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Sugar or salt? The relative roles of the glucocorticoid and mineralocorticoid axes in traumatic shock

Nelson, Daniel W. DO; Black, George E. MD; Thomas, Richard L. MD; Eckert, Matthew J. MD; Hoffer, Zachary S. MD; Martin, Matthew J. MD

Journal of Trauma and Acute Care Surgery: December 2015 - Volume 79 - Issue 6 - p 1023–1029
doi: 10.1097/TA.0000000000000800
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BACKGROUND Glucocorticoid deficiency (GD) has been proposed as a key contributor to shock states, but the presence and role of acute mineralocorticoid deficiency may be of equal or greater significance. We sought to analyze the incidence and degree of acute mineralocorticoid deficiency and GD in an animal model of severe hemorrhage and shock.

METHODS Fifty-seven swine underwent 35% volume-controlled hemorrhage followed by aortic cross-clamping for 50 minutes to induce truncal ischemia-reperfusion. Protocol-guided resuscitation was performed. Laboratory analysis included cortisol, aldosterone, and plasma renin activity. The aldosterone-to-renin ratio (ARR) was calculated at each time point, and changes were correlated to markers of perfusion.

RESULTS Mean baseline cortisol levels were 5.8 μg/dL. Following hemorrhage, there was a significant increase in mean cortisol to 9.2 μg/dL (p < 0.001). After 1 hour of reperfusion, there was no change in mean cortisol levels (9.8 μg/dL, p = 0.12). Mean baseline aldosterone was 13.3 pg/mL. Aldosterone levels before cross-clamp removal increased significantly to 115.1 pg/mL (p < 0.001) and then rapidly declined to 49.2 pg/mL (p < 0.001) after 1 hour of reperfusion. Conversely, baseline plasma renin activity was 0.75 ng/mL per hour and increased significantly before cross-clamp removal (1.8) and at 1 hour (8.9, both p < 0.001). The ARR at baseline was 96.1 and increased to 113.5 (p = 0.68) before cross-clamp removal but significantly declined following 1 hour of reperfusion to 7.6 (p < 0.001). Overall, this represented a 93% reduction in mean ARR following reperfusion. The degree of aldosterone deficiency correlated with degree of systemic shock as measured by arterial base deficit (r = 0.47, p = 0.04), while cortisol showed no correlation.

CONCLUSION Hemorrhagic shock with ischemia-reperfusion injury resulted in only modest impact on the glucocorticoid axis, but major dysfunction of the mineralocorticoid axis and severe hyperreninemic hypoaldosteronism. The degree of aldosterone deficiency may provide prognostic information or offer potential targets for pharmacologic intervention.

LEVEL OF EVIDENCE Diagnostic study, level III.

From the Departments of Surgery (D.W.N., G.E.B., M.J.E., M.J.M.), and Pathology (R.L.T., Z.S.H.), Madigan Army Medical Center, Fort Lewis, Tacoma, Washington.

Submitted: January 20, 2015, Revised: June 3, 2015, Accepted: June 5, 2015, Published: October 1, 2015.

This study was presented at the 45th Annual Meeting of the Western Trauma Association, March 1–6, 2015, in Telluride, Colorado.

The results and opinions expressed in this article are those of the authors and do not reflect the opinions or official policy of the US Army or the Department of Defense.

Address for reprints: Matthew J. Martin, MD, Department of Surgery, Madigan Army Medical Center, 9040-A Fitzsimmons Ave, Tacoma, WA 98431; email: matthew.j.martin16.mil@mail.mil.

© 2015 Lippincott Williams & Wilkins, Inc.