Cardiovascular changes after naloxone administration in propofol-sedated piglets during opioid overdose.

BACKGROUND: Naloxone is an opioid receptor antagonist. Even when used in modest doses, it has been associated with serious cardiopulmonary side-effects. In this experimental porcine study, we examined the cardiac effects of naloxone during an opioid overdose. METHODS: Cardiac parameters, changes in the left ventricular compliance and the magnitude of catecholamine release were evaluated in eight spontaneously breathing piglets under propofol sedation. Cardiac parameters were recorded every 30 s and transthoracic echocardiography was used for the continuous assessment of cardiac performance. Respiratory arrest was induced by morphine (8 mg/kg). Ten minutes after morphine administration, naloxone (80 microg/kg) was injected intravenously. Every 5 min, arterial blood gases were measured and, every 10 min, a sample for the analysis of plasma catecholamines was drawn. RESULTS: There were no statistically significant changes in left ventricular ejection fraction and no signs of pulmonary hypertension. There was a statistically significant increase in the mean arterial pressure immediately after naloxone administration and in norepinephrine concentration before naloxone administration. After naloxone administration, the plasma catecholamine levels decreased in all but one animal. Two animals developed cardiac arrest (pulseless electrical activity and ventricular fibrillation) shortly after receiving naloxone. Although they were both administered naloxone prematurely due to hypoxic bradycardia, naloxone could have contributed to the development of ventricular fibrillation. CONCLUSION: Naloxone did not cause changes in ejection fraction or mean pulmonary artery pressure in hypoxic and hypercarbic conditions. After naloxone administration, the plasma catecholamine levels returned to baseline in all but one animal, and two animals developed cardiac arrest.

Epinephrine added to a lumbar epidural infusion of a small-dose ropivacaine-fentanyl mixture after arterial bypass surgery of the lower extremities.

BACKGROUND: The addition of epinephrine (2 micro g.ml-1) to a thoracic epidural infusion of an opioid-local anesthetic mixture improves analgesia. Here, we studied whether epinephrine could improve analgesia also at lumbar level, when added to an epidural infusion of a low-dose ropivacaine-fentanyl mixture after arterial bypass surgery of the legs. METHODS: Patients in group RFE (n = 21) received a postoperative epidural infusion containing ropivacaine (1 mg.ml-1), fentanyl (2 micro g.ml-1), and epinephrine (2 micro g.ml-1). Patients in group RF (n = 25) received a similar infusion without epinephrine. The infusion speed was 1 ml.10 kg-1. h-1. The infusion was scheduled for 48 h. RESULTS: Epinephrine did not reduce the need for rescue pain medication. Visual analog scale scores (VAS) for pain at rest were low and similar in the groups. Pain intensity was stronger during leg movement [mean VAS 1.5-2.6 (range 0-9)], but it was not affected by the coadministration of epinephrine. The groups did not differ concerning frequency and severity of side-effects. Epinephrine did not reduce fentanyl plasma concentrations. Ropivacaine concentrations were slightly lower in group RFE only in the samples 6 h from the start of the infusion, but not anymore on the first and second postoperative day. CONCLUSION: In the dosage used here, epinephrine did not improve epidural lumbar analgesia. Different distances from the epidural application site to the alpha2-adrenergic receptors of the spinal cord, and differing epinephrine dose requirements may explain why epinephrine as an additive improves epidural analgesia at thoracic, but not at lumbar level.

Anabolic androgenic steroids produce dose-dependant increase in left ventricular mass in power atheletes, and this effect is potentiated by concomitant use of growth hormone.

Power athletes abuse anabolic androgenic steroids (AASs) and growth hormone (GH) to gain their muscular mass and strength. We wanted to determine how massive, self-administered doses of AASs with or without GH affect the left ventricular (LV) dimensions in power athletes. These substances are assumed to increase LVmass mainly by thickening the ventricular walls. Anecdotal evidence suggests a higher risk of cardiovascular events in AAS abusers. We were interested to see if LV dimensions and function in AAS abusers would indicate this increased risk. Twenty healthy male power athletes using massive doses of AAS without (n = 16) or with (n = 4) GH volunteered for the study. The controls were 15 sedentary male non-users of hormones. LV mass, geometry and filling were studied using standard echocardiographic methods. We found a significant association between LV mass and AAS dose (r = 0.54, p < 0.015). In contrast to the controls, LV mass (274 g in the athletes, 167 g in the controls) among the AAS abusers did not correlate with body weight or height. Concomitant use of AAS and GH further increased LV mass and associated with concentric remodelling of LV. Multiple regression analysis indicated that the mean AAS dose accounted for 29 %, age for 14 % and systolic blood pressure for 17 % of the variance in LV mass. We concluded that AAS abuse associates dose-dependently with myocardial hypertrophy and that concomitant use of GH associates with concentric remodelling of the LV. Our findings suggest that AASs and GH have a direct effect on the myocardium.

Morphine or oxycodone in cancer pain?

Oxycodone is an opioid analgesic that closely resembles morphine. Oxymorphone, the active metabolite of oxycodone, is formed in a reaction catalyzed by CYP2D6, which is under polymorphic genetic control. The role of oxymorphone in the analgesic effect of oxycodone is not yet clear. In this study, controlled-release (CR) oxycodone and morphine were examined in cancer pain. CR oxycodone and morphine were administered to 45 adult patients with stable pain for 3-6 days after open-label titration in a randomized, double-blind, cross-over trial. Twenty patients were evaluable. Both opioids provided adequate analgesia. The variation in plasma morphine concentrations was higher than that of oxycodone, consistent with the lower bioavailability of morphine. Liver dysfunction affected selectively either oxycodone or morphine metabolism. Three patients with markedly aberrant plasma opioid concentrations are presented. Significant individual variation in morphine and oxycodone metabolism may account for abnormal responses during treatment of chronic cancer pain.

Fentanyl-prilocaine mixture for intravenous regional anaesthesia in patients undergoing surgery.

The effect of the addition of 0.1 mg or 0.2 mg fentanyl to 40 ml 0.5% prilocaine in intravenous regional anaesthesia of the arm was investigated in 37 patients in a randomised, double-blind study. The characteristics of the sensory and motor block were studied. There was no difference in the speed of onset of analgesia in the groups (mean latency approximately 4 min in each group). However, significantly more patients in the fentanyl 0.2 mg group (7/12) had complete anaesthesia at 15 min than in the fentanyl 0.1 mg group (1/13) and the control group (2/12) (p less than 0.05). There were no differences in the incidence of tourniquet pain immediately before cuff deflation (tourniquet time 45-87 min). After cuff deflation, in those patients who complained of wound pain within 30 min, on average the pain appeared later in the fentanyl 0.2 mg group (six patients, mean 14.3 min) than in the control group (eight patients, mean 9.4 min) (ns). In the fentanyl groups, the incidence of central nervous system side effects was greater than in the control group (fentanyl 0.1 mg 7/13 patients, fentanyl 0.2 mg 6/12 patients, control 1/12 patients) (p less than 0.05). The plasma concentrations of prilocaine after cuff deflation were higher, in a dose-dependent fashion, in the fentanyl groups than in the control group, but the concentrations of prilocaine and fentanyl did not correlate with the symptoms. Postoperative nausea occurred only in the patients who had received fentanyl.