Comparison of halothane, isoflurane, alfentanil, and ketamine in experimental septic shock.
The effects of four commonly used anesthetic agents, halothane, isoflurane, alfentanil, and ketamine, on cardiovascular function and oxygen balance were studied in a dog model of septic shock. After initial pentobarbital administration, the dogs were given Escherichia coli endotoxin (3 mg/kg) and, after 30 min, fluids to restore cardiac filling pressures to baseline levels. This resulted in a low resistance shock in all animals. Dogs were then given for 2 h either halothane (n = 9, 0.5 MAC), isoflurane (n = 9, 0.5 MAC), or alfentanil (n = 9, 150 micrograms/kg IV plus 2 micrograms.kg-1.min-1) or ketamine (n = 9, 2 mg/kg IV plus 0.2 mg.kg-1.min-1) or no anesthetic (control: n = 9). Mean arterial pressure increased in the control group (+11 +/- 18 mm Hg) and with ketamine (+10 +/- 20 mm Hg), remained unchanged with isoflurane (-2 +/- 11 mm Hg), and decreased with halothane (-22 +/- 23 mm Hg) and alfentanil (-9 +/- 23 mm Hg). Heart rate tended to increase in the control group but decreased with the four anesthetic agents, especially with alfentanil and halothane. Cardiac index and left ventricular stroke work index increased in the control group and in each anesthetic group except the halothane group. Systemic vascular resistance decreased in all groups except in the ketamine group. In the control group, the increase in cardiac index was associated with significant increases in oxygen delivery and consumption, and with a significant decrease in blood lactate levels. There was a dramatic decrease in oxygen consumption in all anesthetic groups, whereas oxygen delivery failed to increase only with halothane. Blood lactate increased significantly with halothane (5.0 +/- 1.5 to 6.3 +/- 1.4 mM/L) and isoflurane (4.8 +/- 1.1 to 5.3 +/- 1.2 mM/L), remained unchanged with alfentanil (4.5 +/- 1.5 and 4.6 +/- 0.8 mM/L), and tended to decrease with ketamine (4.9 +/- 1.4 to 4.5 +/- 1.4 mM/L). In conclusion, among the four anesthetic agents tested, halothane had the least desirable effects. Ketamine best preserved cardiovascular function and appeared to have the least deleterious effects on the hypoxic tissues. Thus, ketamine could be the anesthetic agent of choice in septic shock.
Department of Anesthesiology, Erasme University Hospital, Free University of Brussels, Belgium.
P
P
Van der Linden
E
E
Gilbart
E
E
Engelman
D
D
Schmartz
M
M
de Rood
J L
JL
Vincent
D015760:Alfentanil / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli; D006221:Halothane / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D007530:Isoflurane / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D007773:Lactates / Q000097:blood; D008954:Models, Biological; D012772:Shock, Septic / Q000503:physiopathology*
D007773:Lactates; D015760:Alfentanil; D007649:Ketamine; D007530:Isoflurane; D006221:Halothane