Effect of Low-Dose Supplementation of Arginine Vasopressin on Need for Blood Product Transfusions in Patients With Trauma and Hemorrhagic Shock: A Randomized Clinical Trial

Importance Current therapies for traumatic blood loss focus on hemorrhage control and blood volume replacement. Severe hemorrhagic shock, however, is associated with a state of arginine vasopressin (AVP) deficiency, and supplementation of this hormone may decrease the need for blood products in resuscitation. Objective To determine whether low-dose supplementation of AVP in patients with trauma (hereinafter referred to as trauma patients) and with hemorrhagic shock decreases their need for transfused blood products during resuscitation. Design, Setting, and Participants This randomized, double-blind placebo-controlled clinical trial included adult trauma patients (aged 18-65 years) who received at least 6 U of any blood product within 12 hours of injury at a single urban level 1 trauma center from May 1, 2013, through May 31, 2017. Exclusion criteria consisted of prehospital cardiopulmonary resuscitation, emergency department thoracotomy, corticosteroid use, chronic renal insufficiency, coronary artery disease, traumatic brain injury requiring any neurosurgical intervention, pregnancy, prisoner status, or AVP administration before enrollment. Data were analyzed from May 1, 2013, through May 31, 2017, using intention to treat and per protocol. Interventions After administration of an AVP bolus (4 U) or placebo, participants received AVP (≤0.04 U/min) or placebo for 48 hours to maintain a mean arterial blood pressure of at least 65 mm Hg. Main Outcomes The primary outcome was total volume of blood product transfused. Secondary end points included total volume of crystalloid transfused, vasopressor requirements, secondary complications, and 30-day mortality. Results One hundred patients underwent randomization (49 to the AVP group and 51 to the placebo group). Patients were primarily young (median age, 27 years [interquartile range {IQR}, 22-25 years]) and male (n = 93) with penetrating trauma (n = 79). Cohort characteristics before randomization were well balanced. At 48 hours, patients who received AVP required significantly less blood products (median, 1.4 [IQR, 0.5-2.6] vs 2.9 [IQR, 1.1-4.8] L;P = .01) but did not differ in requirements for crystalloids (median, 9.9 [IQR, 7.9-13.0] vs 11.0 [8.9-15.0] L;P = .22) or vasopressors (median, 400 [IQR, 0-5900] vs 1400 [IQR, 200-7600] equivalent units;P = .22). Although the groups had similar rates of mortality (6 of 49 [12%] vs 6 of 51 [12%];P = .94) and total complications (24 of 44 [55%] vs 30 of 47 [64%];P = .37), the AVP group had less deep venous thrombosis (5 of 44 [11%] vs 16 of 47 [34%];P = .02). Conclusions and Relevance Low-dose AVP during the resuscitation of trauma patients in hemorrhagic shock decreases blood product requirements. Additional research is necessary to determine whether including AVP improves morbidity or mortality. Trial Registration ClinicalTrials.gov identifier:NCT01611935