Comparison of Arginine Vasopressin, Terlipressin, or Epinephrine to Correct Hypotension in a Model of Anaphylactic Shock in Anesthetized Brown Norway Rats

Abstract

Arginine vasopressin (AVP) and terlipressin were proposed as alternatives to catecholamines in shock states characterized by decreased plasma AVP concentrations. The endogenous plasma AVP profile in anaphylactic shock is unknown. In an ovalbumin-sensitized anesthetized anaphylactic shock rat model, the authors investigated (1) plasma AVP concentrations and (2) the dose versus mean arterial pressure response for exogenous AVP and terlipressin and compared them with those of epinephrine. In a first series of rats (n = 12), endogenous plasma AVP concentrations were compared with a model of pharmacologically induced hypotension (nicardipine, n = 12). A second series was randomly assigned to three groups (AVP, n = 7; terlipressin, n = 7; epinephrine, n = 7) and dose (AVP: 8 doses, 0.03-100 U/kg; terlipressin: 7 doses, 0.03-30 microg/kg; epinephrine: 7 doses, 0.3-300 microg/kg)-response mean arterial pressure curves were plotted. Data are expressed as mean +/- SD. Endogenous plasma AVP concentrations were significantly lower in anaphylactic shock (57 +/- 26 pg/ml) than in the nicardipine group (91 +/- 43 pg/ml; P < 0.05). The ED50 was 10.6 microg/kg (95% confidence interval, 7.1-15.9) for epinephrine and 4.1 U/kg (95% confidence interval, 3.0-5.6) for AVP. Terlipressin did not change mean arterial pressure, regardless of the dose used. In a rat model, anaphylactic shock is associated with inadequately low plasma AVP concentrations. For clinically relevant doses, AVP and epinephrine had comparable effects on mean arterial pressure and heart rate values, whereas, unexpectedly, terlipressin was ineffective. These results are consistent with reports in humans experiencing anaphylaxis where AVP injection restored arterial pressure.