3 Tumescent Anesthesia for Abdominal Liposuction
Timothy D. Parish
3.1
Introduction
Tumescent anesthesia may be defined as a subcutane- ous, periadipose, hyperhydrostatic pressurized, mega- dosed, ultra-dilute, epinephrinized, local anesthetic field block [1]. The procedure was first popularized by the dermatologic surgeon Jeffrey Klein in the late 1980s [2, 3]. The majority of the literature revolves around the use of lidocaine as the local anesthetic, although bupi- vacaine, ropivacaine, and prilocaine have also been uti- lized [4 – 9]. Tumescent anesthesia utilizing lidocaine will be the basis of this review.
3.2
Pharmacokinetics
Currently, two standards of care for the safe dosage of lidocaine should now be utilized [10, 11]. First, for commercially available formulations (0.5 – 2 % lido- caine with epinephrine) a 7 mg/kg maximum safe dos- age limit. Second, for tumescent anesthesia using ultra- dilute lidocaine 500 – 1,500 mg/l (0.05 – 0.15 %) with epinephrine (0.5 – 1.5 mg/l) [12 – 14]. The diluent is normal saline with the addition of 10 – 15 mEq sodium bicarbonate per liter. Lactated Ringer’s solution may be used and has been documented to prolong the stability of epinephrine secondary to a more acidic pH of 6.3 [13]. A dose of 35 mg/kg of lidocaine can be considered the optimal therapeutic threshold with dosages up to 55 mg/kg approaching the margins of the safe thera- peutic window [14 – 16]. These latter dosage recom- mendations are based on the clinical experience of large numbers of physicians performing this procedure on a large patient population, together with studies uti- lizing supplementary anesthetic techniques, including oral (PO), intravenous (IV), and general anesthesia in a total of 163 patients [3, 7, 9, 13, 14, 16, 18 – 24].
Traditional lidocaine pharmacokinetics utilizing commercial preparations by IV, subcostal, epidural, etc., administration follows the two-compartment model. However, with subcutaneous injection, there is a slower rate of absorption and lower peak serum
CMAX compared with equal doses used at other sites of administration [15 – 24]. The two-compartment model is biphasic and follows the rapid attainment of CMAX in the highly vascular central compartment preceding an accelerated distribution phase until equilibrium with less vascular peripheral tissue is reached. From the point of equilibrium, there is a slow plasma decline secondary to metabolism and excretion [16]. Less than 5 % of lidocaine is excreted by the kidneys. In the healthy state, lidocaine clearance approximates plasma flow to the liver equal to 10 ml/kg/min. Lidocaine has a hepatic extraction ratio of 0.7 (i.e., 70 % of lidocaine en- tering the liver is metabolized and 30 % remains un- changed). If there is a 50 % reduction in the rate of lido- caine metabolism, there will be a corresponding dou- bling of the CMAX plasma lidocaine [17].
Tumescent anesthesia, with highly diluted lidocaine with epinephrine, exhibits the properties of a one-com- partment pharmacokinetic model similar to a slow-re- lease tablet. In a one-compartment model, the body is imagined as a single homogeneous compartment in which drug distribution after delivery is presumed to be instantaneous, so that no concentration gradients exist within the compartment, resulting in decreased concentration solely by elimination of the drug from the system. The rate of change of concentration is pro- portional to the concentration. This is an essential pre- mise of a first-order process. In a one-compartment model, the location of the drug pool for systemic re- lease is kinetically insulated from the central compart- ment [18].
The reason that tumescent anesthesia behaves as a
one-compartment model is related to the delayed ab-
sorption rate into the plasma from the subcutaneous
adipose tissue [37]. This is theorized to occur for a
number of reasons (Figs. 3.1 – 3.3): (1) decreased blood
flow related to vasoconstriction or vessel collapse pro-
portional to increasing interstitial hydrostatic pres-
sure; (2) formation of an ultra-dilute interstitial lake
with a low concentration gradient relative to plasma
and increased diffusion distance from the microcircu-
lation; and (3) the high lipophilic nature of lidocaine
leads to subcutaneous adipose tissue absorption, act-
ing for a 1,000 mg/l lidocaine formulation (0.1 %), as a
0 0.5 1 2 3
1.5 2.5
0
Time (hours)
Plasma Lidocaine (mcg/ml)
Increasing mg/kg Lidocaine dose.
4 8 12 16 20 24 28 32 36 40 44 48
0
0 3
0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
12 23
Time (hours)
Serum Lidocaine Level (mcg/ml)
16.3 25.9 28.3 22.4 23.4 30.3 18.1 25.4 16.1 9.8 1.8
0 0.5 1 1.5 2 2.5
12 23
Time (hours)
Serum Lidocaine Level (mcg/ml)
26.2 35.8 38.3 17.4 14.9 21.9 24.7 24.3 13.9
0 3 11.2
Fig. 3.1. Pharmacokinetics of tumescent liposuction. (Modified from Klein [49]. Reprinted with permission of Mosby Inc.)
Fig. 3.2. Serum lidocaine levels in patients undergoing tumes- cent liposuction alone. Total dosage of lidocaine (mg/kg) is listed to the right. The patient with the peak lidocaine level at 3 h received 50 mg lidocaine IV. (From Burk et al. [50]. Reprint- ed with permission of Lippincott, Williams & Wilkins)
Fig. 3.3. Serum lidocaine levels in patients undergoing tumes- cent liposuction combined with other aesthetic surgery. Total dosage of lidocaine (mg/kg) is listed to the right. (From Burk et al. [50]. Reprinted with permission of Lippincott, Williams &
Wilkins)
large 1 mg of lidocaine to 1,000 mg of adipose tissue buffer [10, 19]. This buffering effect is aided by the threefold greater partition coefficient of adipose tissue compared to muscle, enabling lidocaine to bind tightly to fat [20].
At equilibrium, the fat-blood concentration ratio of lidocaine is between 1 : 1 and 2 : 1. With increased dos- ing of lidocaine from 15 mg/kg, there is a well-defined peak CMAX that occurs 4 – 14 h after infiltration. With doses up to 60 mg/kg there is progressive flattening of the peak and a plateau effect that may persist for up to 16 h [21]. The flattening of the curve denotes saturation of the system and then elimination of a constant amount, as opposed to a fraction of the drug per unit
time, which signifies zero-order elimination. Although lidocaine levels appear to be below serum concentra- tions associated with toxicity, it is known that concen- trations of 4 – 6 µg/ml have been found in deaths caused by lidocaine toxicity [22, 23]. However, there is no doc- umented data concerning lidocaine stability in post- mortem blood and tissues and none related to the fate or physiologic impact of the active metabolites of lido- caine, lidocaine monoethylglycinexylidide, or glycine- xylidide [24]. At the same time, because of the slow-re- lease phenomena, toxicity will be present for longer with increased dosing on a milligram per kilogram ba- sis of lidocaine. It is this slow-release process that makes the use of longer-acting local anesthetics irrele- vant [13, 14, 25, 26]. According to Klein, liposuction re- duces the bioavailability of lidocaine by 20 % [14, 40].
This is further facilitated by open drainage from wounds.
It is the non-protein-bound portion of lidocaine that exhibits toxicity. With increasing total plasma lidocaine levels, there is an increasing proportion of unbound to bound plasma lidocaine as the [ 1-acid glycoprotein buffer becomes saturated. In the therapeutic range of 1 – 4 µg/ml of lidocaine, up to 40 % of lidocaine is un- bound. Surgery and smoking increase serum [ 1-acid glycoprotein, and oral hormones decrease it. There- fore, increased serum levels of [ 1-acid glycoprotein re- sult in increased lidocaine binding, decreased free lido- caine, and a buffering of potentially toxic manifesta- tions (Fig. 3.4) [27 – 29, 36, 40].
In a study of 18 patients by Butterwick et al. [20]
(Fig. 3.5) using 0.05 – 0.1 % lidocaine with 0.65 – 0.75 mg/l of epinephrine at infusion rates of 27 – 200 mg/min over 5 min to 2 h using dosages between 7.4 and 57.7 mg/kg, there was no correlation between the maximum dose of
Fig. 3.4. Continuum of toxic effects produced by increasing li- docaine plasma concentrations. (Modified from Barash PG et al. [51]. Reprinted with permission of Lippincott, Williams, &
Wilkins)
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2
120 Time (minutes)
Lidocaine Concentration (mcg/ml)
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
0 15 30 45 60
0
0 3
100 200 300 400 500 600
12 23
Time (hours)
Serum Epinephrine Level (pg/ml)
4.1 7.25 8 4.7 6 7 10 6 5.35 4.1
0
0 3
100 200 300 400 500 600 700
12 23
Time (hours)
Serum Epinephrine Level (pg/ml)
5.5 5.8 3.75 7 4.5 6.5 2.15 2.2 2.2 4
Fig. 3.5. Lidocaine levels over 2 h. (From Butterwick et al. [52].
Reprinted with permission of Blackwell Science, Inc.)
lidocaine (mg/kg) or the rate of lidocaine delivered (mg/ml) with plasma levels of lidocaine. Increased rates of infiltration are associated with increased pain and need for increased sedation [28].
The pharmacokinetics of epinephrine (0.5 – 1 mg/l) are felt to mimic the one-compartment model of the li- docaine. In one study on 20 patients by Burk et al. [19]
(Figs. 3.6, 3.7) using epinephrine doses up to 5 mg, the CMAX of 5 times the upper normal limit of epineph- rine was reached at 3 h, returning to normal at 12 h.
Fig. 3.6. Serum epinephrine levels in patients undergoing tu- mescent liposuction alone. The total dose of epinephrine (mg) is listed in the figure legend at right. (From Burk et al. [50]. Re- printed with permission of Lippincott, Williams & Wilkins)
Fig. 3.7. Serum epinephrine levels in patients undergoing tu- mescent liposuction combined with other aesthetic surgery.
The total dose of epinephrine (mg) is listed in the figure legend at right. (From Burk et al. [50]. Reprinted with permission of Lippincott, Williams & Wilkins)
3.3
Important Caveats
3.3.1
Drug Interactions
All enzyme systems have the possibility of saturation [29, 30], and once the subcutaneous adipose tissue res- ervoir is saturated, any free drug has the potential to be absorbed rapidly following the two-compartment pharmacokinetic model with an accelerated rise and decline in the blood lidocaine level; therefore, the pru- dent favor the currently held safest therapeutic margins and do not stray to the boundaries [10, 31]. All patients taking drugs interfering with the CYP3A4 system should optimally have these medications withheld before surgery. The time of preoperative withdrawal depends upon each drug’s kinetic elimination profile [32 – 34] (Table 3.1). The withholding of some of these medications for more than 2 weeks may be the optimal plan. Patients should, therefore, have relevant medical clearance for such an action, according to the basic standards of preanesthetic care (Table 3.2) [35]. Klein suggests that if it is not feasible to discontinue a medi- cation that is metabolized by the cytochrome P450 sys- tem, then the total dosage of lidocaine should be de- creased. It is not clear how much the dose should be re- duced. In the case of thyroid dysfunction, the patient should be euthyroid at the time of surgery. This is an anesthetic truism.
In the author’s opinion, all patients should have complete preoperative liver function studies, as well as a screen for hepatitis A, B, and C. However, the free fractions of basic drugs, such as lidocaine, are not in- creased in patients with acute viral hepatitis; this im- plies that drug binding to [ 1-acid glycoprotein is mini- mally affected in patients with liver disease [35]. The physician should also inquire about over-the-counter herbal remedies and recommend withholding those for 2 weeks before surgery. The cocaine addict’s surgery should be canceled, and the nasal-adrenergic addict should be guided into withdrawal from this medica- tion.
All systemic anesthetics, particularly general anes-
thesia, have the potential to decrease hepatic blood
flow. However, general anesthesia has the greatest po-
tential, although the potpourri approach probably in-
creases this likelihood. General anesthesia decreases
hepatic blood flow, resulting in decreased lidocaine
metabolism. Inhalational anesthetics, hypoxia, and hy-
percarbia are potentially arrhythmagenic, and the in-
terface of this with mega doses of ultra-dilute epineph-
rine perhaps increases this potential. The counterbal-
ance of the increased dose of lidocaine is poorly under-
stood, and in animal studies lidocaine toxicity may pre-
sent as marked hypotension and bradycardia in lethal
doses that occurs without arrhythmias [36]. The ideal
Table 3.1. Drugs which inhibit cytochrome P450. (Modified from Shiffman [34], McEvory [53], and Gelman et al.
[54])
Drug Plasma half-life
Acebutolol Biphasic: [ phase 3 h, q phase 11 h
Amiodarone (Cordarone) Biphasic: [ phase 2.5–10 days, q phase 26–107 days (average 53 days)
Atenolol 7 h
Carbamazepine (Tegretol, Atretol) 25 – 65 h
Cimetidine (Tagamet) 2 h
Chloramphenicol (Chloromycetin) 68 – 99 % excretion in 72 h Clarithromycin (Biaxin) 3 – 7 h
Cyclosporin (Neoral, Sandimmune) 10 – 27 h (average 19 h)
Danazol (Danocrine) 4 – 5 h
Dexamethasone (Decadron) 1.8 – 2.2 h Diltiazam (Cardizem) 3 – 4.5 h
Erythromycin 1 – 3 h
Esmolol (Brevibloc) Biphasic: [ phase 2 min, q phase 5–23 min (average 9 min) Flucanazole (Diflucan) 20 – 50 h
Fluoxetine (Prozac) 1 – 3 days after acute administration, 4 – 6 days after chronic administration
Norfluoxetine (active metabolite) 4 – 16 days
Flurazepam (Dalmane) 47 – 100 h
Isoniazid (Nydrazid, Rifamate, Rifater) Excreted within 24 h
Itracanazole (Sporanox) 24 h after single dose, 64 h at steady state Ketoconazole (Nizoral) Biphasic: [ phase 2 h, q phase 8 h Labetalol (Normodyne, Trandate) 6 – 8 h
Methadone (Dolophine) 25.0 h
Methylprednisolone (Medrol) 2 – 3 h Metoprolol (Lopressor) 3 – 7 h
Metronidazole (Flagyl) 6 – 14 h (average 8 h)
Miconazole (Monistat) IV 24 h
Midazolam (Versed) Biphasic; [ phase 6–20 min, q phase 1–4 h Nadolol (Corgard, Corzide) 10 – 24 h
Nefazodone (Serzone) 1.9 – 5.3 h, active metabolite 4 – 9 h Nicardipine (Cardene) Average 8.6 h
Nifedipine (Procardia, Adalat) 2 h (extended release in 6 – 17 h, average 8 h)
Paroxetine (Paxil) 17 – 22 h
Pentoxifylline (Trental) 1 – 1.6 h
Pindolol (Visken) 3 – 4 h
Propranolol (Inderal) 4 h
Propofol (Diprivan) 1 – 3 days
Quinidine 6 – 12 h
Sertraline (Zoloft) Average 26 h, active metabolite 62 – 104 h
Tetracycline 6 – 12 h
Terfenadine (Seldane) Mean 6 h
Thyroxine (levothyoxine) 5 – 9 days Timolol (Timolide, Timoptic) 3 – 4 h
Triazolam (Halcion) 1.5 – 5.5 h
Valporic acid (Depakene) 6 – 16 h Verapamil (Calan, Isoptin, Verelan) 4 – 12 h
Zileuton (Zyflo) 2.1 – 2.5 h
Table 3.2. Basic standard for preanesthesia care. (Modified from ASA Standards, Guidelines, and Statement. American So- ciety of Anesthesiologists. Available at: http://www.ASAhg.org.
Accessed October 1999)
The development of an appropriate plan of anesthesia care is based on:
1. Reviewing the medical record.
2. Interviewing and examining the patient to:
a) Discuss the medical history, previous anesthetic expe- riences, and drug therapy
b) Assess those aspects of the physical condition that might affect decisions regarding perioperative risk and management
3. Obtaining or reviewing tests and consultations necessary to the conduct of anesthesia
4. Determining the appropriate prescription of preoperative medications as necessary to the conduct of anesthesia
preoperative anesthetic, says Klein, is clonidine 0.1 mg (PO) and lorazepam 1 mg (PO). These can be taken 1 h before surgery, although lorazepam can be taken the night before surgery. This preoperative regimen is ad- ministered to patients who have a blood pressure great- er than 105/60 mm Hg and a pulse greater than 70 beats/min. Lorazepam does not interfere with the CYP3A4 hepatic enzyme system [37].
3.3.1.1
Volume of Distribution
Thin patients have a smaller volume of distribution,
and therefore, potentially, a greater CMAX than an
obese patient, given an identical dosage of lidocaine
[38, 39]. Similarly, men have a smaller volume of distri- bution for lidocaine, secondary to increased lean body mass. In these two situations, the maximum allowable dose should be decreased by up to 20 % with a maxi- mum dosage of 45 mg/kg being a reasonable upper lim- it. Older patients have a relative decrease in cardiac out- put leading to decrease in hepatic perfusion, and there- fore maximum safe dosages should be decreased ap- proximately 20 %. This 20 % decrease has a greater mar- gin of safety if applied to a 35 mg/kg maximum safe dosage of lidocaine than it does if applied to a 50 mg/kg maximum safe dosage of lidocaine.
3.3.1.2
Classifications of Patients
As an elective outpatient procedure, ideally only ASA I and II patients, should be selected. Morbid obesity may be classified as an ASA III-type patient and significant- ly increases the risk of any form of anesthetic.
3.3.1.3
Two Sequential Procedures are Better than One
The risk of perioperative morbidity and mortality in- creases with increasing time of the procedure and size of the procedure. This includes separate procedures performed under the same anesthetic. This is an anes- thetic truism. The AACS 2000 Guidelines for Liposuc- tion Surgery state that the maximal volume extracted may rise to 5,000 ml of supernatant fat in the ideal pa- tient with no comorbidities. The guidelines also state that the recommended volumes aspirated should be modified by the number of body areas operated on, the percentage of body surface area operated on, and the percentage of body weight removed. Currently held conservative guidelines limit the total volume of super- natant fat aspirate to less than or equal to 4 l in liposuc- tion cases [40, 41]. The more fat removed, the greater the risk for injury and potential complications.
3.3.1.4
Intravenous Fluids
Tumescent anesthesia significantly decreases blood loss associated with liposuction [13, 42, 43]. Studies have shown that between 10 and 70 ml of blood per liter
Table 3.3. Recommended concentrations for effective tumescent anesthesia utiliz- ing normal saline as the dil- uent. (Modified from Klein [55, 56])
Concentration Approximate volume
aAreas Lidocaine
(mg/l)
Epine- phrine (mg/l)
Sodium bicarbonate (mEq/l)
Small patient (ml)
Large patient (ml) Female abdomen 1,000 – 1,250 1.0 10 800 – 1,400 2,000 – 2,800 Male abdomen 1,000 – 1,250 1.0 10
Basic/checking 500 0.5 10
a
