THE ABSENCE OF CIRCADIAN CUES DURING RECOVERY FROM SEPSIS MODIFIES PITUITARY-ADRENOCORTICAL FUNCTION AND IMPAIRS SURVIVAL

Lighting and other environmental cues in the intensive care unit rarely adhere to a consistent daily pattern. To determine the influence of the daily light/dark (LD) cycle on recovery from sepsis, male Sprague Dawley rats were acclimated to lights-on condition at 6 AM and lights-off condition at 6 PM for 6 to 14 days. Catheter placement and cecal ligation and puncture (CLP) were performed under ketamine and xylazine. Rats were returned to the established LD cycle, to constant light (LL), or to constant dark (DD) at 6 PM. One-week survival was 83.33% during LD (n = 24), 62.5% during LL (n = 16), and 31.25% during DD (n = 16; P < 0.01 for difference from the LD group). Both plasma adrenocorticotropin (ACTH) and corticosterone levels in the morning of the first day after CLP were greater during DD than during LD (P < 0.05 in each case). The early elevation in ACTH was independent of survival. However, the greater frequency of nonsurviving DD rats accounted for the elevation of corticosterone in the DD group. Overall, most nonsurviors had a unique response pattern composed of an early elevation of corticosterone in relation to plasma ACTH that then declined to a value above the normal circadian peak despite a late increase in endogenous ACTH when death was imminent. We conclude that the circadian cues provided by the LD cycle improve survival after CLP. Removal of these cues by DD increases the early appearance and incidence of a hormonal response pattern that is associated with a lethal outcome.

[1]  L. Lubarsky,et al.  Glucocorticoid insufficiency in patients who present to the hospital with severe sepsis: a prospective clinical trial. , 2003, Critical care medicine.

[2]  J Licinio,et al.  Plasma leptin levels are increased in survivors of acute sepsis: associated loss of diurnal rhythm, in cortisol and leptin secretion. , 1998, The Journal of clinical endocrinology and metabolism.

[3]  R. Macleod,et al.  Differential release of tumor necrosis factor and IL-6 from adrenal zona glomerulosa cells in vitro. , 1995, The American journal of physiology.

[4]  D. Carlson.  Adrenocorticotropin correlates strongly with endotoxemia after intravenous but not after intraperitoneal inoculations of E. coli. , 1997, Shock.

[5]  Djillali Annane,et al.  Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis , 2004, BMJ : British Medical Journal.

[6]  G. Weinhouse,et al.  Sleep in the critically ill patient. , 2006, Sleep.

[7]  I. Chaudry,et al.  Sepsis and septic shock--a review of laboratory models and a proposal. , 1980, The Journal of surgical research.

[8]  F. Keleştimur,et al.  Adrenal functions in patients with sepsis. , 2009, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[9]  Robert L. Mason,et al.  Statistical Principles in Experimental Design , 2003 .

[10]  I. Chaudry,et al.  Adrenal insufficiency during the late stage of polymicrobial sepsis , 1999, Critical care medicine.

[11]  Charles Natanson,et al.  Meta-Analysis: The Effect of Steroids on Survival and Shock during Sepsis Depends on the Dose , 2004, Annals of Internal Medicine.

[12]  W. Engeland,et al.  Splanchnicotomy increases adrenal sensitivity to ACTH in nonstressed rats. , 1997, The American journal of physiology.

[13]  B. McEwen.  Mood disorders and allostatic load , 2003, Biological Psychiatry.

[14]  P. Molina.  NEUROBIOLOGY OF THE STRESS RESPONSE: CONTRIBUTION OF THE SYMPATHETIC NERVOUS SYSTEM TO THE NEUROIMMUNE AXIS IN TRAUMATIC INJURY , 2005, Shock.

[15]  R. Mortimer,et al.  Evaluation of Random Plasma Cortisol and the Low Dose Corticotropin Test as Indicators of Adrenal Secretory Capacity in Critically Ill Patients: A Prospective Study , 2005, Anaesthesia and intensive care.

[16]  J. Hazelzet,et al.  Endocrine and metabolic responses in children with meningoccocal sepsis: striking differences between survivors and nonsurvivors. , 2000, The Journal of clinical endocrinology and metabolism.

[17]  A. Turnbull,et al.  Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action. , 1999, Physiological reviews.

[18]  John D. Bell,et al.  Stimulation by interleukin-6 and inhibition by tumor necrosis factor of cortisol release from bovine adrenal zona fasciculata cells through their receptors , 2000, Endocrine.

[19]  P. Wang,et al.  Mechanism of adrenal insufficiency following trauma and severe hemorrhage: role of hepatic 11beta-hydroxysteroid dehydrogenase. , 1999, Archives of surgery.

[20]  M. Menaker,et al.  Chronic jet-lag increases mortality in aged mice , 2006, Current Biology.

[21]  G. H. Jacobs,et al.  Cone-based vision of rats for ultraviolet and visible lights. , 2001, The Journal of experimental biology.

[22]  P. Bollaert,et al.  Baseline Cortisol Levels, Cortisol Response to Corticotropin, and Prognosis in Late Septic Shock , 2003, Shock.

[23]  George L. Brengelmann,et al.  Circadian temperature and cortisol rhythms during a constant routine are phase-delayed in hypersomnic winter depression , 1997, Biological Psychiatry.

[24]  B. Allolio,et al.  Cortisol response to corticotropin and survival in septic shock , 1991, The Lancet.

[25]  Y. Ulrich‐Lai,et al.  Adrenal splanchnic innervation contributes to the diurnal rhythm of plasma corticosterone in rats by modulating adrenal sensitivity to ACTH. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[26]  J. Siddiqui,et al.  Six at Six: Interleukin-6 Measured 6 H After the Initiation of Sepsis Predicts Mortality Over 3 Days , 2002, Shock.

[27]  W. Nicholson,et al.  Rapid radioimmunoassay for corticotropin in unextracted human plasma. , 1984, Clinical chemistry.

[28]  A. Chang,et al.  Corticosteroid/antibiotic treatment of adrenalectomized dogs challenged with lethal E. coli. , 1985, Circulatory shock.

[29]  W. Chiu,et al.  Central neural distribution of immunoreactive Fos and CRH in relation to plasma ACTH and corticosterone during sepsis in the rat , 2007, Experimental Neurology.

[30]  S. Tschoeke,et al.  PLASMA CYTOKINE MEASUREMENTS AUGMENT PROGNOSTIC SCORES AS INDICATORS OF OUTCOME IN PATIENTS WITH SEVERE SEPSIS , 2005, Shock.

[31]  W. Scherbaum,et al.  Impaired adrenal stress response in Toll-like receptor 2-deficient mice. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[32]  T. Scalea,et al.  Cecal ligation and puncture in rats interrupts the circadian rhythms of corticosterone and adrenocortical responsiveness to adrenocorticotrophic hormone , 2006, Critical care medicine.

[33]  I. Chaudry,et al.  Differential alterations in systemic and regional oxygen delivery and consumption during the early and late stages of sepsis. , 1999, The Journal of trauma.

[34]  R. Houghtling,et al.  Rapid elevation of plasma interleukin-6 by morphine is dependent on autonomic stimulation of adrenal gland. , 2002, The Journal of pharmacology and experimental therapeutics.