morphinans and Hypercapnia

Topics: Adult; Alkalosis, Respiratory; Analgesics; Anesthesia, Intravenous; Bicarbonates; Blood; Carbon Dioxide; Clinical Trials as Topic; Depression, Chemical; Dose-Response Relationship, Drug; Drug Antagonism; Drug Synergism; Humans; Hydrogen-Ion Concentration; Hypercapnia; Infusions, Parenteral; Male; Morphinans; Naloxone; Oxymorphone; Placebos; Respiration; Sodium Chloride; Spirometry

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 micrograms.kg-1 fentanyl IV. This caused a significant decrease in heart rate (HR) (P less than 0.001), mean arterial blood pressure (MAP) (P less than 0.001), and plasma concentrations of norepinephrine (NE) (P less than 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 (EPI) (P less than 0.02) and NE (P less than 0.001). Administration of 20 micrograms.kg-1 NX to six dogs resulted in immediate increases in HR (P less than 0.01) and MAP (P less than 0.01), and a further rise in CA levels to greater than pre-fentanyl baseline values. In six other dogs, NBPH (0.3 mg.kg-1) caused increases in HR (P less than 0.001) and MAP (P less than 0.001) only, and the MAP rise was significantly less than that seen in the NX group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Animals; Blood Pressure; Dogs; Epinephrine; Fentanyl; Heart Rate; Hypercapnia; Morphinans; Nalbuphine; Naloxone; Norepinephrine

The efficacy of the neuroleptanalgesic combinations of fentanyl-fluanisone with diazepam; and etorphine-methotrimeprazine, either alone, or with diazepam, was investigated in the rabbit. The effects of these drugs on some cardiovascular variables were studied in chronically catheterized rabbits. Fentanyl-fluanisone and diazepam produced good surgical anaesthesia. Although respiratory depression occurred, this had little effect on blood gas values. In contrast, etorphine-methotrimeprazine and diazepam produced severe respiratory depression with consequent hypercapnia and acidosis.

Topics: Acidosis; Animals; Butyrophenones; Diazepam; Drug Combinations; Etorphine; Fentanyl; Hypercapnia; Methotrimeprazine; Morphinans; Neuroleptanalgesia; Rabbits; Respiration; Time Factors