naloxone and Bacterial-Infections

To determine whether naloxone infusion is efficacious in severe hyperdynamic septic shock, we conducted a prospective study of 22 patients randomly assigned to a naloxone or placebo group. Patients were treated 12 +/- 2 h (SEM) after the onset of shock, with a mean arterial pressure (MAP) of 63 +/- 3 mm Hg. All patients had clinical evidence of an infectious process and required dopamine 20 +/- 2 micrograms/kg.min. Five (46%) of 11 patients in the naloxone group and one (9%) of the other 11 patients in the placebo group responded clinically. The MAP among the five responders increased from 62 +/- 5 to 89 +/- 4 mm Hg within 20 min of naloxone treatment (p less than .01). This favorable hemodynamic response was sustained throughout the patients' clinical course. In contrast, the MAP did not change significantly in the nonresponders who received naloxone, nor did it change in the placebo group. More patients in the naloxone group than in the placebo group received steroids concurrently. Survival rate was 100% in those who responded to naloxone clinically. However, overall survival rate in each group was essentially the same. No adverse effects were observed, except for mild agitation in some of the patients receiving naloxone. We conclude that naloxone infusion is clinically efficacious in improving the hemodynamic profile of a subgroup of patients with severe early hyperdynamic septic shock, but does not appear to improve the overall survival rate.

Topics: Aged; Bacterial Infections; Female; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Naloxone; Pneumonia; Prospective Studies; Randomized Controlled Trials as Topic; Shock, Septic; Steroids

We determined how the following drugs affected survival of 350-gm Sprague-Dawley rats subjected to intra-abdominal sepsis according to the method of Wichterman et al (J Surg Res 29:189-201, 1980): gentamicin (4.5 mg/kg/day), clindamycin (30 mg/kg/day), naloxone (2 mg/kg/hr), or methylprednisolone given either as a continuous infusion (2 mg/kg/hr) or as a bolus (30 mg/kg). A control group received only saline in a volume equal to the drug vehicle volume. Treatment was started immediately after cecal ligation and puncture. Drugs not given by bolus were infused by Alzet mini-pump (Model 2001) for 7 days. Percent of original population surviving at 10 days was (size of original population): saline--48% (92), antibiotics--86% (43), naloxone--30% (43), continuous methylprednisolone--14% (43), bolus methylprednisolone--93% (45). Survival of animals receiving either antibiotics or bolus methylprednisolone was significantly increased over the control population.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Cecum; Disease Models, Animal; Drug Administration Schedule; Ligation; Male; Methylprednisolone; Naloxone; Punctures; Rats; Rats, Inbred Strains

A 0.01 and 0.1-mg/kg dose of iv naloxone was administered to seven patients in septic shock, in order to evaluate naloxone's hemodynamic effect and possible relation to changes in plasma beta-endorphin and catecholamine levels. Naloxone failed to modify cardiac index, blood pressure, heart rate, and systemic vascular resistance. Plasma beta-endorphin, norepinephrine, and epinephrine were elevated but did not change after naloxone administration. These results suggest that beta-endorphin release is a consequence but not a cause of shock, and that the beneficial hemodynamic effects of naloxone in animal studies could be related to species differences or nociceptive stimulations.

Topics: Adult; Aged; Bacterial Infections; beta-Endorphin; Endorphins; Epinephrine; Female; Hemodynamics; Humans; Male; Middle Aged; Naloxone; Norepinephrine; Shock, Septic

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Drug Synergism; Drug Therapy, Combination; Glucocorticoids; Gram-Negative Bacteria; Humans; Immunization, Passive; Naloxone; Rabbits; Rats; Shock, Septic