Pharmacokinetics of fentanyl at various temperature levels during operations with cardiopulmonary bypass

114 ~II~~~&~coI~-~~ICS

OPERATIONS D.

Olthoff,

WITH

OF FENTANYL AT VRItIOUS TEllPEiiATU~ CARDIOPUL.&IONI1;~YDYPASS

B. Vetter

and

LEVELS

DURING

C. Deutrich

Clinic of Anesthesiology and Intensive Iledicine, Fled.ical School, Karl-Marx-University, Leipzig, DDR-7010 Because of light anaesthesia the possibility of patient awareness is a problem in cardiac surgery, especially during the rewarming period. on cardiopulmonary bypass.In some cases the recall of pain has been reported. Our anaesthesia technique, which is orientated. on a short postoperative ventilation period and. early extubation within 2 hours after operation, avoids high doses of 0pioid.s because of respiratory depression.Ve use fentanyl only as an anlgesic supplement with a maximum of 20 pg/kg (whole dose). Therefore we investigated the fentanyl pharmacoof kinetics after 3 bolus injections 7 F_‘g/kg at various conditions in the same patient in order to obtain informations for the maintenance of analgesic fentanyl levels following standardized cardiac operations. Methods:Following informed written consent 16 patients for coronary artery surgery have been investigated (mean2age 58,6 years, mean surface area 1,82 m ; induction of anaesthesia with 0,2 mg/kg diazepam and. 0,2 mg/kg etomidate under with panN20/0 , 2:1, and relaxation curon 2 um 0,l mg/kg). The first fentanyl injection was applied shortly before sternotomy (36,8 C nasopharyngeal temperature), t$e second after aortic cross clamping (27 C) and. the third after rewarming in the reperfusion time (38,5'~) Before and after fentanyl injection 7 blood samples were taken and analyzed. for the fentanyl contents by rad.ioimmunassay (R 4263 RIA kit, Jenssen Life Sci.Prod..). The calculations were based on a two compartment mod.el. Hesults:In comparison to other studies the pharmacokinetic parameters reflect once more the great variability in fentanyl kinetics (I).~-Iowever the results describe well the specific changes in relation to different temperature levels (prolongation of distribution and elimination times at low temperatures and during extracorporeal circulation).o 27,0 t l/2 a min ?";," 2915 ?"A', c t 112 D 11 min 2;,0 38,l 3187 61,3 50,9 69,9 VDS (l/kg) CL Qml/kg/min) 0,88 0,81 0,51

But,

the simple plasma concentration curves demonstrate more dotails of' clinical interost. The accumulation of fentenyl after only three repeated small 7 pg/kg boluses is remarkable. lith the exception of the late part after the first injection stabile enalgesic concentrations of% 3 &ml fentanyl have been reached during the three observation periods ad.apted to typical intraoperative phases. fentany I plasma concentration I&ml 1

i

2ot

3

1

3

6

.- -. 36.K

;

...a 27pc;

12

24 -

36

c min

3t3.5.c

This impliees a modification of the administration to a higher initial dose and a reduction in the late part of operation.Determinations of fentanyl following the mzdified technique with the same dose ( /3 of the whole dose before cardiopulmonary bypass) showed analgesic consentrations during and nondepressive concentrations (Cl ng/ml) two hours after operation.In contrast, the use of initial bolus injection followed by infusion leds to a higher fentenyl dose and plasma concentrations of>2 ng/ml two hours after operation. The study underlines the necessity of drug measurements to achieve desired drug concentrations and clinical effects. (1) P.S.Sebel a. J.G.Bovill Opioid analgesics in oardiac anesthesia in: Cardiac Anesthesia, Vol. 1 (Ed. J.A.Kaplan), Grune a. Stratton, 1987, 67-123