| PRS 0409-756 Brown
Brown SA, Lipschitz AH, Kenkel JM, Sorokin E, Shepherd G, Grebe S, Oliver LK,
Luby M, Rohrich RJ.
Pharmacokinetics and safety of epinephrine use in liposuction.
Plast Reconstr Surg. 2004 Sep 1;114(3):756-63; discussion 764-5. PMID: 15318058
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.
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.
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