The impact of early hypoglycemia and blood glucose variability on outcome in critical illness

Sean M Bagshaw, Rinaldo Bellomo, Michael J Jacka, Moritoki Egi, Graeme K Hart, Carol George, ANZICS CORE Management Committee, Sean M Bagshaw, Rinaldo Bellomo, Michael J Jacka, Moritoki Egi, Graeme K Hart, Carol George, ANZICS CORE Management Committee

Abstract

Introduction: In critical illness, the association of hypoglycemia, blood glucose (BG) variability and outcome are not well understood. We describe the incidence, clinical factors and outcomes associated with an early hypoglycemia and BG variability in critically ill patients.

Methods: Retrospective interrogation of prospectively collected data from the Australia New Zealand Intensive Care Society Adult Patient Database on 66184 adult admissions to 24 intensive care units (ICUs) from 1 January 2000 to 31 December 2005. Primary exposure was hypoglycemia (BG < 4.5 mmol/L) and BG variability (BG < 4.5 and >or= 12.0 mmol/L) within 24 hours of admission. Primary outcome was all-cause mortality.

Results: The cumulative incidence of hypoglycemia and BG variability were 13.8% (95% confidence interval (CI) = 13.5 to 14.0; n = 9122) and 2.9% (95%CI = 2.8 to 3.0, n = 1913), respectively. Several clinical factors were associated with both hypoglycemia and BG variability including: co-morbid disease (P < 0.001), non-elective admissions (P < 0.001), higher illness severity (P < 0.001), and primary septic diagnosis (P < 0.001). Hypoglycemia was associated with greater odds of adjusted ICU (odds ratio (OR) = 1.41, 95% CI = 1.31 to 1.54) and hospital death (OR = 1.36, 95% CI = 1.27 to 1.46). Hypoglycemia severity was associated with 'dose-response' increases in mortality. BG variability was associated with greater odds of adjusted ICU (1.5, 95% CI = 1.4 to 1.6) and hospital (1.4, 95% CI = 1.3 to 1.5) mortality, when compared with either hypoglycemia only or neither.

Conclusions: In critically ill patients, both early hypoglycemia and early variability in BG are relatively common, and independently portend an increased risk for mortality.

Figures

Figure 1
Figure 1
Incidence of hypoglycemia stratified by degree of hypoglycemia within 24 hours of intensive care unit admission.

References

    1. Finney SJ, Zekveld C, Elia A, Evans TW. Glucose control and mortality in critically ill patients. JAMA. 2003;290:2041–2047. doi: 10.1001/jama.290.15.2041.
    1. Mitchell I, Knight E, Gissane J, Tamhane R, Kolli R, Leditschke IA, Bellomo R, Finfer S. A phase II randomised controlled trial of intensive insulin therapy in general intensive care patients. Crit Care Resusc. 2006;8:289–293.
    1. Thomas G, Rojas MC, Epstein SK, Balk EM, Liangos O, Jaber BL. Insulin therapy and acute kidney injury in critically ill patients a systematic review. Nephrol Dial Transplant. 2007;22:2849–2855. doi: 10.1093/ndt/gfm401.
    1. Berghe G Van den, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354:449–461. doi: 10.1056/NEJMoa052521.
    1. Berghe G Van den, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359–1367. doi: 10.1056/NEJMoa011300.
    1. Hermans G, Wilmer A, Meersseman W, Milants I, Wouters PJ, Bobbaers H, Bruyninckx F, Berghe G Van den. Impact of intensive insulin therapy on neuromuscular complications and ventilator dependency in the medical intensive care unit. Am J Respir Crit Care Med. 2007;175:480–489. doi: 10.1164/rccm.200605-665OC.
    1. Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858–873. doi: 10.1097/01.CCM.0000117317.18092.E4.
    1. Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr. 2003;27:355–373. doi: 10.1177/0148607103027005355.
    1. Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hébert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360:1283–1297. doi: 10.1056/NEJMoa0810625.
    1. Klaff LS, Wisse BE. Current controversy related to glucocorticoid and insulin therapy in the intensive care unit. Endocr Pract. 2007;13:542–549.
    1. Schultz MJ, Royakkers AA, Levi M, Moeniralam HS, Spronk PE. Intensive insulin therapy in intensive care: an example of the struggle to implement evidence-based medicine. PLoS Med. 2006;3:e456. doi: 10.1371/journal.pmed.0030456.
    1. Devos P, Preiser JC. Current controversies around tight glucose control in critically ill patients. Curr Opin Clin Nutr Metab Care. 2007;10:206–209.
    1. Preiser JC, Devos P. Clinical experience with tight glucose control by intensive insulin therapy. Crit Care Med. 2007;35:S503–507. doi: 10.1097/01.CCM.0000278046.24345.C7.
    1. Angus DC, Abraham E. Intensive insulin therapy in critical illness. Am J Respir Crit Care Med. 2005;172:1358–1359. doi: 10.1164/rccm.2508009.
    1. Vanhorebeek I, Langouche L, Berghe G Van den. Tight blood glucose control: what is the evidence? Crit Care Med. 2007;35:S496–502. doi: 10.1097/01.CCM.0000278051.48643.91.
    1. Vanhorebeek I, Langouche L, Berghe G Van den. Tight blood glucose control with insulin in the ICU: facts and controversies. Chest. 2007;132:268–278. doi: 10.1378/chest.06-3121.
    1. Orford NR. Intensive insulin therapy in septic shock. Crit Care Resusc. 2006;8:230–234.
    1. Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA. 2008;300:933–944. doi: 10.1001/jama.300.8.933.
    1. Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Schaefer M, Kern P, Kuhnt E, Kiehntopf M, Hartog C, Natanson C, Loeffler M, Reinhart K. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358:125–139. doi: 10.1056/NEJMoa070716.
    1. Krinsley JS, Grover A. Severe hypoglycemia in critically ill patients: risk factors and outcomes. Crit Care Med. 2007;35:2262–2267. doi: 10.1097/01.CCM.0000282073.98414.4B.
    1. Dossett LA, Cao H, Mowery NT, Dortch MJ, Morris JM, Jr, May AK. Blood glucose variability is associated with mortality in the surgical intensive care unit. Am Surg. 2008;74:679–685. discussion 685.
    1. Egi M, Bellomo R, Stachowski E, French CJ, Hart G. Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology. 2006;105:244–252. doi: 10.1097/00000542-200608000-00006.
    1. Hirshberg E, Larsen G, Van Duker H. Alterations in glucose homeostasis in the pediatric intensive care unit: hyperglycemia and glucose variability are associated with increased mortality and morbidity. Pediatr Crit Care Med. 2008;9:361–366. doi: 10.1097/PCC.0b013e318172d401.
    1. Krinsley JS. Glycemic variability: a strong independent predictor of mortality in critically ill patients. Crit Care Med. 2008;36:3008–3013. doi: 10.1097/CCM.0b013e31818b38d2.
    1. Stow PJ, Hart GK, Higlett T, George C, Herkes R, McWilliam D, Bellomo R. Development and implementation of a high-quality clinical database: the Australian and New Zealand Intensive Care Society Adult Patient Database. J Crit Care. 2006;21:133–141. doi: 10.1016/j.jcrc.2005.11.010.
    1. Mitchell I, Finfer S, Bellomo R, Higlett T. Management of blood glucose in the critically ill in Australia and New Zealand: a practice survey and inception cohort study. Intensive Care Med. 2006;32:867–874. doi: 10.1007/s00134-006-0135-4.
    1. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8:R204–212. doi: 10.1186/cc2872.
    1. Williams TA, Dobb GJ, Finn JC, Knuiman M, Lee KY, Geelhoed E, Webb SA. Data linkage enables evaluation of long-term survival after intensive care. Anaesth Intensive Care. 2006;34:307–315.
    1. Vriesendorp TM, DeVries JH, van Santen S, Moeniralam HS, de Jonge E, Roos YB, Schultz MJ, Rosendaal FR, Hoekstra JB. Evaluation of short-term consequences of hypoglycemia in an intensive care unit. Crit Care Med. 2006;34:2714–2718. doi: 10.1097/01.CCM.0000241155.36689.91.
    1. Preiser JC. Intensive glycemic control in med-surg patients (European Glucontrol trial) Society of Critical Care Medicine 36th Critical Care Congress: 17–21 February 2007; Orlando, Florida.
    1. Vriesendorp TM, van Santen S, DeVries JH, de Jonge E, Rosendaal FR, Schultz MJ, Hoekstra JB. Predisposing factors for hypoglycemia in the intensive care unit. Crit Care Med. 2006;34:96–101. doi: 10.1097/01.CCM.0000194536.89694.06.
    1. Grey NJ, Perdrizet GA. Reduction of nosocomial infections in the surgical intensive-care unit by strict glycemic control. Endocr Pract. 2004;10(Suppl 2):46–52.
    1. Langouche L, Vanhorebeek I, Vlasselaers D, Perre S Vander, Wouters PJ, Skogstrand K, Hansen TK, Berghe G Van den. Intensive insulin therapy protects the endothelium of critically ill patients. J Clin Invest. 2005;115:2277–2286. doi: 10.1172/JCI25385.
    1. Treggiari MM, Karir V, Yanez ND, Weiss NS, Daniel S, Deem SA. Intensive insulin therapy and mortality in critically ill patients. Crit Care. 2008;12:R29. doi: 10.1186/cc6807.
    1. Wittenberg MD, Gattas DJ, Ryan A, Totaro R. Introduction of intensive glycaemic control into a neurosurgical intensive care unit: a retrospective cohort study. Crit Care Resusc. 2008;10:203–208.
    1. Andersen SK, Gjedsted J, Christiansen C, Tonnesen E. The roles of insulin and hyperglycemia in sepsis pathogenesis. J Leukoc Biol. 2004;75:413–421. doi: 10.1189/jlb.0503195.
    1. Egi M, Bellomo R, Stachowski E, French CJ, Hart GK, Hegarty C, Bailey M. Blood glucose concentration and outcome of critical illness: the impact of diabetes. Crit Care Med. 2008;36:2249–2255. doi: 10.1097/CCM.0b013e318181039a.
    1. Bilotta F, Caramia R, Cernak I, Paoloni FP, Doronzio A, Cuzzone V, Santoro A, Rosa G. Intensive insulin therapy after severe traumatic brain injury: a randomized clinical trial. Neurocrit Care. 2008;9:159–166. doi: 10.1007/s12028-008-9084-9.
    1. Bilotta F, Spinelli A, Giovannini F, Doronzio A, Delfini R, Rosa G. The effect of intensive insulin therapy on infection rate, vasospasm, neurologic outcome, and mortality in neurointensive care unit after intracranial aneurysm clipping in patients with acute subarachnoid hemorrhage: a randomized prospective pilot trial. J Neurosurg Anesthesiol. 2007;19:156–160. doi: 10.1097/ANA.0b013e3180338e69.
    1. Oksanen T, Skrifvars MB, Varpula T, Kuitunen A, Pettila V, Nurmi J, Castren M. Strict versus moderate glucose control after resuscitation from ventricular fibrillation. Intensive Care Med. 2007;33:2093–2100. doi: 10.1007/s00134-007-0876-8.
    1. Godoy DA, Pinero GR, Svampa S, Papa F, Di Napoli M. Hyperglycemia and short-term outcome in patients with spontaneous intracerebral hemorrhage. Neurocrit Care. 2008;9:217–229. doi: 10.1007/s12028-008-9063-1.
    1. Ali NA, O'Brien JM, Jr, Dungan K, Phillips G, Marsh CB, Lemeshow S, Connors AF, Jr, Preiser JC. Glucose variability and mortality in patients with sepsis. Crit Care Med. 2008;36:2316–2321. doi: 10.1097/CCM.0b013e3181810378.
    1. Waeschle RM, Moerer O, Hilgers R, Herrmann P, Neumann P, Quintel M. The impact of the severity of sepsis on the risk of hypoglycaemia and glycaemic variability. Crit Care. 2008;12:R129. doi: 10.1186/cc7097.
    1. Ingels C, Debaveye Y, Milants I, Buelens E, Peeraer A, Devriendt Y, Vanhoutte T, Van Damme A, Schetz M, Wouters PJ, Berghe G Van den. Strict blood glucose control with insulin during intensive care after cardiac surgery: impact on 4-years survival, dependency on medical care, and quality-of-life. Eur Heart J. 2006;27:2716–2724. doi: 10.1093/eurheartj/ehi855.
    1. Berghe G Van den, Wouters PJ, Bouillon R, Weekers F, Verwaest C, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P. Outcome benefit of intensive insulin therapy in the critically ill: insulin dose versus glycemic control. Crit Care Med. 2003;31:359–366. doi: 10.1097/01.CCM.0000045568.12881.10.

Source: PubMed

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