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Characterization of Persistent Hyperglycemia: What Does It Mean Postinjury?

Sperry, Jason L. MD, MPH; Frankel, Heidi L. MD; Nathens, Avery B. MD, PhD, MPH; O’keefe, Grant E. MD, PhD; Cuschieri, Joseph MD; Moore, Ernest E. MD; Maier, Ronald V. MD; Minei, Joseph P. MDThe Inflammation and the Host Response to Injury Investigators

The Journal of Trauma: Injury, Infection, and Critical Care: April 2009 - Volume 66 - Issue 4 - p 1076-1082
doi: 10.1097/TA.0b013e31817db0de
Original Articles

Background: Strict glycemic control has been shown to reduce both morbidity and mortality in critically ill surgical patients; however, overly aggressive management of hyperglycemia may also be associated with deleterious effects. We sought to characterize clinical outcomes associated with different levels of persistent hyperglycemia (PH) in a cohort of severely injured patients with trauma, when a strict glycemic control protocol (target glucose 80–110 mg/dL) was implemented.

Methods: Data were obtained from a multicenter prospective cohort study evaluating clinical outcomes in blunt injured adults with hemorrhagic shock. Glycemic control was analyzed using the average maximum daily glucose values from postinjury day 2 (>48 hours after injury) to postinjury day 5. PH was defined as a mean glucose value >130 mg/dL, and was categorized into three different severity levels (I–III) based on the distribution of mean 4-day glucose values for the cohort. Separate Cox proportional hazard regression models were then used to determine whether PH was independently associated with mortality and nosocomial infection (NI), and the level of glycemic control that was associated with these poor outcomes.

Results: Overall mortality and NI rates for the study population (n = 862) were 10.8% and 49.6%, respectively. Cox proportional hazard regression revealed that PH was independently associated with almost an 80% higher mortality in patients with mean 4-day glucose values >145 mg/dL (group II) and almost a twofold higher mortality in patients with >165 mg/dL (group III). However, PH was not independently associated with a higher risk of NI at any level. Patients with PH did have a higher incidence of early multiple organ failure (within first 48 hours: 30.2% vs. 41.6% p = 0.001), which preceded the documentation of PH in the majority of patients.

Conclusion: Maintenance of daily maximum glucose values <145 mg/dL was independently associated with a survival benefit after injury. Patients with PH, despite aggressive insulin therapy, had a higher incidence of multiple organ failure and an associated higher risk of mortality. However, the strict glycemic control protocol in the current trauma cohort seems to have prevented the association of PH and infectious complications, which has been documented in prior studies. This analysis further validates the importance of strict glycemic control after injury, and highlights the need for further studies on the mechanism responsible for these findings.

From the Division of Trauma and General Surgery (J.L.S.), University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Division of Burn, Trauma, Critical Care (H.L.F., J.P.M.), University of Texas Southwestern Medical Center, Dallas, Texas; Division of General Surgery and Trauma (A.B.N.), St. Michael’s Hospital and the Department of Surgery, University of Toronto, Toronto, Canada; Division of General Surgery and Trauma (G.E.O., J.C., R.V.M.), Harborview Medical Center and the Department of Surgery, University of Washington, Washington; and Department of Surgery (E.E.M.), Denver Health Medical Center and The University of Colorado Health Sciences Center, Denver, Colorado.

Submitted for publication October 26, 2007.

Accepted for publication April 24, 2008.

Supported by funding from the National Institutes of Health (NIH NIGMS U54 GM062119-1).

Presented at the Surgical Infection Society 27th annual meeting, Toronto, Ontario, Canada, April 2007.

Address for reprints: Jason L. Sperry, MD, MPH, Division of General Surgery and Trauma, Department of Surgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213; email:

© 2009 Lippincott Williams & Wilkins, Inc.