Background: Although rapid fluid resuscitation continues to be an important component of the initial therapy for trauma patients, it remains unknown whether the rate of fluid administration after trauma-hemorrhage has any deleterious or beneficial effects on immunity.
Methods: Male C3H/HeN mice were subjected to sham operation or soft-tissue trauma (midline laparotomy) and hemorrhagic shock (mean arterial blood pressure of 35+/-5 mm Hg for 90 minutes) followed by resuscitation with four times the volume of shed blood in the form of lactated Ringer's solution over 30 minutes (rapid rate), 60 minutes (moderate rate), or 120 minutes (slow rate). The animals were killed at either 4 hours or 4 days after the end of trauma-hemorrhage. Spleens were harvested and splenocyte interleukin (IL)-3 and interferon-gamma (IFN-gamma) release as well as splenic macrophage IL-1beta and IL-6 release were determined.
Results: The results indicate that at 4 hours after trauma-hemorrhage, splenocyte IL-3 and IFN-gamma release were significantly depressed in all animals subjected to trauma-hemorrhage compared with sham-operated animals. At 4 days after trauma-hemorrhage, splenocyte IL-3 and IFN-gamma release were restored in mice resuscitated with the slow rate of resuscitation; however, the release of these cytokines remained significantly depressed in animals resuscitated with the moderate or rapid rates. Splenic macrophage IL-1beta and IL-6 release were significantly depressed at 4 hours after trauma-hemorrhage. At 4 days after trauma-hemorrhage, the release of these proinflammatory cytokines was still depressed in animals resuscitated with the rapid rate. In contrast, splenic macrophage IL-1beta and IL-6 release were restored in mice receiving the slow rate of resuscitation.
Conclusion: These results suggest that a slower rate of fluid resuscitation after trauma-hemorrhage leads to a faster restoration of the depressed cell-mediated immunity, whereas rapid fluid resuscitation produces a prolonged depression of immune responses. In view of this, we propose that a prospective clinical study of this type must be performed in a select group of trauma patients to determine whether or not a slower rate of fluid resuscitation also improves immune responses in trauma patients.