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Cardiovascular Effects of Fentanyl Reversal by Naloxone at Varying Arterial Carbon Dioxide Tensions in Dogs

Received from the Department of Anesthesiology, University of California, Los Angeles, Center for the Health Sciences, Los Angeles, California.

Abstract

Clinical reports, as well as animal studies, have described cardiovascular and sympathetic stimulation after the administration of naloxone (NX) to reverse opioid-induced respiratory depression. This investigation examines the effect of Paco₂ on hemodynamic and adrenergic responses to NX, by means of 24 experiments carried out in six dogs. Each dog underwent NX reversal of fentanyl (FEN) at three different Paco₂ levels: 20, 35, and 60 mm Hg. In a final series of six experiments, the dogs were exposed to increasing Paco₂ after autonomic block by total spinal anesthesia and vagotomy. During enflurane anesthesia, 50 µg/kg FEN decreased mean arterial blood pressure (MAP), heart rate (HR), and plasma concentrations of norepinephrine (NE) and epinephrine (EPI) significantly. NX 0.4 mg promptly returned HR and MAP to baseline or above in all experiments; catecholamine (CA) levels increased only in hypercapnic dogs. Increases in HR were the same in all series. MAP, EPI, and NE levels were significantly greater than pre-FEN baseline values only in hypercapnic dogs 1 minute after NX and were also significantly higher in hypercapnic than in hypocapnic dogs at this time. NE levels were greater in hypercapnic dogs at all time periods after NX. In blocked dogs, neither F nor NX had any effects on hemodynamic functions or plasma CA levels; the institution of hypercapnia caused significant decreases in HR, MAP, and systemic vascular resistance. This direct circulatory depressant action of an elevated Pco₂ may have attenuated the indirectly mediated excitatory hemodynamic effects of NX in intact dogs, thus explaining the relatively greater effect of hypercapnia on adrenergic than on hemodynamic responses to reversal. This study suggests that abrupt increases in blood pressure and plasma CA levels after naloxone can be blunted if normocapnia or hypocapnia is established before naloxone administration.

Key Words: ANTAGONISTS, NARCOTIC—naloxone • ANESTHETICS, INTRAVENOUS—fentanyl • ANALGESICS—fentanyl

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999