Differing effects of epinephrine, norepinephrine, and vasopressin on survival in a canine model of septic shock.
During sepsis, limited data on the survival effects of vasopressors are available to guide therapy. Therefore, we compared the effects of three vasopressors on survival in a canine septic shock model. Seventy-eight awake dogs infected with differing doses of intraperitoneal Escherichia coli to produce increasing mortality were randomized to receive epinephrine (0.2, 0.8, or 2.0 microg.kg(-1).min(-1)), norepinephrine (0.2, 1.0, or 2.0 microg.kg(-1).min(-1)), vasopressin (0.01 or 0.04 U/min), or placebo in addition to antibiotics and fluids. Serial hemodynamic and biochemical variables were measured. Increasing doses of bacteria caused progressively greater decreases in survival (P <0.06), mean arterial pressure (MAP) (P <0.05), cardiac index (CI) (P <0.02), and ejection fraction (EF) (P=0.02). The effects of epinephrine on survival were significantly different from those of norepinephrine and vasopressin (P=0.03). Epinephrine had a harmful effect on survival that was significantly related to drug dose (P=0.02) but not bacterial dose. Norepinephrine and vasopressin had beneficial effects on survival that were similar at all drug and bacteria doses. Compared with concurrent infected controls, epinephrine caused greater decreases in CI, EF, and pH, and greater increases in systemic vascular resistance and serum creatinine than norepinephrine and vasopressin. These epinephrine-induced changes were significantly related to the dose of epinephrine administered. In this study, the effects of vasopressors were independent of severity of infection but dependent on the type and dose of vasopressor used. Epinephrine adversely affected organ function, systemic perfusion, and survival compared with norepinephrine and vasopressin. In the ranges studied, norepinephrine and vasopressin have more favorable risk-benefit profiles than epinephrine during sepsis.
Critical Care Medicine Department, National Institutes of Health, 10 Center Dr., Bldg 10, Rm 7D43, Bethesda, MD 20892, USA. pminneci@mail.cc.nih.gov
Peter C
PC
Minneci
Katherine J
KJ
Deans
Steven M
SM
Banks
Renee
R
Costello
Gyorgy
G
Csako
Peter Q
PQ
Eichacker
Robert L
RL
Danner
Charles
C
Natanson
Steven B
SB
Solomon
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000401:mortality; D007262:Infusions, Intravenous; D009638:Norepinephrine / Q000494:pharmacology*; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D009638:Norepinephrine; D004837:Epinephrine