The opiate sufentanil alters the inflammatory, endocrine, and metabolic responses to endotoxin in dogs.
Sufentanil is a synthetic mu-opioid receptor agonist frequently used in anesthesia and critically ill patients. To evaluate the effects of sufentanil on the inflammatory, neuroendocrine, and metabolic responses to endotoxin, we studied six dogs during saline infusion (control), during sufentanil infusion (1.5 microg . kg-1 . h-1), after endotoxin injection (1.0 microg/kg iv), and during combined endotoxin and sufentanil administration. The rate of appearance of glucose was determined by infusion of [6,6-2H2]glucose. Sufentanil depressed the endotoxin-induced increase in body temperature (36.9 +/- 0.3 vs. 40.6 +/- 0.5 degrees C, P < 0.05). Sufentanil depressed the tumor necrosis factor (TNF) response to endotoxin by approximately 60% (P < 0.01) but increased the interleukin-6 (IL-6) response by approximately 70% (P < 0.01). Sufentanil per se induced a transient neuroendocrine activation. Sufentanil also increased plasma concentrations of insulin and catecholamines after endotoxin (P < 0.05 vs. endotoxin alone) and increased plasma glucose levels by approximately 36% (from 6.1 +/- 0.1 to 8.3 +/- 0.6 mmol/l, P < 0.05 vs. endotoxin alone). Endotoxin stimulated glucose production transiently by 95% (24.2 +/- 3.2 vs. control 12.4 +/- 1.0 micromol . kg-1 . min-1, P < 0.05). Paradoxically, sufentanil inhibited this endotoxin-induced stimulation of glucose production (P < 0.05 vs. endotoxin alone). In conclusion, sufentanil modulates the response to intravenous endotoxin by dissociating the TNF and IL-6 response, increasing insulin and catecholamine levels, and depressing the increase in glucose production. Therefore, opiates alter inflammatory, endocrine, and metabolic regulation in endotoxemia.
Moeniralam
H S
HS
Department of Internal Medicine, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands.
Endert
E
E
Ackermans
M T
MT
Van Lanschot
J J
JJ
Sauerwein
H P
HP
Romijn
J A
JA
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D003903:Deuterium; D004285:Dogs; D019446:Endotoxemia / Q000276:immunology / Q000503:physiopathology*; D004731:Endotoxins / Q000633:toxicity*; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006728:Hormones / Q000097:blood* / Q000378:metabolism; D006854:Hydrocortisone / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011865:Radioisotope Dilution Technique; D017450:Receptors, Opioid, mu / Q000819:agonists; D012016:Reference Values; D017409:Sufentanil / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D001786:Blood Glucose; D004731:Endotoxins; D006728:Hormones; D007328:Insulin; D015850:Interleukin-6; D017450:Receptors, Opioid, mu; D014409:Tumor Necrosis Factor-alpha; D005934:Glucagon; D017409:Sufentanil; D003903:Deuterium; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine