Comparative effects of early versus delayed use of norepinephrine in resuscitated endotoxic shock.
OBJECTIVE
To assess hemodynamic, tissue oxygenation, and tissue perfusion changes by comparing traditional therapy (fluid resuscitation followed by vasopressor treatment) and alternative therapy (early vasopressor treatment) in a hyperkinetic and sedated model of endotoxic shock.


METHODS
Prospective controlled experimental study.


METHODS
Animal research laboratory.


METHODS
Male Wistar rats.


METHODS
Rats were anesthetized, mechanically ventilated, paralyzed, and instrumented to measure mean arterial pressure, heart rate, pulse pressure variation, aortic and mesenteric blood flow, muscle and liver tissue oxygen pressure, blood gas, and lactate. Rats were randomly divided into five groups (n = 7): endotoxin alone (Endo), endotoxin plus norepinephrine (Endo/NE), endotoxin plus fluid therapy alone (ENDO/Fl), endotoxin plus fluid therapy plus late catecholamine (Endo/Fl/Late NE), and endotoxin plus fluid therapy plus simultaneous norepinephrine administration (Endo/Fl/Early NE).


RESULTS
Mean arterial pressure increased to baseline values only in the catecholamine-treated group (p < .05). In ENDO/Fl, Endo/Fl/Late NE, and Endo/Fl/Early NE, aortic blood flow was maintained. Mesenteric blood flow was maintained at baseline values only in the catecholamine-treated groups. Mesenteric/aortic blood flow ratio was higher in the early catecholamine group (p < .05). Endo and ENDO/Fl were associated with a marked decrease in liver PO2, which was maintained in catecholamine-treated groups (p < .01). Plasma lactate was lower in the Endo/Fl/Early NE group. Volume resuscitation was higher in Endo and Endo/Fl/Late NE groups with 28 +/- 6 and 27 +/- 4 mL, respectively, when compared with the Endo/Fl/Early NE group (19 +/- 3 mL) (p < .05).


CONCLUSIONS
The use of norepinephrine was associated with improved mean arterial pressure, sustained aortic and mesenteric blood flow, and better tissue oxygenation when compared with fluid resuscitation alone, irrespective of time of administration. The early use of norepinephrine plus volume expansion was associated with a higher proportion of blood flow redistributed to the mesenteric area, lower lactate levels, and less infused volume. Thus, the early use of norepinephrine is safe and may decrease the need for volume resuscitation.
Sennoun
Nacira
N
Equipe Avenir Inserm, U684, Shock Research Group, Nancy Université, Nancy, France.
Montemont
Chantal
C
Gibot
Sebastien
S
Lacolley
Patrick
P
Levy
Bruno
B
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004334:Drug Administration Schedule; D004731:Endotoxins; D005440:Fluid Therapy / Q000379:methods*; D006339:Heart Rate / Q000187:drug effects; D020896:Hypovolemia / Q000188:drug therapy* / Q000628:therapy; D019344:Lactic Acid / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage* / Q000494:pharmacology; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000188:drug therapy* / Q000628:therapy; D013152:Splanchnic Circulation / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000494:pharmacology
D004731:Endotoxins; D014662:Vasoconstrictor Agents; D019344:Lactic Acid; D009638:Norepinephrine