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Canadian Journal of Anaesthesia

, Volume 37, Issue 2, pp 238–244 | Cite as

Narcotic reversal in hypercapnic dogs: comparison of naloxone and nalbuphine

  • Christopher A. Mills
  • Joan W. Flacke
  • Werner E. Flacke
  • Byron C. Bloor
  • Marvin D. Liu
Laboratory Investigations

Abstract

Reversal of opioid effects by naloxone (NX) can lead to significant cardiovascular problems. We have reported previously that hypercapnic dogs develop greater increases in blood pressure and plasma catecholamine (CA) levels than hypocapnic ones when reversed with naloxone. We have also demonstrated differences between NX and nalbuphine (NBPH) in producing excitatory adrenergic responses when administered during normocapnia. The present study was designed to investigate possible dissimilarities in cardiovascular and sympathetic events after administration of either NX or NBPH in dogs made hypercapnic following fentanyl administration. After induction of anaesthesia with thiopentone and intubation, two groups of dogs were maintained with controlled ventilation on enflurane in oxygen anaesthesia and given 50 μg · kg-1 fentanyl IV. This caused a significant decrease in heart rate (HR) (P < 0.001), mean arterial blood pressure (MAP) (P < 0.001), and plasma concentrations of norepinephrine (NE) (P < 0.002). Then, ventilation was decreased to produce a PaCO2 of 60 mmHg; this was accompanied by a significant elevation in plasma level of both epinephrine (EP1) (P < 0.02) and NE (P < 0.001). Administration of 20 μg · kg-1 NX to six dogs resulted in immediate increases in HR (P < 0.01) and MAP (P < 0.01), and a further rise in CA levels to greater than prefentanyl baseline values. In six other dogs, NBPH (0.3 mg · kg-1) caused increases in HR (P < 0.001) and MAP (P < 0.001) only, and the MAP rise was significantly less than that seen in the NX group (P < 0.01). Neither NE nor EPI levels increased after NBPH. Absolute levels of EPI one minute after reversal with NBPH were not greater than baseline and were significantly less than after NX (P < 0.05). Addition of NX after NBPH caused a further significant increase in EPI to levels greater than baseline (P < 0.002). This study suggests that the abrupt, significant, and sustained increases in MAP and plasma levels of CA which accompany narcotic reversal with NX during hypercapnia are blunted if nalbuphine rather than naloxone is used.

Key words

analgesics: fentanyl antagonists, narcotic: nalbuphine, naloxone carbon dioxide: hypercarbia 

Résumé

L’antagonisme des effets des opiacés par le naloxone (NX) peut amener des problèmes cardiovasculaires significatifs. On a rapporté dans le passé que des chiens hypercapniques développaient une plus grande augmentation de la pression artérielle et des catécholamines plasmatiques (CA) que ceux qui sont hypocapniques lors de l’antagonisme avec le naloxone. On a aussi démontré des différences entre le naloxone et la nalbuphine (NBPH) dans la production de réponses adrénergiques lorsqu’administrés en normocapnie. Cette étude a été conçue afin d’investiguer les différences possibles dans les réponses sympathiques et cardiovasculaires après administration de soit NX ou NBPH chez des chiens rendus hypercapniques après administration de fentanyl. Après l’induction de l’anesthésie avec du thiopentone et intubation, deux groupes de chiens ont été maintenus avec une ventilation contrôlée sous enflurane et oxygène et ont reçu 50 μg · kg-1 de fentanl par voie intraveineuse. Ceci amena une diminution significative de la fréquence cardiaque (HR) (P < 0,001), pression artérielle moyenne (MAP) (P < 0,001), et des concentrations plasmatiques de norépinéphrine (NE) (P < 0,002). Par la suite, la ventilation fut diminuée afin de produire une PaCO2 de 60 mmHg; ceci fut accompagné par une augmentation significative des niveaux plasmatiques d’épinéphrine (EPI) (P < 0,02) et de norépi-néphrine (P < 0,001).L’administration de20μg · kg-1 de NX à six chiens a occasionne une augmentation immédiate de la fréquence cardiaque HR(P < 0,01) et de la MAP (P < 0,01), et une augmentation de la CA à un niveau supérieur aux valeurs de contrôle avant-fentanyl. Chez les six autres chiens, du NBPH (0,3 mg · kg-1)a occasionné une augmentation de HR et de la MAP (P < 0,001) uniquement, et l’augmentation de la MAP était significativement moindre que celle observée dans le groupe NX (P < 0,01). Ni les niveaux de NE ou EPI augmentèrent après le NBPH. Les niveaux absolus de EPI une minute après antagonisme avec le NBPH ne furent pas supé-rieurs à ceux de la valeur de contrôle et étaient significativement moindres qu’aprés NX (P < 0,005). L’addition de NX après NBPH a occasionné une augmentation significative des niveaux de EPI supérieurs à celui du contrôle (P < 0,002). Cette étude suggère qu’une augmentation brusque, significative, et soutenue de la MAP et des niveaux plasmatiques de CA qui accompagnent l’antagonisme des narcotiques avec le NX durant l’hypercapnie sont amoindris si le nalbuphine plutôt que le naloxone est utilisé.

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Copyright information

© Canadian Anesthesiologists 1990

Authors and Affiliations

  • Christopher A. Mills
    • 1
  • Joan W. Flacke
    • 1
  • Werner E. Flacke
    • 1
  • Byron C. Bloor
    • 1
  • Marvin D. Liu
    • 1
  1. 1.Department of AnesthesiologyUniversity of Califronia, Los Angeles, Center for the Health SciencesLos Angeles

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