Adrenergic vasopressor agents and mechanical ventilation for the treatment of experimental septic shock.
OBJECTIVE
Vasopressor agents and mechanical ventilation are routine interventions for the treatment of sepsis complicated by hypotension. It was our hypothesis that such treatment singly or in combination increases the duration of survival.


METHODS
Prospective, randomized, controlled study.


METHODS
University research laboratory.


METHODS
Thirty male Sprague-Dawley rats anesthetized with intraperitoneal injection of pentobarbital.


METHODS
Peritonitis was induced by cecal ligation and spillage of cecal contents into the abdominal cavity. The first phase of this study was performed on 15 spontaneously breathing Sprague-Dawley rats that were randomized to three groups of five animals each. One group received treatment with dopamine. The second group received norepinephrine. The third group received only the diluent as a placebo. Concentrations of the vasopressor agents were increased such that mean arterial pressure was maintained at approximately 80% of baseline values; the volumes infused were kept constant. For the second phase of this study, the grouping of animals and the techniques of study were identical, except that rats were mechanically ventilated.


RESULTS
Mean arterial pressure was best maintained with norepinephrine. However, no statistically significant differences in duration of survival, cardiac index, arterial blood lactate concentration, or arterial and venous PCO2 and PO2 values were identified between groups. With mechanical ventilation, survival was prolonged (p < .01). Survival was increased from an average of 291 mins to 342 mins with dopamine, from 257 mins to 352 mins in placebo controls, and from 280 mins to 329 mins with norepinephrine. Again, no significant differences in hemodynamic and blood gas measurements, or in the duration of survival between vasopressor-treated and control animals were documented.


CONCLUSIONS
No benefit or detriment was demonstrated when vasopressor agents were administered to sustain arterial pressure in the course of experimental peritonitis in this murine model of septic shock. This finding contrasted with highly significant prolongation of survival when animals were mechanically ventilated. There was no evidence that routine vasopressor therapy, under these controlled experimental conditions in rats, improved duration of survival.
Tang
W
W
Institute of Critical Care Medicine, University of Health Sciences, Chicago Medical School, IL, USA.
Pakula
J L
JL
Weil
M H
MH
Noc
M
M
Fukui
M
M
Bisera
J
J
D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D003131:Combined Modality Therapy; D004298:Dopamine / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000032:analysis; D007773:Lactates / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000627:therapeutic use*; D010538:Peritonitis / Q000150:complications; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D012772:Shock, Septic / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
D000316:Adrenergic alpha-Agonists; D006454:Hemoglobins; D007773:Lactates; D014662:Vasoconstrictor Agents; D004298:Dopamine; D009638:Norepinephrine