LIPOSUCTION TEXTBOOK

PART III:
Clinical Pharmacology
Chapter 16:
Pharmacology of Tumescent Technique

Part III of this book focuses on the unique aspects of lidocaine pharmacology as it applies to the tumescent technique using local anesthesia, with subcutaneous infiltration of extremely dilute lidocaine and epinephrine. The pharmacokinetics of tumescent lidocaine, which involves the fate of dilute lidocaine, dilute epinephrine, and the isotonic solvent after delivery into subcutaneous fat, is not widely appreciated.

Every surgeon and anesthesiologist knows that lidocaine is potentially toxic. Some physicians are unaware, however, that the tumescent delivery of large volumes of subcutaneous isotonic solutions of electrolytes obviates the need for intravenous (IV) fluid supplementation with tumescent liposuction. The greatest danger of the tumescent technique is not potential for lidocaine toxicity but lack of knowledge. Surgeons and anesthesiologists who use tumescent anesthesia may not appreciate (1) the risks of IV fluid overload leading to pulmonary edema and (2) the dangers of excessive liposuction that are independent of the risks of blood loss.

This chapter considers the clinical toxicology of tumescent lidocaine and the determination of the optimal effective lidocaine dilution. The following chapters consider the statistical, philosophic, and ethical criteria for estimating a maximum safe dose of lidocaine for tumescent liposuction.

Lidocaine Dose Recommendations

What is the maximum safe dose of tumescent lidocaine? This question has no simple, well-defined numeric answer. Instead, several acceptable answers exist, depending on objective pharmacology, statistical estimation, and subjective medical ethics.

Such answers do not remain valid over time. With more clinical experience and new insights into the pharmacokinetics of the tumescent technique, this estimate will need to be reassessed periodically. The current answer is based on both objective clinical research and subjective clinical experience.

As explained later, lidocaine toxicity correlates directly with the magnitude of plasma lidocaine concentration. The smaller the peak plasma lidocaine concentration, the smaller is the risk of lidocaine toxicity. The fundamental reason for the great safety of tumescent anesthesia is the slow rate of lidocaine absorption. For any given mg/kg dosage of lidocaine, the slower the rate of lidocaine absorption, the smaller the peak lidocaine plasma levels, and thus the smaller is the probability of a toxic event.

My present recommendation for the maximum dosage of tumescent lidocaine in healthy, young female patients is as follows:

45 mg/kg (thin patients)

50 mg/kg (average to overweight patients)

Lidocaine doses must be reduced by at least 30% to 40% in patients who are taking drugs that interfere with lidocaine metabolism (e.g., sertraline, erythromycin, ketoconazole).

The following three reasons explain the dramatically slow rate of absorption of tumescent lidocaine from subcutaneous fat:

1. Subcutaneous fat has a low volume of blood flow.
2. Dilute epinephrine produces a prolonged and profound degree of vasoconstriction.
3. Lidocaine is lipophilic and is readily sequestered in fat.

Males, whose percentage of body fat is usually 10% to 20% less than females, have a smaller volume of distribution for lidocaine. Therefore the maximum allowable dose should be reduced by about 10% for males.

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

Obese Versus Thin Patients

Based on clinical experience, obese patients seem to tolerate higher mg/kg doses of lidocaine better than relatively thin patients. A higher incidence of lidocaine toxicity occurs among coronary care unit patients weighing less than 70 kg (150 pounds).¹ Thus thin patients may have a smaller volume of distribution for lidocaine. In other words, given identical mg/kg dosages of lidocaine, the thinner patient may have a greater peak plasma lidocaine concentration than the obese patient.

Although uncommon, thinner patients seem more likely to complain of nausea, dysarthria, mild confusion, and unsteadiness of gait at doses that exceed 50 to 55 mg/kg. Three of my patients, all relatively thin, have experienced such symptoms; in each case the plasma lidocaine levels were below 3.2 mg/L. Because these symptoms can be attributed to either lidocaine or benzodiazepines, tumescent liposuction patients should not take a benzodiazepine within 18 hours after surgery.

In some situations even an obese patient might not tolerate 50 mg/kg of lidocaine. An obese female undergoing liposuction was also taking the antidepressant and selective serotonin reuptake inhibitor sertraline (Zoloft) and the benzodiazepine flurazepam (Dalmane). Both these drugs inhibit the hepatic enzyme cytochrome P450 3A4, which is responsible for lidocaine metabolism. This patient had a plasma lidocaine concentration of 6.1 mg/L 12 hours after 59 mg/kg of tumescent lidocaine (see Chapter 18).

Toxicologic Methodology

Studying the maximum safe dose for lidocaine is essentially a toxicologic study. A scientific study of a drug’s toxicity involves some type of statistical estimation of the “average toxic dose.” If toxicity is defined in terms of lethality, a statistical approach to quantifying the lethality would be to estimate the LD₅₀ dose for lidocaine, that is, the median lethal dose that causes death in at least 50% of the animals tested.

Because lidocaine-induced seizures occur long before lidocaine-induced cardiac arrest, human studies have preferred to estimate the ED₅₀ dose of lidocaine, that is, the median epileptogenic dose. If the occurrence of an epileptiform seizure is used to define a drug’s toxicity, the drug’s ED₅₀ can be used to predict toxicity. The ED₅₀ is the dose that will cause a seizure in at least 50% of the test subjects.

In the 1960’s this research design was used for studying the toxicity of lidocaine as an antiarrhythmic drug in human volunteers. At present the use of human volunteers to explore the safety of IV lidocaine raises serious ethical questions. The process of establishing a safe maximum recommended dose of lidocaine for tumescent liposuction cannot use the same statistical methodology as in estimating ED₅₀.

The toxicity of a local anesthetic is a function of its peak plasma concentration, which in turn depends on such factors as rate of systemic absorption and total mg/kg dosages.² Different routes of lidocaine delivery produce different rates of lidocaine absorption and have different dosage limits.

The rapid subcutaneous infiltration of lidocaine for a facelift proved fatal at a dose of 2.5 g at a commercially available concentration.³ Instantaneous absorption occurs with an IV injection of lidocaine, and a dosage of 20 mg/kg can produce cardiovascular collapse and generalized convulsions.⁴ On the other hand, when lidocaine is given as tumescent anesthesia, the slow systemic absorption permits safe dosages of 50 mg/kg or more.

Traditional pharmacokinetic studies of local anesthesia have largely been limited to regional anesthesia injected deeply into highly vascular tissues to block nerves in the axillary, intercostal, or epidural spaces. Anesthesiology literature has largely ignored the study of the pharmacokinetics of lidocaine with epinephrine infiltrated into relatively avascular subcutaneous fat. Larger subcutaneous doses were known to be safe, but specific limits were never defined.

For local anesthesia the traditional dosage limit for lidocaine is 7 mg/kg when used with epinephrine. This limitation arbitrarily groups all sites and types of local anesthesia into one generic category. It makes no distinction between the highly vascular epidural space, where lidocaine absorption is rapid, and the subcutaneous fat, where absorption is significantly slower.

On first learning about the tumescent technique, many physicians are startled at the magnitude of the lidocaine dosages that are given safely. The initial published estimate of a safe tumescent dosage for subcutaneous lidocaine was 35 mg/kg.⁵ This remains a conservative estimate for the maximum safe dosage of lidocaine.

After years of careful clinical experience, some dermatologic surgeons are cautiously using 50 to 55 mg/kg as a maximum safe lidocaine dosage for tumescent liposuction. Because there is significant interpatient variability in lidocaine pharmacokinetics, cautious clinical judgment is always needed when using these relatively high dosages.

True Tumescent Anesthesia

The effect of tumescent anesthesia on sensory nerves is a function of the product of the local anesthetic concentration and the length of the nerve exposed to the anesthetic solution.

Tumescent anesthesia is different from all other forms of local anesthesia. Tumescent anesthesia is not a field block. Most field blocks would be inadequate at concentrations of local anesthetics employed with the tumescent technique.

Tumescent anesthesia is not systemic anesthesia. If the proper technique is used, the effects of tumescent anesthesia are local, not systemic. Some surgeons claim, however, that tumescent anesthesia is indeed systemic anesthesia. These surgeons may not be able to perform “tumescent liposuction” without systemic anesthesia. Using systemic anesthesia or systemic (IV) fluid infusions with tumescent infiltration carries a risk of systemic complications. Surgeons who assert that tumescent local anesthesia is systemic anesthesia usually have not achieved adequate tumescence.

The following chapters focus on the safety of using lidocaine and other local anesthetics, as well as ancillary drugs that can be used in conjunction with tumescent liposuction. The information should help physicians develop a better understanding of how to evaluate safety and avoid toxicity.

Definitions

An important convention used in this book distinguishes between the words dosage and dose. All the pharmacologic discussions assume the following definitions.

Dosage. Dosage is expressed in mg/kg units, where mg = milligrams of the drug and kg = patient’s weight expressed in kilograms. In general, this book uses dosage to describe the amount of a drug given to a patient as expressed in units that are “normalized” with respect to the patient’s total body weight. The normalized aspect of dosage, in contrast to dose, facilitates the clinical comparison of specified therapeutic interventions among patients. Dosage can refer either to a single administration or to the sum of many administrations within a specified time interval.

By multiplying the dose (total milligrams) of a drug given to a patient by the inverse of the patient’s weight (1/kg), one obtains the dosage of the drug. Expressing amount of an administered drug in terms of mg/kg dosage also facilitates comparison of drug effects by eliminating the patient’s weight as a confounding variable.

Normalized. A mathematical entity (a series, function, or variable) is said to be normalized when it has been multiplied by a factor that facilitates making comparisons between different entities. In mathematics, for example, every nonzero vector can be normalized by multiplying the vector (υ) by the inverse of its magnitude (1|υ|). This results in a normalized vector having direction only, with a magnitude equal to 1, thereby facilitating comparison of vectors in terms of their direction, without regard to their magnitude.

Dose. Dose is expressed in mg units, where mg = total milligrams of drug given to a patient. Dose does not take into account the patient’s total body weight. Dose describes the total amount of the drug that is administered but ignores the basic pharmacokinetic parameters, such as volume of distribution.

Thus, when dose is used to specify the amount of drug that has been administered, it is difficult to predict either therapeutic effect or toxicity, both of which depend pharmacokinetically on the amount of drug per kilogram of a patient’s body weight. Dose can refer either to a single administration or to the sum of many administrations within a specified time interval.

References

1. Pfeifer HJ et al: Clinical use and toxicity of intravenous lidocaine: a report from the Boston Collaborative Drug Surveillance Program, Am Heart J 92:168-173, 1976.
2. Rowland M, Tozer TN: Clinical pharmacokinetics: concepts and applications, ed 2, Philadelphia, 1989, Lea & Febiger.
3. Sunshine I, Fike WW: Value of thin-layer chromatography in two fatal cases of intoxication due to lidocaine and mepivacaine, N Engl J Med 271:487, 1964.
4. Yukioka H, Hayashi M, Fujimori M: Lidocaine intoxication during general anesthesia, Anesth Analg 7:207, 1990.
5. Klein JA: Tumescent technique for regional anesthesia permits lidocaine doses of 35 mg/kg for liposuction, J Dermatol Surg Oncol 16:248-263, 1990.