Nitric oxide inhalation and glucocorticoids as combined treatment in human experimental endotoxemia.
OBJECTIVE
Inhaled nitric oxide and glucocorticoids as a combination therapy may attenuate endotoxin-induced inflammatory responses in humans as indicated by levels of cytokines and clinical signs. Since other authors have shown that combined inhaled nitric oxide and steroids improved the histologic damage both in pulmonary and systemic organs in a porcine endotoxin model, we examined if an anti-inflammatory interaction could be demonstrated in humans.


METHODS
Double-blind, crossover, placebo-controlled randomized study.


METHODS
The intensive care unit in a university hospital.


METHODS
Fifteen healthy white volunteers (4 women, 11 men).


METHODS
Endotoxin (2 ng/kg) was administered intravenously. Thirty minutes thereafter the volunteers were given glucocorticoids (2 mg/kg) intravenously and inhaled nitric oxide 30 ppm or placebo (nitrogen) administered through a nasal cannula. Blood samples and clinical signs were collected before and up to 5.5 hrs after the endotoxin infusion.


RESULTS
Following endotoxin body temperature and heart rate increased significantly compared with baseline. There were no differences observed between the treatments. Endotoxin challenge also markedly elevated the plasma levels of tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, and IL1-ra concentrations during the study period. No difference between placebo/glucocorticoids and inhaled nitric oxide/glucocorticoids treatment was seen in the cytokine response.


CONCLUSIONS
In a human experimental inflammatory model using endotoxin, inhaled nitric oxide and glucocorticoids in low doses given after the endotoxin challenge did not modify the inflammatory cascade as monitored in this study.
Hållström
Lars
L
Department of Anesthesiology and Intensive Care, Karolinska University Hospital, Huddinge and Solna, Stockholm, Sweden. lars.hallstrom@karolinska.se
Berghäll
Elisabeth
E
Frostell
Claes
C
Sollevi
Alf
A
Soop
Anne L
AL
D000280:Administration, Inhalation; D000328:Adult; D001831:Body Temperature; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D019446:Endotoxemia / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006339:Heart Rate; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000031:analogs & derivatives; D007275:Injections, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage*
D016207:Cytokines; D005938:Glucocorticoids; D009569:Nitric Oxide; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone