Urine catecholamine excretion after large doses of fentanyl, fentanyl and diazepam and fentanyl, diazepam and pancuronium

  • Wen-Shin Liu
  • Arun V. Bedwai
  • Judd K. Lunn
  • Theodore H. Stanley


The effects of fentanyl (0.5 mg/kg iv), fentanyl with diazepam (1 mg/kg iv) and fentanyl, diazepam and pancuronium (0.1 mg/kg iv) on heart rate (HR), mean arterial blood pressure (BP), cardiac output (Qt), urine flow rate and urine epinephrine and norepinephrine excretion were determined in nine dogs. Fentanyl did not significantly change Qt or BP but did reduce HR and urine flow rate ( P < 0.05). Urine epinephrine and norepinephrine excretion rates were significantly increased by fentanyl ( P < 0.05 ). Diazepam caused no significant further changes in Qt, BF or HR 30 minutes after administration, but urine epinephrine and norepinephrine excretion rates were reduced to control (pre-fentanyl ) levels. Addition of pancuronium after fentanyl and diazepam increased urine flow rate to prefentanyl levels and elevated Qt, BP and HR above controls but produced no significant change in urine epinephrine or norepinephrine excretion. These data suggest that fentanyl increases catecholamine blood levels and imply that the latter may be one mechanism by which cardiovascular dynamics are maintained stable during fentanyl anaesthesia. Our findings also demonstrate that cardiovascular stimulation after pancuronium is not associated with increased urinary catecholamine excretion.


Le Fentanyl à forte dose, associé au Diazepam et au Pancuronium, affecte peu la dynamique cardio-vasculaire et, pour cette raison, cette association a été suggérée chez les grands malades. On ne connaît pas ľinfluence de cette technique sur les taux sanguin et urinaire de catécholamines.

Nous avons donc étudié les effets du Fentanyl (0.5 mg/kilo i.v. ), du Fentanyl associé au Diazepam ( 1 mg/kilo i.v. ), et de ľaddition de Pancuronium ( 0.1 mg/kilo i.v. ) aux deux autres, ceci chez neuf chiens. Ľon a également déterminé les variations de la fréquence cardiaque, de la pression artérielle moyenne, et le débit cardiaque.

Le Fentanyl n’a pas modifié significativement la pression moyenne, ni le débit cardiaque, mais il a diminué ( p < 0.5 ) la fréquence cardiaque et le débit urinaire. Les taux ďEpinéphrine et de Norépinéphrine urinaires ont été significativement élevés (p < 0.05) par le Fentanyl.

Trente minutes après son administration, ľaddition de Diazepam n’avait pas modifié la fréquence, la pression moyenne et le débit cardiaque, mais les taux ďexcrétion urinaire ďEpinéphrine et de Norépinéphrine étaient redescendus aux niveaux observés avant ľadministration de Fentanyl. Enfin, ľaddition de Pancuronium à la suite du Fentanyl et du Diazepam augmentait le débit urinaire aux chiffres observés avant ľadministration de Fentanyl, élevait la pression moyenne, la fréquence et le débit cardiaques, mais n’amenait pas de modification dans ľexcrétion urinaire ďEpinéphrine et de Norépinéphrine.


  1. 1.
    Liu, W.S., Bidwai, A.V., Stanley, T.H., Loeser, E.A., &Bidwai, V. The cardiovascular effects of diazepam and of diazepam and pancuronium during fentanyl and oxygen anesthesia. Canad. Anaesth. Soc. J.23: 395 ( 1976).PubMedGoogle Scholar
  2. 2.
    Stanley, T.H., Isern-Amaral, J., &Lathrop, G.D. The effects of morphine and halothane anesthesia on urine norepinephrine during and after coronary artery surgery. Canad. Anaesth. Soc. J.22: 478 ( 1975).PubMedGoogle Scholar
  3. 3.
    Stanley, T.H., Iserx-Amaral, J., &Lathrop, G.D. Urine norepinephrine excretion in patients undergoing mitral or aortic valve replacement with morphine anesthesia. Anesth. &Analg.54: 509 (1975).Google Scholar
  4. 4.
    Stanley, T.H., Isern-Amaral, J., &Lathrop, G.D. The effects of morphine and halothane anaesthesia on urine norepinephrine during surgery for congenital heart disease. Canad. Anaesth. Soc. J.23: 58 ( 1976).PubMedCrossRefGoogle Scholar
  5. 5.
    Warner, H.R., Gardner, F.M., &Toronto, A.R. Computer-based monitoring of cardiovascular functions in post-operative patients. Circulation38: 68 (1968).Google Scholar
  6. 6.
    Viktora, J.K., Baukal, A., &Wolff, F.W. New automated flurometric methods for estimation of small amounts of adrenaline and noradrenaline. Anal. Biochem.28: 513 (1968).CrossRefGoogle Scholar
  7. 7.
    Anton, A.H., Gravenstein, J.S., &Wheat, M.W. Extracorporeal circulation and endogenous epinephrine and norepinephrine in plasma, atrium and urine in man. Anesthesiology25: 262 (1964).PubMedCrossRefGoogle Scholar
  8. 8.
    Vasko, J.S., Henney, R.P., Brawley, R.K., Oldham, H.N., &Morrow, A.G. Effects of morphine on ventricular function and myocardial contractile force. Amer. J. Physiol.210: 329–334 (1966).PubMedGoogle Scholar
  9. 9.
    Liu, W.S., Bidwai, A.V., Stanley, T.H., &Isern-Amaral, J. Cardiovascular dynamics after large doses of fentanyl and fentanyl plus N20 in the dog. Anesth. & Analg.55: 168 (1976).Google Scholar
  10. 10.
    Freye, E. Cardiovascular effects of high doses of fentanyl, meperidine and naloxone in dogs. Anesth. & Analg.53: 40 ( 1974).CrossRefGoogle Scholar
  11. 11.
    Dalen, J.E., Evans, G.L., Banas, J.S., Brooks, H.L., Paraskos, J.A., &Dexter, L. The hemodynamic and respiratory effects of diazepam (valium). Anesthesiology30: 259 (1969).PubMedCrossRefGoogle Scholar
  12. 12.
    Prindle, K.H., Gold, H.K., Cardon, P.V., &Epstein, S.E. Effects of psychopharmacologic agents on myocardial contractility. J. Pharmacol. Exp. Ther.173: 133 (1970).PubMedGoogle Scholar
  13. 13.
    Stoelting, R.K. The hemodynamic effects of pancuronium and d-tubocurarine in anesthetized patients. Anesthesiology36: 612 (1972).PubMedCrossRefGoogle Scholar
  14. 14.
    Kelman, G.R. &Kennedy, B.R. Cardiovascular effects of pancuronium in man. Brit. J. Anaesth.43: 335 (1971).PubMedCrossRefGoogle Scholar
  15. 15.
    Clough, C. &Dykes, J.R.W. Assay of urinary catecholamines in patients treated with muscle relaxant drugs. Brit. J. Anaesth.45: 617 ( 1973).PubMedCrossRefGoogle Scholar
  16. 16.
    BontA, I.L. Pharmacological interaction between pancuronium bromide and anaesthetics. Eur. J. Pharmacol.4: 83 (1968).PubMedCrossRefGoogle Scholar
  17. 17.
    Saxena, P.R. &BontA, I.L. Specific blockade of cardiac muscarinic receptors by pancuronium bromide. Arch. Int. Pharmacodyn.189: 410 ( 1971 ).PubMedGoogle Scholar

Copyright information

© Canadian Anesthesiologists 1977

Authors and Affiliations

  • Wen-Shin Liu
    • 1
  • Arun V. Bedwai
    • 1
  • Judd K. Lunn
    • 1
  • Theodore H. Stanley
    • 1
  1. 1.Department of AnesthesiologyUniversity of Utah College of MedicineSalt Lake City

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