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Results of a Pilot Multicenter Genotype-based Randomized Placebo-controlled Trial of Propranolol to Reduce Pain After Major Thermal Burn Injury

Orrey, Danielle C. BA*; Halawa, Omar I. MD*; Bortsov, Andrey V. MD, PhD*; Shupp, Jeffrey W. MD; Jones, Samuel W. MD*; Haith, Linwood R. MD; Hoskins, Janelle M. PhD*; Jordan, Marion H. MD; Bangdiwala, Shrikant I. PhD*; Roane, Brandon R. BS*; Platts-Mills, Timothy F. MD, MSc*; Holmes, James H. MD§; Hwang, James MD*; Cairns, Bruce A. MD*; McLean, Samuel A. MD, MPH*

doi: 10.1097/AJP.0000000000000086
Original Articles

Background: Results of previous studies suggest that β-adrenoreceptor activation may augment pain, and that β-adrenoreceptor antagonists may be effective in reducing pain, particularly in individuals not homozygous for the catechol-O-methyltransferase (COMT) high-activity haplotype.

Materials and Methods: Consenting patients admitted for thermal burn injury at participating burn centers were genotyped; those who were not high-activity COMT homozygotes were randomized to propranolol 240 mg/d or placebo. Primary outcomes were study feasibility (consent rate, protocol completion rate) and pain scores on study days 5 to 19. Secondary outcomes assessed pain and posttraumatic stress disorder symptoms 6 weeks postinjury.

Results: Seventy-seven percent (61/79) of eligible patients were consented and genotyped, and 77% (47/61) were genotype eligible and randomized. Ninety-one percent (43/47) tolerated study drug and completed primary outcome assessments. In intention-to-treat and per-protocol analyses, patients randomized to propranolol had worse pain scores on study days 5 to 19.

Conclusions: Genotype-specific pain medication interventions are feasible in hospitalized burn patients. Propranolol is unlikely to be a useful analgesic during the first few weeks after burn injury.

*Department of Surgery, University of North Carolina, Chapel Hill

§Wake Forest Baptist Medical Center, Winston-Salem, NC

Washington Hospital Center, Washington, DC

Crozer Chester Medical Center, Upland, PA

D.C.O., O.I.H., A.V.B., S.I.B.: seen the original study data, reviewed the analysis of the data, and approved the final manuscript; J.W.S., S.W.J., L.R.H., J.M.H., M.H.J., B.R., T.F.P.-M., J.H.H., J.H., B.A.C.: reviewed the analysis of the data and approved the final manuscript; S.A.M.: seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.

Supported by Award Number UL1RR025747 from the National Center for Research Resources, the National Center for Advancing Translational Sciences, and the National Institutes of Health (Bethesda, MD), the NC Jaycee Burn Center Fund (Chapel Hill, NC), the Firefighters Research Fund, the DC Firefighters Burn Foundation (Washington, DC), and UNC Institutional Resources (Chapel Hill, NC). The authors declare no conflict of interest.

Reprints: Samuel A. McLean, MD, MPH, Department of Surgery, University of North Carolina at Chapel Hill, 101 Manning Drive, Medical School Wing C, Room B45, Chapel Hill, NC 27599-7010 (e-mail: smclean@aims.unc.edu).

Received September 17, 2013

Received in revised form March 14, 2014

Accepted February 11, 2014

© 2015 by Lippincott Williams & Wilkins