AVERT Shock: Arginine Vasopressin During the Early Resuscitation of Traumatic Shock
Condition: Traumatic Shock
MeSH terms: Diabetes Insipidus; Shock; Shock, Traumatic
Study type: Interventional
Phase: Phase 2

Summary: 
      Trauma patients, who are transfused with multiple blood products to treat shock due to blood
      loss, frequently develop inappropriately low vasopressin levels. Vasopressin is a hormone
      necessary to maintain an adequate blood pressure and low levels have been associated with the
      need for increased transfusions, vasopressors and additional morbidity. Vasopressin is
      routinely used in the ICU to treat septic shock and other disease processes resulting in
      decreased vasopressin levels and low blood pressure. This study will investigate the
      potential benefit of early vasopressin supplementation during the resuscitation of trauma
      patients and the applicability of using copeptin as a vasopressin biomarker. Trauma patients
      who receive 6 or more units of blood product within 12 hours of arrival will be randomized to
      receive a vasopressin bolus plus infusion or a similar volume of a placebo (normal saline)
      for 48 hours. Serial blood samples will be taken for 5 days post-injury. Clinical and
      demographic data will be recorded prospectively.
    

Detailed description: 
      Trauma remains the leading cause of death for those under the age of 40 in the United States,
      with a large percentage of patients dying from blood loss within the initial post-injury
      hours. Although resuscitation with intravenous fluids and blood products has remained the
      gold standard over the last twenty years, vigorous volume resuscitation may not be curative
      and has been associated with the development of serious complications including coagulopathy,
      acute lung injury, and abdominal compartment syndrome. Massive resuscitation also profoundly
      alters the neuroendocrine milieu needed to maintain vasomotor tone and these severely injured
      patients may progress to a state of recalcitrant hypotension, multi-organ failure, and
      ultimately death. The inclusion of vasoactive hormones during resuscitation could potentially
      prevent the profound hypotension seen in late stage shock, limit the need for aggressive
      volume and blood product resuscitation, and decrease the incidence of
      resuscitation-associated complications. As such, there exists an urgent need to evaluate
      novel resuscitation strategies that target neuroendocrine deficiencies in hemorrhagic shock.
      The hormone arginine vasopressin (AVP), in particular, may prove a useful adjunct during
      resuscitation. Secreted by the posterior pituitary, vasopressin is essential for maintaining
      vasomotor tone during hemorrhagic shock and low levels are associated with the development of
      catecholamine-resistant hypotension and profound venodilation. Trauma patients who require
      more than 5 units of blood products during their initial resuscitation are at risk for
      developing a vasopressin insufficiency, the need for vasopressor support, and often require
      longer ICU stays. Vasopressin has enjoyed widespread off-label use as a vasopressor in
      cardiac arrest, septic shock, and post-cardiopulmonary vasodilatory shock. The central
      hypothesis is that trauma patients who present in hemorrhagic shock are at risk for
      vasopressin deficiency and would benefit from early vasopressin supplementation. This study
      will investigate if early use of vasopressin during the resuscitation of traumatic shock
      results in fewer blood transfusions, a decreased need for crystalloid resuscitation, and a
      lower incidence of resuscitation related complications.
    

Intervention name(s): Vasopressin
Intervention type(s): Drug
Intervention description(s): After receiving greater than 6 units of blood product within the first 12 hours of admission, trauma patients will be randomized to either normal saline or vasopressin. Subjects will receive an initial 4 unit bolus followed by an infusion of 0 to 0.04 units titrated to maintain a mean arterial blood pressure of equal to or greater than 65 mmHg for a total of 48 hours.
Intervention MeSH terms: Vasopressins; Arginine Vasopressin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: trauma; shock; vasopressin; blood transfusion