Antagonism of Morphine With Naloxone in Dogs: Cardiovascular Effects With Special Reference to the Coronary Circulation

Abstract

The cardiovascular effects of naloxone 15 microgram/kg following morphine 2.0 mg/kg were studied in closed-chest dogs during light nitrous oxide-halothane anaesthesia. The bolus injection of naloxone caused an increase in heart rate (73%), cardiac output (20%) and mean arterial pressure (20%). Total peripheral resistance was unaffected. LV dP/dt max and LV dP/dt max/IP increased by 25% and 14% respectively, but positive inotropic effects could not be shown when load data, heart rate and the decrease in left ventricular ejection fraction (22%) were taken into consideration. The cardiovascular stimulation resulted in an increase in myocardial oxygen demand (66%) which was met by an increase in coronary blood flow (59%). The data suggest that the antagonism of narcotics with high doses of naloxone may impair the myocardial oxygen supply in patients suffering from coronary insufficiency. It is concluded that naloxone should be titrated for each patient to ensure adequate reversal of respiratory depression and to avoid circulatory stress.

Naloxone dosage for opioid reversal: current evidence and clinical implications

“…Naloxone administration is generally associated with an increase in heart rate, cardiac output and arterial blood pressure in humans and in dogs, 60 and studies in the latter have shown increased coronary blood flow and myocardial oxygen consumption. 61,62 Initially, studies of the administration of high doses of naloxone to patients with OUD under general anesthesia for purposes of detoxification produced no significant changes in heart rate, mean arterial pressure, cardiac index, peripheral resistance or oxygen saturation. 63 However, later studies found that such treatment with naloxone is accompanied by a 30-fold and 3-fold increase in epinephrine and norepinephrine plasma concentrations respectively, and that this catecholamine surge is associated with significant increases in cardiac index, stroke volume index, heart rate, whole-body oxygen consumption and a systemic vascular resistance index decrease, all consistent with the effect of epinephrine.…”

Heroin intoxication in a dog

“…Dosing of naloxone for opioid overdose remains an area of continued debate in human medicine. There have been several experimental studies involving opioid reversal with naloxone in dogs using various doses 26–28 . In one such study, a dose of 0.01 mg/kg IV or 0.04 mg/kg IM temporarily reversed most of the effects of oxymorphone 28 .…”

“…There have been several experimental studies involving opioid reversal with naloxone in dogs using various doses. [26][27][28] In one such study, a dose of 0.01 mg/kg IV or 0.04 mg/kg IM temporarily reversed most of the effects of oxymorphone. 28 The suggestion is to begin with a 0.01 mg/kg intravenous bolus and repeat every 2 minutes at increased doses, up to a maximum dose of 15 mg, 10,25 which would be 37.5 mL of the 0.4 mg/mL solution.…”

Use of narcotic antagonists in anaesthesia.

“…An acute abstinence syndrome can appear when reversal takes place so abruptly, accompanied by a metabolic stimulation directly proportional to the dose of opiate used, to the interval which precedes the reversal, to the dose of antagonist used, to the speed of antagonist administration, and to the rapidity of its antagonist action (De Castro, 1976). For example, a serious imbalance between myocardial oxygen requirement and available oxygen (MVO2 demand/MO2 supply) Premedication Pure analgesic anaesthesia Potentialised analgesic anaesthesia General anaesthesia; "balanced anaesthesia" Analgosedation Complement to local -regional anaesthesia Post-operative analgesia Acute pain Chronic pain Unwanted overdosage Deliberate overdosage: in obstetrics Sequential analgesic anaesthesia Potentialised analgesic anaesthesia can result in ischemia in coronary patients (Patschke, 1977).…”