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Pharmacokinetics of alfentanil and clinical responses during cardiac surgery

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Abstract

This study assessed the pharmacokinetic and pharmacodynamic behaviour of alfentanil during and after coronary artery bypass grafting (CABG). Twenty-eight patients with good ventricular function having CABG were divided into three groups and premedicated with morphine 0.1 mg · kg−1 IM, scopolamine 0.005 mg · kg−1 IM and diazepam 0.1 mg · kg−1 PO. Group I patients received an infusion of 250 μg · kg−1 of alfentanil over one hour coincidental with a second infusion at 2.5 μg · kg−1 · min−1 which was continued to the end of surgery. Patients in group II received 300 μg · kg−1 and 3.0 μg · kg−1 · min−1 and patients in group III 350 μg · kg−1 and 3.5 μg · kg−1 · min−1. The tracheas of all patients were intubated after receiving alfentanil 96 μg-kg−1 and pancuronium 0.15 μg · kg−1. Haemodynamic responses to intubation and surgical stimuli (≥ 20 per cent increase in heart rate and/or systolic blood pressure from control) were treated with isoflurane, one to two per cent inspired, until abolished. Blood samples were taken during and after surgery for plasma alfentanil concentrations which were determined by radioimmunoassay. After surgery the times to awakening and extubation, and alfentanil elimination half-life (t1/2B = 0.6931−k) were determined for each patient. Haemodynamic responses occurred in 20 patients. There were no significant differences in any variable among the groups. The times to awakening and extubation for all patients were 3.2 ± 0.6 and 8.8 ± 1.2 hr (mean ± SEM) respectively. The elimination half-life for all patients was 5.1 ± 1.0 hr(mean ± SEM). We conclude that alfentanil given at these rates of infusion provides inadequate adrenergic suppression for CABG yet does not allow early postoperative tracheal extubation. The elimination half-time appears prolonged after cardiopulmonary bypass compared with values obtained from volunteers or from patients undergoing non-cardiac surgery.

Résumé

Cette étude évalue la pharmacocinétique et la pharmacodynamie de l’alfentanil lors d’un pontage aorto coronarien. Vingthuit patients ayant une bonne fonction ventriculaire et devant subir un pontage aorto coronarien furent divisés en trois groupes et prémédiques avec de la morphine 0,1 mg · kg−1 IM, scopolamine 0,005 mg · kg−1 IM et diazepam 0,1 mg · kg−1 PO. Pour le groupe I les patients ont reçu une perfusion de 250 μg · kg−1 d’alfentanil pour une période d’une heure suivie d’une seconde perfusion de 2,5 μg · kg−1 · min−1 qui fut continuée jusqu’ à la fin de la chirurgie. Les patients du groupe II ont reçu 300 μg · kg−1 et 3,0 μg · kg−1 · min−1 et les patients du groupe III 350 μg · kg−1 et 3,5 μg · kg−1. L’intubation trachéale fut accomplie après une dose d’alfentanil de 96 μg · kg−1 et du pancuronium 0,15 μg · kg−1. Les réponses hémodynamiques suite l’intubation et la stimulation chirurgicale (≥ 20 pour cent dans la fréquence cardiaque et/ou la pression artérielle partir du contrôle) furent traitées avec l’isoflurane, 1–2 pour cent jusqu’ à normalisation. Les échantillons sanguins furent pris durant et après la chirurgie pour des concentrations plasmatiques d’ alfentanil déterminées par radioimmunoessai. Après la chirurgie les temps de réveil et d’extubation ainsi que la demivie d’élimination (t1/2B = 0,6931−k) ont été déterminés pour chaque patient. Les réponses hémodynamiques sont survenues chez 20 patients. Il n’y avait aucune différence significative dans les variables étudies entre les groupes. Les temps de réveil et d’extubation pour tous les patients étaient de 3,2 ± 0,6 et 8,8 ±1,2 heures (moyenne ± SEM) respectivement. La demivie d’élimination pour tous les patients était de 5,1 ± 1,0 heure (moyenne ± SEM). On conclut que l’alfentanil administré à ces doses de perfusion amène une abolition de la réponse adrénergique inadéquate pour des pontages aorto coronariens et ne permet pas une extubation précoce en période postopératoire. Le demitemps d’élimination apparaît prolongé après pontage aorto coronarien comparé aux valeurs obtenues chez des volontaires ou chez des patients n’avant pas subi des opérations cardiaques.

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Correspondence to David G. Whalley.

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Robbins, G.R., Wynands, J.E., Whalley, D.G. et al. Pharmacokinetics of alfentanil and clinical responses during cardiac surgery. Can J Anesth 37, 52 (1990). https://doi.org/10.1007/BF03007484

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Key words

  • anaesthesia: cardiovascular
  • anaesthetics, intravenous: alfentanil
  • complications: hypertension, tachycardia
  • pharmacokinetics: kinetics, plasma concentration
  • surgery cardiovascular, cardiopulmonary bypass