Skip to main content
Top
Published in: Neurocritical Care 2/2008

01-10-2008 | Original Article

Intensive Insulin Therapy After Severe Traumatic Brain Injury: A Randomized Clinical Trial

Authors: Federico Bilotta, Remo Caramia, Ibolja Cernak, Francesca Paola Paoloni, Andrea Doronzio, Vincenzo Cuzzone, Antonio Santoro, Giovanni Rosa

Published in: Neurocritical Care | Issue 2/2008

Login to get access

Abstract

Introduction

To investigate the risks and possible benefits of routine versus intensive insulin therapy, assessed by the frequency of hypoglycemic events defined as a glucose concentration less than 80 mg/dl (<4.44 mmol/l) in patients admitted to the intensive care unit (ICU) after severe traumatic brain injury (TBI).

Methods and Results

Ninety-seven patients admitted after severe TBI, were enrolled and randomly assigned to two groups of target glycemia. Insulin was infused at conventional rates when blood glucose levels exceeded 220 mg/dl (12.22 mmol/l) or at intensive rates, to maintain glycemia at 80–120 mg/dl (4.44–6.66 mmol/l). The following primary and outcome variables were measured during follow-up: hypoglycemic episodes, duration of ICU stay, infection rate, and 6-month mortality and neurologic outcome measured using the Glasgow Outcome Scale (GOS). Episodes of hypoglycemia (defined as blood glucose <80 mg/dl or 4.44 mmol/l) were significantly higher in patients receiving intensive insulin therapy: median (min–max) conventional insulin therapy 7 (range 0–11) vs. intensive insulin therapy 15 (range 6–33); P<0.0001. Duration of ICU stay was shorter in patients receiving intensive insulin therapy (7.3 vs. 10.0 days; P < 0.05); while infection rates during ICU stay (25.0% vs. 38.8%, P = 0.15), and GOS scores and mortality at 6 months were similar in the two groups.

Conclusions

Intensive insulin therapy significantly increases the risk of hypoglycemic episodes. Even though patients receiving intensive insulin therapy have shorter ICU stays and infection rates similar to those receiving conventional insulin therapy, both groups have similar follow-up mortality and neurologic outcome. Hence if intensive insulin therapy is to be used, great effort must be taken to avoid hypoglycemia.
Appendix
Available only for authorised users
Literature
1.
go back to reference Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345:1359–67.PubMedCrossRef Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345:1359–67.PubMedCrossRef
2.
go back to reference Van den Berghe G, Schoonheydt K, Becx P, et al. Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology. 2005;64:1348–53.PubMed Van den Berghe G, Schoonheydt K, Becx P, et al. Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology. 2005;64:1348–53.PubMed
3.
go back to reference Krinsley JS, Grover A. Severe hypoglycemia in critically ill patients: risk factors and outcomes. Crit Care Med. 2007;35(10):2262–7.PubMed Krinsley JS, Grover A. Severe hypoglycemia in critically ill patients: risk factors and outcomes. Crit Care Med. 2007;35(10):2262–7.PubMed
4.
go back to reference Turina M, Christ-Crain M, Polk HC Jr. Diabetes and hyperglycemia: strict glycemic control. Crit Care Med. 2006;34(9 Suppl):291–300.CrossRef Turina M, Christ-Crain M, Polk HC Jr. Diabetes and hyperglycemia: strict glycemic control. Crit Care Med. 2006;34(9 Suppl):291–300.CrossRef
5.
go back to reference Van den Berghe G, Wilmer A, Milants I, et al. Intensive insulin therapy in mixed medical/surgical intensive care units. Diabetes. 2006;55(11):3151–9.PubMedCrossRef Van den Berghe G, Wilmer A, Milants I, et al. Intensive insulin therapy in mixed medical/surgical intensive care units. Diabetes. 2006;55(11):3151–9.PubMedCrossRef
6.
go back to reference Yamada K, Milbrandt EB, Moore J. Intensive insulin therapy in the medical ICU – not so sweet? Crit Care. 2007;11(4):311.PubMedCrossRef Yamada K, Milbrandt EB, Moore J. Intensive insulin therapy in the medical ICU – not so sweet? Crit Care. 2007;11(4):311.PubMedCrossRef
7.
go back to reference 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(10):2849–55.PubMedCrossRef 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(10):2849–55.PubMedCrossRef
8.
go back to reference Mechanick JI, Handelsman Y, Bloomgarden ZT. Hypoglycemia in the intensive care unit. Curr Opin Clin Nutr Metab Care. 2007;10(2):193–6.PubMedCrossRef Mechanick JI, Handelsman Y, Bloomgarden ZT. Hypoglycemia in the intensive care unit. Curr Opin Clin Nutr Metab Care. 2007;10(2):193–6.PubMedCrossRef
9.
go back to reference Pulsinelli WA, Levy DE, Sigsbee B, et al. Increased damage after ischemic stroke in patients with hyperglycemia with or without established diabetes mellitus. Am J Med. 1983;74:540–4.PubMedCrossRef Pulsinelli WA, Levy DE, Sigsbee B, et al. Increased damage after ischemic stroke in patients with hyperglycemia with or without established diabetes mellitus. Am J Med. 1983;74:540–4.PubMedCrossRef
10.
go back to reference Scott JF, Robinson GM, French JM, et al. Glucose potassium insulin infusions in the treatment of acute stroke patients with mild to moderate hyperglycemia. Stroke. 1999;30:793–9.PubMed Scott JF, Robinson GM, French JM, et al. Glucose potassium insulin infusions in the treatment of acute stroke patients with mild to moderate hyperglycemia. Stroke. 1999;30:793–9.PubMed
11.
go back to reference Bhalla A, Tilling K, Kolominsky-Rabas P, et al. Variation in the management of acute physiological parameters after ischemic stroke: a European perspective. Eur J Neurol. 2003;10(1):25–33.PubMedCrossRef Bhalla A, Tilling K, Kolominsky-Rabas P, et al. Variation in the management of acute physiological parameters after ischemic stroke: a European perspective. Eur J Neurol. 2003;10(1):25–33.PubMedCrossRef
12.
go back to reference Bilotta F, Spinelli A, Giovannini F, et al. Effects of intensive insulin infusion on infection rates, vasospasm and neurologic outcome in patients with acute subarachnoid hemorrhage admitted to a postoperative neurosurgical intensive care unit after surgical clipping of intracranial aneurysms a prospective randomized trial. J Neurosurg Anesth. 2007;19(3):156–60.CrossRef Bilotta F, Spinelli A, Giovannini F, et al. Effects of intensive insulin infusion on infection rates, vasospasm and neurologic outcome in patients with acute subarachnoid hemorrhage admitted to a postoperative neurosurgical intensive care unit after surgical clipping of intracranial aneurysms a prospective randomized trial. J Neurosurg Anesth. 2007;19(3):156–60.CrossRef
13.
go back to reference Walia S, Sutcliffe AJ. The relationship between blood glucose, mean arterial pressure and outcome after head injury: an observational study. Injury 2002;33:339–44.PubMedCrossRef Walia S, Sutcliffe AJ. The relationship between blood glucose, mean arterial pressure and outcome after head injury: an observational study. Injury 2002;33:339–44.PubMedCrossRef
14.
go back to reference Robertson CS, Goodman JC, Narayan RK, Contant CF, Grossman RG. The effect of glucose administration on carbohydrate metabolism after head injury. J Neurosurg. 1991;74(1):43–50.PubMed Robertson CS, Goodman JC, Narayan RK, Contant CF, Grossman RG. The effect of glucose administration on carbohydrate metabolism after head injury. J Neurosurg. 1991;74(1):43–50.PubMed
15.
go back to reference Bergsneider MA, Hovda DA, Shalmon E, et al. Cerebral hyperglycolysis following severe human traumatic brain inyury: a positron emission tomography study. J Neurosurg. 1997;86:241–51.PubMed Bergsneider MA, Hovda DA, Shalmon E, et al. Cerebral hyperglycolysis following severe human traumatic brain inyury: a positron emission tomography study. J Neurosurg. 1997;86:241–51.PubMed
16.
go back to reference Hamlin GP, Cernak I, Wixey JA, et al. Increased expression of neuronal glucose transporter 3 but not glial glucose transporter 1 following severe diffuse traumatic brain injury in rats. J Neurotrauma. 2001;18(10):1011–8.PubMedCrossRef Hamlin GP, Cernak I, Wixey JA, et al. Increased expression of neuronal glucose transporter 3 but not glial glucose transporter 1 following severe diffuse traumatic brain injury in rats. J Neurotrauma. 2001;18(10):1011–8.PubMedCrossRef
17.
go back to reference Vespa P, Boonyaputthinkul R, McArthur DL, et al. Intensive insulin therapy reduces microdialysis glucose values without altering glucose utilization or improving the lactate/pyruvate ratio after traumatic brain injury. Crit Care Med. 2006;34(3):850–6.PubMedCrossRef Vespa P, Boonyaputthinkul R, McArthur DL, et al. Intensive insulin therapy reduces microdialysis glucose values without altering glucose utilization or improving the lactate/pyruvate ratio after traumatic brain injury. Crit Care Med. 2006;34(3):850–6.PubMedCrossRef
18.
go back to reference Vespa P, O’Phelan K, McArthur D, Miller C, Eliseo M, Hirt D, Glenn T, Hovda DA. Pericontusional brain tissue exhibits persistent elevation of lactate/pyruvate ratio independent of cerebral perfusion pressure. Crit Care Med. 2007;35(4):1153–60.PubMedCrossRef Vespa P, O’Phelan K, McArthur D, Miller C, Eliseo M, Hirt D, Glenn T, Hovda DA. Pericontusional brain tissue exhibits persistent elevation of lactate/pyruvate ratio independent of cerebral perfusion pressure. Crit Care Med. 2007;35(4):1153–60.PubMedCrossRef
19.
go back to reference Le Galle JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1994;271(17):1321.CrossRef Le Galle JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1994;271(17):1321.CrossRef
20.
go back to reference University of Minnesota Medical Center Continuous Intravenous Insulin Infusion Orders Protocol. APSF Newsletter Summer 2006. apsf.org. University of Minnesota Medical Center Continuous Intravenous Insulin Infusion Orders Protocol. APSF Newsletter Summer 2006. apsf.​org.
21.
go back to reference Krinsley JS. Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc. 2004;79(8):992–1000.PubMed Krinsley JS. Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc. 2004;79(8):992–1000.PubMed
23.
go back to reference Himanen L, Portin R, Isoniemi H, Helenius H, Kurki T, Tenovuo O. Longitudinal cognitive changes in traumatic brain injury: a 30-year follow-up study. Neurology. 2006;66(2):187–92.PubMedCrossRef Himanen L, Portin R, Isoniemi H, Helenius H, Kurki T, Tenovuo O. Longitudinal cognitive changes in traumatic brain injury: a 30-year follow-up study. Neurology. 2006;66(2):187–92.PubMedCrossRef
24.
go back to reference Luukinen H, Viramo P, Koski K, Laippala P, Kivela SL. Head injuries and cognitive decline among older adults: a population-based study. Neurology. 1999;52(3):557–62.PubMed Luukinen H, Viramo P, Koski K, Laippala P, Kivela SL. Head injuries and cognitive decline among older adults: a population-based study. Neurology. 1999;52(3):557–62.PubMed
25.
go back to reference Horan TC, Gaynes RP. Surveillance of nosocomial infections In: Mayhall CG, editor. Hospital and infection control, 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2004. p. 1659–702. Horan TC, Gaynes RP. Surveillance of nosocomial infections In: Mayhall CG, editor. Hospital and infection control, 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2004. p. 1659–702.
26.
go back to reference Weinstein MP, Towns ML, Quartey SM, et al. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis. 1997;24:584–602.PubMed Weinstein MP, Towns ML, Quartey SM, et al. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis. 1997;24:584–602.PubMed
27.
go back to reference Pittas AG, Siegel RD, Lau J. Insulin therapy for critically ill hospitalized patients: a metanalysis of randomized controlled trials. Arch Intern Med. 2004;164(18):2005–11.PubMedCrossRef Pittas AG, Siegel RD, Lau J. Insulin therapy for critically ill hospitalized patients: a metanalysis of randomized controlled trials. Arch Intern Med. 2004;164(18):2005–11.PubMedCrossRef
28.
go back to reference Widom B, Simonson DC. Glycemic control and neuropsychologic function during hypoglycemia in patients with insulin-dependent diabetes mellitus. Ann Intern Med. 1990;112(12):904–12.PubMed Widom B, Simonson DC. Glycemic control and neuropsychologic function during hypoglycemia in patients with insulin-dependent diabetes mellitus. Ann Intern Med. 1990;112(12):904–12.PubMed
29.
go back to reference Boyle PJ, Schwartz NS, Shah SD, et al. Plasma glucose concentrations at the onset of hypoglycemic symptoms in patients with poorly controlled diabetes and in nondiabetics. N Engl J Med. 1988;318:1487–92.PubMedCrossRef Boyle PJ, Schwartz NS, Shah SD, et al. Plasma glucose concentrations at the onset of hypoglycemic symptoms in patients with poorly controlled diabetes and in nondiabetics. N Engl J Med. 1988;318:1487–92.PubMedCrossRef
30.
go back to reference Li PA, Shamloo M, Smith ML, et al. The influence of plasma glucose concentrations on ischemic brain damage is a threshold function. Neurosci Lett. 1994;177:63–5.PubMedCrossRef Li PA, Shamloo M, Smith ML, et al. The influence of plasma glucose concentrations on ischemic brain damage is a threshold function. Neurosci Lett. 1994;177:63–5.PubMedCrossRef
31.
32.
go back to reference Wass CT, Lanier WL. Glucose modulation of ischemic brain injury: review and clinical recommendations. Mayo Clin Proc. 1996;71:801–12.PubMedCrossRef Wass CT, Lanier WL. Glucose modulation of ischemic brain injury: review and clinical recommendations. Mayo Clin Proc. 1996;71:801–12.PubMedCrossRef
33.
go back to reference Preiser JC, Devos P. Clinical experience with tight glucose control by intensive insulin therapy. Crit Care Med. 2007;35:S503–7.PubMedCrossRef Preiser JC, Devos P. Clinical experience with tight glucose control by intensive insulin therapy. Crit Care Med. 2007;35:S503–7.PubMedCrossRef
34.
go back to reference Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183–97. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183–97.
35.
go back to reference CRASH Trial Collaborators. Effect of intravenous corticosteroids on death within 14 days in 10,008 adults with clinically significant head injury (MRC CRASH Trial): randomised, placebo-controlled trial. Lancet. 2004;364:1321–8.CrossRef CRASH Trial Collaborators. Effect of intravenous corticosteroids on death within 14 days in 10,008 adults with clinically significant head injury (MRC CRASH Trial): randomised, placebo-controlled trial. Lancet. 2004;364:1321–8.CrossRef
Metadata
Title
Intensive Insulin Therapy After Severe Traumatic Brain Injury: A Randomized Clinical Trial
Authors
Federico Bilotta
Remo Caramia
Ibolja Cernak
Francesca Paola Paoloni
Andrea Doronzio
Vincenzo Cuzzone
Antonio Santoro
Giovanni Rosa
Publication date
01-10-2008
Publisher
Humana Press Inc
Published in
Neurocritical Care / Issue 2/2008
Print ISSN: 1541-6933
Electronic ISSN: 1556-0961
DOI
https://doi.org/10.1007/s12028-008-9084-9

Other articles of this Issue 2/2008

Neurocritical Care 2/2008 Go to the issue

PRACTICAL PEARL

Stone Silent