Could Beta blockade improve outcome after injury by modulating inflammatory profiles?
BACKGROUND
Cardioprotection with beta-receptor antagonists improves outcome in high risk patients undergoing elective surgery. Recent trials have demonstrated an association between beta blocker (BB) use and improved outcomes after injury. The mechanisms through which BB result in improved outcomes remain poorly elucidated. In vitro evidence supports that BB modulates the postinjury inflammatory response. The purpose of this study was to examine the effects of BB on inflammatory profiles in injured patients at increased risk for heart disease.


METHODS
A pseudo-randomized, controlled trial of injured patients over 55 admitted to the intensive care unit was conducted. Patients were randomized to receive continuous BB or standard of care. Patients with a reported history of prehospital BB use were enrolled into an observational arm of the trial, continued on BB, and analyzed with the continuous BB group. Plasma interleukin (IL)-6 and IL-1beta levels were measured by enzyme-linked immunosorbent assay at baseline and day 1, 2, and 4 after BB initiation. Cytokine data were log transformed for normality assumptions. Repeated measures analysis of variance was used to test for within-group differences in cytokine levels over time.


RESULTS
Forty-two patients were enrolled. Seventeen patients were randomized to the control group and 25 patients received continuous BB (10 randomized/15 observational). There was no difference in gender, age, prior history of heart disease, or admission heart rate, systolic blood pressure or initial base deficit between groups. Baseline levels of IL-6 and IL-1beta did not differ between groups. Levels of IL-6, but not IL-1beta, decreased over time in patients receiving BB (p = 0.04), whereas levels in controls remained unchanged (p = 0.27). There were no BB related complications.


CONCLUSIONS
Use of BB decreases serum IL-6 levels over time in injured patients at risk for heart disease. This may contribute to improved outcomes noted in trauma patients receiving BB. Additionally, BB use in this population of patients is safe after endpoints of resuscitation have been met.
Friese
Randall S
RS
Division of Burn, Trauma, Critical Care, Department of Surgery, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA. randall.friese@utsouthwestern.edu
Barber
Robert
R
McBride
Dara
D
Bender
Jessica
J
Gentilello
Larry M
LM
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis*; D015601:Injury Severity Score; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D018570:Risk Assessment; D016019:Survival Analysis; D014193:Trauma Centers; D016896:Treatment Outcome; D019037:Urban Health Services; D014947:Wounds and Injuries / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy
D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6