Vasopressin during uncontrolled hemorrhagic shock: less bleeding below the diaphragm, more perfusion above.

I n 1990, about 5 million people died worldwide as a result of injury, and it seems likely that the global epidemic of deadly trauma is only beginning. By 2020, deaths from injury are expected to increase to 8 million worldwide (2), and 30% of these fatalities will be attributable to uncontrolled hemorrhagic shock (3). Resuscitation of patients in uncontrolled hemorrhagic shock remains one of the most challenging aspects of emergency care, and trauma patients with complete cardiovascular collapse have an extremely poor chance of survival. For example, in a 1993 study of 138 trauma patients requiring cardiopulmonary resuscitation at the accident scene or during transport, none of the initially successfully resuscitated patients survived to hospital discharge (4). Accordingly, prevention of cardiac arrest has been considered to be the primary goal of trauma care (5). Unfortunately, trauma-related cardiac arrest is only the tip of the iceberg. Because hemorrhage-induced hypotension in trauma patients is predictive of frequent mortality and morbidity (6), fighting prolonged hypotension may be equally important. For hemodynamic stabilization of critically injured patients with uncontrolled hemorrhagic shock current trauma guidelines recommend infusion of crystalloid or colloid solutions in addition to catecholamine vasopressors. In a large clinical study of penetrating torso trauma, patients receiving delayed fluid resuscitation had better survival rates than those receiving immediate fluid resuscitation (7). Roberts et al. (8) further found no scientific evidence for the effectiveness of immediate fluid resuscitation in uncontrolled hemorrhagic shock. And a Cochrane review of randomized controlled trials found no evidence either for or against early or large volume IV fluid administration in uncontrolled hemorrhage (9). At present, therefore, we have no clearly proven fluid resuscitation strategy for uncontrolled hemorrhagic shock, and it seems expedient to consider alternative strategies to prevent immediate or delayed cardiac arrest in these patients. There are experimental and clinical data showing promising effects of infusing vasopressin in severe hemorrhagic shock. For example, vasopressin improved shortand long-term survival in a porcine model of uncontrolled hemorrhagic shock after penetrating liver trauma (10,11). In patients with intraabdominal bleeding and subsequent shock which was unresponsive to volume replacement, vasopressin was reported to be beneficial to stabilize cardiocirculatory status almost 20 yr ago (12). In addition to the strong vasopressor effect of vasopressin during catecholamine-refractory shock, another beneficial effect of vasopressin may be that blood is shifted away from a given subdiaphragmatic site of injury to the heart and brain, thus decreasing bleeding and optimizing vital organ perfusion. This specific effect of vasopressin may be especially life-saving in patients with uncontrolled hemorrhage resulting from subdiaphragmatic injury. In agreement with this hypothesis, we observed beneficial effects of vasopressin in both blunt and penetrating trauma patients with uncontrolled hemorrhagic shock (13) and were able to resuscitate a blunt trauma patient with uncontrolled hemorrhagic shock (14). Despite these promising observations, some researchers are concerned about vasopressin-related problems such as negative cardiac inotropy and myocardial ischemia (15,16), and others have questioned Data from a previous study (1) are being used for a vasopressin registration application process by Aguettant, Lyon, France, in Europe. Aguettant has once supported our working group with grant support. No author has a financial interest in drugs being discussed in this manuscript. Supported by science project no. 10618 and 9513 of The Austrian National Bank, Vienna, Austria. Accepted for publication April 20, 2005. Address correspondence to Karl H. Stadlbauer, MD, Innsbruck Medical University, Department of Anesthesiology and Critical Care Med, Anichstrasse 35, 6020 Innsbruck, Austria. Address electronic mail to [email protected]. Address reprint requests to Karl H. Lindner, MD, Innsbruck Medical University, Department of Anesthesiology and Critical Care Medicine, Anichstrasse 35, 6020 Innsbruck, Austria.