title: Spontaneous high systemic oxygen delivery increases survival rate in awake sheep during sustained endotoxemia.
abstract: OBJECTIVE
  To study the natural evolution of systemic oxygen delivery (Do2) and oxygen consumption (Vo2) in sheep infused with low or high doses of endotoxin.
  
  
  METHODS
  Prospective, controlled experimental study.
  
  
  METHODS
  Animal research laboratory at a medical university.
  
  
  METHODS
  Twenty-nine chronically instrumented awake sheep (25-35 kg).
  
  
  METHODS
  Awake animals were continuously infused with saline (n = 8) or two doses of Escherichia coli endotoxin (20 or 40 ng/kg/min; n = 21) for 72 hrs. No attempt was made to increase Do2, but respiratory failure was treated by mechanical ventilation and metabolic acidosis was corrected.
  
  
  RESULTS
  The mortality rate was 25% in the group infused with the low dose and 89% in the group infused with the high dose of endotoxin. During the first 12 hrs of endotoxemia, both surviving (S group; n = 10) and nonsurviving (NS group; n = 11) sheep developed similar pulmonary hypertension, left ventricular failure, and hypotension with low systemic vascular resistance. However, S sheep had less interstitial lung edema (pulmonary lymph protein clearance at 8 hrs was 13+/-3 mL/hr vs. 27+/-6 mL/hr in the NS group and 4+/-1 mL/hr in the control group). During this early phase of endotoxemia, Do2, Vo2, and oxygen extraction ratio did not change significantly in any group. After this phase, animals that ultimately survived had a persistent hyperdynamic syndrome with high cardiac output and hypotension. In this group, the Do2 increase was greater than the Do2 measured in controls and remained steady up to 48 hrs after the start of the endotoxin infusion. Because systemic Vo2 did not change significantly, oxygen extraction ratio decreased progressively to values less than those measured in controls. In contrast, animals that ultimately died had a hypotensive and normokinetic syndrome associated with pulmonary hypertension, persistent depressed left ventricular function, hypothermia, and a progressive deterioration of gas exchange. Systemic Do2 was not significantly different from that in the control group. In contrast, Vo2 decreased progressively to values significantly lower than those measured in controls and remained low until death.
  
  
  CONCLUSIONS
  Our results indicate that in the absence of treatment such as fluid challenge or inotropic drugs in sheep infused with endotoxin, the occurrence of spontaneous hyperdynamic syndrome and high Do2 improves the survival rate.
authors.affiliation: Division d'Investigations Anesthésiologiques, Centre Médical Universitaire, Geneva, Switzerland.
authors.forename: J F
authors.initials: JF
authors.lastname: Pittet
authors.forename: C M
authors.initials: CM
authors.lastname: Pastor
authors.forename: D R
authors.initials: DR
authors.lastname: Morel
mesh_terms: D000138:Acidosis / Q000382:microbiology / Q000628:therapy; D000818:Animals; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000150:complications / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D004927:Escherichia coli Infections / Q000150:complications / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000382:microbiology; D007262:Infusions, Intravenous; D008297:Male; D009102:Multiple Organ Failure / Q000382:microbiology; D010101:Oxygen Consumption; D011659:Pulmonary Gas Exchange; D012131:Respiratory Insufficiency / Q000382:microbiology / Q000628:therapy; D012756:Sheep; D016019:Survival Analysis; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000382:microbiology; D014851:Wakefulness