Semin Respir Crit Care Med 2016; 37(01): 057-067
DOI: 10.1055/s-0035-1570354
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Sweet Spot: Glucose Control in the Intensive Care Unit

Roosmarijn T. M. van Hooijdonk
1   Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Dieter Mesotten
2   Department of Intensive Care Medicine, Catholic University of Leuven, University Hospitals Leuven, Leuven, Belgium
,
James S. Krinsley
3   Division of Critical Care, Stamford Hospital, Columbia University College of Physicians and Surgeons, Stamford, Connecticut
,
Marcus J. Schultz
4   Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

Publication Date:
28 January 2016 (online)

Abstract

Hyperglycemia, hypoglycemia, and glycemic variability are all independently associated with morbidity and mortality of critically ill patients. A strategy aiming at normoglycemia (so-called tight glycemic control) could improve outcomes of critically ill patients, but results from randomized controlled trials of tight glycemic control are conflicting. Strict glycemic control is associated with an increased risk of hypoglycemia, which could offset the benefit of this intervention. Notably, the risk of hypoglycemia is not necessarily removed with less tight glucose control regimens. The best targets of blood glucose control in critically ill patients, therefore, remain a matter of debate. It should be realized that blood glucose control is a complex intervention, consisting of many critical aspects that have the potential to affect its efficacy and safety. Efficacy, and in particular safety, of blood glucose control could still improve. First, glucose algorithms could overcome the lack of knowledge and skills of nursing staff when they are less experienced in safe and efficient blood glucose control. Several computerized glucose control algorithms have been developed over recent years, but they all need clinical validation. Also, the workload induced by such algorithms should be evaluated. Second, continuous blood glucose monitoring has the potential to improve safety and efficacy. Until recently, blood glucose levels were monitored manually using point-of-care devices with significant inaccuracies. Various continuous monitoring systems have been developed, but studies testing their accuracies and usefulness in an intensive care unit setting are highly needed.

 
  • References

  • 1 Mizock BA. Alterations in fuel metabolism in critical illness: hyperglycaemia. Best Pract Res Clin Endocrinol Metab 2001; 15 (4) 533-551
  • 2 McCowen KC, Malhotra A, Bistrian BR. Stress-induced hyperglycemia. Crit Care Clin 2001; 17 (1) 107-124
  • 3 Falciglia M, Freyberg RW, Almenoff PL, D'Alessio DA, Render ML. Hyperglycemia-related mortality in critically ill patients varies with admission diagnosis. Crit Care Med 2009; 37 (12) 3001-3009
  • 4 Bagshaw SM, Egi M, George C, Bellomo R. Australia New Zealand Intensive Care Society Database Management Committee. Early blood glucose control and mortality in critically ill patients in Australia. Crit Care Med 2009; 37 (2) 463-470
  • 5 Finney SJ, Zekveld C, Elia A, Evans TW. Glucose control and mortality in critically ill patients. JAMA 2003; 290 (15) 2041-2047
  • 6 Krinsley JS. Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. Mayo Clin Proc 2003; 78 (12) 1471-1478
  • 7 van den Berghe G, Wouters P, Weekers F , et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001; 345 (19) 1359-1367
  • 8 Van den Berghe G, Wilmer A, Hermans G , et al. Intensive insulin therapy in the medical ICU. N Engl J Med 2006; 354 (5) 449-461
  • 9 Vlasselaers D, Milants I, Desmet L , et al. Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study. Lancet 2009; 373 (9663) 547-556
  • 10 Dellinger RP, Carlet JM, Masur H , et al; Surviving Sepsis Campaign Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004; 32 (3) 858-873
  • 11 Finfer S, Chittock DR, Su SY-S , et al; NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360 (13) 1283-1297
  • 12 Annane D, Cariou A, Maxime V , et al; COIITSS Study Investigators. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA 2010; 303 (4) 341-348
  • 13 Arabi YM, Dabbagh OC, Tamim HM , et al. Intensive versus conventional insulin therapy: a randomized controlled trial in medical and surgical critically ill patients. Crit Care Med 2008; 36 (12) 3190-3197
  • 14 Brunkhorst FM, Engel C, Bloos F , et al; German Competence Network Sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008; 358 (2) 125-139
  • 15 De La Rosa GdelC, Donado JH, Restrepo AH , et al; Grupo de Investigacion en Cuidado intensivo: GICI-HPTU. Strict glycaemic control in patients hospitalised in a mixed medical and surgical intensive care unit: a randomised clinical trial. Crit Care 2008; 12 (5) R120
  • 16 Preiser J-C, Devos P, Ruiz-Santana S , et al. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med 2009; 35 (10) 1738-1748
  • 17 Dellinger RP, Levy MM, Rhodes A , et al; Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013; 39 (2) 165-228
  • 18 Jacobi J, Bircher N, Krinsley J , et al. Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. Crit Care Med 2012; 40 (12) 3251-3276
  • 19 Finfer S, Liu B, Chittock DR , et al; NICE-SUGAR Study Investigators. Hypoglycemia and risk of death in critically ill patients. N Engl J Med 2012; 367 (12) 1108-1118
  • 20 Krinsley J, Schultz MJ, Spronk PE , et al. Mild hypoglycemia is strongly associated with increased intensive care unit length of stay. Ann Intensive Care 2011; 1 (1) 49
  • 21 Egi M, Bellomo R, Stachowski E , et al. Hypoglycemia and outcome in critically ill patients. Mayo Clin Proc 2010; 85 (3) 217-224
  • 22 Krinsley JS, Grover A. Severe hypoglycemia in critically ill patients: risk factors and outcomes. Crit Care Med 2007; 35 (10) 2262-2267
  • 23 Vriesendorp TM, DeVries JH, van Santen S , et al. Evaluation of short-term consequences of hypoglycemia in an intensive care unit. Crit Care Med 2006; 34 (11) 2714-2718
  • 24 Mesotten D, Gielen M, Sterken C , et al. Neurocognitive development of children 4 years after critical illness and treatment with tight glucose control: a randomized controlled trial. JAMA 2012; 308 (16) 1641-1650
  • 25 Suh SW, Gum ET, Hamby AM, Chan PH, Swanson RA. Hypoglycemic neuronal death is triggered by glucose reperfusion and activation of neuronal NADPH oxidase. J Clin Invest 2007; 117 (4) 910-918
  • 26 Ceriello A, Novials A, Ortega E , et al. Hyperglycemia following recovery from hypoglycemia worsens endothelial damage and thrombosis activation in type 1 diabetes and in healthy controls. Nutr Metab Cardiovasc Dis 2014; 24 (2) 116-123
  • 27 Ceriello A, Novials A, Ortega E , et al. Evidence that hyperglycemia after recovery from hypoglycemia worsens endothelial function and increases oxidative stress and inflammation in healthy control subjects and subjects with type 1 diabetes. Diabetes 2012; 61 (11) 2993-2997
  • 28 Krinsley JS. Glycemic variability: a strong independent predictor of mortality in critically ill patients. Crit Care Med 2008; 36 (11) 3008-3013
  • 29 Mackenzie IMJ, Whitehouse T, Nightingale PG. The metrics of glycaemic control in critical care. Intensive Care Med 2011; 37 (3) 435-443
  • 30 Meyfroidt G, Keenan DM, Wang X, Wouters PJ, Veldhuis JD, Van den Berghe G. Dynamic characteristics of blood glucose time series during the course of critical illness: effects of intensive insulin therapy and relative association with mortality. Crit Care Med 2010; 38 (4) 1021-1029
  • 31 Brunner R, Adelsmayr G, Herkner H, Madl C, Holzinger U. Glycemic variability and glucose complexity in critically ill patients: a retrospective analysis of continuous glucose monitoring data. Crit Care 2012; 16 (5) R175
  • 32 Ling Y, Li X, Gao X. Intensive versus conventional glucose control in critically ill patients: a meta-analysis of randomized controlled trials. Eur J Intern Med 2012; 23 (6) 564-574
  • 33 Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA 2008; 300 (8) 933-944
  • 34 Krinsley JS, Egi M, Kiss A , et al. Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study. Crit Care 2013; 17 (2) R37
  • 35 Egi M, Bellomo R, Stachowski E , et al. Blood glucose concentration and outcome of critical illness: the impact of diabetes. Crit Care Med 2008; 36 (8) 2249-2255
  • 36 Sechterberger MK, Bosman RJ, Oudemans-van Straaten HM , et al. The effect of diabetes mellitus on the association between measures of glycaemic control and ICU mortality: a retrospective cohort study. Crit Care 2013; 17 (2) R52
  • 37 Schultz MJ, Spronk PE, van Braam Houckgeest F. Glucontrol, no control, or out of control?. Intensive Care Med 2010; 36 (1) 173-174 , author reply 175–176
  • 38 Brunkhorst FM, Engel C, Ragaller M , et al; German Sepsis Competence Network (SepNet). Practice and perception—a nationwide survey of therapy habits in sepsis. Crit Care Med 2008; 36 (10) 2719-2725
  • 39 Hirshberg E, Lacroix J, Sward K, Willson D, Morris AH. Blood glucose control in critically ill adults and children: a survey on stated practice. Chest 2008; 133 (6) 1328-1335
  • 40 Schultz MJ, Binnekade JM, Harmsen RE , et al. Survey into blood glucose control in critically ill adult patients in the Netherlands. Neth J Med 2010; 68 (2) 77-83
  • 41 Ilan R, Fowler RA, Geerts R, Pinto R, Sibbald WJ, Martin CM. Knowledge translation in critical care: factors associated with prescription of commonly recommended best practices for critically ill patients. Crit Care Med 2007; 35 (7) 1696-1702
  • 42 McMullin J, Brozek J, Jaeschke R , et al. Glycemic control in the ICU: a multicenter survey. Intensive Care Med 2004; 30 (5) 798-803
  • 43 Mackenzie I, Ingle S, Zaidi S, Buczaski S. Tight glycaemic control: a survey of intensive care practice in large English hospitals. Intensive Care Med 2005; 31 (8) 1136
  • 44 Mitchell I, Finfer S, Bellomo R, Higlett T. ANZICS Clinical Trials Group Glucose Management Investigators. 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 (6) 867-874
  • 45 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 (12) e456
  • 46 Kaukonen K-M, Bailey M, Pilcher D, Orford N, Finfer S, Bellomo R. Glycaemic control in Australia and New Zealand before and after the NICE-SUGAR trial: a translational study. Crit Care 2013; 17 (5) R215
  • 47 Niven DJ, Rubenfeld GD, Kramer AA, Stelfox HT. Effect of published scientific evidence on glycemic control in adult intensive care units. JAMA Intern Med 2015; 175 (5) 801-809
  • 48 Schultz MJ, Harmsen RE, Spronk PE. Clinical review: Strict or loose glycemic control in critically ill patients—implementing best available evidence from randomized controlled trials. Crit Care 2010; 14 (3) 223
  • 49 Van den Berghe G, Schetz M, Vlasselaers D , et al. Clinical review: intensive insulin therapy in critically ill patients: NICE-SUGAR or Leuven blood glucose target?. J Clin Endocrinol Metab 2009; 94 (9) 3163-3170
  • 50 Rattan R, Nasraway SA. The future is now: software-guided intensive insulin therapy in the critically ill. J Diabetes Sci Tech 2013; 7 (2) 548-554
  • 51 Marvin MR, Inzucchi SE, Besterman BJ. Computerization of the Yale insulin infusion protocol and potential insights into causes of hypoglycemia with intravenous insulin. Diabetes Technol Ther 2013; 15 (3) 246-252
  • 52 Scott MG, Bruns DE, Boyd JC, Sacks DB. Tight glucose control in the intensive care unit: are glucose meters up to the task?. Clin Chem 2009; 55 (1) 18-20
  • 53 Saager L, Collins GL, Burnside B , et al. A randomized study in diabetic patients undergoing cardiac surgery comparing computer-guided glucose management with a standard sliding scale protocol. J Cardiothorac Vasc Anesth 2008; 22 (3) 377-382
  • 54 Davidson PC, Steed RD, Bode BW, Hebblewhite HR, Prevosti L, Cheekati V. Use of a computerized intravenous insulin algorithm within a nurse-directed protocol for patients undergoing cardiovascular surgery. J Diabetes Sci Tech 2008; 2 (3) 369-375
  • 55 Juneja R, Roudebush C, Kumar N , et al. Utilization of a computerized intravenous insulin infusion program to control blood glucose in the intensive care unit. Diabetes Technol Ther 2007; 9 (3) 232-240
  • 56 Kalfon P, Giraudeau B, Ichai C , et al; CGAO-REA Study Group. Tight computerized versus conventional glucose control in the ICU: a randomized controlled trial. Intensive Care Med 2014; 40 (2) 171-181
  • 57 Vogelzang M, Zijlstra F, Nijsten MWN. Design and implementation of GRIP: a computerized glucose control system at a surgical intensive care unit. BMC Med Inform Decis Mak 2005; 5: 38
  • 58 Chase JG, Shaw G, Le Compte A , et al. Implementation and evaluation of the SPRINT protocol for tight glycaemic control in critically ill patients: a clinical practice change. Crit Care 2008; 12 (2) R49
  • 59 Amrein K, Kachel N, Fries H , et al. Glucose control in intensive care: usability, efficacy and safety of Space GlucoseControl in two medical European intensive care units. BMC Endocr Disord 2014; 14 (1) 62
  • 60 Van Herpe T, De Moor B, Van den Berghe G, Mesotten D. Modeling of effect of glucose sensor errors on insulin dosage and glucose bolus computed by LOGIC-Insulin. Clin Chem 2014; 60 (12) 1510-1518
  • 61 Van Herpe T, Mesotten D, Wouters PJ , et al. LOGIC-insulin algorithm-guided versus nurse-directed blood glucose control during critical illness: the LOGIC-1 single-center, randomized, controlled clinical trial. Diabetes Care 2013; 36 (2) 188-194
  • 62 Plank J, Blaha J, Cordingley J , et al. Multicentric, randomized, controlled trial to evaluate blood glucose control by the model predictive control algorithm versus routine glucose management protocols in intensive care unit patients. Diabetes Care 2006; 29 (2) 271-276
  • 63 Wilinska ME, Hovorka R. Glucose control in the intensive care unit by use of continuous glucose monitoring: what level of measurement error is acceptable?. Clin Chem 2014; 60 (12) 1500-1509
  • 64 Lanspa MJ, Hirshberg EL, Phillips GD, Holmen J, Stoddard G, Orme J. Moderate glucose control is associated with increased mortality compared with tight glucose control in critically ill patients without diabetes. Chest 2013; 143 (5) 1226-1234
  • 65 Krinsley JS, Bruns DE, Boyd JC. The impact of measurement frequency on the domains of glycemic control in the critically ill—a Monte Carlo simulation. J Diabetes Sci Tech 2015; 9 (2) 237-245
  • 66 Krinsley JS. Glycemic control in the critically ill: what have we learned since NICE-SUGAR?. Hosp Pract (1995) 2015; 43 (3) 191-197
  • 67 Krinsley JS, Preiser J-C. Time in blood glucose range 70 to 140 mg/dl >80% is strongly associated with increased survival in non-diabetic critically ill adults. Crit Care 2015; 19 (1) 179
  • 68 Penning S, Chase JG, Preiser J-C , et al. Does the achievement of an intermediate glycemic target reduce organ failure and mortality? A post hoc analysis of the Glucontrol trial. J Crit Care 2014; 29 (3) 374-379
  • 69 Omar AS, Salama A, Allam M , et al. Association of time in blood glucose range with outcomes following cardiac surgery. BMC Anesthesiol 2015; 15 (1) 14
  • 70 Aragon D. Evaluation of nursing work effort and perceptions about blood glucose testing in tight glycemic control. Am J Crit Care 2006; 15 (4) 370-377
  • 71 Cengiz E, Tamborlane WV. A tale of two compartments: interstitial versus blood glucose monitoring. Diabetes Technol Ther 2009; 11 (Suppl. 01) S11-S16
  • 72 Foubert LA, Lecomte PV, Nobels FR, Gulino AM, De Decker KH. Accuracy of a feasibility version of an intravenous continuous glucose monitor in volunteers with diabetes and hospitalized patients. Diabetes Technol Ther 2014; 16 (12) 858-866
  • 73 Brunner R, Kitzberger R, Miehsler W, Herkner H, Madl C, Holzinger U. Accuracy and reliability of a subcutaneous continuous glucose-monitoring system in critically ill patients. Crit Care Med 2011; 39 (4) 659-664
  • 74 Joseph JI, Hipszer B, Mraovic B, Chervoneva I, Joseph M, Grunwald Z. Clinical need for continuous glucose monitoring in the hospital. J Diabetes Sci Tech 2009; 3 (6) 1309-1318
  • 75 Flower OJ, Bird S, Macken L , et al. Continuous intra-arterial blood glucose monitoring using quenched fluorescence sensing: a product development study. Crit Care Resusc 2014; 16 (1) 54-61
  • 76 van Hooijdonk RT, Winters T, Fischer JC , et al. Accuracy and limitations of continuous glucose monitoring using spectroscopy in critically ill patients. Ann Intensive Care 2014; 4 (1) 8
  • 77 Oliver NS, Toumazou C, Cass AE, Johnston DG. Glucose sensors: a review of current and emerging technology. Diabet Med 2009; 26 (3) 197-210
  • 78 Finfer S, Wernerman J, Preiser J-C , et al. Clinical review: consensus recommendations on measurement of blood glucose and reporting glycemic control in critically ill adults. Crit Care 2013; 17 (3) 229
  • 79 Wernerman J, Desaive T, Finfer S , et al. Continuous glucose control in the ICU: report of a 2013 round table meeting. Crit Care 2014; 18 (3) 226
  • 80 van Hooijdonk RTM, Spronk PE, Schultz MJ. Choosing the correct metrics for glucose control. Crit Care 2014; 18 (2) 414
  • 81 Dellinger RP, Levy MM, Rhodes A , et al; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013; 41 (2) 580-637
  • 82 Van Hooijdonk RTM, Leopold JH, Schultz MJ. Continuous glucose monitoring devices for use in the ICU. Annu Updat Intensive Care Emerg Med 2014; 2014: 613-625
  • 83 van Hooijdonk RTM, Abu-Hanna A, Schultz MJ. Glycemic variability is complex—is glucose complexity variable?. Crit Care 2012; 16 (6) 178
  • 84 Ballesteros D, Martínez Ó, Blancas Gómez-Casero R , et al. Continuous tissue glucose monitoring correlates with measurement of intermittent capillary glucose in patients with distributive shock. Med Intensiva 2015; 39 (7) 405-411
  • 85 Boom DT, Sechterberger MK, Rijkenberg S , et al. Insulin treatment guided by subcutaneous continuous glucose monitoring compared to frequent point-of-care measurement in critically ill patients: a randomized controlled trial. Crit Care 2014; 18 (4) 453
  • 86 De Block C, Manuel-Y-Keenoy B, Van Gaal L, Rogiers P. Intensive insulin therapy in the intensive care unit: assessment by continuous glucose monitoring. Diabetes Care 2006; 29 (8) 1750-1756
  • 87 Holzinger U, Warszawska J, Kitzberger R, Herkner H, Metnitz PGH, Madl C. Impact of shock requiring norepinephrine on the accuracy and reliability of subcutaneous continuous glucose monitoring. Intensive Care Med 2009; 35 (8) 1383-1389
  • 88 Holzinger U, Warszawska J, Kitzberger R , et al. Real-time continuous glucose monitoring in critically ill patients: a prospective randomized trial. Diabetes Care 2010; 33 (3) 467-472
  • 89 Kosiborod M, Gottlieb RK, Sekella JA , et al. Performance of the Medtronic Sentrino continuous glucose management (CGM) system in the cardiac intensive care unit. BMJ Open Diabetes Res Care 2014; 2 (1) e000037
  • 90 Leelarathna L, English SW, Thabit H , et al. Accuracy of subcutaneous continuous glucose monitoring in critically ill adults: improved sensor performance with enhanced calibrations. Diabetes Technol Ther 2014; 16 (2) 97-101
  • 91 Logtenberg SJ, Kleefstra N, Snellen FT , et al. Pre- and postoperative accuracy and safety of a real-time continuous glucose monitoring system in cardiac surgical patients: a randomized pilot study. Diabetes Technol Ther 2009; 11 (1) 31-37
  • 92 Punke MA, Decker C, Wodack K, Reuter DA, Kluge S. Continuous glucose monitoring on the ICU using a subcutaneous sensor. Med Klin Intensivmed Notfmed 2015; 110 (5) 360-363
  • 93 Rabiee A, Andreasik V, Abu-Hamdah R , et al. Numerical and clinical accuracy of a continuous glucose monitoring system during intravenous insulin therapy in the surgical and burn intensive care units. J Diabetes Sci Tech 2009; 3 (4) 951-959
  • 94 Schaupp L, Plank J, Köhler G , et al. Prediction of glucose concentration in post-cardiothoracic surgery patients using continuous glucose monitoring. Diabetes Technol Ther 2011; 13 (2) 127-134
  • 95 Schierenbeck F, Franco-Cereceda A, Liska J. Evaluation of a continuous blood glucose monitoring system using central venous microdialysis. J Diabetes Sci Tech 2012; 6 (6) 1365-1371
  • 96 Siegelaar SE, Barwari T, Hermanides J, van der Voort PHJ, Hoekstra JBL, DeVries JH. Microcirculation and its relation to continuous subcutaneous glucose sensor accuracy in cardiac surgery patients in the intensive care unit. J Thorac Cardiovasc Surg 2013; 146 (5) 1283-1289
  • 97 Umbrello M, Salice V, Spanu P , et al. Performance assessment of a glucose control protocol in septic patients with an automated intermittent plasma glucose monitoring device. Clin Nutr 2014; 33 (5) 867-871
  • 98 van Hooijdonk RT, Leopold JH, Winters T , et al. Point accuracy and reliability of an interstitial continuous glucose-monitoring device in critically ill patients: a prospective study. Crit Care 2015; 19: 34