, Joris I: Cells, Tissues, and Disease: Principles of General Anesthesia. Cambridge, MA, Blackwell Science, 1994.

[2] Odland GF: Structure of Skin. In Goldsmith LA (ed): Physiology, Biochemistry, and Molecular Biology of the Skin, ed. 2. New York, Oxford University Press, 1991, pp 19-20.

[3] Guyton AC, Hall JE: The microcirculation and the lymphatic system: Capillary fluid exchange, interstitial fluid, and lymph flow.In Guyton AC, Hall JE (eds): Textbook of Medical Physiology, ed. 9. Philadelphia, WB Saunders, 1996, pp 193-196.

[4] Pitman GH: Liposuction and Aesthetic Surgery. St. Louis, Quality Medical Publishing, Inc., 1993, p 67.

[5] Straudinger P: Compression therapy: Low or short stretch bandage and graduated compression stockings for leg edema [letter]. Dermatol Surg 21:106, 1995.

JEFFREY A. KLEIN, MD

NORMA KASSARJDIAN, MD

We report a case of mild lidocaine toxicity. A reduced rate of lidocaine metabolism following tumescent liposuction may result from an inhibition of cytochrome P450 3A4 (CYP3A4) by sertraline (Zoloft) and flurazepam (Dalmane).

When two or three drugs are each substrates for the same enzyme, there is a possibility for an adverse drug reaction when used simultaneously. Lidocaine is rapidly and almost exclusively eliminated by CYP3A4. The newer antidepressant selective serotonin reuptake inhibitors (SSRI) such as sertraline are metabolized by the hepatic enzymes CYP3A4 and CYP2D6. The benzodiazepines such as midazolam (Versed) and diazepam (Valium) are also metabolized by the CYP 3A4 isoenzymes. The specific cytochrome P450 enzyme responsible for the metabolism of flurazepam has not been identified.

Since 1994 there has been a rapid expansion of information about the specificity of hepatic microsomal enzymes of the cytochrome P450 family for the metabolism of different drugs. This new information permits a knowledgeable clinician to anticipate some adverse drug interactions.

Surprisingly high doses of lidocaine are well tolerated when delivered subcutaneously by the tumescent technique. For several years 60-mg/kg doses of lidocaine for tumescent liposuction had been the de facto, unpublished, recommended maximum safe dose. Until now there have been no reports of untoward consequences.

The safety of such high doses has yet to be well documented by rigorous pharmacologic studies involving a large number of patients. One study with 10 patients concluded that tumescent anesthesia with a lidocaine dose of 55 mg/kg is safe for liposuction.1 We have personally performed tumescent liposuction on more than 400 patients using lidocaine doses in the range of 50-60 mg/kg without evidence of lidocaine toxicity.

Case Report: Lidocaine Toxicity

Our patient was a 39-year-old female weighing 80 kg, on whom we performed two tumescent liposuction surgeries. Five years earlier, a breast cancer was treated by chemotherapy, radiation, and bone marrow transplantation. She had a long history of treatment with sertraline (Zoloft) 200 mg daily for anxiety disorder, panic attacks, and mild depression. Sertraline was not discontinued prior to either surgery.

The first surgery, liposuction of the hips and outer thighs, was uneventful. Perioperative sedation consisted of 10 mg PO zolpidem tartrate (Ambien). The dose of tumescent lidocaine totaled 59 mg/kg (lidocaine 800 mg/L, epinephrine 0.65 mg/L, sodium bicarbonate 10 meq/L) in 0.9% NaCI at 37C. Liposuction produced of 2,700 mL of supernatant fat, and 250 mL of infranatant blood-tinged anesthetic solution.

One month later she returned for liposuction of the inner thighs, inner knees, and buttocks. Perioperative sedation on this occasion of 30 mg PO of flurazepam (Dalmane), instead of the zolpidem that was used for the first surgery. Between 11:20 a.m. and 13:00 p.m. she received 58 mg/kg of tumescent lidocaine (lidocaine 900 mg/L, epinephrine 0.65 mg/L, bicarbonate 10 meq/L) in 0.9% NaCI at 37C. The liposuction was uneventful, yielding 1,800 mL of supernatant fat, and 650 mL of infranatant blood-tinged anesthetic solution. She was discharged at 17:20 p.m. alert and fully ambulatory.

Ten hours after completion of the tumescent infiltration of lidocaine, the patient awoke, experiencing nausea, vomiting, unsteady gate, mild confusion, and dysarthria. Physical examination in a local emergency room revealed anxiety, short-term memory impairment, and slight pallor; otherwise, the neurologic and cardiovascular findings, the ECG, and routine laboratory studies were unremarkable. Blood drawn at 23:48 p.m. had a plasma lidocaine concentration of 6.3 mg/L by immunoassay (IA), and confirmed by gas chromatography (GC) to be 6.1 mg/L. Lidocaine plasma levels greater than 6 mg/L are associated with an increased risk of toxicity. Admitted to the hospital for overnight observation, she was discharged the next morning after a 06:45 a.m. lidocaine level was 2.9 mg/L by IA, and confirmed at 3.0 mg/L by GC.

Discussion

To the best of my knowledge, that was the first documented case of tumescent liposuction totally by local anesthesia where a standard dose of lidocaine, widely recognized as safe, has led to potentially toxic plasma lidocaine concentrations. It demonstrates the possibility of serious interactions between tumescent lidocaine and commonly used oral medications. Both sertraline and flurazepam have the potential for significantly reducing lidocaine clearance via inhibition of CYP3A4 and thereby increasing plasma lidocaine concentrations above the threshold for toxicity. It is unclear whether or not our patients prior treatment for breast cancer affected her ability to metabolize lidocaine.

Perhaps sertraline and flurazepam had an additive effect on reducing the rate of lidocaine metabolism. During the first surgery, when the patient had taken sertraline but not flurazepam, there were no symptoms of lidocaine toxicity. It is possible that lidocaine plasma concentrations were elevated asymptomatically. Flurazepam has been taken by the majority of our tumescent liposuction patients and, other than the present patient, none had ever had evidence of elevated lidocaine blood levels.

Cytochrome P450 System

The cytochrome P450 (CYP450) family of enzymes is essential for most drugs eliminated by hepatic metabolism.2 The P450 designation is derived from the fact that these enzymes have 450 nm as the wavelength of maximum absorption in the reduced state in the presence of carbon monoxide. Based the homology of amino acid sequences, the CYP450 enzymes a have been categorized into families, subfamilies and individual enzymes.3

Microsomes are the microvesicles formed from fragments of endoplasmic reticulum after liver tissue has been homogenized and centrifuged. These enzymes located in the endoplasmic reticulum are referred to as microsomal enzymes. Metabolic drug interactions are usually studied in vitro using liver tissue.

Cytochrome P450 evolved over billions of years as an important means of converting potentially harmful concentrations of lipid soluble nutrients and environmental substances into more easily eliminated water soluble compounds. In humans there are 12 known families of CYP250 isoenzymes, of which only five are important in drug metabolism: 3A4, 1A2, 2C9, 2C19, and 2D6.

When two drugs, both requiring the same enzyme for metabolism, are given concurrently, there is a potential for an adverse drug reaction. Many factors determine the relative effects of one drug on the metabolism of another drug. Drug concentration and relative enzyme affinity determine metabolic drug interactions.

There is a significant degree of interpatient variability with respect to the enzymatic activity of the cytochrome P450 isoenzymes. This makes it difficult to predict the probability of any specific drug interaction.4

Hepatic Metabolism of Lidocaine

Lidocaine is rapidly eliminated by hepatic metabolism.5 The liver metabolizes 70% of the lidocaine that enters the hepatic circulation at any given moment. When 1 L of blood passes through the hepatic circulation of a healthy volunteer, more than 700 mL of the blood is completely cleared of its lidocaine content.6 Lidocaine is said to have a hepatic extraction ratio of 0.7. With such a high hepatic extraction ratio of 0.7, lidocaine metabolism is said to be flow rate limited. In other words, the rate of lidocaine metabolism usually depends on the rate of blood flow to the liver.

Table 1. Cytochrome P450 3A4 Inhibitors49

• amiodarone
• benzodiazepines
• midazolam
• triazolam
• cimetidine
• clarithromycin
• chloramphenicol
• cyclosporin
• danazol
• dexametasone
• diltiazam
• erythromycin
• fluconazole
• itraconazole
• isoniazid
• ketoconazole
• methadone
• methylprednisolone
• metronidazole
• miconazole
• nicardipine
• nifedipine
• pentoxifylline
• propofol
• propranolol
• quinidine
• SSRI antidepressants
• tetracycline
• terfenidine
• thyroxine
• verapamil
• antiseizure medications
• carbamazepine
• valproic acid
• verapamil

At typical therapeutic plasma concentrations of lidocaine, metabolism of lidocaine is so efficient that lidocaine does not seem to cause any substrate inhibition of the enzyme CYP3A4 Lidocaine clearance can be reduced by any drug that inhibits CYP3A4 enzymes, such as erythromycin or ketoconazole. Similarly any condition that reduces hepatic blood flow, such as decreased cardiac output associated with congestive heart failure, or shock will decrease lidocaine clearance. The β-blocker drugs, such as propranolol decrease lidocaine by both mechanisms, propranolol inhibits CYP3A4 and is decreases cardiac output and therefore hepatic blood flow.7 Patients with cirrhosis of the liver have a reduced lidocaine clearance; however, in renal insufficiency, lidocaine clearance is normal.

The metabolism of lidocaine by CYP3A4 is a sensitive means for evaluating hepatic function. Determining the amount of the lidocaine metabolite monoethylglycine-xylidide (MEGX) produced in a patients liver has been used as a measure the degree of liver dysfunction and to predict the survival in critically ill patients.8 Lidocaine metabolism is used to evaluate the enzymatic activity in a bioartificial liver.9

CYP3A4

The most abundant of all human cytochrome P450 enzymes, the isoenzyme cytochrome P450 34A, is responsible for the metabolism of more drugs, and a broader range of drugs, than any other hepatic enzyme. CYP3A4 metabolizes a wide variety of drugs such as lidocaine, antidepressants, carbamazepine10 (Tegretol), nifedipine, (Procardia),11 methadone, 11 and alfentanil. 12,13

Certain drugs will augment the enzymatic activity of CYP3A4. Rifampicin induces CVP3A4 and augments the metabolism of lidocaine14 and triazolam (Halcion). 15 An infusion of heme arginate induces CYP3A4 and augments lidocaine metabolism in patients with variegate porphyrial. 16

Whereas CYP3A4 is inducible by some drugs, the CYP2D6 is not inducible but it can be inhibited by certain drugs. 17 Potent in vitro inhibitors of both CYP3A4 and CYP2D6 include sertraline (Zoloft), fluoxetine (Prozac), fluoxamine (Luvox), and paroxetine (Praxil), all of which are selective serotonin reuptake inhibitors (SSRI). 18 All of the available newer antidepressants, including the SSRIs, and as well as nefazodone (Serzone), an antidepressant unrelated to SSRI, inhibit cytochrome, P450 3A4, and are associated with clinically significant drug interactions.

The use of SSRI drugs is becoming more ubiquitous. Antidepressant medications are widely prescribed, and may be taken by prospective liposuction patients. For example, fluoxetine at 20 mg per day is used in the treatment of premenstrual dysphoria. 19

Similarly, alprazolam (Xanax) has also been found to have a role in the treatment of severe premenstrual syndrome (PMS). 20 It is plausible that potential tumescent liposuction patients might be taking a combination of fluoxetine and alprazolam. The combination of an SSRI and a benzodiazepine might inhibit lidocaine metabolism, in a fashion analogous to the present case.

Drug Interactions and CYP3A4

There is a growing number of examples of drug interactions that are mediated by inhibition or induction of CYP3A4. Drug interactions mediated by CYP450 3A4 can have devastating consequences. For example, the nonsedating antihistamines terfenadine (Seldane), and astemizole 21 (Hismanal), as well as cisapride (Propulasid), used to treat nocturnal heart burn due to gastroesophageal reflux disease, are metabolized by cytochrome P450 3A4. However, ketoconazole (Nizoral), itraconazole, (Sporanox), erythromycin, and clarithromycin, (Biaxin) are potent inhibitors of P450 3A4 and block the metabolism of terfenadine, astemizole, and cisapride. The resulting elevation of plasma terfenadine, astemizole, or cisapride can cause fatal QT prolongation and torsades des pointes-type ventricular tachycardias.

Erythromycin inhibits the ability to CYP3A4 to metabolize midazolam. This interaction can result in a prolonged coma. 22

Not all macrolide antibiotics inhibit CYP3A4. Azithromycin (Zithromax) and dirithromycin (Dynabac) are eliminated by a combination of hepatic metabolism and biliary excretion. There are no reports of the effects of azithromycin or dirithromycin inhibiting CYP 3A4, however, clinical pharmacologic studies have shown that these drugs do not cause elevated terfenidine (Seldane) blood levels.

Methadone is extensively metabolized by CYP3A4 Fluvoxamine (Luvanox), a new SSRI antidepressant, is a potent mixed type inhibitor of methadone metabolism. Conversely, the metabolism of nifedipine (Procardia) by CYP3A4 is potently inhibited by methadone. 11

The apparent decrease of enzymatic activity with advancing age, 23 might simply by secondary to changes in liver blood flow, size, or drug binding and distribution with age. 24 Dietary factors, such a grapefruit juice, can inhibit CYP450 3A4 found in intestinal mucosa.

Fluoxetine (Prozac) via its metabolite norfluoxetine inhibits CYP3A4 and impairs the metabolism of warfarin (Coumadin).

Sertraline and Other SSRI

The majority of the newer antidepressants of the SSRI type, including sertraline are associated with clinically significant drug interactions mediated by the inhibition of cytochrome P450 enzymes. 25 Sertraline can inhibit both CYP2D6 and CYP3A4.

The usual oral dose of sertraline ranges from 50 to 200 mg once daily. Based on an elimination half-life (t½) of 26 hours, steady-state plasma sertraline levels are achieved after 7 days of once-daily dosing in patients with healthy hepatic metabolism. Conversely, in patients who have a healthy liver, 1 week is required for the body’s content of sertraline to be 98% eliminated after discounting the drug. In patients with mild cirrhosis, more than 2-3 weeks in required for sertraline to be eliminated. In vitro, sertraline shows inhibition of cytochrome P450 3A4 isoenzyme. But sertraline need not necessarily affect the metabolism of all drugs that are metabolized by CYP3A4. In vivo, sertraline does not seem to affect the metabolism of diazepam. 26

Sertraline is tightly bound to plasma proteins, and may competitively displace other protein-bound drugs such as lidocaine, increasing the amount of free (unbound) drug, and increasing the potential for toxic reactions.

After discontinuing Zoloft, it might be prudent to wait 7-14 days before starting any drug known to have potential adverse cytochrome P450 (metabolic pathway) interactions. SSRIs are known to interact with monoamine oxidase inhibitors (MOAI) to produce fatal reactions. Fatal drug interactions have even occurred in patients who have discontinued an SSRI and were then started on an MAOI.

Benzodiazepines

The specific cytochrome P450 isoenzyme that is responsible for the metabolism of flurazepam has not been identified (personal communication, Roche Laboratories). The half-life of flurazepam in plasma is 2-3 hours, but its major active metabolite (N-desalkylflurazepam) has a half-life of 47-100 hours.

Benzodiazepines are metabolized by several different microsomal enzymes. Approximately 75% of the available benzodiazepines are significantly metabolized by CYP3A4. Cytochrome P450 3A4 metabolizes alprazolam. 27 (Xanax), triazolam28 (Halcion), diazepam29,30 (Valium), midazolam31 (Versed), and other benzodiazepines. Plasma concentrations of these benzodiazepines increase when they are administered with drugs that inhibit CYP3A4, including most newer SSRI antidepressants. 25 There can be a considerable variation in the rate of metabolism of midazolam and triazolam among healthy volunteers.

The antipsychotics clozapine (Clozaril), and the antifungal ketoconazole (Nizoral), all noncompetitively inhibit midazolam metabolism. The metabolism of midazolam (Versed) is significantly decreased by the inhibition of CYP3A4 by Ketoconazole (Nizoral), itraconazole (Sporanox), and fluconazole (Diflucan). 32 The antipsychotic olanzapine has little effect on midazolam metabolism. 34 Fluoxetine (Prozac) appears to impair the metabolism of alprazolam (Xanax) but not the clonazepam (Klonopin). 34

Nefazodone (Serzone), an antidepressant, is a competitive inhibitor CYP3A4 in the metabolism of alprazolam (Xanax) 27 and triazolam (Halcion) [personal communication, Roche Laboratories]). 27 In contrast, the metabolic clearance of lorazepam (Ativan) depends on conjugation rather than hydroxylation, and this it is not inhibited by nefazodone (personal communication, Roche Laboratories).

Fluoxetine (Prozac) may impair the metabolism of both diazepam (Valium) and warfarin (Coumadin). However fluoxetine does not impair lorazepam (Ativan), or oxazepam (Serax). 35

Although the SSRI fluoxetine does not affect the metabolism of triazolam (Halcion), 36 the combination of the tricyclic antidepressant amitriptyline and triazolam has been associated with a fatality. 37

Based on the present experience we now recommend lorazepam as the benzodiazepine of choice. A 2-4 mg oral dose of lorazepam produces more consistent and longer lasting anxiolysis, sedation, and anterograde amnesia that is comparable with 10-20 mg of diazepam (Valium). 38, 39 Lorazepam appears to increase respiratory drive and attenuate the respiratory depression associated with meperidine. 40 Lorazepam is the only benzodiazepine that is not metabolized by cytochrome P450 enzymes, and therefore is less susceptible to adverse drug interactions. In its initial metabolic reaction lorazepam is conjugated to lorazepam-glucuronide, which had no CNS activity, and excreted in the urine. Available in 0.5-, 1-, and 2-mg tables, lorazepam at 2 mg is equivalent in peak effectiveness to 10 mg of diazepam .

Lidocaine and CYP3A4

Lidocaine is principally metabolized by the CYP3A4. CYP3A4 oxidizes a diversity of substrates including drugs, carcinogens, and steroids. 41 CYP3A4 alters lidocaine by a sequential process of oxidativeN-dealkylation, first by oxidative deethylation of the amino nitrogen yielding, mono-ethyl glycine xylidine (MEGX). Next, an additional oxidative reaction removes the residual eythyl group from MEGX, yielding glycine xylidine (GX). 42

By competitive inhibition or by enzyme induction, drugs can either inhibit or accelerate lidocaine metabolism. Sertraline (Zoloft) has been shown to have some inhibition of cytochrome P450 3A4 in vitro although the clinical significance of this has not been established. The combination of lidocaine and the antiarrhythimic amiodarone43 (Cordarone), both metabolized by CYP3A4, is associated with bradycardia and seizures. 44 Antiepileptic drugs appear to compete with lidocaine for CYP3A4 and slow lidocaine metabolism. 45 Although the clinical significance is not clear, in rat liver microsomes lidocaine and propranolol exhibit mutual metabolic inhibition. 46

Drugs that inhibits enzymatic activity of CYP 3A4 have the potential for elevating the plasma concentrations of lidocaine. In the setting of tumescent liposuction where patients’ lidocaine blood levels are typically in the low therapeutic range between 1 and 3.5 mg/L, anything that causes a diminution of lidocaine metabolism can result in lidocaine levels above the 6-mg/L threshold for potential toxicity.

Recommended Maximum ‘Safe’ Doses of Tumescent Lidocaine

Our present recommendation for maximum allowable doses of tumescent lidocaine in healthy, young female patients is as follows: 45 mg/kg for thin patients, 55 mg/kg for average patients, and 60 mg/kg for overweight patients.

Doses as high as 80-90 mg of tumescent lidocaine might be safe in a majority of patients, however, the true risk of toxicity is unknown. Administering such high doses, without well-documented toxicology studies based on large numbers of patients, is cavalier at best. Serial liposuction procedures separated by 1 week or more are safer than 1-day heroic mega-liposuction sessions imprudent utilizing doses of lidocaine. The fundamental philosophy of tumescent liposuction is ‘safety first and convenience second.’

Maximal lidocaine doses must be reduced in certain situations. In patients who are taking drugs that interfere with lidocaine metabolism, such as the newer SSRI antidepressant sertraline (Zoloft), lidocaine doses must be reduced by at least 30-40%.

It is our clinical impression that obese patients tolerate higher mg/kg doses of lidocaine better than relatively thin patients. There is a higher incidence of lidocaine toxicity among coronary care unit patients weighing less than 70 kg. 47 Thus, thin patients may have a smaller volume of distribution, and a slower clearance for lidocaine. In other words, given identical mg/kg doses of lidocaine, thinner patients will have greater peak plasma lidocaine concentration than obese patients.

Males, whose percentage of body fat is usually 10-20% less than females, have a smaller volume of distribution of lidocaine and therefore the maximum allowable dose should be reduced by 10-20%

Younger patients tolerate more lidocaine than older patients. This is attributed to the decrease in cardiac output, and the consequence decrease in hepatic perfusion associated with advancing age. Thus, older patients should be given smaller doses of tumescent lidocaine.

The present case illustrates the possibility of an unanticipated toxic drug interaction. A lidocaine dose that would be safe under normal circumstances might be toxic as a result of unanticipated drug interactions. Because patients do not always provide an accurate clinical history, one cannot rely on a history for eliminating the possibility of an adverse drug reaction. One needs to be cautious and conservative when using more than 35 mg/kg of lidocaine for tumescent liposuction.

Drugs that potentially interfere with lidocaine metabolism should be discontinued at least 2 weeks before using tumescent technique for local anesthesia when high doses of lidocaine are anticipated. If it is not reasonable to discontinue a drug that might interfere with lidocaine metabolism, then the surgery should be limited to smaller total doses of lidocaine.

References

1.     Ostad A, Kageyama N, Moy RL. Tumescent anesthesia with a lidocaine dose of 55 mg/kg is safe for liposuction. Dermatol Surg. 1997;22:921-7.

2.     Wrightson SA, Stevens JC. The human hepatic cytochromes P450 involved in drug metabolism. Crit Rev Toxicol 1992;22:1-21.

3.     Nelson DR, Kamataki T, Waxman DJ, et al. The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature, DNA and Cell Biol 1993;12:1-51.

4.     May JR. Adverse drug reactions and interactions. In DiPiro JT, et al, eds. Pharmacotherapy: A Pathophysiologic Approach; 2nd ed, New York: Elsevier Science Inc., 1992:78.

5.     Bennett PN et al. Pharmacokinetics of lidocaine and its deethylated and metabolite. Dose and time dependency studies in man. J Pharmacokinet Biopharm 1982;10:265-81.

6.     Mather LE, Thomas J. Metabolism of lidocaine in man. Life Sci 1972:11:915-9.

7.     Stenson RE, et al, Interrelationship of hepatic blood flow, cardiac output and blood levels lidocaine in man. Circulation 1971;48:205-11.

8.     Schroter J, Wandel C, Bohrer H, et al. Lignocaine metabolite formation: an indicator for liver dysfunction and predictor of survival in surgical intensive care patients. Anaesthesia 1995;50:850-4.

9.     Nyberg SL, Mann HJ, Remmel RP, Hu WS, Cerra FB. Pharmacokinetic analysis verifies P450 function during in vitro and in vivo application of a bioartifiaial liver. ASAIO J 1993;39:M252-6.

10.  Spina E, Pisani F, Perucca E. Clinically significant pharmadcokinetic drug interactions with carbamazepine. An update. Clin Pharmacokinet. 1996;31:198-214.

11.  Iribarne C, Dreano Y, Bardou LG, Menez JF, Berthou F. Interaction of methadone with substrates of human hepatic cytochrome P450 3A4. Toxicology 1997;14:13-23.

12.  Bartkowski RR, Goldber ME, Larijani GE: Inhibition of alfentanil metabolism by erythromycin. Clin Pharmacol Ther 1989;46:99.

13.  Yun C-H, Wood M, Wood AJJ, Guengerich FP: identification of the pharmacogenetics determinants of alfentanil metabolism: cytochrome P-450 3A4. Anesthesiology 1992;77:467.

14.  Li AP, Rasmussen A, Xu L, Kaminski DL. Rifampicin induction of lidocaine metabolism in cultured human hepatocytes. J Pharmacol Exp Ther 1995;274:673-7.

15.  Villikka K, Kivisto KT, Backman JT, Olkkola KT, Neuvonen PJ. Triazolam is ineffective in patients taking rifampin. Clin Pharmacol Ther 1997;61:8-14.

16.  Mustajoki P, Mustajoki S, Rautino A. Arvela P, Pelkonen O. Effects of heme arginate on cytochrome P450-mediated metabolism of drugs in patients with variegate porphyria and in healthy men. Clin Pharmacol Ther 1994;56:9-13.

17.  Riesenamn C. Antidepressant drug interactions and the cytochrome P450 system: a critical appraisal. Pharmacotherapy 1995;15(Suppl 6):84-99.

18.  Nemeroff CB, DeVane LC, Pollock BG. Newer antidepressants and the cytochrome P450 system. Am J Psychiatry 1996;153:311-20.

19.  Steiner M, Steinberg S, Stewart D, et al. Fluoxetine in the treatment of premenstrual dysphoria. N Engel L Med 1995;332:1529-34.

20.  Freeman EW, Rickels K, Sondheimer SJ, Ploansky M. A double-blind trial of oral progesterone, alprazolam, and placebo in the treatment of severe premenstrual syndrome. J Am Med Assoc 1995;274:51-7.

21.  Robinson DS, Roberts DL, Smith JM, et al, The safety profile of nefazodone, J Clin Psychiatry 57 (Suppl) 1996;2:31-8.

22.  Hiller A, Olkkola KT, Isohanni P, Saarnivaara L: Unconsciousness associated with midazolam and erythromycin. Br J Anaesth 1990;65:826.

23.  Sotaniemi EA, Lumme P, Arvela P, Rautio A. Age and CYP3A4 and CYP2A6 activities marked by the metabolism and lignociane and coumarin in man. Therapie 1996;51:363-6.

24.  Hunt CM, Westerkam WR, Stave GM. Effect of age and gender on the activity of human hepatic CYP3A. Biochem Pharmacol 1992;44:275-83.

25.  Nemeroff CB, DeVane CL, Pollack BG. Newer antidepressants and the cytochrome P450 system. AM J Psychiatry 1996;153:311-20.

26.  Gardner MJ, Baris BA, Wilmer KD, Preskorn SH. Effect of sertraline on the pharmacokinetics and protein binding of diazepam in healthy volunteers. Clin Pharmacokinet 1997;32 (Suppl 1):43-9.

27.  Greene DS, Salazar DE, Dockens RC, Kroboth P, Barbhaiya RH. Coadministration of nefazodone and benzodiazepines. III. A pharmacokinetic interaction study with alprazolam. J Clin Psychopharmacol 1995;15:399-408.

28.  Barbhaiya RH, Shukla UA, Kroboth PD, Greene DS. Coadministration of nefazondone and benzodiazepines: II. A pharmacokinetic interaction study with triazolam. J Clin Psychopharmacol 1995;15:320-6.

29.  Ono S, Hatanaka T, Miyazawa S, et al. Human liver microsomal diazepam metabolism using cDNA-expressed cytochrome P450s: role of CYP2B6, 2C19, and the 3A subfamily. Xenobiotice 1996;26:1155-66.

30.  Perucca E, Gatti G, Cipolla C, et al. Inhibition of diazepam metabolism by fluvoxamine: a pharmacologic study of normal volunteers. Clin Pharmacol Ther 1994;56:471-6.

31.  Wendel C, Becker R, Behrer H, et al. Midazolam is metabolized by at least three different cytochrome P450 enzynes. Br J Anaesthesia 1994;73:658-61.

32.  Von Moltke LL, Greenbalt DJ, Schmider J, et al. Midazolam hydroxylation by human liver microsomes in vitro: inhibition by flouxetine, norfluoxetine, and by azole antifungal agents. J Clin Pharmacol 1996;36:783-91.

33.  Ring BJ, Binkley SN, Vandenbranden M, Wrightton SA. In vitro interaction of the antipsychotic agent olanzapine with human cytochrome P450 CYP2C9, CYP2C19, CYP2D6, and CYP3A. Br J Clin Pharmacol 1996;41:181-6.

34.  Greenblatt, DJ, Preskorn SH, Contreau MM, Horst WD, Harmatz JS. Fluoxetine impairs clearance of alprazolam but not of clonazepam. Clin Pharmacol Ther 1992;52:479-86.

35.  Dent LA, Orrock MW. Warfarin-fluoxetine and diazepam -fluoxetine interaction, Pharmacotherapy 1997;17:170-2.

36.  Wright CE, Lasher-Sisson TA, Steenwyk RC, Swanson CN. A pharmokinetic evaluation of the combined administration of triazolam and fluoxetine. Pharmacotherapy 1992;12:103-6.

37.  Kudo K, Imamura T, Jitsufuchi N, et al. Death attributed to the toxic interaction of triazolam amitriptyline other psychotropic drugs. Forensic Sci Int 1997;18:35-41.

38.  McKay AC, Dundee JW. Effect of oral benzodiazepines on memory. Br J Anaesth 1980;52:1247.

39.  Fragen RJ, Caldwell N. Lorazepam premedication: lack of recall and relief of anxiety. Anesth Analg 1976;55:792.

40.  Paulson BA, Becker LD, Way WL. The effects of intravenous lorazepam alone and with meperidine on ventilation in man. Acta Anaesthesiol Scand 1983;27:400.

41.  Ueng YF, Kuwabara T, Chun YJ, Guengerich FP. Cooperativity in oxygenations catalyzed by cytochrome P450 3A4. Biochemistry 1997;36:370-81.

42.  Cohen LJ, De Vane CL. Clinical implications of antidepressant pharmacokinetics and pharmacogenetics. Ann Pharmacother 1996;30:1471-80.

43.  Ha HR, Cardinas R, Steiger B, Merey UA, Follath F. Interaction between amiodarone and lidocaine. J Cardiovasc Pharmacol 1996;28:533-9.

44.  Physicians’ Desk Reference. Montvale, NJ: Medical Economics Company, 1997:2823.

45.  Sotaniemi EA, Rautio A, Backstrom M, Arvela P, Pelkonen O. CYP3A4 and CYP2A6 activities marked by the metabolism of lignocaine and coumarin in patients with liver and kidney diseases and epiletic patients. Br J Clin Pharmacol 1995;39:71-6.

46.  Suzuki T, Ishida R, Matsui S, Masubuchi Y, Narimatzu S. Kinetic analysis of mutual metabolic inhibition of lidocaine and propranolol in rat liver microsomes. Biochem Pharmacol 1993;45:1528-30.

47.  Pfeifer HJ, et al. Clinical use and toxicity of intravenous lidocaine. A report from the Boston Collaborative Drug Surveillance Program. Am Heart J 1976;92:168-73.

48.  Park GR. Molecular mechanisms of drug metabolism in the critically ill. Br J Anaesthesia 1996;77:32-49.

Jeffrey A. Klein, M.D.

The tumescent technique for local anesthesia improves the safety of large-volume liposuction (>1500ml) of fat) by virtually eliminating surgical blood loss and by completely eliminating the risks of general anesthesia. Results of two prospective studies of large-volume liposuction using the tumescent technique are reported.

In 112 patients, the mean lidocaine dosage was 33.3 mg/kg, the mean volume of aspirated material was 2657 ml, and the mean volume of supranatant fat was 1945 ml. The mean volume of whole blood aspirated by liposuction was 18.5 ml. For each 1000 ml of fat removed, 9.7 ml of whole blood was suctioned. In 31 large volume liposuction patients treated in 1991, the mean difference between preoperative and 1-week postoperative hematocrits was -1.9 percent. The last 87 patients received no parenteral sedation.

In a second study, a 75-kg woman received 35 mg/kg of lidocaine on two separate occasions, first without liposuction and 25 days later with liposuction; peak plasma lidocaine concentrations occurred at 14 and 11 hours after beginning the infiltration and were 2.37 and 1.86 ųg/ml, respectively. (Plast. Reconstr. Surg.92:1085, 1993.)

Among the greatest risks of liposuction surgery are the dangers associated with general anesthesia and excessive bleeding.1,2 Utilizing copious volumes of very dilute lidocaine , the tumescent technique for liposuction eliminates or minimizes these risks. It permits liposuction of more than 3000 ml of fat totally by local anesthesia without sedation. The estimated maximum safe lidocaine dosage using the tumescent technique is 35 mg/kg. 3

This paper presents data showing that the tumescent technique for large-volume liposuction not only eliminates the need for general anesthesia, IV sedation, and narcotic analgesics but also virtually eliminates surgical blood loss.

Patients and Methods

One-hundred and twelve patients who had liposuction of at least 1500 ml of supranatant fat from February of 1989 through October of 1992 were included in this prospective study. All patients were treated as outpatients in an office-based surgical facility or in a state-licensed multispecialty ambulatory surgicenter. None of the patients were hospitalized.

Patients were prescribed antibiotics, cefadroxil, 500 mg, or doxycycline, 100 mg, taken twice daily for 6 days, beginning the day before surgery. No narcotic analgesics were used in any patients. As a safety precaution, all patients had an IV line for infusion of physiologic saline to maintain vascular access.

Flurazepam, 30 mg, the night before surgery or the morning of surgery, was available to all patients, although only a few took it. In 1991, the routine use of parenteral sedation was discontinued. Because of anxiety, 1 of 40 patients treated in 1991 required IV sedation, receiving a total of two 1-mg doses of IV midazolam. None of the last 87 patients received any IV or IM sedation.

Anesthesia was achieved by direct infiltration into subcutaneous fat of a solution of lidocaine, 400 to 1000 mg, epinephrine, 0.5 to 1.0 mg, and sodium bicarbonate, 10mEq in 1 liter of physiologic saline. Beginning in late 1991, triamcinolone, 10 mg/liter, was added to the anesthetic solution (Table I). A motor-driven peristaltic pump (Wells-Johnson Company, Tucson, Ariz.) permitted efficient infiltration into subcutaneous fat at rates of 50 to 200 ml/min depending on the patient’s tolerance and the area of infiltration. Infiltration was accomplished with a 20-gauge spinal needle, an 18-gauge intradiscal needle, and a blunt-tipped two-hole 14-gauge infiltrating cannula. The entire infiltration process was completed before starting liposuction.

The liposuction cannulas were made from fully hard-tempered stainless steel hypodermic needle stock in 12 gauge = 2.47 mm inside diameter (ID) and 10 gauge = 3.10mm ID. Small cannulas permit efficient liposuction both deeply and superficially and, together with the tumescent technique, minimize the risk of surgically induced irregularities of the skin. Details of the operative technique have been described. 4 Liposuction was accomplished with the assistance of a Wells-Johnson Aspirator II medical-grade vacuum pump.

The volume of whole blood aspirated by liposuction, Vol ASPIRATED WHOLE BLOOD, was calculated with the following equation:

Vol ASPIRATED WHOLE BLOOD

= [(VolINFRA + (0.16) VOL SUPRA)] X Hct INFRA

_________________________________

Hct VENOUS BLOOD

Where

Hct VENOUS BLOOD = Preoperative hematocrit of venous blood

Hct INFRA = Hematocrit of the infranatant blood-tinged anesthetic solution removed by liposuction

Vol INFRA = Volume of the infranatant blood-tinged anesthetic solution removed by liposuction measured after separation by gravity for at least 30 minutes

VOL SUPRA = Volume of the supranatant fat, defined as the volume of fat that is measured after separation by gravity for at least 30 minutes.

TABLE I

Recipe for the Tumescent Anesthetic Solution for Liposuction

Lidocaine – Epinephrine

500 mg (0.05%) with 0.5 mg (1:2 million) or

750 mg (0.75%) with 0.75 mg (1:1.5 million) or

1000 mg (0.1%) with 0.75 mg (1:1.5 million)

Sodium bicarbonate 10mEq (10 ml of 8.4% NaHCO3)

Triamcinolone 10 mg (an optional ingredient)

Physiologic saline 1000 ml of 0.9% NaCI

When 10-ml samples of gravity-separated supranatant fat are centrifuged for 5 minutes, the average separation yields 8.4 ml of pure yellow fat essentially devoid of residual red blood cells and an additional 1.6 ml of blood-tinged anesthetic solution.

All samples of blood were obtained from peripheral veins. Plasma lidocaine levels were measured by high-pressure gas chromatography.5 Hematocrit was measured by an automated technique (Sesmex NE 8000 TOA). The expected hematocrit after a 40:1 dilution of venous blood matched the measured hematocrit quite closely, confirming the accuracy of the automated measurement of the hematocrit of the very dilute infranatant fluid.

The following data were recorded: total doses of lidocaine and epinephrine, total volume of IV fluids, preoperative and 1-week postoperative hematocrit, preoperative and immediately postoperative urine specific gravity, intraoperative urine output, and postoperative orthostatic blood pressure and heart rate. The pulse rate and cardiac rhythm were monitored continuously, and electrocardiogram tracings and blood pressure were automatically recorded periodically.

In 31 of the 40 patients treated in 1991, hematocrits were obtained 1 week postoperatively and compared with preoperative values. Of the remaining 9 patients, postoperative hematocrits were not obtained in 5 patients because they declined to participate in the study, in 2 patients because the staff neglected to ask the patients to participate, and in 2 patients because they returned home to a foreign country within 7 days of the surgery.

In the second part of this study, a 75-kg woman received 2625 mg (35 mg/kg) of lidocaine in 5.25 liters of physiologic saline (lidocaine 0.05%, epinephrine 1:2 million, NaHCO3 10 mEq/liter) infiltrated subcutaneously, first without liposuction, and then 25 days later, after an identical infiltration, with liposuction. After each infiltration, sequential changes in plasma lidocaine concentrations, hematocrit, weight, cumulative urine volumes, and urine specific gravity were measured.

After liposuction of the body using the tumescent technique, patients were two postoperative unisex elastic support garments until the drainage has ceased, usually in 2 to 5 days.

TABLE II

Summary of Results for 112 Large-Volume Liposuction Patients

RESULTS

The 112 patients in the present study, 108 of whom were female, had liposuction of between 1500 and 3400 ml of supranatant fat (Table II). The mean weight for females was 68.6 kg (range 55.6 to 100.9 kg), and for males, 93.1 kg (range 87.7 to 98.6 kg). The mean total lidocaine dosage was 33.3 mg/kg range (range 11.0 to 52.1 mg/kg)

The mean volume of local anesthetic solution was 4608.9 ml (range 2050 to 7275 ml). The mean volume of intravenous infusion of physiologic saline given during the surgery was 429.7 ml (range 200 to 1000 ml).

The mean volume of aspirate (supranatant fats plus infranatant blood-tinged anesthetic solution) was 2657 ml (range 1840 to 4575 ml), of which the mean volume of supranatant fat was 1945.1 ml (range 1500 to 3400 ml)

The mean preoperative hematocrit was 40.8 percent, and the mean postoperative hematocrit was 38.9 percent, with the mean change being -1.9 percent (range -5.2 to +1.3 percent). For each liter of supranatant fate removed by liposuction, there was only a 1 percent change in hematocrit. The calculated mean volume of aspirated whole blood was 18.5 ml (range 4.0 to 37.3 ml). The mean volume of whole blood removed by liposuction was 9.5 ml per liter of supranatant fat. The mean volume of whole blood was 7.0 ml per liter of aspirated material (Fig. 2).

No patient received a blood transfusion or intravascular fluid expanders. There were no serious complications. There were no infections, no episodes of clinical hypovolemia, no adverse drug reactions, no seromas, and no hematomas. Aesthetic results were good and within the patients’ range of expectations.

Postoperatively, the mean supine and standing systolic blood pressures were 119 and 121

mmHg, respectively; the mean supine and standing diastolic blood pressures were 71 and 72 mmHg, respectively; the mean supine and standing pulse rates were 88 and 96 beats per minute, respectively. Preoperative and postoperative urine specific gravities were 1.020 and 1.016, respectively. The mean cumulative intraoperative urine volume was 575 ml.

The mean preoperative pulse rate was 72.6 beats per minute, and the mean immediately postoperative pulse rate was 85.1 beats per minute. The range of the difference between preoperative and postoperative pulse rates was -14 and 33 beats per minute.

In the second part of this study, a peak lidocaine plasma concentration of 2.37 ųg/ml was achieved 14 hours after the infiltration was begun in a 75-kg woman who was given 2625 mg (35.0 mg/kg) of lidocaine in 5.25 liters of physiologic saline infiltrated subcutaneously without liposuction.

Twenty-five days later, after an identical infiltration, the patient had liposuction of 1550 ml of supranatant fat. In this instance, the peak lidocaine plasma level of 1.86 ųg/ml was attained 11 hours after initiating the infiltration. The peak lidocaine level following liposuction was 78.5 percent of the peak attained without liposuction.

After each infiltration there was significant sequential change in hematocrit, with the hemodilution caused by the large volume of anesthetic solution infiltrated subcutaneously. Liposuction had little effect on the hematocrit during and after surgery. Adequate intraoperative urine volume, low urine specific gravity, and minimal postoperative differences between supine and standing pulse rates suggest that liposuction using the tumescent technique caused no deficit of intravascular fluid volume.

DISCUSSION

The tumescent technique for liposuction totally by local anesthesia without sedation was developed by surgeons who traditionally do not use general anesthesia. The description of the tumescent technique has appeared almost exclusively in the literature of dermatology. 6-10

Large-volume liposuction totally by local anesthesia has not been described in the literature of other specialties. 19-23 The chapter on suction lipectomy in a recent textbook of plastic surgery devoted only one sentence to anesthesia: “Use general anesthesia if: suctioning multiple areas, removing more than 1500 cc of fat, or anticipating autologous blood transfusion (for this an overnight admission is advisable).” 24 The tumescent technique used concomitantly with general anesthesia has been described. 25-27

Advantages of the technique include (1) profound local anesthesia, (2) reduced surgical blood loss, (3) the reduction of IV fluid requirements, and (4) enhanced aesthetic results. “Expansion of the fat compartment increases the margin of safety and reduces the likelihood of creating surface irregularities.” 28

Because there is an increased risk of excessive blood loss when more than 1500 ml is aspirated, autologous blood transfusions have been recommended for liposuction of more than 1500 ml.1, 29, 30 It is this 1500-ml threshold volume that motivates the definition oflarge-volume liposuction. The tumescent technique permits liposuction of more than 3000 ml of supranatant fat without transfusion.

Improved Hemostasis

The degree to which infiltration with vasoconstrictive local anesthetic solutions is used in liposuction to maximize hemostasis varies among different techniques. At one end of the spectrum is the dry technique, which uses general anesthesia with infiltration of any vasoconstrictive solution. The official guidelines of the American Academy of Dermatology state that “because of the availability of safer methods, the dry technique is now rarely indicated.” 31 The dry technique is the liposuction technique that causes the greatest degree of blood loss, with between 20 and 45 percent of the aspirate consisting of blood. 1, 2, 30 –33 In a recent study of 108 patients who had large-volume liposuction (>1500 ml of aspirated fat and blood) by the dry technique, on average, a third of everything that was removed was blood, and every patient was given a blood transfusion. 2

The wet technique, intermediate with respect to the degree of hemostasis that can be obtained in liposuction, relies on general anesthesia and the use of relatively small volumes of dilute epinephrine infiltrated subcutaneously. With the wet technique, between 15 and 30 percent of the aspirate is blood. 34-39 In one study of the wet technique, half the patients who had 2500 ml or more of aspirate required hospitalization because of a tendency to develop hypotension.36

The tumescent technique uses the greatest volume of vasoconstrictive subcutaneous infiltration and produces the greatest degree of hemostasis. Using the tumescent technique, less than 1 percent of the suctioned material is whole blood, and most patients lose more blood during routine preoperative laboratory studies than during large-volume liposuction. The unique aspect of the tumescent technique is that it is the only technique that permits large-volume liposuction totally by local anesthesia without sedation or narcotic analgesics.

Intravascular Fluid Status

In none of the 112 large-volume liposuction patients was there any clinical evidence of intravascular volume depletion despite minimal IV infusion (mean 429 ml) of physiologic saline. Preoperative urine specific gravity was generally greater than postoperative values. Perioperative urine output was greater than 70 ml/h, the traditional textbook normal hourly urine output.40 Similarly, the differences between supine and standing postoperative pulse and blood pressure were unremarkable. Plasma volume depletion is indicated by significant changes in blood pressure and pulse rate.41

The hemodilution and the urine dilution that occurred in the second study are consistent with the finding that there was no clinical evidence of the intravascular fluid depletion with the tumescent technique for large-volume liposuction. The injection of large volumes of fluid into subcutaneous tissues for hydration, known ashypodermoclysis, delivers fluids to the exact site where tissue injury will be induced by liposuction. It is an efficient method of preventing third spacing at the site of injury on intravascular fluid deficits (Table III).

Safety of Local versus General Anesthesia

General anesthesia is more dangerous than local anesthesia.42, 43 Many of the deaths associated with general anesthesia, having occurred in healthy young patients, are the result of human error and are considered preventable.44,45 Deaths due to anesthesia are believed to occur at least once in every 2500 to 10,000 administrations of general anesthesia.46-48 The anesthetic agents fentanyl, halothane, and isoflurane are independent predictors of severe outcome, including death.49 Life-threatening complications of general anesthesia are the most dangerous aspects of liposuction surgery. In one study of 2009 healthy liposuction patients, complications includes a cardiac arrest in a 28-year-old, anaphylactic shock in a 36-year-old, and respiratory arrest in a 49-year-old,.1 Cardiac arrest, lack of sufficient oxygenation of the brain, pulmonary thromboembolisms, and malignant hyperthermia are well-known fatal complications of general anesthesia.45,50-54 The high-risk drugs associated with general anesthesia need not be used with the tumescent technique.

Complications are fewer and less catastrophic with local anesthesia than with general anesthesia.43 For example, regional anesthesia is associated with a lower incidence of postoperative thromboembolism.55 There is a reduction of intraoperative blood loss with the use of regional anesthesia for colon, gynecologic, hip, and prostate surgery.56 In a study of dental anesthetic mortality in England from 1970 to 1979, general anesthesia was associated with 110 deaths, compared with only 10 deaths associated with local anesthesia.43 This difference is all the more remarkable because local anesthesia were used far more frequently than general anesthesia.

When nitrous oxide, benzodiazepams, and narcotic analgesics are given in doses sufficient to potentially cause respiratory depression, they are general anesthetics.57

What is a Safe Lidocaine Dose?

The Xylocaine (lidocaine hydrochloride) package insert and the1992 Physicians’ Desk Reference state, “For normal healthy adults, the individual maximum safe dose of lidocaine HCI with epinephrine should not exceed 7 mg/kg of body weight and in general it is recommended that the maximum total dose not exceed 500 mg.” 58

Neither the initial manufacturer of lidocaine, Astra Pharmaceutical Products, Inc., nor the United States Food and Drug Administration (FDA) has any data to support this standard dose limitation.59 In its 1948 application to the FDA for permission to market lidocaine, the manufacturer simply stated that the maximum safe dose of lidocaine is “probably the same as for procaine.” 60

The widely accepted lidocaine dose limitation of 7 mg/kg is appropriate when commercially available lidocaine (1% or 2%) with epinephrine is infiltrated rapidly or into highly vascular tissue. However, much higher doses are clearly quite safe when more dilute lidocaine (0.05% or 0.1%) with epinephrine is infiltrated over a greater time interval into relatively avascular subcutaneous fat.3,16,17 Although 35 mg/kg of lidocaine is the current estimate for a safe maximum lidocaine dose for liposuction by the tumescent technique, doses as high as 52 mg/kg were used in this study without adverse clinical effects. Because there is no well-documented study showing that plasma lidocaine levels are safe with doses greater than 35 mg/kg, caution is necessary when this threshold is exceeded.

Local Anesthetic Toxicity

Lidocaine is the drug of choice for liposuction by local anesthesia. Longer-acting anesthetics have a much greater potential for serious toxicity than lidocaine.61-66 Because the anesthetic effects of lidocaine infiltrated into subcutaneous fat by the tumescent technique last for many hours, there is little clinical justification for using longer-acting and potentially more cardiotoxic local anesthetics such as bupivacaine.

The toxicity of a local anesthetic is a function of its peak plasma concentration. (Table IV). Peak plasma concentration depends as much on its rate of systemic absorption as on its total milligram per kilogram dose.67 The rapid infiltration of 2500 mg lidocaine for a face lift can be fatal.68 When given intravenously, 20 mg/kg of lidocaine can produce cardiovascular collapse and generalized convulsions.69 Doses of 35 mg/kg of lidocaine given by the tumescent technique are safe because systemic absorption occurs over 18 to 36 hours.3

TABLE III

Typical Range of Volumes of Dilute Anesthetic Solutions Used with the Tumescent Technique for Infiltration into Various Areas

Abdomen, upper and lower – 800-2000 ml

Hip (flank, or love handle), each side – 400-1000 ml

Lateral thigh, each side – 500-1200 ml

Anterior thigh, each side – 600-1200 ml

Proximal medial thigh, each side – 250-700 ml

Knee – 200-500 ml

Male breast, each side – 300-800 ml

Submental chin – 100-200 ml

TABLE IV

Plasma Lidocaine Concentration and Toxicity

3-6 ųg/ml – Subjective pharmacologic effects

509 ųg/ml – Objective toxicity

8-12 ųg/ml – Seizures, cardiac depression

12 ųg/ml – Coma

20 ųg/ml – Respiratory arrest

26 ųg/ml – Cardiac arrest

Lidocaine Pharmacokinetics

Factors that determine the rate of systemic absorption of a local anesthetic include the drug’s concentration, the vascularity of the site of injection, the concomitant use of a vasoconstrictive drug such as epinephrine, and the rate of infiltration.70

When plasma lidocaine concentration is plotted as a function of the time after injection, the area under the curve corresponds to the total amount of drug that is absorbed systemically. When a given dose of lidocaine is absorbed rapidly, the peak plasma concentration will be quite high. When an identical dose is absorbed much more slowly, such as when the tumescent technique is used, then the areas under the curves are equal but the peak plasma concentration is significantly lower.71 The safety of these large doses of lidocaine is not the result of removing lidocaine from the body by aspiration, as has been previously assumed72,73

Several recent studies on liposuction have assumed that peak plasma lidocaine concentrations occur within 90 minutes of the infiltration.17,74,75 These assumptions were based on previously published data on lidocaine absorption following subcutaneous infultration76-83 or intramuscular injection or for nerve block injection,84-91 where the peak plasma concentrations occurred within 60 to 90 minutes.

Dilution of lidocaine in a solution containing epinephrine slows its rate of absorption and diminishes its toxicity.92 On two separate occasions 1000 mg of lidocaine at different concentrations, 1% lidocaine with epinephrine 1:100,000 and 0.1% lidocaine with epinephrine 1:1 million, were injected slowly into subcutaneous fat over a 45-minute interval with peak lidocaine concentrations of 1.5 and 1.2 ųg/ml occurring at 10 and 14 hours, respectively.3

A slow rate of infiltration of lidocaine with epinephrine delays systematic absorption and diminishes peak plasma lidocaine concentration.93 When approximately 1 gm of lidocaine (0.5% or 1%) with epinephrine (1:100,000) was infiltrated in less than 5 minutes into subcutaneous fat, potentially toxic plasma lidocaine concentrations greater than 5 ųg/ml were attained within 15 minutes.94,95 When similar amounts and concentrations were infiltrated slowly over 45 minutes, peak lidocaine concentration of 1.5 ųg/ml was reached 10 hours after beginning the infiltration.3

Reduced Pain

With good technique, liposuction by local anesthesia is essentially painless. Because the local anesthetic remains in the affected tissues for over 12 hours after the surgery, there is no immediate postoperative pain. The only postoperative analgesia used is acetaminophen. Virtually every one of my patients who has had liposuction by another surgeon under general anesthesia and then has had liposuction by the tumescent technique has found the latter experience to be far less painful.

Formulation of Anesthetic Solution

There is no canonical formulation of the local anesthetic for the tumescent technique. The recipe should be variable depending on the clinical situation. A number of factors determine the minimal sufficient concentration of lidocaine. By exposing sufficient lengths of sensory axons to minimal blocking concentrations of lidocaine, the tumescent technique can anesthetize large volumes of subcutaneous fat.96 Current recommendations for formulation of the anesthetic solution for liposuction by the tumescent technique are listed in Table I.

The greater the amount of fibrous tissue in fact and the greater the diameter of the liposuction cannula, the greater is the degree of discomfort associated with liposuction by local anesthesia. For liposuction of fibrous areas such as the abdomen, male flanks, and breasts, the 0.1% concentration is preferred. A cannula greater then 4mm in diameter may necessitate using higher lidocaine concentrations or using narcotics or general anesthesia.

Although this has not been proven clinically, lidocaine may reduce the risk of infection because it is bactericidal for many pathogens commonly found on the skin.97 Lidocaine might improve wound healing by reducing release of tissue-toxic substances from leukocytes such as oxygen free radicals and lysozymes.98

The vasoconstrictive effects of epinephrine prolongs anesthesia.99 An epinephrine concentration of 1:1 million (1 mg/liter) provides exquisite hemostasis in subcutaneous fat. Tachycardia is unusual except in patients who either receive epinephrine doses greater than 0.035 mg/kg or are usually sensitive to epinephrine. Clinical experience has shown that 0.5 mg/liter (1:2 million) approaches the minimal effective epinephrine concentration.

Sodium bicarbonate (NaHCO3), by neutralizing the pH of the anesthetic solution, decreases the burning pain upon infiltration.100-102 The acidity of commercially available lidocaine causes pain upon subcutaneous infiltration.103

Triamcinolone acetonide, at 10 mg/liter of solution, seems to decrease the postoperative soreness experienced by patients. The risks and benefits of dilute triamcinolone are currently the subject of a clinical trial.

In order to avoid the patient feeling chilled, the IV bags of physiologic saline are stored in a blanket warmer at 40′C and removed just before the anesthetic solution is mixed. Using chilled saline or cryoanesthesia does not provide better vasoconstriction but does cause the patient unnecessary discomfort and requires monitoring of the patient’s core body temperature.

The use of hyaluronidase is not necessary in the local anesthetic solution for the tumescent technique. It may accelerate systemic absorption of lidocaine, increasing the risk of toxicity by increasing the peak plasma lidocaine concentrations.104,105

Benefits of Avoiding IV Sedation

More than 80 deaths have occurred after the use of midazolam, often in combination with narcotic analgesics, all but three having occurred in patients unattended by anesthesia personnel.106 Employing anesthetic techniques that avoid drugs that cause respiratory depression eliminates one of the most significant risks of anesthesia.107 With the tumescent technique for liposuction totally by local anesthesia, it has been my experience that patients usually do better without IV sedation when IV sedation is used.

In the course of this study it was noticed that patients who had not taken any sedatives often experienced a certain degree of drowsiness. This drowsiness occurred without and with liposuction in the patient described in the second part of the present study. The peak serum lidocaine concentrations were 1.86 and 2.37 ųg/ml.

Postoperative care

With the tumescent technique, patients are discharged ambulatory 30 minutes after the liposuction procedure is completed. If only one area has been treated, some patients are permitted to drive themselves home.

Because of residual local anesthesia, patients experience no significant soreness for the first 10 to 16 hours after surgery. Although patients do not require postoperative analgesia, acetaminophen is recommended (1000 mg four times daily) because of its antipsychotic-inflammatory effects on postoperative trauma.108,109

Patients are encouraged to go for a walk the evening of surgery. There is no postoperative restriction on physical activity; normal exercise may be resumed as soon as it is tolerated. Virtually every patient can return to work at a desk-type job 48 hours after liposuction surgery by the tumescent technique.

CONCLUSIONS

The tumescent technique permits large-volume liposuction totally by local anesthesia. The advantages of using tumescent local anesthesia rather than general anesthesia for liposuction include virtual elimination of surgical blood loss, elimination of the dangers of general anesthesia, elimination of heavy IV sedation, elimination of narcotic analgesics, quicker recovery and improved aesthetic results.

REFERENCES

1. Dillerud, E. Suction lipoplasty: A report on complications, undesired results, and patient satisfaction based on 3511 procedures. Plast. Reconstr. Surg. 88:239, 1991.

2. Courtiss, E.H., Choucair, R.J., and Donelan, M.B. Large-volume suction lipectomy: An analysis of 108 patients. Plast. Reconstr. Surg. 89:1068, 1992.

3. Klein, J.A. Tumescent technique for regional anaethesia permits lidocaine doses of 35 mg/kg for liposuction, J. Dermatol. Surg. Oncol. 16:248 1990.

4. Klein, J.A. Tumescent Liposuction: Totally by Local Anaethesia. In G.P. Lask and R.L. Moy (Eds.), Principles and Practices of Dermatological Surgery. New York: McGraw-Hill 1993.

5. Adiepon-Yamoah, K.K., and Prescott, L.F. Gasliquid chromatographic estimation of lignocaine, ethylglycylxylidide, glycylxylidide, and 4-hydroxylidide in plasma and urine. J. Pharm. Pharmacol. 26:889, 1974.

6. Replogle, S.L. The “standard technique” of liposuction: Viewpoint from a plastic surgeon, Dermatol. Clin. 8:451, 1990.

7. Field, L.M. The Dermatologic Surgeon and Liposculpturing. In P.F. Fournier (Ed.) Liposculpture: The Syringe Technique. Paris: Arnette Blackwell, 1991. Pp. 265-266.

8. Coleman, W.P., III. The history of dermatologic liposuction.Dermatol. Clin. 8:381, 1990.

9. Narins, R.S. Liposuction and anesthesia. Dermatol. Clin. 8:421, 1990.

10. Klein, J.A. The tumescent technique: Anesthesia and modified liposuction technique. Dermatol. Clin. 8:425, 1990.

11. Lillis, P.J. The tumescent technique for liposuction surgery.Dermatol. Clin. 8:439, 1990.

12. Stegman, S.J. Technique variations in liposuction surgery.Dermatol. Clin. 8:457, 1990.

13. Hanke, C.W., Lee, M.W., and Bernstein, G. The safety of dermatologic liposuction surgery. Dermatol. Clin. 8:563, 1990.

14. Lillis, P.J. Liposuction surgery under local anesthesia: Limited blood loss and minimal lidocaine absorption. J. Dermatol. Surg. Oncol. 14:1145, 1988.

15. Klein, J.A. Anesthesia for Dermatologic Cosmetic Surgery. In W.P. Coleman, C.W. Hanke, T.H. Alt, and S. Asken (Eds.), Cosmetic Surgery of the Skin: Principles and Techniques. Philadelphia: B.C. Decker, 1991. Pp. 39-45.

16. Lillis, P.J., and Coleman, W.P., III (Eds.) Liposuction. Dermatol. Clin. 8:381, 1990.

17. Klein, J.A. The tumescent technique for liposuction. Am. J. Cosmetic Surg. 4:263, 1987.

18. Klein, J.A. Anesthesia for liposuction in dermatologic surgery. J. Dematol. Surg. Oncol. 14:1124, 1988.

19. Mladick, R.A. (Ed.) Lipoplasty. Clin. Plast.Surg. 16:1, 1989

20. Hetter, G.P. (Ed.) Lipoplasty: The Theory and Practice of Blunt Suction Lipectomy. Boston: Little, Brown, 1990. Pp. 1-448.

21. Teimourian, B., and Rogers, W.B., III. A national survey of complications associated with suction lipectomy: A comparative study. Plast. Reconstr. Surg. 84:628, 1989.

22. Mladick, R.A. (Ed.). Lipoplasty. Clin. Plast.Surg. 16:1, 1989.

23. Braunstein, M.C. Anesthesia. In G.P. Hetter (Ed.), Lipoplasty: The Theory and Practice of Blunt Suction Lipectomy. Boston: Little, Brown, 1990. Pp. 133-142.

24. Rohrich, R.J., and Mathes, S.J. Suction-Lipectomy. In M.J. Jurkiewitz, T.J. Krizek, S.J. Mathes, and S. Ariyan (Eds.), Plastic Surgery: Principles and Practice. St. Louis: Mosby, 1990. P. 1559.

25. Toledo, L.S. My Experience with Syringe Liposculpture in Brazil. In P.F. Fournier (Ed.), Liposculpture: The Syringe Technique. Paris: Arnette Blackwell, 1991. Pp. 255-257.

26. Grazier, F.M. (Ed.) Atlas of Suction Assisted Lipectomy in Body Sculpture. New York: Churchill-Livingstone, 1992.

27. Fournier P.F. Liposculpture: The Syringe Technique. Paris: Arnette Blackwell, 1991. Pp. 163.

28. Pitman, G.H. Operative Planning and Surgical Strategies: Liposuction and Aesthetic Surgery. St. Louis:Quality Medical Publishing, 1993. P. 46.

29. Dolsky, R.L., Fetzek, J., and Anderson, R. Evaluation of blood loss during liposuction surgery. Am. J. Cosmetic Surg. 4:257, 1987.

30. Ersek, R.A. Severe and Mortal Complications. In G.P. Hetter (Ed.), Lipoplasty: The Theory and Practice of Blunt Suction Lipectomy, 2d Ed. Boston: Little, Brown, 1990. Pp. 223-225.

31. Committee on Guidelines of Care. Guidelines of care for liposuction. J. Am. Acad. Dermatol. 24:489, 1991.

32. Hetter, G.P. Blood and fluid replacement for lipoplasty procedures. Clin. Plast. Surg. 16:245, 1989.

33. Courtiss, E.H., Kanter, M.A., Kanter, W.R., and Ransil, B.J. The effect of epinephrine on blood loss during suction lipectomy. Plast. Reconstr. Surg. 88:801, 1991.

34. Goodpasture, J.C., and Bunkis, J. Quantitative analysis of blood and fat in suction lipectomy aspirates. Plast. Reconstr. Surg.78:765, 1986.

35. Gargan, T.J., and Courtiss, E.H. The risks of suction lipectomy: Their prevention and treatment. Clin. Plast. Surg. 11:457, 1984.

36. Clayton, D.N., Clayton, J.N., Lindley, T.S., and Clayton, J.L. Large volume lipoplasty. Clin. Plast. Surg. 16:305, 1989.

37. Dolsky, R.L. Blood loss during liposuction. Dermatol. Clin. 8:463, 1990.

38. Hetter, G.P. The Use of Low Concentration Epinephrine. In G.P. Hetter (Ed.), Lipoplasty: The Theory and Practice of Blunt Suction Lipectomy, 2d Ed. Boston: Little, Brown, 1990. Pp. 143-145.

39. Hetter, G.P. Blood and Fluid Replacement. In G.P. Hetter (Ed.),Lipoplasty: The Theory and Practice of Blunt Suction Lipectomy, 2d Ed. Boston: Little, Brown, 1990. Pp. 191-195.

40. Woerlee, G.M. Common Perioperative Problems and the Anaesthetist. Boston: Kluwer Academic Press, 1988. P. 350.

41. Levinsky, N.G. Fluid and Electrolytes. In J.D. Wilson, E. Braunwald, K.J. Isselbacher, et al. (Eds.), Harrison’s Principles of Internal Medicine, 12th Ed. New York: McGraw-Hill, 1991, P.280.

42. Kallar, S.K., Keenan, R.L., and Aghdami, A. Complications of Anesthesia. In L.J. Greenfield (Ed.) Complications in Surgery and Trauma, 2d Ed. Philadelphia: Lippincott, 1990. Pp. 231-247.

43. Coplans, M.P., and Curson, I. Deaths associated with dentistry.Br. Dent J. 153:357, 1982.

44. Tinker, J.H., Dull, D.L., Caplan, R.A., Ward, R.J., and Cheney, F.W. Role of monitoring devices in prevention of anesthetic mishaps: A closed claims analysis. Anesthesiology 71: 541, 1989.

45. Taylor, G., Larson, C.P. Jr., and Prestwich, R. Unexpected cardiac arrest during anesthesia and surgery: An environmental study. J.A.M.A. 236: 2758, 1976.

46. Epstein, R.M. Morbidity and mortality from anesthesia: A continuing problem. Anesthesiology 49: 388, 1978.

47. Forrest, J.B., Cahalan, M.K., Rehder, K. et al. Multicenter study of general anesthesia: II. Results Anesthesiology 72: 262, 1990.

48. Keats, A.S. Anesthesia mortality in perspective. Anesth, Analg.71: 113, 1990.

49. Forrest, J.B., Rehder, K., Cahalan, M.K., and Goldsmith, C.H. Multicenter study of general anesthesia: III. Predictors of severe perioperative adverse outcomes. Anesthesiology 76: 3, 1992.

50. Keenan, R.L., and Boynan, C.P. Cardiac arrest due to anesthesia: A study of incidence and causes. J.A.M.A. 253: 2373, 1985.

51. Tarhan, S., Moffitt, E.A., Taylor, W.F., et al. Myocardial infarction after general anesthesia. Anesth. Analg. 56: 455, 1977.

52. Whittington, R.M., Robinson, J.S., and Thompson, J.M. Fatal aspiration (Medelson’s) syndrome despite antacids and cricoid pressure. Lancet 2: 228, 1979.

53. Mangano, D.T. Perioperative cardiac morbidity. Anesthesiology. 72: 153, 1990.

54. Hamilton, W.K. Unexpected deaths during anesthesia: Wherein lies the cause? Anesthesiology 50: 381, 1979.

55. Modig, J., Borg, T., Karlstrom, G. Maripuu, E., and Sahlstedt, B. Thromboembolism after total hip replacement: Role of epidural and general anesthesia. Anesth. Analg. 62: 174, 1983.

56. Modig. J. Regional anesthesia and blood loss. Acta Anesthesiol. Scand. Suppl. 89: 44, 1988.

57. Moller, J.T., Wittrup, M., and Johansen, S.H., Hypoxemia in the postanesthesia care unit: An observer study. Anesthesiology 73: 890, 1990.

58. Physicians’ Desk Reference 1992, 46th Ed. Montvale, N.J.: Medical Economics Data, 1992. Pp. 637-639.

59. Director of Clinical Research, Astra Pharmaceutical Products, Inc., Westboro, Mass., personal communication.

60. The U.S. Food and Drug Administration, Rockville, Md., personal communication. (This information was obtained under the Freedom of Information Act.)

61. Feldman, H.S., Arthur, G.R., and Covina, B.G. Comparative systemic toxicity of convulsant and supraconvulsant doses of ropivacaine, bupivacaine, and lidocaine in the conscious dog.Anesth. Analg. 69: 794, 1989.

62. Morishima, H.O., Pederson, H., Finster, M., et al. Bupivacaine toxicity in pregnant and nonpregnant ewes. Anesthesiology. 63: 134, 1985.

63. Moller, R.A., and Corvino, B.G. Cardiac electrophysiologic effects of lidocaine and bupivacaine. Anesth. Analg. 67: 107, 1988.

64. Tanz, R.D., Heskett, T., Loehning, R.W., and Fairfax, C.A. Comparative cardiotoxicity of bupivacaine and lidocaine in the isolated perfused mammalian heart. Anesth. Analg. 63: 549, 1984.

65. Kasten, G.W. High serum bupivacaine concentrations produce rhythm disturbances similar to Torsades de Pointes in anesthetized dogs. Reg. Anaesth. 11:20, 1986.

66. Chadwick, H.S. Toxicity and resuscitation in lidocaine- and bupivacaine-infused cats. Anesthesiology. 63: 385, 1985.

67. Rowland, M. and Tozer, T.N. Clinical Pharmacokinetics: Concepts and Applications, 2d Ed. Philadephia: Lea & Febiger, 1989. Pp. 33-48.

68. Sunshine, I., and Fike, W.W. Value of thin-layer chromatography in two fatal cases of intoxication due to lidocaine and mepivacaine. N. Engl. J. Med. 271: 487, 1964.

69. Yukioka, H., Hayashi, M., and Fujimori, M. Lidocaine intoxication during general anesthesia. (Letter.) Anesth. Analg. 71:207, 1990.

70. de Jong, R.H., and Bonin, J.D. Local anesthetics: Injection route alters relative toxicity of bupivacaine. Anesth. Analg. 59: 925, 1980.

71. Rowland, M., and Tozer, T.N. Clinical Pharmacokinetics, 2d Ed. Philadelphia: Lea & Febiger, 1989. Pp. 35-37.

72. Asken, S. Liposuction Surgery and Autologous Fat Transplantation. East Norwalk, Conn.: Appleton & Lange, 1988. P. 63.

73. Illouz, Y.G., and de Villers, Y.T. Body Sculpturing by Lipoplasty. Edinburgh: Churchill Livingstone, 1989. P. 115.

74. Gumicio, C.A., Bennie, J.B., Fernando, B., et al. Plasma lidocaine levels during augmentation mammoplasty and suction-assisted lipectomy. Plast. Reconstr. Surg. 84:624, 1989.

75. Lewis, C.M., and Hepper T. The use of high-dose lidocaine in wetting solutions for lipoplasty. Ann. Plast. Surg. 22:307, 1989.

76. Scott, D.B., Jebson, P.J., Braid, D.P., Ortengren, B., and Frisch, P. Factors affecting plasma levels of lignocaine and prilocaine. Br. J. Anaesth. 44: 1040, 1972.

77. Stoelting, R.K. Plasma lidocaine concentrations following subcutaneous or submucosal epinephrine –lidocaine injection.Anesth. Analg. 57:724, 1978.

78. Schwartz, M.L., Covino, B.G., Narang, R.M., et al. Blood levels of lidocaine following subcutaneous administration prior to cardiac catheterization. Am. Heart J. 88:721, 1974.

79. Kosowsky, B.D., Mufti, S.I., Grewal, G.S., et al. Effect of local lidocaine anesthesia on ventricular escape intervals during permanent pacemaker implantation in patients with complete heart block. Am. J. Cardiol. 51: 101, 1983.

80. Nattel, S., Rinkenberger, R.L. Lehrman, L.L., and Zipes, D.P. Therapeutic blood lidocaine concentrations after local anesthesia for cardiac electrophysiologic studies. N. Engl. J. Med. 301: 418, 1979.

81. Maloney, J.M., III, Lertora, J.J., Yarborough, J., and Millikan, L.E. Plasma concentrations of lidocaine during hair transplantation.J. Dermatol. Surg. Oncol. 8:950, 1982.

82. Alfano, S.N., Leicht, M.J., and Skiendzielewski, J.J. Lidocaine toxicity following subcutaneous administration. Ann. Emerg. Med.13: 465, 1984.

83. Eyres, R.L., Kidd, J., Oppenheim, R., and Brown, T.C.K. Local anesthetic plasma levels in children. Anaesth. Intensive Care 6: 243, 1978.

84. Collinsworth, K.A., Kalman, S.M., and Harrison, D.C. The clinical pharmacology of lidocaine as an antiarrhythimic drug. Circulation50: 1217, 1974.

85. Tucker, G.T., Moore, D.C., Bridenbaugh, P.O., et al. Systemic absorption of mepivacaine in commonly used regional block procedures. Anesthesiology 37: 277, 1972.

86. Raj, P.P., Rosenblatt, R., Miller, J., et al. Dynamics of local-anesthetic compounds in regional anesthesia. Anesth. Analg.56:110, 1977.

87. Ecoffey, C., Desparmet, A., Berdeaux, A., et al. Pharmacokinetics of lignocaine in children following caudal anesthesia. Br. J. Anaesth. 56: 1399, 1984.

88. Braid, D.P., and Scott, D.B. Dosage of lignocaine in epidural block in relation to toxicity. Br. J. Anaesth. 38: 596, 1966.

89. Braid, D.P., and Scott, D.B. The systematic absorption of local analgesic drugs. Br. J. Anaesth. 37: 394, 1965.

90. Inoue, R., Suganuma, T., Echizen, H., et al. Plasma concentrations of lidocaine and its principal metabolites during intermittent epidural anesthesia. Anesthesiology 63: 304, 1985.

91. Blano, L.J., Reid, P.R., and King, T.M. Plasma lidocaine levels following paracervical infiltration for aspiration abortion. Obstet. Gynecol. 60: 506, 1982.

92. Gordh, T. Xylocain: A new local anesthetic. Anaesthesia 4: 4, 1949.

93. Scott, D.B., Evaluation of clinical tolerance of local anesthetic agents. Br. J. Anaesth. 47: 328, 1975.

94. Piveral, K. Systemic lidocaine absorption during liposuction (Letter). Plast. Reconstr. Surg. 80: 643, 1987.

95. Richard Hagert, M.D., Department of Plastic and Reconstructive Surgery School of Medicine. University of South Carolina, Charleston, S.C., personal communication.

96. Raymond, S.A., Steffensen, S.C., Gugino, L.D., and Strichartz, G.R. The role of length of nerve exposed to local anesthetics in impulse blocking action. Anesth. Analg. 68: 563, 1989.

97. Miller, M.A., and Shelly, W.B. Antibacterial properties of lidocaine on bacteria isolated from dermal lesions. Arch. Dermatol.121: 1157, 1985.

98. Eriksson, A.S., Sinclair, R., Cassuto, J., and Thomsen, P. Influence of lidocaine on leukocyte function in the surgical wound.Anesthesiology 77: 74, 1992.

99. Myers, R.R., and Heckman, H.M., Effects of local anesthesia on nerve blood flow: Studies using lidocaine with and without epinephrine. Anesthesiology 71: 757, 1989.

100. McKay, W., Morris, R., and Mushlin, P. Sodium bicarbonate attenuates pain on skin infiltration with lidocaine, with or without epinephrine. Anesth. Analg. 66: 572, 1987.

101. Stewart, J.H., Cole, G.W., and Klein, J.A. Neutralized lidocaine with epinephrine for local anesthesia. J. Dermatol. Surg. Oncol. 15: 1081, 1989.

102. Larson, P.O., Raji, G., Swandlby, M., et al. Stability of buffered lidocaine and epinephrine used for local anesthesia. J. Dermatol. Surg. Oncol. 17: 411, 1991.

103. Stewart, J.H., Chinn, S.E., Cole, C.W., and Klein, J.A. Neutralized lidocaine with epinephrine for local anesthesia, part II.J. Dermatol. Surg. Oncol. 16: 842, 1990.

104. Pettersson, L.O., and Akerman, B. Influence of hyaluronidase upon local infiltration anesthesia by lidocaine. Scand. J. Plast. Reconstr. Surg. 18: 297, 1984.

105. Adriani, J. The clinical pharmacology of local anesthetics. Clin. Pharmacol. Ther. 1: 645, 1960.

106. Bailey, P.L., Pace, N.L., Ashburn, M.S. et al. Frequent hypoxemia and apnea after sedation with midazolam and fentanyl.Anesthesiology 73: 826, 1990.

107. Stoddart, J.C. Postoperative respiratory failure: An anesthetic hazard? Br. J. Anaesth. 50: 695, 1978.

108. Lokken, P., and Skoglund, L.A. Medical therapy of osteoarthritis of the knee (Letter). N. Engl. J. Med. 325: 1805, 1991.

109. Skjelbred, P., Lokken, P., and Skoglund, L.A. Postoperative administration of acetaminophen to reduce swelling and other inflammatory events. Curr. Ther. Res. 35:377, 1984.

Modified Liposuction Technique

Jeffrey A. Klein, M.D.

The tumescent technique for liposuction is a new technique that has been developed entirely by dermatologic plastic surgeons. It is a dramatic improvement over the traditional methods that require either general anesthesia or deep intravenous (IV) sedation and narcosis. It is this author’s contention that liposuction by local anesthesia is safer than liposuction by general anesthesia. Furthermore, the tumescent technique is associated with less discomfort, allows a more rapid postoperative recovery, and provides better aesthetic results than when liposuction is performed using other anesthetic techniques.

The tumescent technique for local anesthesia permits regional local anesthesia of the skin and subcutaneous tissues by using direct infiltration rather than a proximal nerve block. By using large volumes of a dilute anesthetic solution consisting of lidocaine (0.1% or 0.05%) and epinephrine (1:1,000,000) in physiologic saline, the tumescent technique produces swelling and firmness, or tumescence, of targeted fatty areas.

Anesthesia for liposuction surgery can be accomplished in a number of ways including general anesthesia, regional spinal anesthesia, local anesthesia with either deep IV sedation or nitrous oxide sedation, and simple infiltration local anesthesia without IV sedation or narcotic analgesia.31

Most of the methods that use local anesthesia for liposuction rely on the concomitant use of narcotics and deep IV sedation to produce a state of consciousness that is equivalent to that produced by general anesthesia. However, with appropriate instrumentation and surgical method, the tumescent technique permits liposuction of large volumes of fat totally by local anesthesia without IV sedation or narcotic anesthesia. The tumescent technique can also be used with general anesthesia or IV sedation.

Recent clinical studies of the absorption pharmacokinetics of lidocaine with the tumescent technique have shown that peak plasma lidocaine levels occur approximately 12 to 15 hours after beginning the infiltration. This remarkably delayed absorption permits a much higher lidocaine dosage than was previously believed possible. Any reduction in a drug’s rate of systemic absorption will reduce magnitude of the drug’s peak plasma levels. The safe upper limit for lidocaine dosage using the tumescent technique has been estimated to be 35 mg/kg. 34 This is approximately five times greater than standard lidocaine dosage limitations. 10, 20, 38, 45

Clinical local anesthesia persists for up to 18 hours, obviating the need for postoperative analgesia. The prolonged and profound anesthesia of skin and subcutaneous tissues that is provided by the tumescent technique is probably a result of exposing sufficient lengths of sensory axons to marginal blocking concentrations of lidocaine. 49

The infiltration of a large volume of dilute epinephrine assures diffusion throughout the entire targeted area while avoiding tachycardia and hypertension. The associated vasoconstriction is so complete that there is virtually no blood loss with liposuction. The mechanical and pharmacologic properties of the fluid is injected subcutaneously prevent the massive shifts of intravascular fluids which are usually seen when liposuction is done by general anesthesia. With the tumescent technique there is no longer any need to replace significant volumes of IV fluids.

Regional Anesthesia Without Nerve Block

There are two reasons why infiltration with local anesthesia has traditionally been limited to relatively small areas of skin: (1) the stinging pain associated with infiltrating the local anesthesia is not easily tolerated, and (2) published dosage limitations have precluded anesthetizing large areas of skin. These limitations have now been overcome with the recognition that (1) adding sodium bicarbonate in order to neutralize the acidity of commercially available local anesthesia solutions of lidocaine and epinephrine dramatically reduces the usual burning-stinging pain of infiltration,56 and (2) using dilute solutions of lidocaine with the tumescent technique permits profound anesthesia of very large areas. The tumescent technique permits regional local anesthesia of skin and subcutaneous tissue by direct infiltration rather than by proximal nerve block.

ADVANTAGES OF THE TUMESCENT TECHNIQUE

Minimal Blood Loss

Blood loss with liposuction is minimized by the tumescent technique. The extensive vasoconstriction produced by large volumes of dilute epinephrine 1:1,000,000 produces less than 12 ml of whole blood for each liter of pure fat removed by liposuction.32 In fact, when the tumescent technique is used, patients will typically lose more blood during phlebotomy for preoperative laboratory studies than during a liposuction procedure that removes more than two liters of pure fat. One week following the liposuction of a liter of fat there is virtually no change in the patient’s peripheral venous hematocrit.33

Rapid Postoperative Recovery

Because there is so little blood loss, there is usually almost no postoperative bruising. Patients may return to a desk-type job within one to two days following liposuction by local anesthesia with the tumescent technique. Elastic support garments arerequired for only three days postoperatively, and exercising may be cautiously resumed three to four days after surgery. Postoperative recovery is quite uneventful.

Prolonged Local Anesthesia

A remarkable aspect of the tumescent technique is that there is so little postoperative discomfort. Treated areas remain at least partially anesthetized for up to 18 hours after surgery. Thus it is not necessary to use local anesthetics that are longer acting and more cardiotoxic than lidocaine.18, 41, 50, 58

After liposuction by the tumescent technique, patients do not require postoperative analgesia. Although some patients do take acetaminophen for soreness, narcotic analgesics are not prescribed.

Improved Aesthetic Results

The tumescent technique minimizes the risks of postoperative irregularities of the skin. With careful and methodical infiltration, one can produce uniform tumescence, avoiding irregularities and distortions. The magnification or enlargement of the targeted fatty compartments and the use of smaller suction cannulas (1.5 mm = 12 gauge and 4.7 mm = 3/16-inch outside diameter) permit liposuction to be done more uniformly and more completely. Because of this “magnification” of subcutaneous fat, focal residual collections of fat are more easily detected and treated before completion of the surgery. These features of the tumescent technique minimize irregularities of the skin, which are more likely to be seen after liposuction when only general anesthesia is used.

Certain areas of the body have traditionally been regarded as areas where it is relatively difficult to achieve good results by liposuction.28 Areas that are prone to develop postsurgical irregularities of the skin or are otherwise difficult to treat by traditional liposuction methods include the medial proximal thighs, anterior thighs, upper abdomen, calves, and ankles. With the use of the tumescent technique, these areas are routinely treated with excellent results. With traditional liposuction techniques, controlling the direction of the cannula through the soft jelly-like fat of the medial thighs is technically difficult. The mobility of this fatty tissue causes the cannula to travel repeatedly along the same path, predisposing to focally excessive fat removal. However, when this fatty compartment has been made firm and swollen by the tumescent technique, smaller liposuction cannulas can easily be directed to achieve a smooth uniform fat reduction.

Decreased Surgical Risk

Massive shifts of fluid out of the vascular space into the areas traumatized by the liposuction cannula and blood loss, which can require an autologous blood transfusion, are major risk factors in liposuction by general anesthesia.27

Blood loss has never been a problem with the tumescent technique. In more than 75 consecutive cases of liposuction using the tumescent technique, the mean blood loss was less than 12 ml of whole blood per liter of pure fax extracted.32 The amount of pure fat extracted ranged from 200 ml to 3050 ml, with 900 ml the mean volume of extracted fat. The volume of whole blood lost during liposuction ranged from 2.5 ml to 24.9 ml, with 9.7 ml the mean volume of blood lost.

With the tumescent technique only minimal amounts of IV fluids are given, although IV access is always established for the unlikely event that it is necessary to administer emergency medications. The tumescent technique essentially eliminates problems associated with the shift of fluids out of the intravascular space. Direct infiltration of large volumes of physiologic saline into the targeted compartments of fat provides sufficient interstitial pressure to preclude additional fluid shifts out of the vascular space. Since the use of morphine and meperidine was discontinued in 1987, there have been no episodes of orthostatic hypotension, even when 2000 to 3000 ml of pure fat has been extracted.

Decreased Anesthetic Risk

The fact that general anesthesia is the current anesthetic method of choice for liposuction is not proof that it is either the safest method or the method that gives the best aesthetic results. Historically, liposuction was developed by surgeons who preferred general anesthesia over local anesthesia. As a consequence, the vast majority of liposuction surgeries are still performed with the use of general anesthesia. The fact that large volume liposuction can be safely and easily accomplished totally by local anesthesia is not well recognized. In fact, in a recent issue of the Clinics in Plastic Surgery devoted to lipoplasty, there was little discussion of anesthesia, and there was no mention of the fact that liposuction by local anesthesia alone is possible.40

That general anesthesia is associated with a significant risk of serious complications has been pointed out in a number of recent books.9, 44 In one study of the mortality associated with general anesthesia, 41 cases of cardiac arrest during surgery were reviewed.23 More than half of the patients were healthy and were categorized as ASA (American Society of Anesthesiology) class 1. The rest were ASA class 2 or 3, meaning that they had only minimal or moderate underlying poor health. Sixteen of the operations were minor, and 32 were elective. The causes of death were categorized as anesthesia mismanagement in 9, cardiovascular abnormality in 9, hypoxemia in 18, and miscellaneous in 5. The possibility of unexpected fatalities with the use of general anesthesia is a strong argument in favor of using local anesthesia whenever it is clinically feasible.

One of the most reliable studies that compares the difference of risk for general and local anesthesia examined the mortality rates for dental surgery in Great Britain from 1970 to 1979.13 Of the 120 deaths associated with dental disease or treatment during this 10-year period, 10 cases had local anesthesia, 100 cases had general anesthesia, 6 had neither, and in 4 cases there was insufficient information to yield a conclusion. Considering deaths in which the anesthesia was the sole cause of death in healthy subjects, the mortality rate with general anesthesia among outpatients was 1:337,000. The annual number of administrations of local anesthesia in Great Britain, although unknown, must be many times greater than the use of general anesthesia. Consequently, the risks of local anesthesia in outpatient dental surgery must be significantly less than the risks of general anesthesia.

There have been a number of reported deaths and serious complication associated with liposuction. Although virtually all of these have been associated with some form of general anesthesia, the immediate cause has usually been attributed to infection, penetration of an abdominal viscus, an excessive amount of liposuction, or liposuction in conjunction with another risky procedure such as abdominoplasty.

To the best of this author’s knowledge, liposuction totally by local anesthesia has not been associated with any serious complications attributable to the local anesthetic.

TECHNICALITIES OF THE TUMESCENT TECHNIQUE

The tumescent technique has evolved substantially since the method was first published in 1987.33 The use of an even more dilute lidocaine solution, 0.05% instead of 0.1%, permits greater tumescence with better vasoconstriction and more uniform anesthesia. The addition of sodium bicarbonate to the anesthetic solution minimizes the pain of infiltration.56 Prior to using sodium bicarbonate in the local anesthetic solution, the stinging-burning pain of infiltration was enough to necessitate the use of IV sedation and narcotic analgesia. With the use of sodium bicarbonate (12.5 mEq/L) to neutralize the pH of the anesthetic solution, the tumescent technique does not require IV sedation or narcotic analgesia (Table1).

Table 1. Recipe for Tumescent Technique Anesthetic Solutions for Body Liposuction (Lidocaine 0.05%, Epinephrine 1:1,000,000)

When only one of two body areas are treated by liposuction, usually no sedation is needed. When two or more areas are treated, requiring the patient to remain recumbent for more than two hours, 2.5 mg to 5 mg of midazolam is given intramuscularly with a 30-gauge needle and is repeated in two to three hours if necessary. Certain patients will also be given 25 mg of meperidine (Demerol) intravenously just prior to beginning liposuction of the abdomen.

Because of the minimal blood loss associated with the tumescent technique and because of the large volumes of normal saline infiltrated into fat, routine IV fluid replacement is not necessary.

When the tumescent technique is used for liposuction totally by local anesthesia, then both the Klein handle and the Klein needle are used. When the tumescent technique is used for liposuction in conjunction with general anesthesia, then only the Klein needle is necessary.

For liposuction totally by anesthesia, the Klein handle is used for the initial infiltration of local anesthetic. It is designed to permit the efficient subcutaneous infiltration of large volumes of a local anesthetic solution while assuring minimal discomfort in patients who are fully awake. When using long thin disposable needles, first a spinal needle (20 gauge, 3.5 inches long) and then an intradiscal needle (18 gauge, 6 inches long) are necessary. The 20-gauge needle is used initially because it causes less discomfort than an 18-gauge needle when passed through unanesthetized tissue. These needles are inserted at sites around the periphery of the targeted fatty compartment either through intact skin or through the incision sites that will be used to insert the liposuction cannula. The sites of needle insertion are initially anesthetized using a 30-gauge needle on a 6-cc syringe to infiltrate a small bleb of the local anesthetic solution intradermally.

The Klein needle consists of a 30-cm-long, 4-mm-outside diameter needle welded to a syringe handle. Because it is blunt-tipped, the Klein needle is less likely than a sharp needle to puncture subjacent fascia. When used for regional local anesthesia without IV sedation, the needle is used for the last stage of the infiltration of the anesthesia solution after using the Klein handle. In an awake patient, the blunt tip will cause discomfort when it encounters an area not previously well anesthetized. Upon detecting an area not adequately anesthetized, the surgeon or anesthesiologist can immediately infiltrate anesthetic exactly where it is needed. When testing for completeness of anesthesia, the Klein needle is an essential part of the tumescent technique for liposuction totally by local anesthesia.

The Klein needle is the only instrument needed when the tumescent technique is used in conjunction with general anesthesia or deep IV sedation. Profound vasoconstriction can be achieved over large areas by systematically passing this blunt-tipped needle throughout the targeted fatty compartment along the same pathways that will be used by the liposuction cannula. The anesthetic solution must be infiltrated carefully and methodically to ensure that no areas are missed and that the tissues are made swollen in a uniform, proportionate fashion.

Uniform infiltration is most easily accomplished by using a grid pattern drawn preoperatively with a felt-tipped pen on the overlying skin. By infiltrating anesthetic solution as the needle is advanced, large volumes can be instilled quickly and uniformly, producing firm tumescence , extensive vasoconstriction, and local anesthesia.

Filling a 60-cc syringe with anesthetic is the first step in using the Klein handle or needle. An IV line is attached to the bottle containing the anesthetic solution. Next, using a Klein connector the IV line is connected to a 60-cc syringe, the IV line flow-regulator clamp is opened, and the syringe plunger is retracted. Once the syringe is full, it is removed from the connector and IV line.

When inserting to 60-cc syringe into the Klein handle, the syringe is turned until it is engaged with the Luer-Lok attachment. After removing the connector from the IV line, the IV line is attached directly to the side-port of the handle, and either a 20-gauge 3.5-inch-long spinal needle or an 18-gauge 6-inch-long intradiscal needle is attached to the end of the handle. Finally the needle is inserted through anesthetized skin into subcutaneous fat, and the infiltration begins.

In certain areas where the adipose tissue is regularly more sensitive, the infiltration must be done more slowly than in other area. Areas that are always rather sensitive include the distal-lateral and posterior thighs, upper abdomen and waist near the costal margin, the periumbilical areas, and the medial knees. Except in these areas, most patients can barely detect any sensation as the anesthetic solution is injected.

If not used carefully, a sharp spinal or intradiscal needle may inadvertently penetrate the tissue underlying the subcutaneous fat. To minimize the risk of puncturing the peritoneum or causing a pneumothorax, one must continuously pay careful attention to the exact location of the needle tip within the subcutaneous fat. The safe use of the Klein handle requires that the surgeon or anesthesiologist palpate the tip of the needle while it is being gently advanced along its intended path. To anesthetize deep tissue planes, the thumb and fingers of one hand gently grasp and elevate the skin and subcutaneous fat while simultaneously palpating the needle tip. At the same time the other hand grips the handle and simultaneously advances the needle and depresses the syringe plunger. Refilling the 60-cc syringe is easily accomplished: without removing the needle from the subcutaneous fat simply open the IV-flow regulator clamp and retract the syringe plunger.

By repeating these maneuvers systemically and directing the needle radically in many directions, large regions of the skin and subcutaneous tissue are efficiently anesthetized and vasconstricted. Well-anesthetized areas are easily recognized visually by the pallor and tactually by both the coolness induced by the vasoconstriction and the firmness of the tumescent technique.

A substantial volume of anesthetic solution must be injected in order to produce tumescence and complete anesthesia of a fatty compartment (Table 2). Postoperatively there is considerable drainage of slightly blood-tinged anesthetic solution. This typically continues for up to 18 hours.

SPECIAL LIPOSUCTION TECHNIQUES

In order to accomplish liposuction surgery over extensive areas without the use of general anesthesia, narcotic analgesia, of IV sedation, the standard liposuction technique must be modified.

Originally the tumescent technique for liposuction surgery used an anesthetic solution containing 0.1% lidocaine (1 gm/L). By using cannulas specifically designed to minimize the discomfort of liposuction, the lidocaine concentration can be reduced to less than 0.05% (500 mg/L).

Table 2: Typical Range of Volumes of Dilute Anesthetic Solutions

Used with the Tumescent Technique for Infiltration into Various Areas

Traditional liposuction techniques with general anesthesia use 6-mm, 8-mm, and even 10-mm cannulas. It is difficult to precisely control the direction of such large cannulas since they tend to track repeatedly along previous paths. This can result in the removal of too much fat along one path. An inadvertent approach too near the skin by a larger cannula is more likely to result in an undesirable cutaneous ripple or depression.

In order to optimize accuracy and minimize discomfort, liposuction is accomplished using a two-stage microcannula method. Initially a 12-gauge (1.5 mm) microcannula attached to a Klein microcannula handle is used. Because a 12-gauge cannula penetrates the fibrous septae in adipose tissue with minimal resistance, the cannula’s direction and relative distance from skin are controlled more easily. The tunnel pattern produced by a 12-gauge cannula is more precise and evenly distributed. Subsequently a Klein lamprey cannula (4.7 mm = 3/16-inch outside diameter) is used to complete the final stage of liposuction. The 4.7-mm cannula follows the paths already made by the 12-gauge cannula. Approximately 80% of the extracted fat is removed by the larger cannula during the second stage of liposuction.

Smaller cannulas are most suited for liposuction by local anesthesia. Clinical experience indicates that a cannula with a large inside diameter is more likely to cause discomfort during liposuction by local anesthesia than is a smaller cannula. Larger cannulas exert greater traction on fibrous structures within adipose tissue. This may cause pain is tissues located beyond the effects of the local anesthesia.

The use of a 12-gauge cannula is a final test for complete anesthesia. If an incompletely anesthetized area is encountered during liposuction, a 12-gauge cannula causes minimal discomfort compared with the startling sensation that a 4-mm or 5-mm cannula might cause.

By reducing the force needed to breach the fibrous septae permeating fatty tissue, the two-stage microcannula method minimizes both the patient’s discomfort as well as the physical stress on the surgeon’s arm.

Ancillary Aspects of the Tumescent Technique

Certain operating room procedures change as a consequence of patients being awake and conversant throughout a liposuction procedure.

To maintain warmth and comfort we routinely drape the patient in terry-cloth towels, preheat the bottle of surgical soap by bathing it in comfortably hot water, use the operating room overhead surgical lighting for additional heating when needed, and ask every patient to bring a pair of warm socks to prevent cold toes.

Tactfully maintaining a patient’s modesty while assiduously preserving asepsis requires a common sense approach to preparing and draping patients.

Liposuction removes only a fraction of the anesthetic solution injected with the tumescent technique. Some of the anesthetic fluid drains out during surgery, requiring the use of numerous gauge sponges to soak up the solution. Following surgery there will be drainage of blood-tinged anesthetic solution from the small (3-mm to 5-mm) incision sites used by the cannulas. Bulky gauze sponges are routinely placed under the postoperative elastic support garment. When there is voluminous drainage it may be necessary for the patient to change gauzes several times over the first 12 to 16 hours postoperatively. Warning patients to expect copious postoperative drainage of a blood-tinged anesthetic solution, containing less than 2% whole blood, will mitigate their anxieties. The patient’s attitude toward this drainage becomes more positive when it is understood that maximizing drainage will minimize postoperative bruising.

Relaxing, soothing music should be played in the operating room during surgery. Patients are invited to bring their own favorite relaxing music. During the procedure we either listen to the music or converse casually with the patient. By gently holding the patient’s arm, a nurse can significantly reduce a patient’s anxiety. Skill in these forms of vocal and tactile anesthesia is most beneficial.

When liposuction is planned for multiple areas, the duration of the surgery may be greater than the patient’s bladder capacity. During a lengthy procedure it is not unusual that the patient and the IV pole must be walked to the restroom. Anticipating such a necessity allows the surgeon to choose a convenient moment to call a “time-out”. Once this mission has been accomplished, the patient is escorted back to the operating room, the remaining surgical areas are scrubbed, and the surgery is continued.

Because even mild degrees of urinary retention can cause increased pulse and blood pressure, it is important to give patient’s the opportunity to relieve themselves. Offering patients a choice of a bedpan, urinal, or easy access to a toilet is essential when performing prolonged surgical procedures by local anesthesia. As more advanced dermatologic surgical procedures are accomplished totally by local anesthesia, the advantages of having a patient toilet readily assessable from the operating room will become more widely appreciated.

Using only local anesthetics and eschewing potent respiratory depressant sedatives and narcotics dramatically reduce postoperative recovery time. With the use of the tumescent technique for liposuction totally by local anesthesia, a patient is ready to be discharged home as soon as the elastic support garment is in place and the patient is dressed. Although patients will typically sleep for several hours after returning home, they are encouraged to be as active as they find comfortable, beginning the same day as surgery.

Because of the nausea associated with narcotics, the only postoperative analgesia used is acetaminophen. However, because of the prolonged local anesthesia associated with the tumescent technique, most patients do not take any analgesics postoperatively.

Maximum Safe Lidocaine Dose

Clinical experience with liposuction by local anesthesia has shown that it is safe to exceed the traditional recommended maximum dose of 7 mg/kg of lidocaine and epinephrine. The facile pharmacologic explanation for the safety of using very large doses of lidocaine during liposuction is that a significant amount of lidocaine is removed along with the aspirated fat.1, 25 However, this assertion has never been documented scientifically.

Maximum safe dose of lidocaine for subcutaneous infiltration is dependent on local tissue vascularity. For infiltration into subcutaneous fat which is relatively avascular, surprisingly high doses are safe. An estimate of a safe lidocaine dose with the tumescent technique for liposuction is 35 mg/kg. When infiltrated slowly and as a dilute solution, this dose should correspond to a peak lidocaine plasma level of between 3 and 4 ųg/ml. This is five times the maximum recommended safe dose for local anesthesia listed in the Xylociane (lidocaine) package insert. Although still higher doses might be safe, such safety has not been documented. In one report of liposuction by the tumescent technique, doses as high as 90 mg/kg were used without serious toxicity.37

The peak plasma lidocaine levels are not dramatically reduced by liposuction. It is important to recognize that the removal of lidocaine by liposuction does not dramatically reduce the risk of lidocaine toxicity. It is the inherent slow rate of absorption from fat that accounts for the safety of liposuction by local anesthesia using high doses of lidocaine.

Absorption Rate of Subcutaneous Lidocaine

The finding that peak plasma lidocaine levels with the tumescent technique are delayed for 10 to 14 hours is unprecendented and contrary to accepted dogma. The explanation for such a discrepancy is not obvious. Factors that contribute to delayed absorption include (1) using a dilute lidocaine solution, (2) infiltrating slowly, (3) using epinephrine, and (4) having the site infiltration be relatively avascular tissue.

The current literature substantiates the finding that peak plasma lidocaine levels occur within 60 minutes of giving the dose. This is thought to be valid in healthy patients irrespective of the mode of injection, whether it is given by bolus intravenous infusion; intravenous regional analgesic26; intramuscular injection11,51; caudal, epidural, intercostal, and peripheral nerve blocks6, 7, 19, 29, 48, 63;paracervical infiltration4; or oral administration.

There are few detailed studies of absorption kinetics of lidocaine infiltrated subcutaneously. For subcutaneous infiltration the peak plasma lidocaine level is usually less than 60 minutes.36, 52, 54, 57. An average peak plasma lidocaine level occurring at 62 minutes (range: 30 to 120 minutes) is one of the longest delays documented in the literature.42 When 2% lidocaine with epinephrine 1:2000,000 was infiltrated into the scalp for hair transplantation, peak plasma lidocaine concentration occurred 45 minutes after the initial infiltration in six of six patients.39

The dilution of lidocaine is an important determinant of the absorption rate. As is apparent from the following clinical study, in which there was no liposuction, dilution both delays and diminishes the magnitude of peak plasma lidocaine levels following subcutaneous infiltration. When 1 gm of 0.1% lidocaine with epinephrine 1:1000,000 was infiltrated into subcutaneous fat of the thighs, the peak plasma lidocaine level was 1.2 ųg/ml and occurred 14 hours after beginning of infiltration. Repeating the procedure in the same patient, but using a 10-fold increase in the concentration of lidocaine and epinephrine (1 gm of 1% lidocaine with epinephrine 1:100,000), the peak plasma lidocaine level was 1.5 ųg/ml and occurred approximately 9.5 hours after beginning the infiltration. This is contrary to the observation that lidocaine absorption rates are independent of lidocaine concentration for intramuscular and peridural injections over a concentration range of 1% to 10% lidocaine.15

The rate of subcutaneous infiltration is also an important variable for lidocaine absorption rate. Rapid delivery of lidocaine leads to rapid systemic absorption and increased risk of toxicity.53 When 1% lidocaine in a dose of 1 gm is infiltrated slowly in subcutaneous fat over 45 minutes, the peak level was 1.5 ųg/ml and occurred at 9.5 hours.34 When similar doses are infiltrated rapidly within a few minutes, peak levels occur within 15 minutes and reach potentially toxic concentration at over 5 ųg/ml.46

The site of infiltration is also a factor in lidocaine absorption kinetics. When dilute lidocaine is infiltrated into the subcutaneous tissues of the face, peak lidocaine levels occur within 4 to 5 hours of the infiltration. For facelift surgery using the tumescent technique without narcotic analgesic or IV sedation, the anesthetic solution consists of 0.18% lidocaine and epinephrine 1:563,500 (50 ml of 1% lidocaine, 1 ml of epinephrine 1:1000, 12.5 ml of 8.4% sodium bicarbonate, in 500 ml of physiologic saline). The typical facelift, including submental liposuction, requires approximately 350 ml of this anesthetic solution. In this setting, typical peak plasma lidocaine levels are approximately 0.6 ųg/ml.

Lidocaine Toxicity

Although the risk of lidocaine is minimized by using the tumescent technique, a thorough knowledge of lidocaine toxicology is essential for any surgeon making extensive use of local anesthesia. Lidocaine toxicity is closely correlated with lidocaine plasma levels. Therapeutic plasma lidocaine levels for suppressing ventricular ectopy in the clinical setting of acute myocardial ischemia range between 1 and 5 ųg/ml. Subjective side effects are usually noticed at between 3 and 6 ųg/mg, with objective undesirable side effects, or toxicity, becoming apparent at plasma levels above 5 and 9 ųg/ml.2 Potentially fatal lidocaine toxicity may occur at plasma lidocaine concentrations as low as 9 ųg/ml (Table 3).

Lidocaine toxicity may result from:

• An overdose
• An excessively rapid systemic uptake of an otherwise safe does
• Impaired hepatic metabolic
• Drug interactions

Table 3. Lidocaine Levels and Toxicity

Overdose

An overdose occurs when too much drug (More than a safe amount for a given clinical situation) is given as the result of carelessness or ignorance.

Rapid Systemic Uptake

Excessively rapid subcutaneous infiltration of an otherwise safe dose of lidocaine may be a common cause of toxic plasma lidocaine concentrations. Lidocaine is a capillary vasodilator with a rapid onset of action.14 Epinephrine is a vasoconstrictor with maximum clinical effect delayed approximately 10 to 15 minutes after a rapid injection of a lidocaine and epinephrine solution, systemic lidocaine absorption will be rapid until the epinephrine-induced vasoconstriction has had sufficient time to occur.

Impaired Lidocaine Metabolism

Diseases or drugs that decrease lidocaine metabolism are important causes of lidocaine toxicity. Diseases causing decreased hepatic metabolism can significantly delay elimination of lidocaine from the systemic circulation. Disease of the liver parenchyma decreases lidocaine metabolism directly.55,59 Other diseases that diminish hepatic perfusion, such as heart disease,47,60 or diseases associated with hypotension,21 decrease lidocaine metabolism indirectly.

Drug Interaction

Drugs that decrease hepatic blood flow otherwise decrease lidocaine metabolism can lead to toxic accumulations of lidocaine. Drugs commonly associated with such adverse interactions include cimetidine,22,35 beta-adrenergic receptor blockers,8,12,43,62 and procainamide,30.

Other forms of drug interaction, not necessarily related to lidocaine metabolism, may predispose to severe toxicity. Diazepam (Valium) and other benzodiazepines reduce the risk of seizures associated with excessive plasma lidocaine concentrations16,17 However, with either diazepam (Valium) or midazolam (Versed) premedication, the first sign of local anesthetic toxicity may be cardiovascular collapse with a significantly decreased chance of successful resuscitation.3 Diazepam (Valium) may significantly increase the incidence of malignant arrhythmias induced by local anesthetics.24 The benzodiazepine midazolam reduces the incidence of lidocaine-induced convulsions but has no significant effect on mortality in rats.61

SUMMARY

Using the tumescent technique, liposuction can remove large volumes of fat with minimal blood loss. A maximal safe dosage of dilute lidocaine using the tumescent technique is estimated to be 35 mg/kg.

The slow infiltration of a local anesthetic solution of lidocaine and epinephrine minimizes the rate of systemic absorption and reduces the potential for toxicity. Dilution of lidocaine (0.05% or 0.1%) and epinephrine (1:100,000) further delays absorption of peak plasma lidocaine concentrations. Using the tumescent technique for liposuction, peak plasma lidocaine levels occur 12 hours after the initial injection. Clinically significant local anesthesia persists for up to 18 hours. For liposuction, it is not necessary to use local anesthetics, which are longer acting and potentially more cardiotoxic than lidocaine.

References

1.     Asken S: Liposuction Surgery and Antilogous Fat Transplantation. East Norwalk, Appleton & Lange, 1988, p 63

2.     Benowitz NL, Meister W: Clinical pharmacokinetics of lidocaine . Clin Pharmacokinet 3:177-201, 1978

3.     Bernards CM, Carpenter RL, Rupp SM, et al: Effect of midazolam and diazepam (Valium) premedication on central nervous system and cardiovascular toxicity of bupivacaine in pigs. Anesthesiology 70:318-323, 1989

4.     Blanco LJ, Reid PR, King TM: Plasma lidocaine levels following paracervical infiltration for aspiration absorption. Obstet Gynecol 60:506-508, 1982

5.     Boyes RN, Scott DB, Jebson PJ, et al: Pharmacokinetics of lidocaine in man. Clin Pharmacol Ther 12:105-116, 1971

6.     Braid DP, Scott DB: Dosage of lignocaine in epidural block in relation to toxicity. Br J Anaesth 38:596-602, 1966.

7.     Braid DP, Scott DB: The systemic absorption of local analgesic drugs. Br J Anaesth 37:394-404, 1965.

8.     Branch RA, Shand DS, Wilkinson GR, Nies AS: The reduction of lidocaine clearance by dl propranolol: An example of hemodynamic drug interaction. J Pharmacol Exp Ther 184:515-519, 1973.

9.     Brown DL (ed): Risks and Outcome of Anesthesia. Philadelphia, JB Lippincott Co., 1988

10.  Carrron H, Korbon G, Rowlingston J: Regional Anesthesia: Techniques and Clinical Applications, Orlando, Grune and Stratton, 1984, p 5

11.  Collinsworth KA, Kalman SM, Harrison DC: The clinical pharmacology of lidocaine as an antiarrhythimic drug. Circulation 50:1217-1230, 1974

12.  Conrad, KA, Byers JM III, Finley PR, Burnham L: Lidocaine elimination: Effects of metoprolol and of propranolol. Clin Pharmacol Ther 33:133-138, 1983

13.  Coplans MP, Curson I: Deaths associated with dentistry. Br Dent J 153:357-362, 1982

14.  Covino BG, Vassallo HG: Local Anesthetics: Mechanisms of Action and Clinical Use. New York, Grune and Stratton, 1976, pp105-106

15.  de Jong RH: Local Anesthetics, 2nd ed. Springfield, IL Charles C Thomas, 1977, pp 187-188

16.  de Jong RH: Toxic effects of local anesthetics. JAMA 239:1166-1168, 1978

17.  de Jong RH: Heavner, JE: Convulsions induced by local anesthetic: Time course of diazepam prophylaxis. Can Anaesth Soc J 21:153-158, 1974

18.  de Jong RH, Ronfield RA, DeRose RA: Cardiovascular effects of convulsant and supraconvulsant doses of amide local anesthetics. Anesth Analg 61:3-9, 1982

19.  Ecoffey C, Desparment A, Berdeaux, A, et al: Pharmacokinetics of lignocaine in children following caudal anesthesia. Br J Anaesth 56:1399-1402, 1984

20.  Eriksson E: Illustrated Handbook in Local Anesthesia, 2nd ed. London, Lloyd-Luke, 1979, p 12

21.  Feely J, Wade D, McAllister CB, et al: Effect of hypotension on liver blood flow and lidocaine disposition. N Engl J Med 307:866-869, 1982

22.  Feely J, Wilkinson GR, McAllister CB, Wood AJJ: Increased toxicity and reduced clearance of lidocaine by cimetidine. Ann Intern Med 96:592-594, 1982

23.  Gordon T. Larson CP Jr, Prestwich R: Unexpected cardiac arrest during anesthesia and surgery: An environmental study. JAMA 236:2758-2760, 1976

24.  Gregg RV, Turner PA, Denson DA, et al: Does diazepam really reduce the cardiotoxic effects of intravenous bupivacaine? Anesth Anal 67:9-14, 1988

25.  Gumuncio CA, Bennie JB, Fernando B, et al: Plasma lidocaine levels during augmentation mammaplasty and suction-assisted lipectomy. Plast. Resconst Surg 84:624-627, 1989

26.  Hargrove RL, Hoyle JR, Parker JBR, et al: Blood lignocaine levels following intravenous regional analgesia. Anesthesia 21:37-41, 1966

27.  Hetter GP: Blood and fluid replacement for lipoplasty procedures. Clin Plast Surg 16:245-248, 1989

28.  Illouz YG: Refinements of the lipoplasty technique. Clin Plastic Surg 16:217-232, 1989

29.  Inoue R, Suganuma T, Echizen H, et al: Plasma concentrations of lidocaine and its principal metabolites during intermittent epidural anesthesia. Anesthesiology 63:304-310, 1985

30.  Karlsson E, Collste R, Rowlins MD: Plasma levels of lidocaine during combined treatment with phenytoin and procainamide. Eur J Clin Pharmacol 7:455-459, 1974

31.  Klein JA: Anesthesia for liposuction in dermatologic surgery. J Dermatol Surg Oncol 14:1124-1132, 1988

32.  Klein JA: Reduced blood loss and optimal fluid balance for liposuction: Infiltration regional anesthesia by the tumescent technique. (in preparation)

33.  Klein JA: The tumescent technique for lipo-suction surgery. Am J Cosmet Surg 4:263-267, 1987

34.  Klein JA: Tumescent technique for regional anesthesia permits lidocaine doses of 35 mg/kg for liposuction: Peak plasma lidocaine levels are diminished and delayed 12 hours. J Dermatol Surg Oncol 16:248-263, 1990

35.  Knapp AB, Maguire W, Keren G, et al: The cimetidine-lidocaine interaction. Ann Intern Med 98:174-177, 1983

36.  Kosowsky BD, Shahid IM, Gurinder SG, et al: Effect of local lidocaine anesthesia on ventricular escape intervals during permanent pacemaker implantation in patients with complete heart block. Am J Cardiol 51:101-104, 1983

37.  Lillis PJ: Liposuction surgery under local anesthesia: Limited blood loss and minimal lidocaine absorption. J Derm Surg Oncol 14:1145-1148, 1988

38.  Malamed SF: Handbook of Local Anesthesia, 2nd ed. St. Louis, C.V. Mosby Co, 1986, p-44

39.  Maloney JM, Lertora JJ, Yarborough J, Millikan LE: Plasma concentrations of lidocaine during hair transplantation. J Dermatol Surg Oncol 8:950-954, 1982

40.  Mladick RA (ed) Lipoplasty. Clin Plast Surg 16:217-403, 1989.

41.  Nancarrow C, Rutten AJ, Runciman WB, et al: Myocardial and cerebral drug concentrations and the mechanisms of death after fatal intravenous doses of lidocaine, bupivacaine, and ropivacaine in the sheep. Anesth Analg 69:276-283, 1989.

42.  Nattel S, Rinkenberger RL, Lehrman LL, Zipes DP: Therapeutic blood lidocaine concentrations after local anesthesia for cardiac electrophysiologic studies. N Engl J Med 301:418-420, 1979

43.  Ochs HR, Carstens, G, Greenblatt DJ: Reduction in lidocaine clearance during continuous infusion and coadministration of propranolol. N Engl J Med 303:373-376, 1980

44.  Orkin FK, Cooperman LH (eds): Complications in Anesthesiology, Philadelphia, JB Lippincott Co, 1983

45.  Physician’s Desk Reference. Oradell, NJ, Medical Economics Company

46.  Piveral K: Systemic lidocaine absorption during liposuction (letter). Plast Rescont Surg 80:643, 1987

47.  Prescott LF, Adjepon-Yamoah KK, Talbot RG: Impaired lignocaine metabolism in patients with myocardial infarction and cardiac failure. Br Med J 1:939-941, 1976

48.  Raj PP, Rosenblatt R, Miller J, et al: Dynamics of local-anesthetic compounds in regional anesthesia. Anesth Analg 56:110-117, 1977

49.  Raymond SA, Steffensen SC, Gugino LD, Strichartz GR: The role of length of nerve exposed to local anesthetics in impulse blocking action. Anesth Analg 68:563-570, 1989

50.  Rutten AJ, Nancarrow C, Mather LE, et al: Hemodynamic and central nervous system effects of intravenous bolus doses of lidocaine, bupivacaine, and ropivacaine in sheep. Anesth Analg 68:291-299, 1989

51.  Schwartz ML, Meyer MB, Covino BG, et al: Antiarrythmic effectiveness of intramuscular lidocaine: Influence of different injection sites. J Clin Pharmacol 14:77-83, 1974

52.  Schwartz ML, Covino BG, Narang RM, et al: Blood levels of lidocaine following subcutaneous administration prior to cardiac catheterization. Am Heart J 88:721-723, 1974

53.  Scott BD: Evaluation of clinical tolerance of local anesthetic agents. Br J Anaesth 47:328-333, 1975

54.  Scott DB, Jebson PJR, Braid DP, et al: Factors affecting plasma levels of lignocaine and prilocaine. Br J Anaesth 44:1040-1049, 1972

55.  Selden R. Sasahara AA: Central nervous system toxicity induced by lidocaine: Report of a case in a patient with liver disease. JAMA 202:908-909, 1967

56.  Stewart JH, Cole GW, Klein JA: Neutralized lidocaine with epinephrine for local anesthesia . J Derm Surg Oncol 15:1081-1083, 1989

57.  Stoelting RK: Plasma lidocaine concentrations following subcutaneous or submucosal epinephrine-lidocaine injection. Anesth Analg 57:724-726, 1978

58.  Tanz, RD, Haskett T, Loehning RW, Fairfax CA: Comparative cardiotoxicity of bupivacaine and lidocaine in the isolated perfused mammalian heart. Anesth Analg 63:549-556, 1984

59.  Thomson PD, Melmon KL, Richarson JA, et al: Lidocaine pharmacokinetics in advanced heart failure, liver disease, and renal failure in humans. Ann Intern Med 78:499-508, 1973

60.  Thomson PD, Rowland M, Melmon KL: The influence of heart failure, liver disease, and renal failure on the disposition of lidocaine in man. Am Heart J 82:417-421, 1971

61.  Torbiner ML, Yagiela JA, Mito RS: Effect of midazolam pretreatment on the intravenous toxicity of lidocaine with and without epinephrine in rats. Anesth Analg 68:744-749, 1989

62.  Tucker GT, Bax NDS, Al-Asady S, et al: Effects of β-adrenoceptor antagonists on the pharmacokinetics of lignocaine. Br J Pharmacol 17:21S-28S, 1984

63.  Tucker GR, Moore DC, Bridenbaugh PO, et al: Systemic absorption of mepivacaine in commonly used regional block procedures. Anesthesiology 37:277-287, 1972

Jeffrey A. Klein, M.D.

Abstract

The tumescent technique of liposuction is a modification of the wet technique. A large volume of very dilute epinephrine is infiltrated into a targeted fat compartment prior to liposuction, producing a swelling and firmness. This tumescence of fat permits an increased accuracy in liposuction and minimizes postsurgical irregularities or rippling of the skin. Epinephrine-induced vasoconstriction minimizes blood loss, bruising, and postoperative soreness.

Safe, rapid infiltration of large volumes of solution is achieved using a closed sterile system featuring a newly designed blunt-tipped, 30-cm-long, 4.7-mm-diameter needle having a hollow handle that accommodates a 60-cc syringe. Attached to a liter bottle of anesthetic solution by an intravenous line, the needle is inserted via the same incision and deposits the solution along the same path as that intended for the liposuction cannula. Thus, the solution is infiltrated exactly where it is needed for hemostasis or local anesthesia.

Used in conjunction with general anesthesia, the tumescent technique saves time in achieving maximal vasoconstriction of the targeted fat compartment. If dilute lidocaine (0.1%) is added to the solution, the technique permits liposuction of more than 2 liters of fat totally by local anesthesia. Twenty-six patients, having received a mean lidocaine dose of 1250 mg (18.4 mg/kg or 8.5 mg/kg/hr) infiltrated into subcutaneous fat, had a mean serum lidocaine level of less than 0.36 ųg/ml 1 hour after completion of the infiltration.

Introduction

Liposuction by general anesthesia, with local infiltration of epinephrine, is associated with potentially serious blood loss and massive bruising. Until now, the time-consuming inefficiency of multiple percutaneous injections has discouraged the use of vasoconstrictors and local anesthesia for liposuction.

This article describes the clinical pharmacology and instrumentation of the tumescent technique. When used with general anesthesia, the tumescent technique improves the efficiency and clinical results of the wet technique. When lidocaine is added to the infiltrate, the technique permits the safe and efficient removal of over 2 liters of bloodless fat by liposuction totally by local anesthesia.

Methods and Materials

When the tumescent technique is used with general anesthesia, the concentration of epinephrine is 1:1,000,000. This vasoconstrictive solution is prepared as follows:

1. One liter intravenous (IV) bottle of sterile physiologic normal saline (0.9% NcC1).

2. One ampule (1 ml) of 1:1,000 epinephrine.

In this study, local anesthesia was used. The solution, consisting of lidocaine (~ 0.1%) and epinephrine (~1:1,000,000) in normal saline, was prepared as follows:

1. One-liter IV bottle of sterile physiologic normal saline (0.9% NcCl).

2. Two 50-ml bottles of 1% plain lidocaine (1 gm of lidocaine).

3. One 1-ml ampule of 1:1000 epinephrine (1 mg of epinephrine). The exact concentrations are lidocaine 0.091% and epinephrine 1:1,100,000.

A new instrument (patent pending) consisting of a blunt-tipped 30-cm-long stainless steel needle is employed to infiltrate the anesthesia. It has an outside diameter of 4.0 mm, an inside diameter of 1 mm, and is welded to a 10-cm-long hollow handle that accommodates a 60-cc disposable Luer-Lock syringe. Interposed between needle and handle is a fluid intake port connected to an IV bottle containing the local anesthetic solution by an IV needle. By inserting the needle through the same incisions and infiltrating along the same paths intended for the suction cannula, the solution of anesthetic and vasoconstrictor is deposited in fat exactly along the path where it is needed. The blunt tip precludes inadvertent intravascular drug delivery and minimizes the risk of sharp trauma to structures in and about the targeted deposits of fat.

The IV line connecting the bottle of anesthetic solution to the large needle is the “ADDitIV Primary IV Set” (catalog no. V1466, manufactured by McGaw Laboratories, Inc.. It is equipped with a “macrodrip” drip chamber, and a built-in check valve that prevents retrograde flow of anesthetic solution.

The 60-cc syringe is filled initially by attaching it to the IV line using a (B-D) syringe-filling connector (reorder number 5225, Becton-Dickinson, Rutherford, NJ 07070).

A peripheral IV is maintained during surgery to deliver diazepam (Valium) as needed in 2.5- to 5-mg increments. To avoid an inadvertent switch of solutions, we suggest a plastic bag to contain the peripheral IV solution and a glass bottle to contain the anesthetic solution. Cardiac rhythm is monitored continuously, with a regular printout of ECG rhythm strip and blood pressure.

Felt-tipped indelible ink pens are used to mark the patient’s skin. Straight lines radiating from the incision sites mark the paths for the anesthetic needles. The lines, at most 5 cm apart, provide a grid pattern that assures uniform infiltration of anesthetic solution.

We studied 26 patients who had liposuction by local anesthesia. Peripheral venous blood for serum lidocaine levels was obtained 1 hr after completing the infiltration with local anesthetic. Serum levels of lidocaine and its two principal metabolites, monoethylglyclyxylidide (MEGX) and glycylxlyidide (GX) were obtained by gas-liquid chromatography with a sensitive level of 1 ng/ml.1

In a separate study peripheral venous blood was obtained prior to surgery and again 48-72 hr after surgery, in 10 patients, to determine postoperative change to hematocrit.

Details of the Technique

The 60-cc syringe is initially filled by attaching it directly to the anesthetic IV line using a B-D syringe-filled connector. Once it is full, the syringe is then fastened to the needle handle, which in turn is attached to the bottle of anesthetic by the IV line.

The needle is then inserted via the same incision and advanced through subcutaneous fat along the same paths intended for the liposuction cannula. Continuously palpating the needle tip, the surgeon advances the needle carefully, pausing every 2 to 4 cm to deposit 2 to 4 ml of anesthetic solution.

When general anesthesia is used, rapid infiltration of the solution is desirable. This is achieved by leaving the flow-rate regulator open once the needle tip is in the subcutaneous fat. By using an IV line with a built-in check valve, reflux of solution is prevented when the syringe plunger is depressed. Once the syringe contents has been deposited into fat, the syringe is refilled merely by retracting the syringe plunger, with the needle tip remaining in the subcutaneous fat. With this arrangement, there is no need for a three-way stopcock to regulate direction of the fluid flow.

When local anesthesia is used, infiltration of the solution is slower and more controlled. Closing the flow-regulator clamp while infiltrating prevents the continuous gravity-induced infiltration of the anesthetic during the pauses when not actively pushing the syringe plunger. This conserves anesthetic and allows a more uniform infiltration. There is surprisingly little discomfort with this technique. As the needle is advanced along its initial path, the patient will experience a mild burning discomfort as the anesthetic is injected. Once the initial path is anesthetized, subsequent infiltrations along adjacent paths cause less discomfort. Occasionally the needle tip encounters a fibrous septum that is difficult to penetrate. By injecting a small bolus (3-4 ml) of anesthetic and waiting a few seconds, one may proceed without causing pain. The periumbilical area, upper abdomen, and posterior-lateral thighs are particularly sensitive, and will usually require a little extra anesthesia infiltrated using a 20-gauge spinal needle. After one fat compartment has been anesthetized, liposuction is completed before treating another compartment. This minimizes the systemic absorption of lidocaine.

The range of volumes of solution necessary to anesthetize a given anatomic fat compartment are as follows:

Entire abdomen: 400-1200 cc

Two lateral thighs (“saddle bags”): 500-1000 cc

Two medial thighs: 400-800 cc

Two upper hips (“love handles”): 400-800 cc

Two knees: 300-600 cc

Submental area: 50-100 cc

Incisions are closed with 6-0 nylon interrupted sutures and removed 7 days later. Postoperative drainage of pink-tinged residual anesthetic solution stops within 12 to 24 hr. Because of minimal bleeding and bruising associated with the tumescent technique, an elastic support garment is only strictly required the first 5 days postoperatively. Some patients prefer to wear the garment for 10-14 days for comfort and support. Beginning 24 hr after surgery, patients may remove their elastic garment briefly for a daily shower.

Results

Using the tumescent technique 26 patients (22 female, 4 male), whose mean weight was 69 kg, received a mean total dose of 1250 mg of lidocaine (range: 825 mg to 3100 mg) infiltrated into subcutaneous fat over a 1-5 hr interval. The mean dosage of lidocaine was 18.4 mg/kg of body weight, and the mean lidocaine dosage per unit time was 8.5 mg/kg/hr.

The mean volume of tissue extracted by suction was 1167 ml, of which 915 ml was fat. The remaining 252 ml was slightly blood-tinged anesthetic solution with less than 1.5% packed red cell volume.

The mean serum lidocaine and metabolite levels were: lidocaine = 0.336 ųg/ml; MEGX – 0.052 ųg/ml and GX = 0.023 ųg/ml. The highest serum lidocaine level among the 26 patients was 0.614 ųg/ml.

In a separate study of 10 patients, the mean change in hematocrit was 0% – 1.8%, measured 48-72 hr after liposuction, and the mean volume of tissue extracted was 1025 ml.

Discussion

The tumescent technique provides a more rapid and safer means of infiltrating dilute epinephrine into targeted fat compartments for liposuction than the traditional wet technique using multiple percutaneous injections. It permits liposuction of large volumes of almost bloodless fat.

Using the tumescent technique with lidocaine provides an especially safe and efficient method for doing liposuction by local anesthesia. The lidocaine is deposited exactly along the eventual pathway of the liposuction cannula.

When epinephrine-induced vasoconstriction is the principal goal of the tumescent technique, lidocaine should be omitted from the infiltration solution. One commonly recommended recipe for the solution infiltrated in the wet technique uses 250 ml of saline (0.9%), 75 ml of lidocaine (1%) with epinephrine 1:100,000, and 300 units of Wydase.2 This formulation contains 750 mg of lidocaine. One must be aware of an important lidocaine-epinephrine drug interaction. Although epinephrine delays lidocaine absorption from subcutaneous tissue, lidocaine accelerates the systemic absorption of epinephrine.3 Lidocaine causes vasodilation 4,5 and reduces the vasoconstrictive ability of epinephrine. Furthermore, the large volumes used in the tumescent technique guarantee wide diffusion of the epinephrine; thus, Wydase is unnecessary.

For local anesthesia, the traditional maximum recommended single dose of lidocaine with epinephrine is 7 mg/kg.6 Lidocaine blood levels above 6 ųg/ml are considered potentially toxic. However, the safe maximal dosage varies widely depending on the site of infiltration. The maximal dosage has been well studied for use in highly vascular areas such as in paracervical blocks used in obstetrics, in peripheral nerve blocks, and in epidural anesthesia. An extensive search of the literature failed to find any documentation of dosages for infiltration of lidocaine into subcutaneous fat. In the present study, 26 patients received a mean dose of 1250 mg of lidocaine. The mean maximal lidocaine blood level was 0.336 ųg/ml. The highest lidocaine serum level in any patient was 0.614 ųg/ml as measured by gas-liquid chromatography.

Pharmacologic principles explaining the tumescent technique’s success are as follows:

1. For a given amount of lidocaine injected subcutaneously, the more dilute the solution, the safer it is. The median lethal dose (LD50) of subcutaneously lidocaine in mice increases with increased lidocaine dilution.7

2. The larger the volume of an injected anesthetic solution, the greater its diffusion and the more uniform the resulting anesthesia.

3. Dilute solutions of lidocaine with epinephrine produce very good cutaneous anesthesia, albeit for a shorter duration than standard concentrations.8,9

Despite the unusually large amount of lidocaine used with the tumescent technique, systemic lidocaine absorption is remarkably low. There are several pharmacologic factors that may explain this observation:

1. Lidocaine has a relatively high lipid and low water solubility. A large fraction of the lidocaine dose is partitioned into fat and then extracted by liposuction.

2. Systemic absorption of subcutaneous lidocaine is a function of the blood perfusion rate of local tissue. The relative avascularity of fat and epinephrine-induced vasoconstriction account for the slow lidocaine uptake into the systemic circulation.

3. With a first-pass hepatic extraction ratio of 0.7, lidocaine is rapidly metabolized by the liver.10 In other words 70% of the lidocaine content in a volume of blood is removed with a single pass through the liver. To the extent that epinephrine increases cardiac output and therefore hepatic blood flow, the hepatic metabolism of lidocaine is accelerated. The small amount of lidocaine metabolites detected by gas-liquid chromatography in the present study indicates that only a small amount of lidocaine is actually absorbed.

The large volume of solution is an important aspect of the tumescent technique. The injection of copious amounts of fluid increases the cross section and firmness of a targeted fat compartment. When the infiltration is uniform the fatty compartment is magnified without distorting its relative proportions. A larger tumescent fatty compartment permits liposuction which is more accurate and uniform. It helps reduce the incidence of locally excessive fat extraction.

Conclusion

Liposuction by the tumescent technique offers several important advantages over older techniques: (1) improved efficiency compared to wet technique; (2) less bleeding; (3) better cosmetic results; (4) more rapid postoperative recovery, and (5) reduced risk of lidocaine toxicity.

References

1. Adjpon-Yamoah KK, Prescott LF: Gas-liquid chromatographic estimation of lignocaine, ethylglycylxylidide and 4-hydroxyxylilide in plasma and urine. J Pharm and Pharmacol 26:889-893, 1974.

2. Hetter, GP: The effect of low dose epinephrine on the hematocrit drop following lipolysis. Aesth Plas Surg 8:19, 1984.

3. Ueda W, Hirakawa, M, Mori K: Acceleration of epinephrine absorption by lidocaine. Anesthesiology 63:717-720, 1985.

4. John RA, DiFazio,CA, Longnecker DE: Lidocaine constricts, dilates rats arterioles in a dose-dependent manner. Anesthesiology62:141-144, 1985.

5. Henriksen O: Local reflex in microcirculation in human subcutaneous tissue. Acta Physiol Scand 97:447-456, 1976.

6. Ritchie JM, Green NM: Goodman and Gilman’s Pharmacologic Basis of Therapeutics, 7th edition. New York, Macmillian, 1985, p. 313.

7. Gordh T: Xylocaine – a new local analgesic. Anaesthesia 4:4-9, 21, 1949.

8. Carnegie DM, Hewer AJH: Clinical trial of xylocaine in local anesthesia. Lancet 2:12-14, 1950.

9. Covino BG, Vassallo HG: Local Anesthesics – Mechanisms of Action and Clinical Use. New York, Grune & Stratton, 1976, P 63.

10. Stenson, RE, Constantino RT, Harrison DC: Interrelationship of hepatic blood flow, cardiac output, and blood levels of lidocaine in man. Circulation 43:205, 1971.

Local Anesthesia, Liposuction, and Beyond

Jeffrey A. Klein, M.D.

This article is a personal view of the history of the tumescent technique and a look at its future. Invented and popularized by dermatologists, the tumescent technique has consequences far beyond dermatologic surgery.

As a local anesthetic technique the tumescent technique has revolutionized liposuction by eliminating both the risks of general anesthesia and the massive bleeding once associated with liposuction. Its vasoconstriction has permitted the extensive use of microcannulas and superficial liposuction, thus dramatically improving anesthetic results.

The reality of tumescent liposuction is just the opposite of what one might expect based on common sense and experience. The dilution of a local anesthetic solution of lidocaine and epinephrine does not weaken its effect, it actually enhances the degree of anesthesia, and vasoconstriction. Although microcannulas remove less fat per unit of time, they actually permit the removal of greater volumes of fat than traditional liposuction cannulas with diameters of 6-10 mm. Patients find that there is less pain associated with tumescent liposuction than liposuction by general anesthesia. It is disconcerting when clinical expectations are not congruent with clinical reality. However, the concept is better understood, its applications will extend well beyond its present horizon.

Definitions

A microcannula is defined as liposuction cannula with an inside diameter (ID) of less than 2.0 mm. The small cross-sectional area of a microcannula requires minimal force to penetrate the tough fibrous septa within adipose tissue and allows greater directional control. Greater accuracy and minimal risks of residual skin irregularities allow more superficial liposuction, more complete extraction of fat, and ultimately greater patient satisfaction. In addition to microcannulas, slightly larger cannulas having IDs of 2.2 and 2.7 mm are routinely used with tumescent liposuction. (Table 1)

Table 1. Sizes of Micro-Cannulas

The tumescent technique is a method of drug delivery using a relatively large volume of an exceptionally dilute solution of drug(s), usually in combination with a dilute vasoconstrictor such as epinephrine, infiltrated directly into localized compartment(s).

As a novel means of drug delivery, the tumescent technique has potential applications far beyond the domain of dermatologic surgery. From a theoretical point of view there are several pharmacologic actions that the tumescent technique can provide (Table 2).

Table 2. Goals of the Tumescent Technique

Tumescent liposuction is defined as a combination of the tumescent technique for local anesthesia and a specific method for liposuction . Tumescent liposuction achieves regional local anesthesia of the skin and subcutaneous tissue by direct infiltration of dilute lidocaine, epinephrine, and sodium bicarbonate into the targeted subcutaneous fat. Tumescent liposuction also involves specific surgical methods including the use of microcannulas inserted through multiple small incisions. In order to encourage copious postoperative drainage, these incisions are not closed with sutures.

The current formulation of the local anesthetic solution for tumescent liposuction is described in Table 3. Formulations for tumescent local anesthetic solutions used for other surgical procedures are described elsewhere.1 In addition to liposuction the tumescent technique has many actual and potential applications (Table 4).

Table 3. Formulation of the Local Anesthetic Solution for the Tumescent Liposuction Technique

*Other formulations are used for procedures other than liposuction.

Table 4. Applications of the Tumescent Technique

Local Fallacies

In the early 1980s the pharmacology and absorption kinetics of local anesthesia in skin and subcutaneous tissue were considered trivial, uninteresting, and unworthy of systemic investigation. Years of well-published pharmacokinetics orthodoxy had convinced most surgeons and anesthesiologists that it was impossible to do moderate volume liposuction by local anesthesia. Several fallacious assumptions, many of which persist today, have obscured the potential efficacy of local anesthesia.

Fallacy I: The duration of lidocaine is only effective as a local anesthetic for a relatively short time; and the higher the concentration, the longer the duration of anesthesia.2

Fallacy II: Peak plasma lidocaine levels occur within 60-90 minutes after subcutaneous infiltration. 3,4

Fallacy III: Most of the lidocaine infiltrated for tumescent liposuction is removed along with the aspirated fat.5,6

Fallacy IV: Minimally effective concentration of lidocaine for local anesthesia of skin is 0.4% (0.4 g/100 ml).

Fallacy V. Bupivicaine is as safe as lidocaine, and the combination of lidocaine and bupivicaine for liposuction by local anesthesia is safe and rational.

Fallacy VI: Lidocaine dosage restrictions (7 mg/kg with epinephrine) should be the same for all forms of local anesthesia including epidural, axillary, or intercostal nerve block, and subcutaneous and intradermal infiltration.7,8

Fallacy VII: The rate of absorption is independent of the concentration of the infiltrated lidocaine.9

Having initially accepted the validity of these assumptions, a little clinical experience convinced me that they were wrong. There are many who still accept the validity of these misconceptions.

Antediluvian Liposuction

For many years general anesthesia was an absolute requirement for liposuction. The standard cannulas of the 1980s were huge, having diameters of 6-10 mm and cross-sectional areas 9-25 times greater than today’s 2-mm microcannulas.

The first written description of liposuction was published by Fischer of Italy in 1977. Soon afterwards the French surgeons Illouz and Fournier popularized liposuction using blunt-tipped cannulas. The common adverse sequelae of liposuction were excessive bleeding, prolonged recovery time, and disfiguring irregularities of the skin. Preoperative infiltration of a small volume of a vasoconstrictive solution of epinephrine into the targeted fat was termed the wet technique. Using no preoperative infiltration was known as the dry technique. These coeval antiquated techniques are still used today and continue to produce massive bleeding and often require transfusion.

By 1982, several American dermatologists had been to France to observe Illouz do liposuction using general anesthesia together with a subcutaneous injection of a small volume of a hypotonic solution of epinephrine and hyaluronidase.

By 1983, dermatologists were doing liposuction of lipomas, the submental chin, and limited areas of the body using general anesthesia, epidural regional anesthesia, or heavy IV sedation supplemented by small volumes of local anesthesia. The IV sedation usually involved diazepam and a narcotic analgesic, while the local anesthesia usually consisted of 0.25-0.5% lidocaine with epinephrine 1:200,000. Dermatologists who were prominent in teaching the technique included Drs. Sol Asken, Larry Field, and Richard Glogau.

In late 1984, having just completed residency training and board certification in dermatology, starting a private practice and learning more dermatologic surgery were my primary concerns. At that point, my years of study, that had included masters degrees in mathematics and public health biostatistics, National Institutes of Health research fellowships in clinical pharmacology, and board certification in internal medicine seemed of little practical utility. In retrospect, these years of training provided the concinnity of experience and knowledge that produced the concept of the tumescent technique.

Ironically, upon first hearing about liposuction, my impression was a mixture of curiosity, amusement, and disdain. It was Larry Field, a pioneer of modern dermatologic surgery, who convinced me that liposuction was destined to become an important dermatologic surgical procedure. In February 1985, I attended a liposuction course given by Gary Fenno, MD and sponsored by the American Society for Liposuction Surgery. None of the faculty had done liposuction by local anesthesia. Liposuction by local anesthesia was thought to be impractical if not impossible. The plastic surgery literature stated, without discussion, that liposuction required general anesthesia.

In early 1985, using local anesthesia, I performed my first liposuction procedure. By the end of that year, an elementary form of the tumescent liposuction with IM diazepam (ValiumTM sedation and meperidine (Demerol TM) analgesia had evolved. The tumescent technique was first described in a talk I gave at the Second World Congress of Liposuction Surgery sponsored by the American Academy of Cosmetic Surgery held in Philadelphia in June 1986. The first article describing the tumescent technique was published in the American Journal of Cosmetic Surgery in January 1987.10

At this point in time, some surgeons, who insisted upon doing liposuction by general anesthesia using a technique that often required blood transfusions, were stating publicly that only they were sufficiently trained to do liposuction safely. Meanwhile a number of dermatologists, including Drs. William Coleman, Patrick Lillis, and Rhoda Narins, were busy teaching their dermatologic colleagues how to do tumescent liposuction totally by general anesthesia with virtually no blood loss.

Subsequent years have seen continual improvement. With the tumescent technique, liposuction is now a procedure of exceptional finesse and gentleness that is accomplished totally by local anesthesia. And this process of evolution and refinement is continuing.

Dermatologic Origins of Tumescent

A preference of local anesthesia, an aversion to the high costs of hospital operating rooms, and an impertinent skepticism of established surgical dogma explain why it is dermatologists who invented the tumescent technique.

The tumescent technique has a natural appeal to dermatologists and is uniquely compatible with traditional dermatologic surgical training. Dermatologists prefer local anesthesia for skin surgery and prefer to avoid the complications associated with general anesthesia. They are more likely to have the training, the patience, and the personality to deal with patients who are awake and alert. Without such qualifications, it is nearly impossible to do liposuction without general anesthesia, IV sedation, or narcotic analgesia.

The perceived value of the tumescent technique depends on the surgeon”s education. Training that inculcates a preference for general anesthesia usually does not emphasize the benefit of having an awake patient. The distinction between necessary and convenient forms of anesthesia is often disregarded. Extensive training with general anesthesia does not afford much opportunity to acquire the experience and temperament needed to manage an alert patient during surgery. On the other hand, most dermatologic surgeons are exclusively trained to use local anesthesia. Using general anesthesia is rarely necessary nor desirable.

In light of these distinctions, it is not surprising that dermatologists invented and popularized the tumescent technique for liposuction totally by local anesthesia.

The 7 mg/kg Prevarication

The standard dosage of lidocaine with epinephrine for infiltration anesthesia is authoritatively stated to be 7 mg/kg.11 There were several clues that the 7-mg/kg dose limit for lidocaine might be wrong.

First, there is no scientific publication to support 7 mg/kg as the maximum safe dose of lidocaine with epinephrine when infiltrated into subcutaneous tissue. To a certifiable skeptic, this little bit of pharmacologic obfuscation was a conspicuous hint of the existence of an untrustworthy “fact.”

Second, an experimental study of the lethal dosage of lidocaine published in 1948 reported that the LD50 of subcutaneous lidocaine in mice was inversely proportional to drug concentration. This supported the conjecture that extremely dilute solutions of lidocaine might permit safe doses significantly greater than 7 mg/kg.

Third, many surgeons, including myself, wrongly assumed that liposuction removed a significant amount of lidocaine along with fat. This assumption would seemingly permit a greater safe dose of lidocaine. This motivated the habit of infiltrating just one area and then doing liposuction before infiltrating the next area.

Finally, when blood was sampled 1 hour after a lidocaine dose of 10-20 mg/kg by the tumescent technique, the plasma concentrations were less than 0.3 ųg/ml, well below the 5- ųg/ml threshold for early lidocaine toxicity. This finding provided a confidence, albeit naive, that lidocaine toxicity was a remote risk. This erroneous assumption was based on the belief that peak plasma lidocaine levels occur within 2 hours after infiltration. The perfunctory explanation was that lidocaine was being rapidly metabolized in the liver. Only later was it realized that the peak lidocaine plasma levels were higher and occurred up to 12 hours after completion of tumescent liposuction.

Defying Dogma

In 1987, many surgeons believed that liposuction was safer by general anesthesia than by local anesthesia. A dose of lidocaine in excess of 7 mg/kg was considered more dangerous than either using general anesthesia or the excess surgical bleeding that routinely required autologous blood transfusion.

The Food and Drug Administration (FDA), the sanctifier of scripture relating to promotional information for any drug sold in the United States, must approve every word of a manufacturer’s informational package insert. In 1948, when Astra Pharmaceuticals obtained approval to market lidocaine (XylocaineTM), FSA requirements for substantiation of dose limits were not demanding. In fact, the only justification for the “official” maximal safe lidocaine dosage, 7 mg/kg, was a letter from Astra to the FDA that simply stated, “the maximum safe dosage of lidocaine is probably the same as for procainamide.”

As a published summary of FDA-approved drug information, thePhysicians’ Desk Reference (PDR) has an aura of infallibility comparable to divine scripture. It was dangerous heresy to advocate a lidocaine dosage greater than 7 mg/kg. At a medical meeting in 1987, my report of using 15 mg/kg of lidocaine for tumescent liposuction provoked a public accusation of medical malpractice.

Even today, despite the results of several well documented studies validating the estimate of 35 mg/kg as a safe upper limit for a lidocaine dose with the tumescent technique for liposuction, many surgeons and anesthesiologists persist in a fundamentalist interpretation of the PDR. To the potential detriment of liposuction patients, they continue using antiquated techniques associated with massive bleeding, and potentially fatal complications connected with general anesthesia.

The First Case

The first liposuction that I performed was on April 5, 1985. The volunteer patient, Annie McCoy, RN, had a localized accumulation of fat on the lower abdomen above a transverse hysterectomy scar.

Using only 50 ml of a commercially available local anesthetic formulation containing 500 mg of lidocaine (1%) and 0.5 mg of epinephrine (1:100,000), the result of the procedure was encouraging, but less than satisfactory. Approximately 45 ml of fat was removed. The degree of hemostasis was profound with the aspirated fat containing almost no blood. However, the volume of fat that could be anesthetized using only 50 ml of local anesthetic was too small. The 05. mg of epinephrine at a concentration of 1:100,000 caused tachycardia. The most painful part of the procedure was the burning-stinging sensation caused by the infiltration of the local anesthetic. The actual liposuction, while not painless, was more easily tolerated than the infiltration.

Annie returned for a more extensive liposuction of the lower abdomen and lateral thighs 1 month later. On this occasion, the anesthetic solution was more dilute, and the results were better with fewer side effects. The anesthetic solution consisted of lidocaine (2,000 mg/L) with epinephrine (2 mg/L) in 1,000 ml of physiologic saline, yielding a formulation of roughly 0.2% lidocaine and epinephrine 1:250,000.

This concentration of epinephrine still produced tachycardia (approximately 120/min) but the hemostasis was superb. The aspirate contained 450 ml of bloodless fat and 100 ml of mildly blood-tinged infranatant anesthetic solution. Pain upon infiltration was eased with IM meperidine and diazepam. Lidocaine at a 0.2% concentration was clearly effective and well below the 0.4% (4 gm/L) concentration that was, at that time, the published minimal effective concentration for cutaneous local anesthesia.

Clearly there was a need to perfect the formulation of the anesthetic solution. What might be the minimum concentration of lidocaine and epinephrine? What might be the maximum safe total dose of lidocaine?

Lidocaine: Minimum Effective Concentration

A review of the literature on lidocaine found no studies specifically concerned with local anesthesia of subcutaneous fat. It was clear that the minimally effective concentrations of lidocaine and epinephrine for cutaneous and subcutaneous local anesthesia were not well defined.

Any estimate of the minimal effective lidocaine concentration depends upon multiple variables associated with the surgical technique and patient traits. Surgical factors include the completeness and the uniformity of anesthetic infiltration, the surgeon’s finesse and skill, the cannula diameter, and personality traits of the surgeon and nursing staff. Patient-dependent variables included the anatomic location of the fat, the patient’s age and sex, and patient’s anxiety level. Any use of anodyne drugs such as narcotic analgesics or IV sedatives also affects the threshold of pain. With more clinical experience, it became apparent that a formulation consisting of 0.1% lidocaine (1 gm/L) and 1:100,000 epinephrine (1 mg/L) was effective. However, because of the burning-stinging pain upon infiltration persisted, the process of infiltration was not easily tolerated.

The range of lidocaine concentrations currently recommended for tumescent liposuction totally by local anesthesia is 500-1,000 mg/L. This range was derived with the cooperation of several patients by comparing the subjective effect of a given lidocaine concentration on one thigh and a slightly lower concentration on the opposite thigh. More patients can distinguish between 0.04% and 0.05% lidocaine, than between 0.5% and 0.6%.

Years of clinical experience have shown that 0.075% lidocaine (750 mg/L) is sufficient for liposuction, totally by local anesthesia, of the extremities, hips, and neck/facial areas, provided one uses microcannulas and careful infiltration.

Lidocaine at 0.1% (1,000 mg/L) provides more consistent anesthesia for the more fibrous or the more sensitive areas such as the periumbilical area and the abdomen, female infrascapular and posterior axillary areas, male flanks, and male breasts.

Epinephrine: Minimum Effective Concentration

The vasoconstriction associated with epinephrine has three consequences for tumescent liposuction: it prolongs the local anesthetic effect, it slows the rate of absorption of lidocaine permitting greater doses of lidocaine, and it produces such dramatic hemostasis that clinically significant surgical blood loss is eliminated.

The minimally effective epinephrine concentration was derived by careful clinical observation of cutaneous blanching and pulse rate. Experience has shown that epinephrine (0.65 mg/L) provides consistently excellent vasoconstriction for many hours, with a very low incidence of tachycardia.

Lidocaine: Maximum Safe Dose

The search for a better estimate of the maximum safe dose of lidocaine involved some trepidation. The illuminati of aesthetic surgery felt compelled to publicly state that dermatologists were incapable of doing liposuction safely.

Self-preservation demanded prudence and good documentation in following an intuitive hunch that 7 mg/kg grossly underestimated the maximum safe dose for tumescent lidocaine. After having established that 0.1% lidocaine is effective, this concentration was maintained constant, while a total volume of solution, and thus the total dose of lidocaine, was cautiously increased. Careful clinical observation revealed absolutely no evidence of early lidocaine toxicity as doses were incrementally augmented during succeeding surgeries.

On April 10, 1988, after liposuction on a nurse’s husband, I casually asked her to obtain a few extra venous blood samples at home for determination of additional lidocaine blood levels. Sequential blood samples over 7 hours produced unexpected results. The blood levels increased linearly with time, indicating that the maximum concentration occurred well after 7 hours. Forthwith, with another patient, lidocaine blood levels were determined over a 24-hour interval and showed a maximum at 12 hours. This finding was unprecedented. The prevailing belief was that peak lidocaine blood levels occur less than 2 hours after infiltration. By repeating this study with additional patients, it was determined that peak lidocaine blood levels for tumescent liposuction occur 12 – 3 hours.

By graphing the magnitude of the peak concentrations as a function of dose (mg/kg), a safe dosage for tumescent lidocaine was shown to be at least 35 mg/kg.12 This provided scientific justification for lidocaine doses five times greater than the 7-mg/kg limits stated in the PDR. Previously, in its first published description, it was shown that the tumescent technique eliminates significant liposuction blood loss.13 These two findings were revolutionary, and established dermatologic surgery as the authority on safe liposuction surgery.

Improved Anesthetic Formulation

Adding sodium bicarbonate (10 meq/L) to the anesthetic solution eliminated the burning-stinging pain associated with the acidic pH of commercially available lidocaine preparations.14-16 This simple modification provided a quantum jump in patient comfort and safety. It eliminated the need for parental sedation with benzodiazepines and narcotic analgesia. It eliminated the need for pulse oximetry and its attendant hassles. It was the key to large volume liposuctiontotally by local anesthesia.

It has been my clinical impression that adding triamcinolone (10 mg/L) to the anesthetic solution decreases postoperative inflammation and soreness. Triamcinolone, with its low solubility in water and high partition into lipids, tends to persist locally where infiltrated. Its anti-inflammatory effect reduces symptomatic soreness for up to 6 days postoperatively. It is now a standard part of the anesthetic solution for tumescent liposuction.

The use of a peristaltic infiltrating pump has made it possible to use a tiny 25-gauge spinal needle for the initial stages of infiltration. This has further reduced the discomfort associated with infiltration into the most fibrous areas of fat such as the knees, upper abdomen, the back and flanks, and male breasts. Furthermore, the pump has eliminated the need for the “brute strength” needed to infiltrate using a syringe, and has thereby permitted nurses to do the infiltration.

Hemostasis Permits Microcannulas

One of the least expected consequences of the tumescent technique is that its profound hemostasis permits the extensive use of microcannulas.

Prior to the tumescent technique, blood loss was a limiting factor in determining how much liposuction could safely be done. As shown below, microcannulas cause more surgical bleeding than larger diameter cannulas. Thus, without good hemostasis liposuction surgeons naturally preferred to use large cannulas. By eliminating significant blood loss, the advantages of microcannulas can be realized.

The shape of the wound within fat made by a liposuction cannula is approximately a cylindrical tunnel with a circular cross-section. It can be shown that the relation of the surface area (A) of a cylindrical tunnel to its radius (R) is given by the equation A = 2 V/R, where V is the volume of a cylinder. In other words, for a fixed volume, the surface area of a cylinder is inversely proportional to its radius.

Now, suppose that a particular patient has equal volumes of fat removed by liposuction from each outer thigh, using a small diameter cannula on one thigh, and a larger cannula on the opposite thigh. For this fixed volume of fat, the smallest diameter cannula will have the largest surface area associated with its cylindrical wound. It should be clear that the larger the surface area of a cylindrical wound within fat, the greater the number of transected capillaries, and thus the greater the amount of bleeding. Thus, earlier and bloodier liposuction techniques had to use larger cannulas in order to minimize bleeding.

Microcannula Specifications

Tumescent liposuction microcannulas (ID – 2.0 mm) are constructed from fully hard-tempered, 304 stainless steel hypodermic needle stock. Cannula size is denoted by the corresponding needle gauge. The 16-gauge cannula, used for liposuction of the face and neck, and for relatively thin patients, has an inside diameter (ID) of 1.2 mm. The 14-gauge (1.6 mm ID) is the cannula I use most frequently. The 12-gauge (2.2 mm ID) and the 10-gauge (2.7 mm ID) are larger than microcannulas and are used on a regular basis. The largest cannula that I possess, an anachronistic 4-mm ID lamprey cannula, is used on less than 1% of patients.

The standard configuration of the microcannula tip has two in-line oblong openings. Different and perhaps more efficient microcannula tips are available.

Advantages of Microcannulas

Microcannulas are necessary for optimal results with tumescent liposuction. Among the many advantages of microcannulas are the following.

Less Pain

Microcannulas are less painful than larger cannulas. Obviously minimizing pain is an important component of the technique that enables liposuction totally by local anesthesia.

More Accuracy

Microcannulas are more accurate, and reduce the risk of liposuction-induced irregularities of the skin. Upon changing the direction of a cannula, a larger cannula is more likely to follow a path of least resistance, and be inadvertently advanced along an existing tunnel. A smaller cannula, by being more easily advanced through fibrous tissue, is less likely to deviate from its intended direction. A microcannula reduces the risk of liposuction along an unintended path and produces smoother results.

Greater Finesse

By removing smaller volumes of fat per stroke, microcannulas provide greater assurance against too much fat being removed inadvertently. Proper technique using microcannulas minimizes the risk of irregularities of the skin after liposuction of areas where there is little room for error such as jowls, cheeks, and naso-labial fat pad, medial thighs, and the buttock.

Superficial Liposuction

The superior accuracy in directing the cannula and the more delicate control of fat removal permit a more uniform and smoother results This ability enables a more aggressive and thorough superficial removal of fat and concomitantly minimized risks of irregularities. Superficial, liposuction requires the use of both small cannulas, and the tumescent technique.

More Complete Removal

An increased confidence in achieving uniformly smoother results permits more aggressive liposuction and removal of larger amounts of fat. Thus more fat can be removed using microcannulas than can be removed with larger cannulas. Assuming the results of liposuction are smooth and uniform, patient satisfaction usually directly correlated with the amount of fat removed.

Easier Penetration

Microcannulas can penetrate fibrous fatty tissue with minimal force, thus permitting liposuction of areas that are nearly impossible to treat adequately with larger cannulas. Examples are the glandular tissue of male breasts, and the dorsal-lateral fat pads just below the bra strap on women, and areas previously treated by liposuction.

Smaller Incisions

Microcannulas require only 2-4 mm incisions and yield scars so small that they are eventually imperceptible. This permits the use of numerous incisions, placed almost anywhere, allowing greater accessibility to all subcutaneous fatty compartments.

No Sutures

Small incisions without sutures heal better with smaller scars. Omitting sutures also saves time, and postpones the first follow-up visit for 4-6 weeks postoperatively..

Accelerated Healing

Multiple incisions without sutures accelerate drainage, which reduces bruising, swelling, and soreness. Wounds within fat created by microcannulas are narrow tunnels that heal more rapidly than larger tunnels. The greater net surface area of the walls of these “microtunnels” promote more rapid absorption of residual fluid within the subcutaneous space. The net effect is greatly accelerated healing.

Greater Efficiency

More rapid return to normal activities, with fewer post-operative problems and patient worries, leads to dramatically decreased need for immediate follow-up visits. This saves huge amount of time for the patient and surgeon.

Less Elbow Trauma

The resistance encountered when advancing a cannula through subcutaneous fat is minimized by using microcannulas . This is a great advantage in terms of protecting the surgeon’s elbow from the chronic stress and trauma of performing thousands of liposuction surgeries.

Using Microcannulas

Microcannulas are fragile and cannot be sued as roughly as larger instruments. Microcannulas are easily bent if used as levers within fatty tissue. The direction of the microcannulas cannot be changed while deep within fat. A delicate touch, and a straight “in-and-out” piston-like motion is required.

When one begins infiltrating a new area with anesthetic solution, the initial infiltration should be within the deepest portion of the targeted fatty compartment, with subsequent infiltration done more superficially. Once a plane within the fat is made tumescent, infiltrating more deeply is difficult because of the inability to precisely palpate the location of the fat-muscle fascia interface.

Similarly, for initial stages of liposuction, it is important to initially direct the cannula as deeply within the fat as permitted by common sense clinical judgment and safety. Fourteen-gauge microcannulas are ideal for infiltrating liposuction in a new area. A small cross section produces less discomfort, less resistance, and more accuracy than larger cannulas.

The 14-gauge microcannulas are used to fenestrate the dense fibrous septa and create small tunnels distributed throughout all the targeted fat. After first using 14-gauge microcannulas, it is easier to use the larger 12- and 10-gauge cannulas. The 14- and 12-gauge cannulas are the work horses, and generally remove the greatest proportion of the fat. The 10-gauge cannula is used the least frequently. Its principle use is to remove any residual fat whenever that appears to be resistant to removal by smaller cannulas. Using microcannulas takes a little more time, but the clinical results are far superior to those achieved using larger cannulas.

Although time efficiency is important, the goal is not how fast the fat is removed, but how smoothly and completely fat is removed. I have found that the extra time needed to use microcannulas is actually more time efficient. The use of microcannulas results in higher patient satisfaction and a lower incidence (less than 3%) of secondary “touch-up” procedures. If you don’t have time to do it right the first time, when will you have time to do it right the second time?

Optimal use of microcannulas requires multiple incisions. A small area usually requires four to six incisions, while a large abdomen might have 48 or more.

The cannulas should be advanced through the fat following a fan-like pattern with tunnels radiating from each of the multiple small incisions. Adjacent patterns overlap in a shingle-like fashion and interdigitate on all levels throughout the fat.

The cannula is repeatedly moved from one incision to another, doing a relatively few strokes and just a limited volume of liposuction through any one incision before moving on to another incision. This insures that the reduction is done decrementally, diffusing, and uniformly throughout the entire targeted area fatty compartment. If a large amount of fat were to be removed through one incision before doing liposuction via an adjacent incision, there would be a significant increased risk of postsurgical irregularities of the skin. It is this repeated switching from one incision to another that makes the use of a liposuction pump somewhat more efficient than a hand-held syringe technique.

Microcannula Handle

When an electric-powered vacuum pump is used for liposuction , the microcannula is attached to a handle, which in turn is attached to suction tubing leading to the vacuum pump. This microcannula handle preferably has a thumb-controlled hole or air vent on the handle’s side such that the vacuum is maintained while the thumb covers the hole, but the vacuum disappears when the thumb is lifted from the cannula handle.

With the thumb lifted and no vacuum in the cannula, the resistance against the cannula is dramatically reduced as it is advance through subcutaneous fatty tissues. While the microcannula encounters a seemingly impenetrable fibrous partition within adipose tissue, simply opening the air vent by lifting the thumb is often all that is necessary to advance the cannula. Decreased resistance allows manipulation of the microcannulas with more finesse and better control. This fine control is especially helpful for moderating the suction during facial liposuction when advancing through areas where suction is not desired.

Tumescent Liposuction (TLG) GarmentsTM

Using microcannulas and multiple incisions without sutures yields better aesthetic results, more rapid healing, less swelling, less soreness, and less bruising. But open incision sites and encouraging drainage also creates a messy problem of managing the copious drainage of blood-tinged anesthetic solution. This necessitates the need for specially-designed postoperative dressings and garments. Such dressings must comfortably control the voluminous drainage, and be easily changed and managed by the patient. Because of hastened healing, postoperative Tumescent Liposuction (TLG) GarmentsTM (JK Surgical, Inc. San Juan Capistrano, CA) need only be used 4-6 days instead of the usual 2-6 weeks of compression required with the use of larger cannulas.

The Future

As a novel mode of drug delivery we may anticipate many innovative uses of the tumescent technique. There are potential therapeutic applications of tumescent drug delivery to clinical problems far beyond the current limits of anesthesia for dermatologic surgery. I believe that the tumescent technique will prove useful for the lymphatic delivery of chemotherapeutic agents in the treatment and diagnosis of pathology in the lymphatic system.

Optimizing lymphatic uptake of chemotherapeutic agents for tumor metastases, viral and bacterial infections, and radiocontrast media is a focus of current research.17 The wall of a terminal lymphatic capillary has an interior layer formed by a single thin endothelial cell and an external basal lamina that is widely fenestrated. Between adjacent endothelial cells there are wide gaps in many places. These holes in the lymphatic capillaries facilitate the uptake of macromolecule, proteins, bacteria, blood cells and tumor cells.18 Blood capillaries, having continuous basement membranes and relatively right intracellular junctions, resist absorption of large molecules.

The larger the molecular weight of a drug, the greater the proportion of a subcutaneous dose that is absorbed via the lymphatic system.19 Drugs of large molecular weight or drugs attached to large carrier molecules are thus good candidates for targeted drug delivery to the lymphatics.20

Theoretically, the tumescent technique should selectively increase lymphatic delivery of low molecular weight drugs as well as larger molecules such as proteins, particulate drug carriers such as emulsions and liposomes, and polymeric prodrugs.

Prolonged blood capillary vasoconstriction with the tumescent technique should increase the proportion of drug absorbed via lymphatic capillaries. In the case of cytotoxic drugs, tumescent dilution of the drugs should minimize local irritancy or concentration-dependent toxicity. In the case of chemotherapy or immunotherapy of breast cancer and melanoma, the lymphatic drainage of a particular anatomic area can be specifically targeted.

Snake bite treatment is problematic, with few controlled studies to support specific therapies. Snake venom, a complex mixture of many proteins having different toxic actions, is often preferentially absorbed via the lymphatics. A tumescent technique for the subcutaneous injection of antivenin locally or proximal to the bite might promote lymphatic uptake of the antivenin, and allow neutralization of the venom before it reaches the systemic circulation. The concomitant infiltration of vasoconstrictors, local anesthesia, heparin, or anti-inflammatories might be beneficial.

The future of a continuously evolving tumescent technique for liposuction is expansive. What I regarded as the tumescent technique yesterday is not the same today. There will always be room for improvement. With self-satisfied complacency or encrusted orthodoxy, we risk arrested development.

Conclusion

The invention of the tumescent technique was the result of dermatology’s preference for local anesthesia. It was achieved by pursuing an unchartered path to an unanticipated destination, guided only by clinical observation, and cautious incremental optimization. With time, the basic principles of the tumescent technique will find applications far beyond dermatology. The range of its applications will depend on the imagination of specialists in other disciplines and the nature of the clinical problems that confront them.

Over the past 25 years the American Society for Dermatologic Surgery has evolved into a leading innovator of advanced techniques for plastic and reconstructive surgery of the skin. Dermatologic surgeons have taught other specialties how to do liposuction more safely and with better aesthetic results.

References

1.     Klein, JA. Tumescent Technique: Local Anesthesia, Liposuction, & Dermatologic Plastic Surgery. St. Louis: Mosby-Year Book Publishers. In Preparation.

2.     de Jong RH. Local Anesthetics. St. Louis: Mosby, 1994:149.

3.     Klein, JA. Anesthesia for liposuction in dermatologic surgery. J. Dermatol Surg Oncol 1988;14:1124-32.

4.     Lillis PJ. Liposuction surgery under local anesthesia: limited blood loss and minimal lidocaine absorption. J. Dermatol Surg Oncol 1988;14:1145-8.

5.     Gumuncio CA, Bennie JB, Fernando B, et al. Plasma lidocaine levels during augmentation mammaplasty and suction-assisted lipectomy. Plast Reconstr Surg 1989;84:624-7.

6.     Asken, S. Liposuction Surgery and Autologous Fat Transplantation. East Norwalk, CT: Appleton & Lang, 1988:63.

7.     Astra/Merck Group of Merck & Co., Inc., Xylocaine© : maximum recommended dosages. In: Physicians’ Desk Reference (PDR), 49th edition, 1995:582.

8.     de Jong RH. Local Anesthetics. St. Louis: Mosby, 1994:353.

9.     de Jong RH. Local Anesthetics. St. Louis: Mosby, 1994:147.

10.  Klein JA. The tumescent technique for liposuction surgery. Am J Cosmetic Surg 1987;4:263-7.

11.  Ritchie JM, Greene NM. Local anesthetics. Chapter 15. In: Gilman AG, Rall TW, Nies AS, Taylor P, eds. Goodman and Gilman’s The Pharmacologic Basis of Therapeutics, 8th ed. New York: McGraw Hill, Inc., 1993-323.

12.  Klein JA. The tumescent technique for regional anesthesia permits lidocaine doses of 35 mg/kg for liposuction. J Dermatol Surg Oncol 1990;16:248-63.

13.  Klein JA. The tumescent technique for liposuction surgery. Am J Cosmetic Surg 1987;4:263-7.

14.  Klein, JA. Anesthesia for liposuction in dermatologic surgery. J Dermatol Surg Oncol 1988;14:1124-32.

15.  Stewart JH, Cole GW, Klein JA. Neutralized lidocaine with epinephrine for local anesthesia. J Dermatol Surg Oncol 1989;15:1081-3.

16.  Stewart JH, Chinn SE, Cole GW, Klein JA. Neutralized lidocaine with epinephrine for local anesthesia – II. J Dermatol Surg Oncol 1990;16:842-5.

17.  Charman WN, Stella VJ, eds. Lymphatic transport of drugs. Boca Raton: CRC Press, 1992.

18.  Odland GF. Structure of Skin. In: Goldsmith LA, ed. Physiology, Biochemistry, and Molecular Biology of the Skin, 2nd ed. Oxford: Oxford University Press, 1991:19-20.

19.  Spersaxo A, Hein WR, Steffen H. Effect of molecular weight on the lymphatic absorption of water-soluble compounds following subcutaneous administration. Pharm Res 1990;7:167.

20.  Yoshinobu T, Hashida N, Sezaki H. Lymphatic transport after parental drug administration. In: Charman WN, Stella VJ, eds, Lymphatic Transport of Drugs. Boca Raton: CRC Press, 1992:255-77.

Jeffrey A. Klein, M.D.

Abstract:

The tumescent technique for local anesthesia permits regional local anesthesia of the skin and subcutaneous tissues by direct infiltration. The tumescent technique uses large columns of a dilute anesthetic solution to produce swelling and firmness of targeted areas. This investigation examines the absorption pharmacokinetics of dilute solutions of lidocaine (0.1% or 0.05%) and epinephrine (1:1,000,000) in physiologic saline following infiltration into subcutaneous fat of liposuction surgery patients. Plasma lidocaine concentrations were measured repeatedly over more than 24 hours following the infiltration. Peak plasma lidocaine levels occurred 12-14 hours after beginning the infiltration. Clinical local anesthesia is apparent for up to 18 hours, obviating the need for postoperative analgesia. Dilution of lidocaine diminishes and delays the peak plasma lidocaine concentrations, thereby reducing potential toxicity. Liposuction reduces the total amount of lidocaine absorbed systemically, but does not dramatically reduce peak plasma lidocaine levels. A safe upper limit for lidocaine dosage using the tumescent technique is estimated to be 35 mg/kg. Infiltrating a large volume of dilute epinephrine assures diffusion throughout the entire targeted area while avoiding tachycardia and hypertension. The associated vasoconstriction is so complete that there is virtually no blood loss with liposuction. The tumescent technique can be used with general anesthesia or IV sedation. However, with appropriate instrumentation and surgical method, the tumescent technique permits liposuction of large volumes of fat totally by local anesthesia, without IV sedation or narcotic analgesia. J Dermatol Surg Oncol 1990; 16:248-263.

INTRODUCTION

The rate of systemic absorption and the maximum safe dose of lidocaine following infiltration into subcutaneous fat have never been documented. Traditional dosage limitations for infiltrative local anesthesia are based more on clinical dogma than on scientific data.

For nerve blocks and infiltration local anesthesia, the Physicians’ Desk Reference (PDR) and the Xylocaine (lidocaine hydrochloride) (Astra Pharmaceutical Products, Inc. Westboro, MA) package insert state, “For normal healthy adults, the individual maximum recommended dose of lidocaine HC1 with epinephrine should not exceed 7 mg/kg (3.5 mg/lb) of body weight and in general it is recommended that the maximum total dose not exceed 500 mg.”1 Neither the initial manufacturer of lidocaine nor the United States Food and Drug Administration (FDA) have data to support this recommended maximal safe dosage.2 In its 1948 application to the FDA for permission to market lidocaine, Astra Pharmaceutical Products, Inc. simply stated that the maximum safe dose of lidocaine is “probably the same as for procaine.”3

The present clinical investigation examines the absorption pharmacokinetics of lidocaine and epinephrine infiltrated into subcutaneous fat for liposuction surgery. Guidelines are suggested for maximal safe dosages of dilute lidocaine and epinephrine infiltrated into fat.

Infiltrating subcutaneous fat with large volumes of fluid causes the tissue to become swollen and firm, or tumescent. Infiltrating with large volumes of very dilute lidocaine, epinephrine, and sodium bicarbonate for local anesthesia and hemostasis is known as the tumescent technique. Diluting the anesthetic solution slows the absorption of lidocaine, thus reducing its toxicity. Total lidocaine doses five times greater than the limit traditionally regarded as maximal appear to be safe when infiltrated into subcutaneous fat using the tumescent technique.

In addition to minimizing lidocaine toxicity, the tumescent technique produces extensive and prolonged capillary vasoconstriction, permitting liposuction with almost no blood loss. Since infiltrated tissues remain partially anesthetized for many hours, many patients require no postoperative analgesia.

The tumescent technique for liposuction can be used to supplement general anesthesia. However, the anesthesia produced by the tumescent technique is so complete that it permits liposuction of large volumes of fat totally by local anesthesia, without IV sedation or narcotic analgesia.

MATERIALS

The anesthetic solution containing approximately either 0.05% or 0.1% with epinephrine 1:1,000,000 is prepared by adding either 500 mg or 1000 mg lidocaine (50 or 100 ml of 1% lidocaine), 1 mg epinephrine (1 ml of 1:1000), and 12.5 meq of sodium bicarbonate (1 meq/ml) to 1000 ml of normal saline (0.9% NaC1) (Table 1).4

The subcutaneous infiltration of large volumes of dilute anesthetic solution is accomplished using two instruments, a handle and a needle, specifically designed for use with the tumescent technique. (address inquiries to PO Box 1629, San Clemente, CA 92672) . Both of these instruments accommodate a plastic 60-cc Luer-Lock syringe (Becton-Dickinson, Rutherford, NJ). The handle is attached to disposable, sharp hypodermic needles. The disposable needles are a 3.5-in 20-gauge spinal needle (Becton-Dickinson) and a 6-in 18-gauge intradiscal therapy needle (Becton-Dickinson). The needle consists of a blunt-tipped 4-mm outside-diameter needle welded to a devise that resembles the handle.

A plastic IV bag containing the anesthetic solution is attached to either the handle or the needle by a 94-in-long IV tubing with an in-line check valve ADDitIV Primary IV Set (Kendall McGraw Laboratories, Sabana Grande, Puerto Rico). This check valve prevents retrograde flow of the anesthetic solution back into the IV bag. The syringes are initially filled directly from the IV bag containing the anesthetic solution via the ADDitIV line using a female-female luer connector. (PO Box 1629, San Clemente, CA 92672)

Preoperative sedation consisted of flurazepam (Dalmane, Roche Laboratories, Nutley, NJ) 30 mg by mouth the night before surgery and midazolam (Versed, Roche Laboratories, Nutley, NJ) 2.5 mg intramuscularly just prior to surgery. Neither general anesthesia nor IV sedation was employed. Surgeries were accomplished totally by local anesthesia using the tumescent technique for liposuction.

Table 1

Recipe for Tumescent Technique Anesthetic Solutions for Liposuction

(Lidocaine 0.05%, Epinephrine 1:1,000,000)

METHODS

Each blood sample, obtained by a separate venipuncture, was collected in a heparinized glass container. After separation, plasma was frozen and stored in plastic containers. Lidocaine levels were measured by an enzyme immunoassay.5

This study consisted of the following experimental procedures:

1.     For each of 8 female volunteer patients, ages 33-44, plasma lidocaine concentrations were measured repeatedly over 24-36 hours following liposuction in order to determine the time and magnitude of peak levels. One of these patients participated as a volunteer on three separate occasion. The time and magnitude of an individual patient’s peak lidocaine concentration were determined by plotting sequential plasma levels and connecting the points with a smooth (continuously differentiable) curve. The time of the peak is defined as the length of time between the beginning of the lidocaine infiltration until the occurrence of the peak plasma lidocaine concentration.

2.     Four female volunteers were given local anesthesia by the tumescent technique on two separate occasions, each time followed by sequential determination of plasma lidocaine concentrations over more than 24 hours. After the first filtration there was no liposuction; a week or more later, after second infiltration, liposuction was completed before measuring plasma lidocaine levels. Time and magnitude of peak plasma lidocaine levels, without and with lidocaine, are compared.

3.     On two different days, a 70-kg female volunteer received 1 gm, of lidocaine, 1 mg of epinephrine, and 12.5 meq of sodium bicarbonate infiltrated into subcutaneous fat, with the dose divided evenly between the two medial thighs. On the first day the patient received 1000 ml of a dilute anesthetic solution consisting of lidocaine 0.1% (1 gm/L), epinephrine 1:1,100,000 (1 mg/L), and sodium bicarbonate (12.5 meq/L). One week later the patient received 100 ml of a standard, commercially available solution of lidocaine 1% (1 gm/dl) with epinephrine 1:100,000 (1 mg/dl), to which was added 12.4 meq of sodium bicarbonate (1 meq/ml). On both days the solution was infiltrated over a 45-minute interval (22½ for each thigh). The time and magnitude of peak lidocaine levels were compared.

4.     An 85-kg male volunteer, age 42, had 900 mg of lidocaine 0.1% with epinephrine 1:1,000,000 infiltrated subcutaneously over 45 minutes into the abdomen and flanks without subsequent liposuction. Sequential plasma lidocaine levels were determined at 5 and 15 minutes after beginning the infiltration and then every 30 minutes over the next 6 hours.

TUMESCENT TECHNIQUE METHOD

The tumescent technique has improved since publication in 1987.6 Using an even more dilute lidocaine solution, 0.5% instead of 0.1%, permits greater tumescence with better vasoconstriction and more complete anesthesia. The addition of sodium bicarbonate to the anesthetic solution minimizes the pain of infiltration.7-9 Using a local anesthetic solution without sodium bicarbonate often necessitates the use of IV sedation and narcotic anesthesia. With the tumescent technique, IV sedation and narcotic analgesia are virtually unnecessary.

When only one body area is treated by liposuction, usually no sedation is needed. When multiple areas are treated, requiring the patients to remain recumbent for more than 1 hour, intramuscular midazolam in 2.5-5-mg increments is given every 2-3 hours. Fewer than 5% of patients, those who are exceptionally anxious, will require 25-50 mg of Demerol (Winthrop-Breon Laboratories, New York, NY) given subcutaneously. None of the patients in the present study required Demerol.

The large volume of normal saline infiltrated into fat as part of the tumescent technique is more than sufficient to compensate for insensible fluid losses as well as fluids lost by liposuction. In fact, patients will usually need to urinate during a lengthy procedure. This suggests that there is no significant deficit of intravascular fluids associated with the tumescent technique.

Because there is virtually no blood loss associated with the tumescent technique, routine IV fluid replacement is not necessary. Nevertheless, an IV is routinely established to provide access for resuscitative medications in the unlikely event of an emergency.

The initial infiltration of the anesthetic solution is accomplished using the handle attached first to a 20-gauge 3.5-in-long spinal needle and subsequently to an 18-gauge 6-in-long intradiscal needle. The 20-gauge needle is used initially because it causes less discomfort than an 18-gauge needle when passed through unanesthetized tissue. These needles are inserted at sites around the periphery of the targeted fatty compartment either through intact skin, or the incision sites that will be used to insert the liposuction cannula. The sites of needle insertion are initially anesthetized using a 30-gauge needle on a 6-cc syringe to infiltrate a small bleb of the local anesthetic solution intradermally.

The needle, consisting of a 30-cm-long, 4-mm outside-diameter needle, is the only instrument needed with the tumescent technique is used in conjunction with general anesthesia or deep IV sedation. When used for regional local anesthesia without IV sedation, the needle is used for the last stage of infiltration of the anesthetic solution. Large areas can be completely anesthetized by systemically passing the blunt-tipped needle throughout the targeted fatty compartment along the same pathways that will be used by the liposuction cannula. The anesthetic solution must be infiltrated carefully and methodically to assure that no areas are missed. Uniform infiltration is most easily accomplished by using a grid pattern drawn by a blue felt-tipped pen on the overlying skin pre-operatively.  By infiltrating anesthetic solution as the needle is advanced, large volumes can be instilled quickly and uniformly, producing firm tumescent and extensive vasoconstriction. The blunt tip will cause discomfort when it encounters an area not previously well anesthetized. Upon detecting an area not adequately anesthetized, the surgeon or anesthesiologist can immediately infiltrate additional anesthetic solution exactly where it is needed. Because it is blunt-tipped, the needle can be passed deeply within the fat, with minimal risk of puncturing subjacent structures.

Filling a 60-cc syringe with anesthetic is the first step in using the handle or the needle. An IV line is attached to the IV bag containing the anesthetic solution. Next using the female-female luer connector, the IV line is connected to a 60-cc syringe, the IV-line flow-regulator clamp is opened, and the syringe plunger is retracted. Once the syringe is full, it is removed from the connector and IV line.

Inserting the 60-cc syringe into the handle, the syringe is turned until it is engaged with the luer-lock attachment. After removing the connector, the IV line is attached directly to the side-port of the handle, and either a 20-gauge 3.5-in-long spinal needle or an 18-gauge 6-in-long intradiscal needle is attached to the end of the handle. Next, the needle is inserted into subcutaneous fat.

In certain areas where the adipose tissue is regularly more sensitive, the infiltration must be done more slowly than other areas. Areas that are always rather sensitive include the distal-lateral and posterior thighs, upper abdomen and waist near the costal margin, the periumblical areas, and the medial knees. Except in these areas, most patients can barely detect any sensation as the anesthetic solution is injected.

If not used carefully, a sharp spinal or intradiscal needle may inadvertently penetrate the tissue underlying the subcutaneous fat. To minimize the risk of puncturing the peritoneum or causing a pneumothorax, one must continuously pay careful attention to the exact location of the needle tip within the subcutaneous fat. The safe use of the handle requires that the surgeon or anesthesiologist palpate the tip of the needle while it is being gently advanced along its intended path. To anesthetize deep tissue planes, the thumb and finger of one hand gently grasp and elevate the skin and subcutaneous fat while simultaneously palpating the needle tip. At the same time the other hand grips the handle and simultaneously advances the needle and depresses the syringe plunger. Refilling the 60-cc syringe is easily accomplished; without removing the needle from the subcutaneous fat simply open the IV-flow regulator clamp and retract the syringe plunger.

By repeating these maneuvers systemically, and directing the needle radially in many directions, large regions of the skin and subcutaneous tissue are efficiently anesthetized and vasoconstricted. Well-anesthetized areas are easily recognized visually by the pallor, and tactually by the coolness induced by the vasoconstriction.

The tumescent technique minimizes the risks of postoperative irregularities of the skin. With careful and methodical infiltration one can produce uniform tumescence and avoid irregularities and distortions. Enlarging or magnifying the targeted fatty compartments, and using suction cannulas of less than 5-mm outside diameter, permits liposuction to be done more uniformly and more completely. Because of this “magnification” of subcutaneous fat, focal residual collections of fat are easily detected and treated before completion of the surgery. These features of the tumescent technique minimize irregularities of the skin, which are more likely to be seen after liposuction when only general anesthesia is used.

A substantial volume of anesthetic solution must be injected in order to produce tumescence and complete anesthesia of a fatty compartment (Table 2). Postoperatively there is considerable drainage of slight blood-tinged anesthetic solution. Patients are advised that this typically continues for up to 18 hours. This blood-tinged solution contains approximately 1% packed red blood cells and approximately 2%-3% whole blood. Thus, drainage of 300 ml of this blood-tinged anesthetic solution represents a loss of less than 10 ml of whole blood. For each liter of pure fat removed by liposuction, patients lose approximately 12 ml of whole blood.10 One week following the liposuction of 1 L of fat there is virtually no change in the patient�s peripheral venous hematocrit.6

Table 2

Typical Range of Volumes of Dilute Anesthetic Solutions Used with the Tumescent Technique for Infiltration into Various Areas

MICRO-MACRO 2-STAGE LIPOSUCTION

In order to optimize accuracy and minimize discomfort, liposuction is accomplished using a micro-macro 2-stage liposuction method. Initially a 12-gauge (1.5 mm) micro-cannula is used. Because a 12-gauge cannula penetrates the fibrous septae in adipose with minimal resistance, the cannula’s direction and relative distance from skin are more easily controlled. The tunnel pattern produced by a 12-gauge cannula is more precise and evenly distributed. Subsequently a larger cannula (4.7 mm = 3/16-in outside diameter) is used to complete the final stage of liposuction. The 4.7-mm cannula follows paths already made by the 12-gauge cannula. Approximately 80% of the extracted fat is removed by the larger cannula during the second stage of liposuction.

Smaller cannulas are most suited for liposuction by local anesthesia. Clinical experience indicates that a cannula with a large inside diameter is more likely to cause discomfort during liposuction by local anesthesia than is a smaller cannula. Larger cannulas exert greater traction on fibrous structures with adipose tissue. This may cause pain in tissues located beyond the effects of the local anesthesia. By reducing the force needed to breach the fibrous septae permeating fatty tissue, the two-stage micro-cannula method minimizes both the discomfort for patients as well as the physical stress on the surgeon’s arm.

The use of a 12-gauge cannula is a final test for complete anesthesia. If an incompletely anesthetized area is encountered during liposuction, a 12-gauge cannula causes minimal discomfort compared with the startling sensation that a 4- or 5-mm cannula might cause.

RESULTS

Magnitude and Time of Peak Levels

A typical plasma lidocaine concentration vs. time curve is shown in. The time of the peak is defined as the length of time between the beginning of the lidocaine infiltration until the occurrence of the peak plasma lidocaine concentration. Peak levels occurred between 11 and 15 hours, with most of the peaks occurring at between 12 and 14 hours. The magnitudes of the peak plasma lidocaine concentrations ranged between 0.8 and 2.7 ųg/ml over a dosage range of 11.9-34.1 mg/kg (Table 3).

In 8 female volunteers, some participating more than once, a total of 15 separate studies were completed. Each study consisted of an infiltration of dilute lidocaine and epinephrine using the tumescent technique and then obtaining sequential plasma samples for measuring lidocaine concentration over the next 24-36 hours. In 2 of these 8 volunteers more than one area of the body was treated. In these 2 patients, infiltration and liposuction were completed in one area before infiltrating and doing liposuction on the next area.

Table 3.

Experimental Data

*PT-WT = patient weight (kg). Lido conc = lidocaine concentration in anesthetic solution, % – [(gm of lidocaine)/(100 ml of solution)]. Epinephrine concentration was 1:100,000 except for the only solution in which lidocaine concentration was 1% and epinephrine 1:100,000. Total dose = total dose of lidocaine delivered. Dosage = amount of lidocaine delivered per kg of patient weight. Fat out = the volume of blood-free fat extracted by liposuction, Soln out = the volume of blood-tinged anesthetic solution removed during liposuction procedure. Peak magnitude = peak magnitude of plasma lidocaine. Peak time = the time of the peak is defined as the length of time between the beginning of the lidocaine infiltration until the occurrence of the peak plasma lidocaine concentration.

More than one area of the body was treated. Because infiltration and liposuction were completed in one area before infiltrating and doing liposuction on the next area, infiltration occurred over an extended time interval. Consequently, the peak plasma lidocaine concentration occurred later.

Effects of Liposuction on Peak Levels

There were 4 volunteers who received lidocaine infiltrations on 2 separate occasions at least 1 week apart. On the first occasion infiltration was completed without subsequent liposuction, and on the second occasion liposuction followed the infiltration. For each of these 4 subjects the total dose of lidocaine was always infiltrated without interruption over a single time interval. The results of this study are graphically depicted in.

The area under the curve (AUC) of each graph represents the total amount of lidocaine that was absorbed systemically. AUC was calculated using Archimedes method of exhaustion.11 Liposuction reduced both the total amount of lidocaine absorbed systemically and the peak plasma lidocaine concentrations to a similar degree. Liposuction produced an average reduction in the total amount of lidocaine absorbed systemically by 29.9%. Similarly, liposuction produced an average reduction of the magnitude of peak plasma lidocaine concentration by 25.8% (Table 4). The time of the peak plasma lidocaine concentration was not affected by liposuction.

Table 4

The mean values of * AUC and * PEAK are 29.8% and 25.8%, respectively. Comparing these two percentages it is apparent that liposuction reduces the total amount of lidocaine absorbed systemically and the peak plasma lidocaine concentrations to a similar degree.

Doseo and DoseL represent respective doses of lidocaine in mg/kg associated without and with liposuction.

AUCo and AUCL represent the respective observed AUC without and with liposuction.

AUCEXP = [doseL/ doseo] x AUCo is the AUC one would expect at dose of dose L if liposuction had not been done.

* AUC = [(AUCEXP - AUCL/ AUCEXP] x 100 is the expected percent reduction of AUC resulting from liposuction.

PeakO and PeakL represent the respective peaks observed without and with liposuction.

PeakEXP = [doseL/ doseo] x peakO is the peak one would expect at a dose L if liposuction had not been done.

* peak – [(peakEXP – peakL)/peakEXP] x 100 is the estimated percent reduction of the peak plasma lidocaine concentration resulting from liposuction.

Maximum Safe Dose of 35 mg/kg

The maximum safe dose of lidocaine is estimated by plotting the magnitude of the peak plasma lidocaine concentration versus the dosage (mg/kg) for each study.  Assuming a linear relationship between peak lidocaine levels and dosage, a straight line can be used to predict the maximum safe dosage of lidocaine when using the tumescent technique.

Ideally, a safe maximal dose should yield a peak plasma lidocaine concentration below the toxicity threshold (5 ųg/ml) for at least 99% of patients. Using linear regression analysis to define a least-squares estimate for a straight line that best fits our data would yield an inappropriately high estimate of approximately 50 mg/kg. With such an estimate, one would expect a dose of 50 mg/kg to produce peak plasma lidocaine levels greater than 5 ųg/ml in approximately 50% of patients.

A more conservative choice is the line for which a peak lidocaine concentration of 5 ųg/ml corresponds to a dosage of 35 mg/kg. With appropriate assumptions about linearity, we can expect that a dosage of 35 mg/kg would yield a peak plasma lidocaine concentration of less than 5 ųg/ml in every patient who participated in the present study.

Thus a conservative estimate of the maximal safe dose of dilute lidocaine infiltrated into subcutaneous fat is 35 mg/kg, with or without liposuction (Table 5).

Table 5

Estimated Maximal Safe Dosage of Lidocaine

Using the Tumescent Technique is 35 mg/kg

Dilute Delays Absorption

Following the infiltration of 1 gm of lidocaine as a 1% solution with 1 mg of epinephrine at 1:100,000, the peak plasma level occurred at approximately 9 hours, with a magnitude 1.5 ųg/ml; the maximum pulse rate during this infiltration was 118. In comparison, following the infiltration of 1 gm of lidocaine as a 0.1% solution with 1 mg of epinephrine at 1:1,000,000, the peak plasma lidocaine level occurred at 14 hours, with a magnitude 1.2 ųg/ml; the maximum pulse rate during this infiltration was 78, essentially unchanged from preoperative values. On each occasion infiltration of the entire dose was accomplished over a 45-min interval. As a consequence of this study we see that diluting an anesthetic solution results in a clinically significant delay in occurrence of the peak plasma lidocaine concentration as well as a diminution of its magnitude after infiltration into subcutaneous fat.

Slow Infiltration Delays Absorption

Slow infiltration prevents the rapid lidocaine absorption that can occur immediately after rapid infiltration. After a subcutaneous dose of 900 mg of lidocaine 0.1% with epinephrine 1:1,000,000 infiltrated into subcutaneous fat of an 85-kg male over 45 minutes, the plasma lidocaine levels were less than 0.1 ųg/ml at 5 and 15 minutes after beginning the infiltration. Subsequent plasma concentrations determined every 30 minutes over the next 7 hours were no greater than 0.5 ųg/ml.

DISCUSSION

The tumescent technique uses large volumes of a dilute anesthetic solution to produce swelling and firmness of targeted areas of subcutaneous fat. The prolonged and profound anesthesia of skin and subcutaneous tissues that is provided by the tumescent technique is a result of exposing sufficient lengths of sensory axons to marginal blocking concentrations of lidocaine12. The tumescent technique achieves regional anesthesia by direct subcutaneous infiltration rather than by a proximal nerve block. The technique, which allows liposuction of more than 3 L of fat totally by local anesthesia with negligible bleeding, was first presented in 1986 in Philadelphia at the Second World Congress on Liposuction, and first published in 1987.6

Clinical experience with liposuction by local anesthesia has shown that exceeding the traditional recommended maximum dose of lidocaine with epinephrine of 7 mg/kg is safe. The facile pharmacologic explanation for the safety of using very large doses of lidocaine during liposuction is that a significant amount of lidocaine is removed along with the aspirated fat.13,14 However, this assertion has never been documented scientifically.

An important result of the present study is an estimate of 35 mg/kg as the maximal safe dose of lidocaine using the tumescent technique for liposuction by local anesthesia. This is five times the traditional maximal safe dose of 7 mg/kg of lidocaine for local anesthesia.13

Important factors in determining the fate, efficacy, and toxicity of a drug in the human body include rates of absorption, distribution, metabolism, and elimination. Elegant studies of lidocaine given intravenously (IV) have elucidated it distribution, metabolism, and elimination.15 The few published studies of lidocaine absorption after infiltration into subcutaneous fat have used elementary pharmacologic analyses.4,6,14,16,17 The present study of the clinical pharmacokinetics of the tumescent technique is aimed at a more comprehensive understanding of lidocaine absorption and elimination after infiltration into subcutaneous fat.

Pharmacokinetics of IV Lidocaine

Since lidocaine is relatively lipophilic, tissue membranes are not a significant barrier to lidocaine distribution. The rate of lidocaine distribution into or out of a tissue is perfusion rate-limited.

Immediately after an IV bolus dose, there is a rapid distribution-related fall in plasma lidocaine.18 This occurs as a result of lidocaine diffusing from plasma into highly perfused organs such as the brain, heart, and liver. Once an equilibrium is achieved between lidocaine concentrations in plasma and all well-perfused tissues, plasma levels decline more slowly. This later decline of plasma drugs levels depends on uptake into less well-perfused tissues and on hepatic lidocaine metabolism.

Lidocaine is metabolized by the liver. Hepatic metabolism is so rapid that 70% of lidocaine is extracted from any given volume of blood as it passes through the liver. Following an intravenous bolus injection of lidocaine in a healthy volunteer, half of the drug will have been eliminated after approximately 100 minutes.19,20 In a healthy person, lidocaine clearance is 10 mg/min/kg. Thus, when plasma lidocaine concentration is 2.5 ųg/ml in an 80-kg person, the liver will metabolize 2000 ųg/min or 120 mg/hr of lidocaine.

Hepatic metabolism of lidocaine is so complete that the rate of lidocaine clearance is a direct function of the rate of hepatic blood flow. Any decrease in hepatic blood flow will decrease the rate of lidocaine metabolism, and consequently increase the risk of lidocaine toxicity.

An oral dose of lidocaine is absorbed into the portal circulation and rapidly metabolized by the liver, with relatively little lidocaine reaching the systemic circulation. Thus, lidocaine must be given parenterally when treating life-threatening cardiac arrhythmias.

Absorption Rate of Subcutaneous Lidocaine

The 12-14-hour delay of the peak lidocaine plasma levels following infiltration into subcutaneous fat using the tumescent technique is unprecedented. Dilution of lidocaine and rate of subcutaneous infiltration are important determinants of rate of absorption. The present study has shown that dilution delays and diminishes the magnitude of peak plasma lidocaine levels following subcutaneous infiltration. This is contrary to the observation that lidocaine absorption rates are independent of lidocaine concentration for intramuscular and peridural injections over a range of 1% or 10% lidocaine.21

Rapid subcutaneous infiltration of a standard anesthetic solution of lidocaine and epinephrine may produce toxicity. The more rapidly a local anesthetic is injected, the more rapidly it is absorbed systemically.22 This is true for both intravenous infusion,23 as well as for infiltration into subcutaneous fat.

Peak plasma lidocaine levels in healthy persons are generally assumed to occur within 60 minutes of giving the drug, whether it is given by bolus intravenous infusion; intravenous regional anesthesia;24 intramuscular injection,25,26 caudal, epidural, intercostals, and peripheral nerve blocks,27-32 paracervical infiltration;33 or oral administration.34

An unexpected result of the present study is that 1 gm of a 1% lidocaine solution with epinephrine 1:100,000 slowly infiltrated into subcutaneous fat over 45 minutes is absorbed so slowly. In fact, the peak plasma level occurred 9 hours after beginning the infiltration.

There are few detailed studies of absorption kinetics of lidocaine infiltrated subcutaneously. For subcutaneous infiltration the peak plasma lidocaine level is usually less than 60 minutes.35-38 An average peak plasma lidocaine level occurring at 62 minutes (range 30-120 minutes) is one of the longest delays documented in the literature.39 When 2% lidocaine with epinephrine 1:200,000 is infiltrated into the scalp for hair transplantation, peak plasma lidocaine concentration occurred 45 minutes after the initial infiltration in 6 of 6 patients.40

Regional Anesthesia Without Nerve Block

There are two reasons why infiltrative local anesthesia has traditionally been limited to relatively small areas of skin: (1) the stinging pain associated with infiltrating the local anesthesia is not easily tolerated, and (2) published dosage limitations have precluded anesthetizing large areas of skin. These limitations have now been overcome with the recognition that (1) adding sodium bicarbonate in order to neutralize the acidity of commercially available local anesthetic solutions of lidocaine and epinephrine dramatically reduces the usual burning-stinging pain of infiltration,8 and (2) using dilute solutions of lidocaine with the tumescent technique permits profound anesthesia of very large areas with minimal risk of lidocaine toxicity. The tumescent technique permits regional local anesthesia of skin and subcutaneous tissue by direct infiltration rather than by proximal nerve block.

Prolonged Local Anesthesia

A remarkable aspect of the tumescent technique is that there is so little postoperative discomfort. Treated areas remain at least partially anesthetized for up to 18 hours after surgery. Thus for liposuction, it is not necessary to use local anesthetics that are longer acting and more cardiotoxic than lidocaine.41-44

Following liposuction with the tumescent technique, patients do not require analgesia postoperatively. Although some patients do take acetaminophen for mild to moderate soreness, narcotic analgesics are not prescribed.

There are at least two aspects of lidocaine pharmacology that explain the persistence of analgesia with the tumescent technique. First, the occurrence of peak plasma lidocaine levels more than 12 hours after beginning the infiltration and detectable blood levels well beyond 18 hours indicates that the anesthetic persists in the locally treated areas for up to 18 hours. This is consistent with the clinical observation that slightly blood-tinged anesthetic solution continues to drain from the 5-mm incision sites for approximately 18 hours after the surgery. Second, it has been asserted that a continuous low dose infusion of lidocaine, yielding plasma lidocaine concentration of 1ųg/ml, reduces the severity of postoperative pain and minimizes the necessity for narcotic analgesics.45,46 Lidocaine plasma concentrations of 3-6 ųg/ml lidocaine decrease the anesthetic requirements of nitrous oxide and halothane by 10%-28%.47

Lidocaine Toxicity

Lidocaine toxicity is closely correlated with plasma lidocaine levels. Because toxicity becomes apparent at different levels in different patients, the clinical threshold for lidocaine toxicity is not well defined. It is clinically useful to think of a threshold level for toxicity as being described by a curve similar to that of the bell-shaped curve of a Gaussian (normal) distribution. The point at which 50% of patients can be expected to first manifest toxicity is the median threshold toxic blood level. By definition, 50% of the patients will experience toxicity below this toxic threshold. A corollary statement is that any estimate of a “maximal safe dosage” of lidocaine should account for clinical variation between patients, and the statistical variation between pharmacologic studies.

Therapeutic plasma lidocaine levels for suppressing ventricular ectopy in the clinical setting of acute myocardial ischemia range between 1 and 5 ųg/ml. Subjective side effects can probably be recorded at between 3 and 6 ųg/ml with objective undesirable side effects, or toxicity, becoming apparent at plasma levels above 5-9 ųg/ml.48 Potentially fatal lidocaine toxicity may occur at plasma lidocaine concentrations as low as 9 ųg/ml (Table 6).

The following classification of lidocaine toxicity is intended to provide insight into clinical situations where infiltrating lidocaine subcutaneously can result in an unexpected toxic reaction. Toxicity may result from (1) an overdose, (2) an excessively rapid systemic uptake of an otherwise safe dose, (3) impaired hepatic metabolism, or (4) drug interactions.

Table 6

Lidocaine Levels and Toxicity

These are approximate values abstracted from multiple previously published reports including: Binnion PF et al. Br Med J 3:390-393,1969; Benowitw NL, Meister W. Clinical pharmacokinetics of lidocaine. Clinical Pharmacokinetics 3:177-201, 1978; Mather LE, Cousins MJ. Local anaesthetics and their current clinical use. Drugs 18:185-205, 1979.

OVERDOSE

The following definitions of “overdose” give a perspective on the problem of defining dose-limits for lidocaine in local anesthesia.

A mistaken overdose occurs when too much drug (more than a safe amount) is given as a result of either carelessness or ignorance. A mistaken overdose may or may not cause a toxic reaction.

A retrospective overdose is a dose that retrospectively actually caused a toxic reaction in a specific patient. In some patients a retrospective overdose may occur despite an administered dose that is well below the recommended safe upper dose limit.

A prospective overdose is defined as a dose above which a toxic reaction can be expected in an arbitrary but significant number of patients. Such an overdose is defined prospectively based on (1) route of administration and (2) concepts of population pharmacokinetics and (2) concepts of population pharmacokinetics that take into account intrapatient and interpatient variability. Factors that affect rates of drug absorption and elimination are the variables that define important subpopulations of patients.

A dogmatic overdose is any dose that exceeds a “standard recommended maximum safe dose” that has no scientific basis in fact. A dogmatic overdose may be quite safe. This is obviously true in the case of the tumescent technique where the maximum safe dose of lidocaine when infiltrated into fat, 35 mg/kg, is five times the “standard recommended maximum safe dose” for local anesthesia, 7 mg/kg, as listed in the Xylocaine (lidocaine) package insert. Unfortunately many published dosage limitations for lidocaine in local anesthesia are based more on clinical dogma than on scientific data.

Following an IV bolus dose the initial distribution-related fall in plasma lidocaine concentration is rapid. The half-life of this early distribution-related phase is 8.3 minutes.15 As a consequence, the duration of a toxic reaction following an inadvertent IV injection should be relatively brief.49 Even a massive IV bolus dose is not necessarily fatal.50

On the other hand, toxic reactions to lidocaine that occur after an excessive cumulative dose, such as with a prolonged IV infusion or repeated injections, are more dangerous. The half-life of lidocaine blood levels after a prolonged infusion is approximately 100 minutes in healthy adults and depends on liver metabolism. In this clinical setting toxic plasma concentrations may persist for hours and may be associated with refractory cardiac arrest.

RAPID SYSTEMIC UPTAKE

Inadvertent intravascular injection of an otherwise safe dose of local anesthetic is a relatively common cause of toxicity.51,52 In a 10-year study that includes 9287 regional nerve blocks, there were 8 systemic toxic reactions, and all were attributed to an inadvertent intravascular bolus injection.53

Injection of a lipophilic drug, such as lidocaine, into highly vascular tissue promotes rapid diffusion out of the tissue into the vascular space. Intercostal nerve blocks, which involve injections into very vascular tissue, are particularly likely to result in rapid systemic absorption and toxicity.54 Similarly, cutaneous infiltration of lidocaine prior to laser treatment of a hemangioma can easily produce transiently toxic plasma levels. The potential toxicity of a local anesthetic is less when infiltrated into relatively avascular subcutaneous tissue than when it is injected into the highly vascular intraperitoneal space.55

A highly concentrated lidocaine solution will produce rapid diffusion into the vascular compartment because the rate of drug diffusion across a membrane is proportional to its concentration gradient. When lidocaine is injected subcutaneously in mice, the higher the concentration, the smaller the lethal dose56 (Table 7).

Table 7

Effect of Lidocaine Dilution on Fatal Toxicity in Mice After Subcutaneous Injection56

The 2% lidocaine in dental cartridges is appropriate for nerve blocks but is unnecessarily high for subcutaneous infiltration local anesthesia. A 0.5% lidocaine solution is sufficient for most forms of cutaneous surgery.57 For liposuction by the tumescent technique a 0.5% lidocaine solution is sufficient.

Hyaluronidase is not a component of the anesthetic solution used with the tumescent technique. Hyaluronidase may accelerate systemic absorption of lidocaine and this increase the peak plasma lidocaine levels.58,59

Excessively rapid subcutaneous infiltration of an otherwise safe dose of lidocaine can produce a potentially toxic plasma drug concentration. Lidocaine is a capillary vasodilator with a rapid onset of action.60 Epinephrine is a vasoconstrictor with maximum clinical effect delayed approximately 10-15 minutes after injection. For several minutes after a rapid injection of a lidocaine and epinephrine solution, systemic lidocaine absorption will be rapid until the epinephrine-induced vasoconstriction has had sufficient time to occur.

The contrast between rapid and slow subcutaneous infiltration of lidocaine is well illustrated by the following four cases. In the first instance two patients received a combination of 1% and 0.5% lidocaine with epinephrine 1:100,000 injected rapidly in less than 5 minutes.61 Total doses of 800 mg and 1350 mg of lidocaine resulted in peak lidocaine blood levels of 4.2 and 6.3 ųg/ml, respectively. These potentially toxic levels were attained within 15 minutes of completion of the infiltration (Fig.9).62

In contrast, as illustrated by the present study, the slow infiltration of lidocaine over 45 minutes results in initial plasma lidocaine levels that are almost undetectable. When 900 mg of 0.1% lidocaine with epinephrine 1:100,000 was given over 45 minutes, the plasma lidocaine concentrations were negligible at 5, 15, and 30 minutes after initiating the injection (Fig.9). When 1000 mg of 1% lidocaine with epinephrine 1:100,000 was given over minutes, the peak plasma concentration of 1.5 ųg/ml did not occur until 9 hours after initiating the infiltration.

Epinephrine is a potent vasoconstrictor. The anesthetic effect of lidocaine is prolonged, and its peak plasma concentration is reduced by the addition of epinephrine to the anesthetic solution.63,64 Using a lidocaine solution without epinephrine increases the risk of reaching toxic plasma lidocaine levels.

IMPAIRED LIDOCAINE METABOLISM

Diseases or drugs that decrease lidocaine metabolism are important causes of lidocaine toxicity. Diseases causing decreased hepatic metabolism can significantly delay elimination of lidocaine from the systemic circulation. Disease of liver parenchyma decreases lidocaine metabolism directly.65,66 Other diseases that diminish hepatic perfusion, such as heart disease,67,68 or diseases associated with hypotension,69 decrease lidocaine metabolism indirectly.

DRUG INTERACTIONS

Drugs that decrease hepatic blood flow or otherwise decrease lidocaine metabolism can lead to toxic accumulations of lidocaine. Drugs commonly associated with such adverse interactions include cimetidine,70,71 beta-adrenergic receptor blockers,72-75 phenytoin, and procainamide.76

Other forms of drug interactions, other than impaired metabolism, may be related to lidocaine toxicity. Diazepam (Valium, Roche Laboratories, Nutley, NJ) and other benzodiazepines reduce the risk of seizures associated with excessive plasma lidocaine concentrations.77,78 However, this should not be interpreted to mean that the concomitant use of benzodiazepines will allow a higher safe dose of lidocaine. In pigs, with either diazepam or midazolam (Versed) premedication, the first sign of local anesthetic toxicity may be cardiovascular collapse with a decreased chance of successful resuscitation.79

Diazepam may increase the incidence of malignant arrhythmias induced by local anesthetics.80 The benzodiazepine midazolam reduces the incidence of lidocaine-induced convulsions but has no significant effect on mortality in rats.81

Maximum Safe Dose

Maximum safe dose of lidocaine for subcutaneous infiltration is dependent on local tissue vascularity. For infiltration into subcutaneous fat, which is relatively avascular, surprisingly high dosages are safe. The present study estimates that a dosage of 35 mg/kg, when infiltrated slowly and as a dilute solution, should correspond to a peak lidocaine plasma level of between 3 and 4 ųg/ml. Although still higher doses might be safe, such safety has not been documented.

In one report of liposuction by the tumescent technique , doses as high as 90 mg/kg were used with serous toxicity.16 While some of these patients did experience nausea and vomiting approximately 12 hours postoperatively, these symptoms might have been the result of using oxycodone for postoperative analgesia, rather than side effect of lidocaine.82

When a “standard recommended maximum safe dose” has a limited scientific basis in fact, higher doses may be quite safe. For lidocaine this inconsistency is the result of considering the absorption rate for regional nerve blocks (epidural, intercostal, or pericervical) to be the same as that for subcutaneous infiltration. The tumescent technique for liposuction is a specific example. Using this technique a maximal safe dose of lidocaine infiltrated into fat is 35 mg/kg. This is five times the maximum recommended safe dose of lidocaine with epinephrine for local anesthesia, 7 mg/kg, as listed in the Xylocaine package insert.

The total amount of a dose of lidocaine that is absorbed into the systemic circulation is represented by the area under the curve (AUC) of the graph of concentration vs. time. The AUC is an important parameter in the science of pharmacokinetics. For a given dosage, the AUC is constant. Thus, for a given dosage, accelerated absorption will result in both an early peak plasma lidocaine and a peak of increased magnitude. Similarly, a delay of the peak plasma lidocaine level will result in a diminished peak level.

Liposuction reduces the AUC and therefore reduces the total amount of lidocaine that is absorbed. The peak plasma lidocaine levels are not dramatically reduced. The removal of lidocaine by liposuction does not dramatically reduce the risk of lidocaine toxicity. It is the inherent slow rate of absorption from fat that accounts for the safety of liposuction by local anesthesia using high doses of lidocaine.

Hemostasis with the Tumescent Technique

Blood loss is minimal with the tumescent technique. After remaining undisturbed in the collection bottle for 15-30 minutes, the tissue removed by liposuction using the tumescent technique will separate into a supernatant layer of viscous yellow fat, and an infranatant layer of blood-tinged anesthetic solution. In a recent study of the tumescent technique it has been found that for each liter of fat extracted by liposuction, there is approximately 12 ml of whole blood extracted10.

Because there is so little blood loss, there is frequently almost no postoperative bruising.  Patients may return to a desk-type job within 1-2 days following liposuction with the tumescent technique. Elastic support garments are only required for 4 days postoperatively, and exercising may be cautiously resumed 3 days after surgery.

CONCLUSIONS

(1)  A maximal safe dosage of dilute lidocaine using the tumescent technique is estimated to be 35 mg/kg.

(2)  Slowly infiltrating a local anesthetic solution of lidocaine and epinephrine minimizes the rate of systemic absorption and reduces the potential for toxicity.

(3)  When lidocaine (1%) with epinephrine (1:100,000) is slowly infiltrated into subcutaneous fat, the peak plasma lidocaine level occurs 9 hours after the initial injection.

(4)  Dilution of lidocaine (0.5% or 0.1%) and epinephrine (1:100,000) further delays absorption and reduces the magnitude of peak plasma lidocaine concentrations. Using the tumescent technique for liposuction, peak plasma lidocaine levels occur 12 hours after the initial injection. Clinically significant local anesthesia persists for up to 18 hours. For liposuction, it is necessary to use local anesthetics, which are longer acting and potentially more cardiotoxic than lidocaine.

(5)  Liposuction reduces both the amount of lidocaine absorbed systemically and the peak plasma lidocaine levels by approximately 10%-30%.

(6)  Using the tumescent technique, liposuction can remove large volumes of fat with minimal blood loss, and minimal patient discomfort.

REFERENCES

1.     Physicians’ Desk Reference. Oradell, MJ, Medical Economics Company, Inc, 1989, p 640.

2.     Personal communication. The Director of Clinical Research, Astra Pharmaceutical Products, Inc.

3.     Personal communication. The US Food and Drug Administration. This information was obtained under the Freedom of Information Act.

4.     Klein JA, Anesthesia for liposuction in dermatologic surgery. J. Dermatol Surg Oncol 14:1124-1132, 1988.

5.     Cobb ME, Buckley N, Hu MW, Homogeneous enzyme immunoassay for lidocaine in serum (abstract). Clin Chem 23:1161, 1977.

6.     Klein JA, The tumescent technique for liposuction surgery. Am J Cosmet Surg 4:263-267, 1987.

7.     McKay W, Morris R, Mushlin P. Sodium bicarbonate attenuates pain on skin infiltration with lidocaine, with or without epinephrine. Anesth Analg 66:572-574, 1987.

8.     Stewart JH, Cole GW, Klein JA. Neutralized lidocaine with epinephrine for local anesthesia. J Dermatol Surg Oncol 15:1081-1083, 1989.

9.     Stewart JH, Chen SE, Cole GW, Klein JA. Neutralized lidocaine with epinephrine for local anesthesia, II (In press.)

10.  Klein JA. Infiltration regional anesthesia by the tumescent technique: Reduced blood loss and optimal fluid balance for liposuction. (In preparation.)

11.  Apostol TM. Calculus, Vol I. Waltham, MA, Blaisdell Publishing Co, 1967, pp 2-5.

12.  Raymond SA, Steffensen SC, Gugino LD, Strichartz GR. The role of length of nerve exposed to local anesthetics in impulse blocking action. Anesth Analg 68:563-570, 1989.

13.  Asken S. Liposuction Surgery and Autologous Fat Transplantation. East Norwalk, CT, Appleton & Lang, 1988, p 63.

14.  Gumunico CA, Bennie JB, Fernando B, et al. Plasma lidocaine levels during augmentation mammaplasty and suction-assisted lipectomy. Plast Reconstr Surg 84:624-627, 1989.

15.  Benowitz NL. Clinical applications of the pharmacokinetics of lidocaine. Cardiovasc Clin 6:77-101, 1974.

16.  Lillis PJ. Liposuction surgery under local anesthesia: Limited blood loss and minimal lidocaine absorption. J Dermatol Surg Oncol 14:1145-1148, 1988.

17.  Lewis CM, Hepper T. The use of high-dose lidocaine in wetting solutions for lipoplasty. Ann Plast Surg 22:307-309, 1989.

18.  Rowland M, Tozer TN. Clinical Pharmacokinetics: Concepts and Applications, 2nd Ed. Philadelphia, Lea & Febiger, 1989, Chap 19.

19.  Boyes RN, Scott DB, Jebson PJ, et al. Pharmacokinetics of lidocaine in man. Clin Pharmacol Ther 12:105-116, 1971.

20.  Rowland M, Thomson PD, Guichard A, Melmon KL. Disposition kinetics of lidocaine in normal subjects. Ann N Y Acad Sci 179:383-398, 1971.

21.  de Jong RH. Local Anesthetic, 2nd Ed. Springfield, Ill, Charles C Thomas, 1977, pp 187-188.

22.  Scott DB, Evaluation of clinical tolerance of local anesthetic agents. Br J. Anaesth 47:328-333, 1975.

23.  Campbell D, Adrinani J, Absorption of local anesthetics. JAMA 168:873-877, 1958.

24.  Hargrove RL, Hoyle JR, Parker JBR, et al. Blood lignocaine levels following intravenous regional anesthesia. Anaesthesia 21:37-41, 1966.

25.  Schwartz M, et al. Antiarrthythmic effectiveness of intramuscular lidocaine: Influence of different injection sites. J Clin Pharmacol 14:77-83, 1974.

26.  Collinsworth KA, Kalman SM, Harrison DC. The clinical pharmacology of lidocaine as an antiarrthythmic drug. Circulation 50:1217-1230, 1974.

27.  Tucker, GT, Moore DC, Bridenbaugh PO, et al. Systemic absorption of mepivacaine in commonly used regional block procedures. Anesthesiology 37:277-287, 1972.

28.  Raj PP, Rosenblatt R, Miller J, et al. Dynamics of local anesthetic compounds in regional anesthesia. Anesth Analg 56:110-117, 1977.

29.  Ecoffey C, Desparment A, Berdeaux A, et al. Pharmacokinetics of lidocaine in children following caudal anesthesia. Br J. Anaesth 56:1399-1402, 1984.

30.  Braid DP, Scott DB. Dosage of lignocaine in epidural block in relation to toxicity. Br J Anaesth 38:596-602, 1966.

31.  Braid DP, Scott DB. The systemic absorption of local analgesic drugs. Br J Anaesth 37:394-404, 1965.

32.  Inoue R, Suganuma T, Echizen H, et al. Plasma concentrations of lidocaine and its principal metabolites during intermittent epidural anesthesia. Anesthesiology 63:304-310, 1985.

33.  Blanco LJ, Reid PR, King TM. Plasma lidocaine levels following paracervical infiltration for aspiration abortion. Obstet Gynecol 60:506-508, 1982.

34.  Boyes RN, Scott DB, Jebson PJ, et al. Pharmacokinetics of lidocaine in man. Clin Pharmacol Ther 12:105-116, 1971.

35.  Stoelting RK. Plasma lidocaine concentrations following subcutaneous or submucosal epinephrine-lidocaine injection. Anesth Analg 57:724-726, 1978.

36.  Scott DB, Jebson PJR, Braid DP, et al. Factors affecting plasma levels of lidocaine and prilocaine. Br J Anaesth 44:1040-1049, 1972.

37.  Schwartz ML, Covino BG, Narang RM, et al. Blood levels of lidocaine following subcutaneous administration prior to cardiac catheterization. Am Heart J 88:721-723, 1974.

38.  Kosowsky BD, Shahid IM, Gurinder SG, et al. Effect of local lidocaine anesthesia on ventricular escape intervals during permanent pacemaker implantation in patients with complete heart block. Am J Cardiology 51:101-104, 1983.

39.  Nattel S, Rickenberger RL, Lehrman LL, Zipes DP. Therapeutic blood lidocaine concentrations after local anesthesia for cardiac electrophysiologic studies. N Engl J Med 301:418-420, 1979.

40.  Maloney JM, Lertora JJ, Yarborough J, Millikan LE. Plasma concentrations of lidocaine during hair transplantation. J Dermatol Oncol 8:950-954, 1982.

41.  Nancarrow C, Rutten AJ, Runciman WB, et al. Myocardial and cerebral drug concentrations and the mechanisms of death after fatal intravenous doses of lidocaine, bupivacaine, and ropivacaine in the sheep. Anesth Analg 69:276-283, 1989.

42.  Rutten AJ, Nancarrow C, Mather LE, et al. Hemodynamic and central nervous system effects of intravenous bolus doses of lidocaine, bupivacaine, and ropivacaine in sheep. Anesth Analg 69:291-299, 1989.

43.  Tanz RD, Haskett T, Loehning RW, Fairfax CA. Comparative cardiotoxicity of bupivacaine and lidocaine in the isolated perfused mammalian heart. Anesth Analg 63:549-556, 1984.

44.  de Jong RH, Ronfeld RA, DeRosa RA. Cardiovascular effects of convulsant and supraconvulsant doses of amide local anesthetics. Anesth Analg 61:3-9, 1982.

45.  Cassuto J, Wallin G, Hogstrom S, et al. Inhibition of post-operative pain by continuous low-dose intravenous infusion of lidocaine. Anesth Analg 64:971-974, 1985.

46.  Bartlett EE, Hutaserani, O. Xylocaine for relief of post-operative pain. Anesth Analg 40:296-304, 1961.

47.  Himes RS, DiFazio CA, Burney RG. Effects of lidocaine on the anesthetic requirements for nitrous oxide and halothane. Anesthesiology 47:437-440, 1977.

48.  Benowitz NL, Meister W. Clinical pharmacokinetics of lidocaine. Clin Pharmacokinet 3:177-201, 1978.

49.  Alper MH. Toxicity of local anesthesia. N Engl J Med 295:1432-1433, 1976.

50.  Finkelstein F. Massive lidocaine poisoning (letter). N Engl J Med 301:50, 1979.

51.  Covine BG. Systemic toxicity of local anesthetic agents (editorial). Anesth Analg 57:387-388, 1978.

52.  Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 51:285-287, 1979.

53.  Moore DC, Bridenbaugh LD, Thompson GB, et al. Factors determining dosage of amide-type local anesthetic drugs. Anesthesiology 47:263-268, 1977.

54.  Moore DC, Thompson GE, Crawford RD. Long-acting local anesthetic drugs and convulsions with hypoxia and acidosis. Anesthesiology 56:230-232, 1982.

55.  de Jong RH, Bonin JD. Local anesthetics: Injection route alters relative toxicity of bupivacaine. Anesth Analg 59:925-928, 1980.

56.  Gordh T. Xylocaine – a new local anesthetic. Anaesthesia 4:4-9, 21, 1949.

57.  Bashein G. Use of excessive lidocaine concentrations for local anesthesia (letter). N Engl J Med 302:122, 1980.

58.  Petterson LO, Akerman B. Influence of hyaluronidase upon local infiltration anesthesia by lidocaine. Scand J Plast Reconstr Surgery 18:297-301, 1984.

59.  Adriani J. The clinical pharmacology of local anesthetics. Clin Pharmacol Ther 1:645-673, 1960.

60.  Covino BG, Vassallo HG. Local Anesthetics: Mechanisms of Action and Clinical Use. New York, Grune & Stratton, 1976, pp 105-106.

61.  Personal communication with Richard Hagert, M.D., Department of Plastic and Reconstructive Surgery, School of Medicine, University of South Carolina, Charleston, SC.

62.  Piveral K. Systemic lidocaine absorption during liposuction. Plast Reconstr Surg 80:643, 1987.

63.  Swerdlow, M, Jones R. The duration of action of bupivacaine, prilocaine and lignocaine. Br J Anesth 42:335-339, 1970.

64.  Covino BG. Pharmacology of local anesthetic agents. Br J Anaesth 58:701-716, 1986.

65.  Selden R, Sasahara AA. Central nervous system toxicity induced by lidocaine: Report of a case in a patient with liver disease. JAMA 202:908-909, 1967.

66.  Thomson PD, Melmon KL, Richardson JA, et al. Lidocaine pharmacokinetics in advanced heart failure, liver disease, and renal failure in humans. Ann Intern Med 78:499-508, 1973.

67.  Thomson PD, Rowland M, Melmon KL. The influence of heart failure, liver disease, and renal failure on the disposition of lidocaine in man. Am Heart J 82:417-421, 1971.

68.  Prescott LF, Adjepon-Yamoah KK, Talbot RG. Impaired lignocaine metabolism with patients with myocardial infarction and cardiac failure. B Med J 1:939-941, 1976.

69.  Feely, J, Wade D, McAllister CB, et al. Effect of hypotension on liver blood flow and lidocaine disposition. N Engl J Med 307:866-869, 1982.

70.  Knapp AB, et al. The cimetidine-lidocaine interaction. Ann Intern Med 98:174-177, 1983.

71.  Feely J, Wilkinson GR, McAllister CB, Wood AJJ. Increased toxicity and reduced clearance of lidocaine by cimetidine. Ann Intern Med 96:592-594, 1982.

72.  Tucker GT, Bax NDS, Al-Asady S, et al. Effects of β-adrenoceptor antagonists on the pharmacokinetics of lignocaine. Br J Pharmacol 17:21S-28S, 1984.

73.  Ochs HR, Carstens G, Greenblatt DJ. Reduction in lidocaine clearance during continuous infusion and by coadministration of propranolol. N Engl J Med 303:373-376, 1980.

74.  Branch RA, Shand DS, Wilkinson GR, Nies AS: The reduction of lidocaine clearance by dl propranolol: An example of hemodynamic drug interaction. J Pharmacol Exp Ther 184:515-519, 1973.

75.  Conrad KA, Byers JM III, Finley PR, Burnham L. Lidocaine elimination: Effects of metoprolol and of propranolol. Clin Pharmacol Ther 33:133-138, 1983.

76.  Karlsson E, Collste R, Rowlins MD. Plasma levels of lidocaine during combined treatment with phenytoin and procainamide. Eur J Clin Pharmacol 7:455-459, 1974.

77.  de Jong RH. Toxic effects of local anesthetics. JAMA 239:1166-1168, 1978.

78.  de Jong RH, Heavner JE. Convulsions induced by local anesthetic: Time course of diazepam prophylaxis. Can Anaesth Soc J 21:153-158, 1974.

79.  Bernards CM, Carpenter RL, Rupp SM, et al. Effect of midazolam and diazepam premedication on central nervous system and cardiovascular toxicity of bupivacaine in pigs. Anesthesiology 70:318-323, 1989.

80.  Gregg RV, Turner PA, Denson DA, et al. Does diazepam really reduce the cardiotoxic effects of intravenous bupivacaine? Anesth Anal 67:9-14, 1988.

81.  Torbiner ML, Yagiela JA, Mito RS. Effect of midazolam pretreatment on the intravenous toxicity of lidocaine with and without epinephrine in rats. Anesth Analg 68:744-749, 1989.

82.  Lillis P. Personal communication.