D-β-Hydroxybutyrate and melatonin for treatment of porcine hemorrhagic shock and injury: A melatonin dose-ranging study

Andrea Wolf, Kristine E. Mulier, Sydne L. Muratore, Gregory J. Beilman

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Objective: Treatment with a combination of d-β-hydroxybutyrate (BHB) and melatonin (M) improves survival in hemorrhagic shock models. Our objective was to find the most effective melatonin concentration in combination with 4 molar BHB (4 M BHB). Survival and markers of organ injury were analyzed in pigs exposed to pulmonary contusion, liver crush injury, and hemorrhagic shock and treated with lactated Ringer's solution; 4 M BHB/43 mM M; 4 M BHB/20 mM M; 4 M BHB/10 mM M; 4 M BHB/4.3 mM M; or 4 M BHB/0.43 mM M. This work is an extension of a previously published research study. Results: Survival was highest in pigs receiving 4 M BHB/43 mM M (13/14), followed by lactated Ringer's solution (11/16) and BHB/M with decreased melatonin concentrations (4 M BHB/20 mM M 3/6, 4 M BHB/10 mM M 2/6, 4 M BHB/4.3 mM M 3/6, 4 M BHB/0.43 mM M 1/6, p = 0.011). High mortality was associated with increases in serum lactate, higher liver and muscle injury markers and decreases in PaO2:FiO2 ratios. Our study indicates that treatment with 4 M BHB and melatonin concentrations below 43 mM lack the survival benefit observed from 4 M BHB/43 mM melatonin in pigs experiencing hemorrhagic shock and polytrauma.

Original languageEnglish (US)
Article number649
JournalBMC Research Notes
Issue number1
StatePublished - Nov 29 2017

Bibliographical note

Funding Information:
This work was supported by USDOD ARMY, Grant W81XWH-10-2-0121. Research reported in this publication was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2017 The Author(s).


  • Antioxidant
  • Blood loss
  • Hibernation
  • Ketone bodies
  • Melatonin
  • Resuscitation


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