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Organ dysfunction is associated with hyperglycemia in critically ill children

Ursula G. Kyle| Jorge A. Coss Bu| Curtis E. Kennedy| Larry S. Jefferson
Original
Volume 36, Issue 2 / February , 2010

Pages 312 - 320

Abstract

Objective

To determine the association between organ dysfunction and hyperglycemia in critically ill children receiving intravenous insulin.

Design

Retrospective chart review (cohort study).

Setting

Pediatric intensive care unit in a university hospital.

Patients

n = 110 patients; inclusion criteria: ICU hospitalization from May 2005 to May 2006; insulin drip to manage hyperglycemia. Exclusion criteria: insulin drip <48 h; diabetic patients.

Measurements

Duration of hyperglycemia: sum of hours of hyperglycemia (≥126 mg/dl). Hypoglycemia (blood glucose <40 mg/dl). Organ dysfunction was determined per International Pediatric Sepsis Consensus Conference criteria. Multiple logistic regression models determined the association between ≥3 compared to <3 organ dysfunctions and hyperglycemia, hypoglycemia, and mortality, after adjustment for confounding variables (age, gender, PRISM score, vasopressors, steroids).

Main results

Organ dysfunction ≥3 compared to <3 after adjustment for confounders was associated with intermittent hyperglycemia of ≥24 h (OR 6.1, CI 1.8–21.2; p = 0.004). Hyperglycemia trended towards significance with mortality [3.2 (CI 0.9–11.6, p = 0.079)]. Hypoglycemia, after adjusting for the above, was not associated with mortality.

Conclusions

Organ dysfunction (≥3 versus <3) was significantly associated with hyperglycemia for ≥24 h and hypoglycemia. Hyperglycemia trended toward significance with mortality in critically ill children. There was no association between hypoglycemia and mortality.

Keywords

References

  1. Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R (2001) Intensive insulin therapy in the critically ill patients. N Engl J Med 345:1359–1367
    • View reference on publisher's website
    • View reference on PubMed
  2. Hansen TK, Thiel S, Wouters PJ, Christiansen JS, Van den Berghe G (2003) Intensive insulin therapy exerts antiinflammatory effects in critically ill patients and counteracts the adverse effect of low mannose-binding lectin levels. J Clin Endocrinol Metab 88:1082–1088
    • View reference on publisher's website
    • View reference on PubMed
  3. Krinsley JS (2004) Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc 79:992–1000
    • View reference on publisher's website
    • View reference on PubMed
  4. Meynaar IA, Dawson L, Tangkau PL, Salm EF, Rijks L (2007) Introduction and evaluation of a computerised insulin protocol. Intensive Care Med 33:591–596
  5. Srinivasan V, Spinella PC, Drott HR, Roth CL, Helfaer MA, Nadkarni V (2004) Association of timing, duration, and intensity of hyperglycemia with intensive care unit mortality in critically ill children. Pediatr Crit Care Med 5:329–336
    • View reference on publisher's website
    • View reference on PubMed
  6. Faustino EV, Apkon M (2005) Persistent hyperglycemia in critically ill children. J Pediatr 146:30–34
    • View reference on publisher's website
    • View reference on PubMed
  7. Chiaretti A, De Benedictis R, Langer A, Di Rocco C, Bizzarri C, Iannelli A, Polidori G (1998) Prognostic implications of hyperglycaemia in paediatric head injury. Child’s Nervous Syst 14:455–459
    • View reference on publisher's website
  8. Hall NJ, Peters M, Eaton S, Pierro A (2004) Hyperglycemia is associated with increased morbidity and mortality rates in neonates with necrotizing enterocolitis. J Pediatr Surg 39:898–901; discussion 898–901
    • View reference on publisher's website
    • View reference on PubMed
  9. Cochran A, Scaife ER, Hansen KW, Downey EC (2003) Hyperglycemia and outcomes from pediatric traumatic brain injury. J Trauma 55:1035–1038
    • View reference on publisher's website
    • View reference on PubMed
  10. Rayfield EJ, Ault MJ, Keusch GT, Brothers MJ, Nechemias C, Smith H (1982) Infection and diabetes: the case for glucose control. Am J Med 72:439–450
    • View reference on publisher's website
    • View reference on PubMed
  11. Zochodne DW, Bolton CF, Wells G, Gilbert JJ, Hahn AF, Brown JD, Sibbald WA (1987) Critical illness polyneuropathy A complication of sepsis and multiple organ failure. Brain 110:819–841
    • View reference on publisher's website
    • View reference on PubMed
  12. Bolton CF (1996) Sepsis and the systemic inflammatory response syndrome: neuromuscular manifestations. Crit Care Med 24:1408–1416
    • View reference on publisher's website
    • View reference on PubMed
  13. Fietsam R Jr, Bassett J, Glover JL (1991) Complications of coronary artery surgery in diabetic patients. Am Surg 57:551–557
    • View reference on PubMed
  14. Allen HF, Rake A, Roy M, Brenner D, McKiernan CA (2008) Prospective detection of hyperglycemia in critically ill children using continuous glucose monitoring. Pediatr Crit Care Med 9:153–158
    • View reference on publisher's website
    • View reference on PubMed
  15. Yung M, Wilkins B, Norton L, Slater A, AaNZICS PaediatricStudyGroup (2008) Glucose control, organ failure, and mortality in pediatric intensive care. Pediatr Crit Care Med 9:147–152
    • View reference on publisher's website
    • View reference on PubMed
  16. Rolih CA, Ober KP (1995) The endocrine response to critical illness. Med Clin North Am 79:211–224
    • View reference on PubMed
  17. Kralisch S, Sommer G, Deckert CM, Linke A, Bluher M, Stumvoll M, Fasshauer M (2007) Adipokines in diabetes and cardiovascular diseases. Minerva Endocrinol 32:161–171
    • View reference on PubMed
  18. Preissig CM, Hansen I, Roerig PL, Rigby MR (2008) A protocolized approach to identify and manage hyperglycemia in a pediatric critical care unit. Pediatr Crit Care Med 9:581–588
    • View reference on publisher's website
    • View reference on PubMed
  19. Hoxworth JM, Xu K, Zhou Y, Lust WD, LaManna JC (1999) Cerebral metabolic profile, selective neuron loss, and survival of acute and chronic hyperglycemic rats following cardiac arrest and resuscitation. Brain Res 821:467–479
    • View reference on publisher's website
    • View reference on PubMed
  20. Siesjo BK, Katsura KI, Kristian T, Li PA, Siesjo P (1996) Molecular mechanisms of acidosis-mediated damage. Acta Neurochir Suppl (Wien) 66:8–14
  21. Anderson RE, Tan WK, Martin HS, Meyer FB (1999) Effects of glucose and PaO2 modulation on cortical intracellular acidosis, NADH redox state, and infarction in the ischemic penumbra. Stroke 30:160–170
    • View reference on PubMed
  22. Klein GW, Hojsak JM, Rapaport R (2007) Hyperglycemia in the pediatric intensive care unit. Curr Opin Clin Nutr Metab Care 10:187–192
    • View reference on publisher's website
    • View reference on PubMed
  23. Rosenbaum M, Nonas C, Horlick M, Fennoy I, Vargas I, Schachner H, Kringas P, Stanton K, Weil R (2004) Beta-cell function and insulin sensitivity in early adolescence: association with body fatness and family history of type 2 diabetes mellitus. J Clin Endocrinol Metab 89:5469–5476
    • View reference on publisher's website
    • View reference on PubMed
  24. Cordingley JJ, Vlasselaers D, Dormand NC, Wouters PJ, Squire SD, Chassin LJ, Wilinska ME, Morgan CJ, Hovorka R, Van den Berghe G (2009) Intensive insulin therapy: enhanced model predictive control algorithm versus standard care. Intensive Care Med 35:123–128
  25. Vogelzang M, Loef BG, Regtien JG, van der Horst IC, van Assen H, Zijlstra F, Nijsten MW (2008) Computer-assisted glucose control in critically ill patients. Intensive Care Med 34:1421–1427
  26. 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 (2008) Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 358:125–139
    • View reference on publisher's website
    • View reference on PubMed
  27. Oksanen T, Skrifvars MB, Varpula T, Kuitunen A, Pettila V, Nurmi J, Castren M (2007) Strict versus moderate glucose control after resuscitation from ventricular fibrillation. Intensive Care Med 33:2093–2100
  28. Nguyen N, Ching K, Fraser R, Chapman M, Holloway R (2007) The relationship between blood glucose control and intolerance to enteral feeding during critical illness. Intensive Care Med 33:2085–2092
  29. Cryer PE (2004) Diverse causes of hypoglycemia-associated autonomic failure in diabetes. N Engl J Med 350:2272–2279
    • View reference on publisher's website
    • View reference on PubMed
  30. Mitchell I, Finfer S, Bellomo R, Higlett T (2006) Management of blood glucose in the critically ill in Australia and New Zealand: a practice survey and inception cohort study. Intensive Care Med 32:867–874
  31. Ligtenberg JJ, Meijering S, Stienstra Y, van der Horst IC, Vogelzang M, Nijsten MW, Tulleken JE, Zijlstra JG (2006) Mean glucose level is not an independent risk factor for mortality in mixed ICU patients. Intensive Care Med 32:435–438
  32. Honiden S, Schultz A, Im SA, Nierman DM, Gong MN (2008) Early versus late intravenous insulin administration in critically ill patients. Intensive Care Med 34:881–887
  33. Vlasselaers D, Milants I, Desmet L, Wouters PJ, Vanhorebeek I, van den Heuvel I, Mesotten D, Casaer MP, Meyfroidt G, Ingels C, Muller J, Van Cromphaut S, Schetz M, Van den Berghe G (2009) Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study. Lancet 373:547–556
    • View reference on publisher's website
    • View reference on PubMed
  34. Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hebert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ (2009) Intensive versus conventional glucose control in critically ill patients. N Engl J Med 360:1283–1297
    • View reference on publisher's website
    • View reference on PubMed
  35. Schultz MJ, de Graaff MJ, Kuiper MA, Spronk PE (2008) The new Surviving Sepsis Campaign recommendations on glucose control should be reconsidered. Intensive Care Med 34:779–780; author reply 781–772
  36. Wintergerst KA, Buckingham B, Gandrud L, Wong BJ, Kache S, Wilson DM (2006) Association of hypoglycemia, hyperglycemia, and glucose variability with morbidity and death in the pediatric intensive care unit. Pediatrics 118:173–179
    • View reference on publisher's website
    • View reference on PubMed
  37. Yates AR, Dyke PC 2nd, Taeed R, Hoffman TM, Hayes J, Feltes TF, Cua CL (2006) Hyperglycemia is a marker for poor outcome in the postoperative pediatric cardiac patient. Pediatr Crit Care Med 7:351–355
    • View reference on publisher's website
    • View reference on PubMed
  38. Weber-Carstens S, Deja M, Bercker S, Dimroth A, Ahlers O, Kaisers U, Keh D (2007) Impact of bolus application of low-dose hydrocortisone on glycemic control in septic shock patients. Intensive Care Med 33:730–733
  39. Schoefield WN (1985) Predicting basal metabolic rate, new standards and review of previous work. Human Nutrition. Hum Nutr Clin Nutr 39c (suppl 5–41)
  40. Morris AH, Orme J Jr, Truwit JD, Steingrub J, Grissom C, Lee KH, Li GL, Thompson BT, Brower R, Tidswell M, Bernard GR, Sorenson D, Sward K, Zheng H, Schoenfeld D, Warner H (2008) A replicable method for blood glucose control in critically Ill patients. Crit Care Med 36:1787–1795
    • View reference on publisher's website
    • View reference on PubMed
  41. Morris AH, Orme JF, Rocha BH, Holman J, Clemmer T, Nelson N, Allen J, Jephson A, Sorenson DK, Sward K, Warner H (2008) An electronic protocol for translation of research results to clinical practice: a preliminary report. J Diabetes Sci Technol 2:802–808
    • View reference on PubMed
  42. Thompson BT, Orme JF, Zheng H, Luckett P, Truwit JD, Wilsson DF, Hite RD, Brower RG, Bernard GR, Curley MAQ, Steingrub JS, Sorenson DK, Sward K, Hirshberg E, Morris AH RCCCRI (2008) Multicenter validation of a computer-based clinical decision support tool for glucose control in adult and pediatric intensive care units. J Diabetes Sci Technol 2:357–368
    • View reference on PubMed
  43. Pachler C, Plank J, Weinhandl H, Chassin LJ, Wilinska ME, Kulnik R, Kaufmann P, Smolle KH, Pilger E, Pieber TR, Ellmerer M, Hovorka R (2008) Tight glycaemic control by an automated algorithm with time-variant sampling in medical ICU patients. Intensive Care Med 34:1224–1230
  44. Khatib OMN (2006) Guidelines for the prevention, management and care of diabetes mellitus. In: Khatib OMN (ed) EMRO Technical Publications Series. World Health Organization, Geneva, pp 1–82
  45. Goldstein B, Giroir B, Randolph A, International Consensus Conference on Pediatric Sepsis (2005) International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 6:2–8
    • View reference on publisher's website
    • View reference on PubMed
  46. De León AL, Romero-Gutiérrez G, Valenzuela CA, González-Bravo FE (2005) Simplified PRISM III score and outcome in the pediatric intensive care unit. Pediatr Int 47:80–83
    • View reference on publisher's website
    • View reference on PubMed
  47. Pollack MM, Patel KM, Ruttimann UE (1996) PRISM III: an updated pediatric risk of mortality score. Crit Care Med 24:743–752
    • View reference on publisher's website
    • View reference on PubMed
  48. Leteurtre S, Duhamel A, Grandbastien B, Lacroix J, Leclerc F (2006) Paediatric logistic organ dysfunction (PELOD) score. Lancet 367:897; author reply 900–892
    • View reference on publisher's website
    • View reference on PubMed
  49. Leteurtre S, Martinot A, Duhamel A, Proulx F, Grandbastien B, Cotting J, Gottesman R, Joffe A, Pfenninger J, Lacroix J, Leclerc F (2006) Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study. Lancet 362:192–197
    • View reference on publisher's website
  50. Branco RG, Garcia PC, Piva JP, Casartelli CH, Seibel V, Tasker RC (2005) Glucose level and risk of mortality in pediatric septic shock. Pediatr Crit Care Med 6:470–472
    • View reference on publisher's website
    • View reference on PubMed
  51. Yendamuri S, Fulda GJ, Tinkoff GH (2003) Admission hyperglycemia as a prognostic indicator in trauma. J Trauma 55:33–38
    • View reference on publisher's website
    • View reference on PubMed
  52. Rovlias A, Kotsou S (2000) The influence of hyperglycemia on neurological outcome in patients with severe head injury. Neurosurgery 46:335–342; discussion 342–343
    • View reference on publisher's website
    • View reference on PubMed
  53. Breitkreutz R, Pittack N, Nebe CT, Schuster D, Brust J, Beichert M, Hack V, Daniel V, Edler L, Droge W (2000) Improvement of immune functions in HIV infection by sulfur supplementation: two randomized trials. J Mol Med 78:55–62
    • View reference on publisher's website
    • View reference on PubMed
  54. Paret G, Barzilai A, Lahat E, Feldman Z, Ohad G, Vardi A, Ben-Abraham R, Barzilay Z (1998) Gunshot wounds in brains of children: prognostic variables in mortality, course, and outcome. J Neurotrauma 15:967–972
    • View reference on publisher's website
    • View reference on PubMed
  55. Wilson M, Weinreb J, Hoo GW (2007) Intensive insulin therapy in critical care: a review of 12 protocols. Diabetes Care 30:1005–1011
    • View reference on publisher's website
    • View reference on PubMed
  56. Lacherade JC, Jabre P, Bastuji-Garin S, Grimaldi D, Fangio P, Theron V, Outin H, De Jonghe B (2007) Failure to achieve glycemic control despite intensive insulin therapy in a medical ICU: incidence and influence on ICU mortality. Intensive Care Med 33:814–821
  57. McCowen KC, Malhotra A, Bistrian BR (2001) Stress-induced hyperglycemia. Crit Care Clin 17:107–124
    • View reference on publisher's website
    • View reference on PubMed
  58. Marik PE, Raghavan M (2004) Stress-hyperglycemia, insulin and immunomodulation in sepsis. Intensive Care Med 30:748–756
  59. Van Waardenburg DA, Jansen TC, Vos GD, Buurman WA (2006) Hyperglycemia in children with meningococcal sepsis and septic shock: the relation between plasma levels of insulin and inflammatory mediators. J Clin Endocrinol Metab 91:3916–3921
    • View reference on publisher's website
    • View reference on PubMed

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