Canadian Journal of Anaesthesia

, Volume 44, Issue 10, pp 1071–1076 | Cite as

Interactions between nicardipine and enflurane, isoflurane, and sevoflurane

  • Tomoki Nishiyama
  • Takashi Matsukawa
  • Kazuo Hanaoka
  • Charles M. Conway
Reports of Investigation



Dunng nicardipine induced hypotension, different inhalational anaesthetics may have different effects on haemodynamic variables, sympathetic function and drug metabolism. Therefore, the haemodynamic effects and pharmacokinetics of nicardipine were studied in the presence of the three inhalation anaesthetics enflurane, isoflurane and sevoflurane.


Thirty patients scheduled for neurosurgery were randomly assigned to one of three anaesthetic techniques: enflurane, isoflurane or sevoflurane. Nicardipine (0.017 mg · kg−1) was administered during stable anaesthesia and the following measurements made for 30 min: blood pressure, heart rate, and plasma concentration of norepmephrine, epinephrine and nicardipine.


With sevoflurane, plasma concentrations of nicardipine, five minutes after administration, (39.8 ±3.5 ng · ml−1, mean ±SEM) were higher (P < 0.05) than in the other two groups (28.3 ±2.9 ng · ml−1,32.6 ±4.3 ng · ml−1, enflurane and isoflurane, respectively). With isoflurane, the approximated half-life of nicardipine (14 ±4 min) was shorter and clearance (2.1 ±0.3 l · min−1) more rapid. Peak heart rates were similar in all groups but elevated rates continued longer with isoflurane (> 30 min). Nicardipine-induced reduction in blood pressure was greater with sevoflurane but low pressures persisted for longer with isoflurane. Plasma catecholamine concentrations increased with isoflurane and enflurane, but not with sevoflurane: considerably higher epinephnne concentrations were seen with isoflurane.


This study showed that the action of nicardipine is modified by different inhalational anaesthetic agents. Nicardipine has a prolonged duration of action in the presence of isoflurane and produces greater initial hypotension with sevoflurane.


Isoflurane Sevoflurane Nicardipine Enflurane Hepatic Blood Flow 



Pendant l’hypotension induite à la nicardipine, les anesthésiques peuvent avoir des effets différents sur les variables hémodynamiques, l’activité sympathique et le métabolisme pharmacologique. Les effets hémodynamiques et phamnacocinétiques de la nicardipine ont été recherchés en présence de trois agents d’inhalation, l’enflurane, l’isoflurane et le sévoflurane.


Trente patients programmés pour une intervention neurologique ont été assignés aléatoirement à un des trois anesthésiques: enflurane, isoflurane ou sévoflurane. De la nicardipine (0,017 mg · kg−1) a été administrée une fois l’anesthésie stabilisée. Pendant 30 min, on a ensuite enregistré les variables suivantes: la pression artérielle, la fréquence cardiaque et la concentration plasmatique de la norépinéphrine, de l’épinéphrine et de la nicardipine.


Avec le sévoflurane, les concentrations plasmatiques de nicardipine augmentaient cinq minutes après l’admimstration (39,8 ±3,5 ng · ml−1, moyenne ±ÉT) à un niveau plus élevé (P < 0,05) qu’avec les deux autres agents (enflurane: 28,3 ±2,9 ng · ml−1 vs isoflurane 32,6 ±4,3 ng · ml−1). Avec l’isoflurane, la demi-vie approximative de la nicardipine (14 ±4 min) était plus courte et sa clairance plus rapide (2,1 ±0,3 L · min−1). Les fréquences cardiaques maximales étaient identiques dans tous les groupes mais les fréquences élevées se sont maintenues plus longtemps avec l’isoflurane (< 30 min). La baisse de la pression artérielle provoquée par la nicardipine était plus importante avec le sévoflurane mais les basses pressions ont persisté plus longtemps avec l’isoflurane. Les concentrations plasmatiques de catécholamines augmentaient avec l’isoflurane et l’enflurane mais non avec le sévoflurane: on a observé des concentrations d’épinéphrine beaucoup plus élevées avec l’isoflurane.


Cette étude démontre que l’activté de la nicardipine est modifiée par divers agents inhalatoires. La nicardipine exerce une action prolongée en présence de l’isoflurane mais produit une hypotension initiate plus importante en présence du sévoflurane.


  1. 1.
    Kishi T, Okumura, F, Furuya H. Haemodynamic effects of nicardipine hydrochloride. Studies during its use to control acute hypertension in anaesthetized patients. Br J Anaesth 1984; 56: 1003–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Bongrani S, Razzetti R, Schiantarelli P. Cardiovascular effects of nicardipine in anesthetized open-chest dogs in the absence and presence of β-adrenergic receptor blockade: a comparison with nifedipine and verapamil. J Cardiovasc Pharmacol 1985; 7: 899–905.PubMedCrossRefGoogle Scholar
  3. 3.
    Takeda S, Inada T, Tashiro N, et al. Endocrine effects of hypotension induced by nicardipine in rabbits. (Japanese) Masui 1990; 39: 971–7.PubMedGoogle Scholar
  4. 4.
    Bernard J-M, Pinaud M, Maquin-Mavier I, Remi J-P, Passuti N. Hypotensive anesthesia with isoflurane and enflurane during total hip replacement: a comparative study of catecholamine and renin angiotensin responses. Anesth Analg 1989; 69: 467–72.PubMedCrossRefGoogle Scholar
  5. 5.
    Kito K, Ami T, Mori K, Morikawa S, Inubushi T. Hepatic blood flow and energy metabolism during hypotension induced by prostaglandin El and nicardipine in rabbits: An in vivo magnetic resonance spectroscopic study. Anesth Analg 1993; 77: 606–12.PubMedCrossRefGoogle Scholar
  6. 6.
    Frink EJ Jr, Morgan SE, Coetzee A, Couzen PF, Brown BR Jr. The effects of sevoflurane, halothane, enflurane, and isoflurane on hepatic blood flow and oxygenation in chronically instrumented greyhound dogs. Anesthesiology 1992; 76: 85–90.PubMedCrossRefGoogle Scholar
  7. 7.
    Fukusaki M, Miyako M, Fukui S, Haseba S, Gotoh T. Hemodynamics during induced hypotension with continuous administration of nicardipine. (Japanese) Masui 1986; 35: 551–6.PubMedGoogle Scholar
  8. 8.
    Skovsted P, Sapthavichaikul S. The effects of isoflurane on arterial pressure, pulse rate, autonomic nervous activity, and barostatic reflexes. Can Anaesth Soc J 1977; 24: 304–14.PubMedCrossRefGoogle Scholar
  9. 9.
    Nagayama T, Meguro K, Kurosawa M, Sato A. Effects of different concentrations of an inhaled anesthetic agent, sevoflurane on sympatho-adrenal medullary functions in rats. (Japanese) Masui 1993; 42: 1754–62.PubMedGoogle Scholar
  10. 10.
    Saeki T, Hasegawa Y, Shibamoto T, et al. The effects of sevoflurane, enflurane, and isoflurane on baroreceptorsympathetic reflex in rabbits. Anesth Analg 1996; 82: 342–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Murakawa T, Satoh T, Kudo T, Kudo M, Matsuki A, Oyama T. Effects of sevoflurane anesthesia and surgery on plasma catecholamine levels. (Japanese) Masui 1989; 38: 1456–62.PubMedGoogle Scholar
  12. 12.
    Ray DC, Drummond GB. Haemodynamic responses to nicardipine in humans anaesthetized with halothane. Anaesthesia 1989; 44: 382–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Ebata T, Okazaki H, Sha M, et al. The hypotensive effect and plasma concentration of nicardipine during general anesthesia. (Japanese) Jpn J Clin Anesth 1985; 9: 1071–5.Google Scholar
  14. 14.
    Seyde WC, Longnecker DE. Anesthetic influences on regional hemodynamics in normal and hemorrhaged rats. Anesthesiology 1984; 61: 686–98.PubMedCrossRefGoogle Scholar
  15. 15.
    Conzen PF, Vollmar B, Habazettl H, Frink EJ, Peter K, Messmer K. Systemic and regional hemodynamics of isoflurane and sevoflurane in rats. Anesth Analg 1992; 74: 79–88.PubMedCrossRefGoogle Scholar

Copyright information

© Canadian Anesthesiologists 1997

Authors and Affiliations

  • Tomoki Nishiyama
    • 1
  • Takashi Matsukawa
    • 3
  • Kazuo Hanaoka
    • 2
  • Charles M. Conway
    • 1
  1. 1.Department of AnesthesiologyUniversity of California, San DiegoLa JollaUSA
  2. 2.Department ol AnesthesiologyFaculty of Medicine, The University of TokyoJapan
  3. 3.Department of Anesthesia, Division of Operating RoomYamanashi Medical UniversityJapan

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