Do different rates of fluid resuscitation adversely or beneficially influence immune responses after trauma-hemorrhage?

Background: Although rapid fluid resuscitation continues to be an important component of the initial therapy for trauma patients, it remains unknown w hether the rate of fluid administration after trauma-hemorrhage has any del eterious 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 pres sure 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 ov er 30 minutes (rapid rate), 60 minutes (moderate rate), or 120 minutes (slo w 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-1 beta and IL-6 release were determined. Results: The results indicate that at 4 hours after trauma-hemorrhage, sple nocyte IL-3 and IFN-gamma release were significantly depressed in all anima ls subjected to trauma-hemorrhage compared with sham-operated animals. At 4 days after trauma-hemorrhage, splenocyte IL-3 and IPN-gamma release were r estored 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-1 beta and IL-6 release were significantly depressed at 4 hours after trauma-hemo rrhage, At 4 days after trauma-hemorrhage, the release of these proinflamma tory cytokines was still depressed in animals resuscitated,vith the rapid r ate. In contrast, splenic macrophage IL-1 beta and IL-6 release were restor ed 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 cel l-mediated immunity, whereas rapid fluid resuscitation produces a prolonged depression of immune responses, In view of this, we propose that a prospec tive clinical study of this type must be performed in a select group of tra uma patients to determine whether or not a slower rate of fluid resuscitati on also improves immune responses in trauma patients.