Pharmacokinetics and safety of epinephrine use in liposuction.
Patients are routinely exposed to high-dose epinephrine infiltration during large-volume liposuction. Because of the serious cardiovascular side-effect profile of catecholamine overdose, the authors examined the safety of larger-volume liposuction by assessing epinephrine pharmacokinetics. Five female volunteers with American Society of Anesthesiologists physical status of I or II, aged 29 to 40 years and weighing 75.9 to 95 kg, underwent liposuction. The wetting solution contained 7.3 mg (SEM, 0.7 mg) of epinephrine, corresponding to 0.09 mg/kg (0.04 mg/kg). Total plasma epinephrine and norepinephrine concentrations were assessed by high-performance liquid chromatography. Approximate exogenous epinephrine absorption was calculated after correction for estimated endogenous epinephrine production. Pharmacokinetic assessments were performed using standard equations. The total plasma epinephrine peak occurred at the final intraoperative reading (5 hours after induction) and was 323 pg/ml (24.8 pg/ml), three to four times maximum baseline resting levels. The norepinephrine level was slightly elevated throughout the study period, with a reversal of the normal epinephrine/norepinephrine ratio (<0.5:1) demonstrated intraoperatively (>5:1). Estimated time to peak exogenous epinephrine level ranged from 1 to 4 hours from the start of infiltration. Area under the plasma concentration versus time curve was approximately 2089 to 2610 pg x hour/ml. Peak exogenous epinephrine concentration was estimated to be 286 to 335 pg/ml. Clearance was 764,508 ml/hour and volume of distribution was 0.4 liter/kg (0.006 liter/kg). Total absorbed epinephrine was estimated, 1.8 mg to 2.2 mg, equivalent to 25 to 32 percent of the infiltrated dose. The reversal of the normal epinephrine/norepinephrine ratio and the fact that norepinephrine levels were within normal range implied that the majority of plasma epinephrine measured was exogenously infiltrated and not endogenously synthesized. On the basis of these observations, pharmacokinetic analyses were performed. Although unequivocal toxic epinephrine levels were not demonstrated, epinephrine peaks were three to four times the maximum observed in normal resting patients. Peak levels were comparable to those observed during major physiologic stresses, such as exercising to exhaustion, open abdominal surgery, or cross-clamping the aorta during surgical repair. Furthermore, epinephrine has been associated with myocardial infarction, arrhythmias, and fatal asystole in susceptible patients at these levels. Patients should be carefully screened for clinical evidence of hemodynamic and cardiac pathology before larger-volume liposuction is undertaken, as it may result in unnecessary high risk for patients who have preexisting cardiovascular disorders. Healthy American Society of Anesthesiologists physical status I or II patients should have sufficient cardiac reserve to tolerate these catecholamine levels.
Department of Plastic Surgery, Nancy Lee and Perry R. Bass Advanced Plastic Surgery and Wound Healing Laboratory, the North Texas Poison Center, Dallas, Texas, USA.
Spencer A
SA
Brown
Avron H
AH
Lipschitz
Jeffrey M
JM
Kenkel
Evan
E
Sorokin
Greene
G
Shepherd
Stefan
S
Grebe
Lawrence K
LK
Oliver
Maureen
M
Luby
Rod J
RJ
Rohrich
D000328:Adult; D019540:Area Under Curve; D001834:Body Water; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D004837:Epinephrine / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D015187:Lipectomy / Q000379:methods*; D009638:Norepinephrine / Q000097:blood / Q000493:pharmacokinetics; D012307:Risk Factors; D014662:Vasoconstrictor Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*
D014662:Vasoconstrictor Agents; D009638:Norepinephrine; D004837:Epinephrine