Optimal adrenergic support in septic shock due to peritonitis.
BACKGROUND
The authors evaluated optimal adrenergic support using norepinephrine, dopamine, and dobutamine in a clinically relevant model of septic shock.


METHODS
Twenty-eight mature, female, anesthetized sheep (weight, 30.5 +/- 3.6 kg) underwent cecal ligation and perforation and were randomized into four groups of seven animals to be treated with norepinephrine, dopamine-norepinephrine, dobutamine-norepinephrine, or no adrenergic agent. In all groups, lactated Ringer's solution was administered to restore cardiac filling pressures to baseline. In the norepinephrine group, norepinephrine (0.5-5 microg. kg(-1). min(-1)) was titrated to maintain mean arterial pressure between 75-85 mmHg. In the dopamine-norepinephrine group, dopamine was given first, and norepinephrine was added only when mean arterial pressure remained below 75 mmHg despite the infusion of 20 microg. kg(-1). min(-1) dopamine. In the dobutamine-norepinephrine group, dobutamine was started at the same time as norepinephrine and titrated up to 20 microg. kg(-1). min(-1) to get a 15% increase in cardiac output.


RESULTS
The dobutamine-norepinephrine group had greater cardiac output; superior mesenteric blood flow, oxygen delivery (Do(2)), and oxygen consumption ([OV0312]o(2)); and lower blood lactate concentration and partial pressure of carbon dioxide (Pco(2)) gap than the controls did. Cumulative urine output was significantly higher in the dobutamine-norepinephrine group than in the other groups. Survival time was significantly longer in the dobutamine-norepinephrine (24 +/- 4 h), dopamine- norepinephrine (24 +/- 6 h), and norepinephrine (20 +/- 1 h) groups than the control group (17 +/- 2 h; P < 0.05 vs. other groups), and significantly longer in the combined dopamine-norepinephrine and dobutamine-norepinephrine groups (24 +/- 5 h) than in the norepinephrine alone group (P < 0.05). Histologic examination of lung biopsies revealed less severe lesions in the dobutamine-norepinephrine group than in the control and norepinephrine alone groups. Anatomic alterations in the lung, liver, and small intestine were less severe in the dobutamine-norepinephrine group than in the other groups.


CONCLUSIONS
In this prolonged septic shock model, association of norepinephrine with either dopamine or dobutamine resulted in the longest survival and the least severe pulmonary lesions. The combination of dobutamine with norepinephrine was associated with a better myocardial performance, greater Do(2) and [OV0312]o(2), lower blood lactate concentration and Pco(2) gap, and less anatomic injury.
Sun
Qinghua
Q
Department of Intensive Care, Erasme Hospital, Free University of Brussels, Brussels, Belgium.
Tu
Zizhi
Z
Lobo
Suzana
S
Dimopoulos
George
G
Nagy
Nathalie
N
Rogiers
Peter
P
De Backer
Daniel
D
Vincent
Jean-Louis
JL
D018663:Adrenergic Agents / Q000627:therapeutic use*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use; D004280:Dobutamine / Q000627:therapeutic use; D004298:Dopamine / Q000627:therapeutic use; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D019344:Lactic Acid / Q000097:blood; D009638:Norepinephrine / Q000627:therapeutic use; D010101:Oxygen Consumption / Q000187:drug effects; D010538:Peritonitis / Q000150:complications*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D015656:Respiratory Mechanics / Q000187:drug effects; D012756:Sheep; D012772:Shock, Septic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016019:Survival Analysis; D013566:Sympathomimetics / Q000627:therapeutic use
D018663:Adrenergic Agents; D002316:Cardiotonic Agents; D013566:Sympathomimetics; D019344:Lactic Acid; D004280:Dobutamine; D004298:Dopamine; D009638:Norepinephrine