Physiologic and plasma hormone correlates of survival in endotoxic dogs: effects of opiate antagonists.
Two groups of awake dogs were given an iv bolus of endotoxin (3.0 mg/kg from Salmonella typhimurium); one group (n = 9) was pretreated with either naloxone (2.0 mg/kg iv bolus with 1.7 mg/kg.h; n = 6) or naltrexone (2.0 mg/kg iv bolus with repeat bolus of 1.0 mg/kg at 1, 3 and 5 h; n = 3) and the second group (n = 10) received no opiate antagonist. All of nine dogs that were pretreated with an antagonist survived for 24 h, compared to only five of ten dogs that were not pretreated. Survival correlated with improved BP (mean of 91 vs. 61 mm Hg) and cardiac output (3.9 vs. 2.45 L/min) measured during the first 3 h after the infliction of shock. However, both antagonist-treated and nonantagonist-treated survivors had BP and cardiac output which were statistically lower than their baseline values or saline-treated controls at comparable times. Nonsurvivors had significantly higher levels of norepinephrine (peak level: 1149 ng/ml) and epinephrine (peak level: 31.29 ng/ml) than survivors. Opiate antagonists thus appeared to increase survival in a subgroup of dogs that might not otherwise have survived if they had not been so treated; this survival was associated with improved hemodynamics, but not with increased adrenergic activity.
Murray
M J
MJ
Critical Care Service, Mayo Clinic, Rochester, MN 55905.
Offord
K P
KP
Yaksh
T L
TL
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D004837:Epinephrine / Q000097:blood; D008297:Male; D009270:Naloxone / Q000627:therapeutic use*; D009271:Naltrexone / Q000627:therapeutic use*; D009638:Norepinephrine / Q000097:blood; D011957:Receptors, Opioid / Q000187:drug effects; D012486:Salmonella typhimurium; D012772:Shock, Septic / Q000188:drug therapy*; D001615:beta-Endorphin / Q000097:blood
D004731:Endotoxins; D011957:Receptors, Opioid; D009270:Naloxone; D009271:Naltrexone; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D009638:Norepinephrine; D004837:Epinephrine