Neurologic outcome with hemorrhagic hypotension after closed head trauma in rats: effect of early versus delayed conservative fluid therapy.

Abstract

This study examined (1) whether two previously reported, well-established models in rats, one a model of hemorrhagic hypotension and the other a model of closed head trauma, could be combined to evaluate neurologic outcome when hemorrhage occurs subsequent to head injury, and (2) the ability of the traditional, conservative approach to fluid therapy (3 mL of intravenous fluid for 1 mL of blood loss) to reverse the detrimental effects of hemorrhagic hypotension after closed head trauma. In addition, two strategies of fluid therapy (early and delayed) were examined. Fifty-six Sprague-Dawley male rats were divided into five groups with head injury at time 0 in groups 3 to 5, hemorrhage at 1 hour in groups 1, 2, 4, and 5, and intravenous fluid at 15 minutes (groups 2 and 5) or 60 minutes (groups 1 and 4) after hemorrhage. Head injury was delivered using a weight-drop impact of 0.5 J onto the closed cranium. Neurologic Severity Score (NSS) was determined at 1 hour (just before hemorrhage) and at 4 hours. NSS at 1 hour did not differ between groups 3 to 5 (15.5 (9-24) to 16 (2-21), median (range)). The amount of bleeding did not differ between groups during the first 15 minutes of hemorrhage (2.8 +/- 0.8 to 3.7 +/- 2.0 mL, mean +/- SD). After 60 minutes, cumulative blood loss in the delayed fluid therapy groups was less (3.1 +/- 1.13 mL in group 1 and 4.25 +/- 2.39 mL in group 4) than in the early fluid therapy groups (7.73 +/- 4.41 mL in group 2 and 6.85 +/- 2.36 mL in group 5) (analysis of variance, p < 0.01). The NSS of group 3 (head injury only) improved at 4 hours after injury (12 (5-20)), whereas the NSS of groups 4 and 5 (head injury followed by hemorrhage) deteriorated (24 (17-25) and 19.5 (9-25), respectively) (Kruskal-Wallis test,p < 0.05). In all the hemorrhage groups, fluid therapy failed to restore blood pressure to prehemorrhage levels. It is concluded that the two individual models of hemorrhagic hypotension and closed head trauma in rats can be combined to evaluate outcome when hemorrhage occurs subsequent to head injury. Furthermore, traditional, conservative fluid therapy, whether early or delayed, failed to restore blood pressure or to improve NSS when hemorrhage occurred after head injury. Blood loss was greater with early fluid therapy whether or not head injury was present.