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

Educational Objective To determine the effect of low-dose vasopressin (AVP) administration on the need for blood transfusion in a select injured population with hemorrhagic shock.
1 Credit CME
Key Points

Question  Does low-dose arginine vasopressin supplementation decrease the need for blood product transfusions in patients with trauma and hemorrhagic shock?

Findings  In this randomized clinical trial of 100 adult trauma patients in hemorrhagic shock, arginine vasopressin supplementation significantly decreased the volume of blood products given in the first 48 hours by a median of 1.4 L without increasing complications.

Meaning  Including low-dose arginine vasopressin supplementation when resuscitating trauma patients in hemorrhagic shock may safely decrease the need for blood products.


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 identifier: NCT01611935

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Article Information

Accepted for Publication: May 26, 2019.

Corresponding Author: Carrie A. Sims, MD, PhD, Division of Traumatology, Surgical Critical Care, and Emergency Surgery, Department of Surgery, University of Pennsylvania, 51 N 39th St, Medical Office Building, Ste 120, Philadelphia, PA 19104 (

Published Online: August 28, 2019. doi:10.1001/jamasurg.2019.2884

Author Contributions: Dr Sims and Ms Zimmerman had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Sims, Grill, Reilly.

Acquisition, analysis, or interpretation of data: Sims, Holena, Kim, Pascual, Smith, Martin, Seamon, Shiroff, Raza, Kaplan, Grill, Zimmerman, Mason, Abella.

Drafting of the manuscript: Sims, Grill, Zimmerman, Abella.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Raza, Zimmerman.

Obtained funding: Sims.

Administrative, technical, or material support: Sims, Holena, Pascual, Smith, Martin, Seamon, Raza, Kaplan, Grill, Mason, Abella, Reilly.

Supervision: Sims, Martin.

Conflict of Interest Disclosures: Dr Sims reported receiving grants from the National Trauma Institute/Department of Defense during the conduct of the study. Dr Seamon reported receiving personal fees from Wolters Kluwer outside the submitted work. No other disclosures were reported.

Funding/Support: This study was supported by award NTI-TRA-09-062 from the National Trauma Institute and prime award W81XWH-10-0924 from the Department of the Army (Dr Sims).

Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The US Army Medical Research Acquisition Activity, 820 Chandler St, Fort Detrick, MD 21702, is the awarding and administering acquisition office. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of the Army or the National Trauma Institute.

Data Sharing Statement: See Supplement 3.

Additional Contributions: Joy Steele, RN, served as the Clinical Research Coordinator for this study. Myra Rodriguez, BA, provided administrative assistance, regulatory support, and coordination with the US Food and Drug Administration and the institutional review board of the University of Pennsylvania. Both were paid employees at the University of Pennsylvania.

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