Vasopressin improves survival in a porcine model of abdominal vascular injury

Abstract

Introduction: We sought to determine and compare the effects of vasopressin, fluid resuscitation and saline placebo on haemodynamic variables and short-term survival in an abdominal vascular injury model with uncontrolled haemorrhagic shock in pigs.

Methods: During general anaesthesia, a midline laparotomy was performed on 19 domestic pigs, followed by an incision (width about 5 cm and depth 0.5 cm) across the mesenterial shaft. When mean arterial blood pressure was below 20 mmHg, and heart rate had declined progressively, experimental therapy was initiated. At that point, animals were randomly assigned to receive vasopressin (0.4 U/kg; n = 7), fluid resuscitation (25 ml/kg lactated Ringer's and 25 ml/kg 3% gelatine solution; n = 7), or a single injection of saline placebo (n = 5). Vasopressin-treated animals were then given a continuous infusion of 0.08 U/kg per min vasopressin, whereas the remaining two groups received saline placebo at an equal rate of infusion. After 30 min of experimental therapy bleeding was controlled by surgical intervention, and further fluid resuscitation was performed. Thereafter, the animals were observed for an additional hour.

Results: After 68 +/- 19 min (mean +/- standard deviation) of uncontrolled bleeding, experimental therapy was initiated; at that time total blood loss and mean arterial blood pressure were similar between groups (not significant). Mean arterial blood pressure increased in both vasopressin-treated and fluid-resuscitated animals from about 15 mmHg to about 55 mmHg within 5 min, but afterward it decreased more rapidly in the fluid resuscitation group; mean arterial blood pressure in the placebo group never increased. Seven out of seven vasopressin-treated animals survived, whereas six out of seven fluid-resuscitated and five out of five placebo pigs died before surgical intervention was initiated (P < 0.0001).

Conclusion: Vasopressin, but not fluid resuscitation or saline placebo, ensured short-term survival in this vascular injury model with uncontrolled haemorrhagic shock in sedated pigs.

Figure 1

Flow chart of the experimental protocol. BL, baseline; MAP, mean arterial pressure.

Figure 2

Mean arterial blood pressure. Values are expressed as mean (± standard deviation) arterial blood pressure before, during and after administration of a 0.4 U/kg bolus dose and 0.08 U/kg per min continuous infusion of vasopressin (n = 7), fluid resuscitation (divided into survivors [n = 1] and nonsurvivors [n = 6]), and saline placebo (n = 5). 'Uncontrolled haemorrhage' indicates the non-intervention interval after vessel injury; 'experimental therapy' indicates vasopressin treatment, fluid resuscitation, or saline placebo administration without bleeding control; and 'surgical intervention' indicates surgical management of the mesenteric shaft to control bleeding. The x-axis does not reveal the true time slope. BL, baseline; DA, drug administration.

Figure 3

Total blood loss. Values are expressed as mean (± standard deviation) total blood loss before, during, and after administration of a 0.4 U/kg bolus dose and 0.08 U/kg per min continuous infusion of vasopressin (n = 7), fluid resuscitation (divided into survivors [n = 1] and nonsurvivors [n = 6]), and saline placebo (n = 5). 'Uncontrolled haemorrhage' indicates the non-intervention interval after vessel injury; 'experimental therapy' indicates vasopressin treatment, fluid resuscitation, or saline placebo administration without bleeding control; and 'surgical intervention' indicates surgical management of the mesenteric shaft to control bleeding. The x-axis does not reveal the true time slope. BL, baseline; DA, drug administration.

Figure 4

Heart rate. Values are expressed as mean (± standard deviation) heart rate before, during, and after administration of a 0.4 U/kg bolus dose and 0.08 U/kg per min continuous infusion of vasopressin (n = 7), fluid resuscitation (divided into survivors [n = 1] and nonsurvivors [n = 6]), and saline placebo (n = 5). 'Uncontrolled haemorrhage' indicates the non-intervention interval after vessel injury; 'experimental therapy' indicates vasopressin treatment, fluid resuscitation, or saline placebo administration without bleeding control; and 'surgical intervention' indicates surgical management of the mesenteric shaft to control bleeding. The x-axis does not reveal the true time slope. BL, baseline; DA, drug administration.

Figure 5

End-tidal carbon dioxide. Values are expressed as mean (± standard deviation) end-tidal carbon dioxide before, during, and after administration of a 0.4 U/kg bolus dose and 0.08 U/kg per min continuous infusion of vasopressin (n = 7), fluid resuscitation (divided into survivors [n = 1] and nonsurvivors [n = 6]), and saline placebo (n = 5). 'Uncontrolled haemorrhage' indicates the non-intervention interval after vessel injury; 'experimental therapy' indicates vasopressin treatment, fluid resuscitation, or saline placebo administration without bleeding control; and 'surgical intervention' indicates surgical management of the mesenteric shaft to control bleeding. The x-axis does not reveal the true time slope. BL, baseline; DA, drug administration.

Figure 6

Kaplan-Meier survival curves. Shown are Kaplan-Meier survival curves before, during, and after administration of a 0.4 U/kg bolus dose and 0.08 U/kg per min continuous infusion of vasopressin (n = 7), fluid resuscitation (n = 7), and saline placebo (n = 5). 'Uncontrolled haemorrhage' indicates the non-intervention interval after vessel injury; 'experimental therapy' indicates vasopressin treatment, fluid resuscitation, or saline placebo administration without bleeding control; and 'surgical intervention' indicates surgical management of the mesenteric shaft to control bleeding. The x-axis does not reveal the true time slope. P < 0.0001. BL, baseline; DA, drug administration.