ESPEN Congress Lisbon 2004 Water and electrolytes Hyperglycemia management G Van Den Berghe
Intensive Insulin Therapy in ICU G. Van den Berghe M.D., Ph.D. Department of Intensive Care Medicine University of Leuven (K.U.Leuven) LEUVEN, BELGIUM ESPEN, Lisbon, 2004
Hyperglycemia in the ICU Common Caused by insulin resistance in liver and muscle Admission hyperglycemia related to adverse outcome in AMI and stroke Adaptive : provides glucose for brain, red cells, wounds Only treated when blood glucose > 215 mg/dl (> 12 mmol/l)
A high IGFBP-1 in long-stayers predicts intensive care mortality IGFBP-1 (µg/l) 120 80 40 p = 0.001 IGFBP-1 (µg/l) 300 250 200 150 100 50 R = - 0.47 p = 0.002 0 0 Survivors Non-survivors 0 20 40 60 80 100 120 Insulin (µiu/ml) 140 Van den Berghe et al. JCEM, G.V.d.B., 1999 K.U.Leuven & 2001
Results : Blood glucose control Conventional Intensive 200 P < 0.0001 Blood glucose (mg/dl) 150 100 50 0 0 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 22 29 Days in ICU M ± SEM Van den Berghe G et al. NEJM. 2001; 345: 1359-1367 & CCM 2003; 31: 359-366
Overview Why treat hyperglycemia? the facts Why go down as low as <110 mg/dl (<6.1 mm)? How is blood glucose lowered by insulin during critical illness? What other metabolic and non-metabolic pathways are affected by intensive insulin therapy? What does it cost? How to do it? a few practicalities
Why treat hyperglycemia in the SICU?
Results : Mortality Insulin Treatment Conventional Intensive P (N = 783) (N = 765) ICU deaths (N = 1548) 8.0% 4.6% 0.005* 5-days mortality rate 1.8% 1.7% 0.9 ICU deaths among 451 long-stayers 20.2% 10.6% 0.005 In-hospital deaths (N = 1548) 10.9% 7.2% 0.01 In-hospital deaths among 451 long-stayers 26.3% 16.8% 0.01 * after correction for multiple interim analyses, adjusted P = 0.036 Van den Berghe G et al. N Engl J Med. 2001; G.V.d.B., 345: 1359-1367 K.U.Leuven
Mortality : causes of death Insulin treatment Conventional Intensive (N = 783) (N = 765) P Causes of death -- total no. 0.02 Acute cardiovascular collaps 7 10 Severe brain damage 5 3 Multiple organ failure, no septic focus 18 14 Multiple organ failure, with septic focus 33 8 Van den Berghe G et al. N Engl J Med. 2001; 345: 1359-1367
Mortality (%) effect : cardiac surgery patients vs. others? Insulin Treatment Conventional Intensive (N = 783) (N = 765) RRR ICU deaths (ALL, N=1548) 8.0% 4.6% - 43% ICU deaths long-stay patients (N=451) 20.2% 10.6% - 48% ICU deaths (cardiac surgery) (N = 970) ICU deaths long-stay cardiacs (N=146) 5.1 % 2.1 % 23.9 % 6.9 % - 59% - 71% ICU deaths (others) (N = 578) ICU deaths long-stay others (N=305) 13.1 % 8.7 % 18.1 % 12.0 % - 34% - 34%
Mortality (%) effect : cardiac surgery patients vs. others? Insulin Treatment Conventional Intensive (N = 783) (N = 765) RRR ICU deaths (ALL, N=1548) 8.0% 4.6% - 43% ICU deaths long-stay patients (N=451) 20.2% 10.6% - 48% ICU deaths (cardiac surgery) (N = 970) ICU deaths long-stay cardiacs (N=146) 5.1 % 2.1 % 23.9 % 6.9 % - 59% - 71% ICU deaths (others) (N = 578) ICU deaths long-stay others (N=305) 13.1 % 8.7 % 18.1 % 12.0 % - 34% - 34%
Mortality (%) effect : others? admitted because of sepsis Insulin Treatment Conventional Intensive (N = 783) (N = 765) RRR P-value Non-cardiac surgery (others) (N = 578) Septic complications after thoracic surgery (N = 122) ICU deaths 17.9 % 7.6 % - 58% 0.08 Hospital deaths 23.2 % 7.6 % - 67% 0.01
Morbidity Relative Risk Reduction (%) 60 40 20 0 Blood stream infections - 46 % Critical illness polyneuropathy - 44 % **** Mechanical ventilation > 14 days - 37 % ** ( - 2 days) ICU stay > 14 days - 27 % ( - 3 days) ** Antibiotics > 10 days - 35 % ** Dialysis / CVVH - 41 % ** ** ** p 0.01 **** p < 0.0001 Van den Berghe G et al. N Engl J Med. 2001; 345: 1359-1367
Mortality (%) effect : patients who develop bacteremia ICU? Insulin Treatment Conventional Intensive (N = 783) (N = 765) RRR P-value ICU deaths (ALL, N=1548) 8.0% 4.6% - 43% 0.005 ICU deaths (bacteremia) (N = 93) 29.5 % 12.5 % - 58% 0.05 ICU deaths (others) (N = 1455) 6.2 % 4.2 % - 32% 0.08
Results : Benefit was present regardless of feeding type Among patients in ICU > 5 days (N = 451): 60% received enteral nutrition (up to 68% of caloric intake) Exclusively parenterally fed (N = 184) : ICU mortality 22.3 % --> 11.1 % (RRR = 50% ; p < 0.05) Combined enterally/parenterally fed (N = 267) : ICU mortality 18.8 % --> 10.2 % (RRR = 46% ; p < 0.05) Van den Berghe G et al. N Engl J Med, 2002: 346: 1586-1588
Acute morbidity effects on central nervous system (unpublished) Subgroup : 63 patients after isolated brain injury (two intervention groups were matched) Insulin Treatment Conventional Intensive p (N = 30) (N = 33) Mean ICP (mm Hg) 13 (10-16) 11 (9-14) 0.003 Max ICP (mm Hg) 19 (15-26) 16 (13-22) < 0.0001 Mean CPP (mm Hg) 80 (74-87) 81 (74-87) 0.6 Daily dose of norepinephrine (mg) 12.1 (7.2-22.6) 1.5 (0.4-9.9) 0.01 Diabetes insipidus 47 % 17 % 0.06 Seizures 12.9 % 3.9 % < 0.0001 Van den Berghe G et al. In submission
Karnofsky Performance Status (KPS) Scale KPS (%) level of activity and medical care requirement 100 normal 90 able to do normal activity, minor signs / symptoms 80 normal activity with effort, some signs / symptoms 70 cares for self, unable to do normal activity or to work 60 requires occasional assistance, able to care for own needs 50 requires considerable assistance and medical care 40 disabled, requires special care and assistance 30 severely disabled, hospitalisation indicated, death imminent 20 hospitalisation necessary, very sick, active treatment 10 moribund, fatal processes progressing rapidly 0 dead Yates JW et al. Cancer G.V.d.B., 1980; 45: K.U.Leuven 2220-2224
Functional recovery in neurosurgery/neurology survivors (unpublished) KARNOFSKY PERFORMANCE SCORE (%) 100 90 80 70 60 50 40 30 20 10 0 Hosp Discharge (N=42) p = 0.02 p = 0.1 6 months (N=39) NS p = 0.08 12 months (N=38) Intensive Conventional (P25-P50-P75) 12 months Karnofsky 60 %: 50 % 81 % (p = 0.05) Van den Berghe G et al. In submission
Why go down to as low as <110 mg/dl (<6.1 mm)?
Is strict normoglycemia necessary? Patients in ICU for > 5 days (N = 451) Cumulative Hazard (%) (in hospital death) 45 40 35 30 25 20 15 10 5 0 P = 0.0009 P = 0.026 > 150 mg / dl 110-150 mg / dl < 110 mg / dl 0 50 100 150 200 250 Days after inclusion Van den Berghe G et al. CCM G.V.d.B., 2003; K.U.Leuven 31: 359-366
Is strict normoglycemia necessary? Patients in ICU for > 5 days (N = 451) 80 70 60 ** **** * * * <110 mg/dl (N=201) 110-150 mg/dl (N=143) >150 mg/dl (N=107) % risk 50 40 30 20 10 0 ICU death CIPNP bacteremia > 2 PC transf. A R F Van den Berghe G et al. CCM G.V.d.B., 2003; K.U.Leuven 31: 359-366
Hyperglycemia & risk of polyneuropathy : a continuum Risk of Critical Illness Polyneuropathy (%) 18 16 Rho = 1.0 14 p < 0.0001 12 10 8 6 4 2 54-89 90-125 126-161 162-197 198-232 Blood glucose level (mg/dl) Van den Berghe G et al. N Engl J Med. 2001; 345: 1359-1367
Insulin effect or effect of blood glucose control? Multivariate logistic regression analysis of effect on ICU mortality : (corrected for all univariate determinants of outcome) OR 95% CI P-value Daily insulin dose (per 20 units added) : 1.120 1.040-1.180 0.005 (e.g. : 70 IU vs. 50 IU insulin : risk + 24 %) Mean blood glucose level (per 50 mg/dl added): 1.750 1.450-2.050 <0.0001 (e.g. : 150 mg/dl vs. 100 mg/dl : risk + 75 %) (e.g. : 200 mg/dl vs. 100 mg/dl : risk + 150 %) Van den Berghe G et al. N Engl J Med 2002; 346: 1586-1588 Van den Berghe G et al. CCM 2003; G.V.d.B., 31: K.U.Leuven 359-366
How is blood glucose lowered by insulin in the critically ill?
Which tissues are affected by intensive insulin therapy? IGFBP-1 GK?? glucose glycogen liver? PEPCK glucose? amino acids HXK-II GLUT-4 skeletal muscle FFA TG? adipose tissue
Which tissues are affected by intensive insulin therapy? IGFBP-1 GK?? glucose glycogen liver?? PEPCK glucose? amino acids HXK-II GLUT-4 skeletal muscle FFA TG? adipose tissue
Intensive Insulin Therapy does NOT affect IGFBP-1 in prolonged critical illness Serum IGFBP-1 (ng/ml) 100 all p = NS 80 60 40 20 0 adm d1 d8 last day N = 363 > 7 days in ICU Intensive Insulin Conventional Insulin Mesotten D et al. J Clin Endocrinol Metab, 2002; 87: 5516-5523
IGFBP-1 & mortality in prolonged critical illness Serum IGFBP-1 (ng/ml) 140 120 100 80 60 40 20 0 * *** ** ** *** * ** *** adm d1 d8 d15 d22 d29 Days in ICU N = 363 (> 7 days ICU) Non-survivors Survivors p < 0.05 p < 0.01 p < 0.001 Mesotten D et al. J Clin Endocrinol Metab, 2002; 87: 5516-5523
Hepatic IGFBP-1 mrna unaltered by insulin Relative BP-1 expression 1.5 1 0.5 0 p = 0.5 C I Serum BP-1 (ng/ml) R = 0.42 p = 0.0012 1000 100 10 1 10 100 1000 N = 37 N = 22 IGFBP-1 gene expression Mesotten D et al. J Clin Endocrinol Metab, 2002; 87: 5516-5523
Which tissues are affected by intensive insulin therapy? IGFBP-1 GK? No! glucose glycogen liver PEPCK FFA TG?? glucose? adipose tissue? amino acids HXK-II GLUT-4 skeletal muscle
Hepatic PEPCK mrna unaltered by insulin Relative PEPCK expression 1.5 1 0.5 0 R = 0.58 p = 0.4 p < 0.0001 C I BP-1 expression 1000 100 10 1 1 10 100 1000 N = 33 N = 21 PEPCK gene expression Mesotten D et al. J Clin Endocrinol Metab, 2002; 87: 5516-5523
Which tissues are affected by intensive insulin therapy? IGFBP-1 GK? No! glucose glycogen liver No! PEPCK glucose? amino acids HXK-II GLUT-4 skeletal muscle? FFA TG? adipose tissue
Hepatic Glucokinase (GK) mrna unaltered by insulin Relative expression GK (mrna) 1.6 1.2.8.4 0 p = 0.9 C I N = 38 N = 24 Mesotten D et al. J Clin Endocrinol Metab, G.V.d.B., 2004; K.U.Leuven 89: 219-226
Which tissues are affected by intensive insulin therapy? IGFBP-1 No! No! glucose glucose HXK-II GLUT-4 GK liver No! glycogen PEPCK?? amino acids skeletal muscle FFA TG? adipose tissue
Insulin increases muscle GLUT-4 & HXK-II mrna Relative GLUT 4 expression 2 1 0 Relative HXK II expression p = 0.02 p = 0.03 C I N = 38 N = 24 N = 38 N = 24 2 1 0 C I Mesotten D et al. J Clin Endocrinol Metab, G.V.d.B., 2004; K.U.Leuven 89: 219-226
Which tissues are affected by intensive insulin therapy? IGFBP-1 GK No! No! glucose glycogen liver No! PEPCK glucose Yes! amino acids HXK-II GLUT-4 skeletal muscle FFA TG adipose tissue Mesotten D et al. J Clin Endocrinol Metab 2002, 2004
Which tissues are affected by intensive insulin therapy? IGFBP-1 GK No! No! glucose glycogen liver No! PEPCK glucose Yes! amino acids HXK-II GLUT-4 skeletal muscle? FFA TG adipose tissue
What other metabolic effects, besides blood glucose control, and what other non-metabolic pathways are affected by intensive insulin therapy?
Mechanisms... Lipid metabolism? Inflammation? Mitochondrial function? Innate immunity? Endothelial dysfunction? Coagulation & Fibrinolysis?
Dyslipidemia is associated with risk of death % mortality 40 30 20 40 30 30 20 20 10 10 10 0 0 0 10 20 30 40 50 60 70 80 90 100 <10 - - - - - - - - - - 19 29 39 49 59 69 79 89 99 155 <100 100-199 200-299 300 + <5 5-14 15-24 25-34 35 + TG (mg/dl) linear LDL (mg/dl) < 20 mg/dl = high risk HDL (mg/dl) < 15 mg/dl = high risk Mesotten D et al. J Clin Endocrinol Metab, 2004; 89: 219-226
Intensive insulin therapy suppresses circulating triglycerides % change in Triglycerides 120 p < 0.0001 80 40 p = 0.003 0 admission Day 1 Day 8 Conventional N = 363 in ICU > 7 days Intensive Mesotten D et al. J Clin Endocrinol Metab, G.V.d.B., 2004; K.U.Leuven 89: 219-226
Intensive insulin therapy increases the low HDL and LDL LDL < 20 mg/dl RRR : - 38 % p = 0.005 HDL < 15 mg/dl RRR : -37% p < 0.0001 50 p = 0.007 20 p = 0.005 40 LDL (mg/dl) 30 20 10 HDL (mg/dl) 15 10 5 0 admission 0 Day 8 admission Day 8 Conventional Intensive N = 363 in ICU > 7 days Mesotten D et al. J Clin Endocrinol Metab, G.V.d.B., 2004; K.U.Leuven 89: 219-226
Mechanisms... Lipid metabolism? Yes! Inflammation? Mitochondrial function? Innate immunity? Endothelial dysfunction? Coagulation & Fibrinolysis?
Effect on C-Reactive Protein (CRP) (ICU stay > 5d, N = 451) C-Reactive Protein (mg/l) 180 160 140 120 100 80 60 40 20 p = 0.8 p = 0.02 p = 0.004 p = 0.04 M ± SEM Conventional Intensive 0 Admission Day 5 Day 15 Last day Hansen TK et al. J Clin Endocrinol Metab, 2003; 88: 1082-1088
Effect on Mannose-binding lectin (MBL) (ICU stay > 5d, N = 451) p = 0.01 MBL change from baseline (%) 200 150 100 50 0 p = 0.006 p = 0.02 M ± SEM Conventional Intensive Admission Day 5 Day 15 Last day Hansen TK et al. J Clin Endocrinol Metab, 2003; 88: 1082-1088
Multivariate logistic regression analysis for the effect of intensive insulin therapy on ICU mortality (N=363 > 1 week in ICU) Intensive insulin therapy P=0.02 Non-cardiac surgery Pos. malignancy Pos. diabetes Adm. blood glucose >11mM APACHE II d1 (per 1 added) Age (per added year) P=0.27 P=0.37 P=0.28 P=0.67 P=0.014 P=0.003 0 1 2 3 4 OR (95% CI) Mesotten D et al. J Clin Endocrinol Metab, G.V.d.B., 2004; K.U.Leuven 89: 219-226
Multivariate logistic regression analysis for the effect of intensive insulin therapy on ICU mortality (N=363 > 1 week in ICU) Intensive insulin therapy LDL d8 20mg/dL HDL d8 15mg/dL TG d8 (per 100mg/dL) CRP d8 (per 50mg/L) Blood glucose d8 (per 1mM) Insulin dose d8 (per IU/day) Non-cardiac surgery Pos. malignancy Pos. diabetes Adm. blood glucose >11mM APACHE II d1 (per 1 added) Age (per added year) P=0.74 P=0.003 P=0.016 P=0.60 P=0.087 P=0.87 P=0.77 P=0.76 P=0.33 P=0.78 P=0.69 P=0.012 P=0.0002 OR (95% CI) (effects after 1 week of treatment) 0 1 2 3 4 Mesotten D et al. J Clin Endocrinol Metab, 2004; 89: 219-226
Mechanisms... Lipid metabolism? Yes! Inflammation? Yes! Mitochondrial function? M. Singer s data in Lancet 2002! Innate immunity? Endothelial dysfunction? Coagulation & Fibrinolysis?
Mitochondria : production of cellular fuel (ATP) Intermembrane space Outer membrane Matrix Inner membrane (contains respiratory chain complexes)
Oxidative phosphorylation in mitochondria Intermembrane space H + H + H + Basal leak Inducible leak C Mitochondrial inner membrane I e - Qe - e - e - e - III II IV F 0 NADH 2 NADSuccinate Fumarate O 2 F 1 H 2 O ADP + Pi H + ATP H + H + Mitochondrial matrix
Electron microscopy : liver biopsies (N=20) Conventional : 7/9 abnormal <P=0.002> Intensive : 1/11 abnormal Vanhorebeek I, De Vos R, Van den Berghe G. Lancet 2004 in press
Respiratory chain activity (N=36) (spectrophotometry; normalized for Citrate Synthase) Complex I : P = 0.02 Complex II : P = 0.5 Complex III : P = 0.4,8,7,6,5,4,3,2,1 0 4,5 4 3,5 3 2,5 2 1,5 1,5 3 2,8 2,6 2,4 2,2 2 1,8 1,6 1,4 1,2 1 Complex IV: P = 0.03,4,35,3,25,2,15,1,05 Complex V : P = 0.9 2,2 2 1,8 1,6 1,4 1,2 1,8,6,4,2 Conventional (N=18) Intensive (N=18) (Medians / quartiles / centiles) Vanhorebeek I, De Vos R, Van den Berghe G. Lancet 2004 in press
Mechanisms... Lipid metabolism? Yes! Inflammation? Yes! Mitochondrial function? Yes! Innate immunity? Endothelial dysfunction? Coagulation & Fibrinolysis?
Rabbit model of prolonged critical illness (9 days) Injury + randomisation for blood glucose control Alloxan + TPN + exogenous insulin Blood glucose (mg/dl) 700 600 500 400 300 200 100 0 p < 0.01-3 -2-1 0 1 2 3 4 5 7 9 days insulin (IU per survival day) 14 12 10 8 6 4 2 0 p = 0.001 C I conventional insulin (BG 200-300 mg/dl) (N=7) intensive insulin (BG = 100 mg/dl) (N=8) Weekers F et al. Endocrinology G.V.d.B., 2003, 144: K.U.Leuven 5329-5338
Effect on macrophage function (rabbit model) 80 fresh cells after 24h incubation after LPS challenge ** Fagocytosis (% cells) 60 40 20 (*) (*) ** * (*) 0 1d post injury 3d post injury 1d post injury 3d post injury 1d post injury 3d post injury conventional insulin (BG = 300 mg/dl) (N=7) intensive insulin (BG = 100 mg/dl) (N=8) (*) P = 0.065 * P 0.05 ** P < 0.01 Weekers F et al. Endocrinology G.V.d.B., 2003, 144: K.U.Leuven 5329-5338
Mechanisms... Lipid metabolism? Yes! Inflammation? Yes! Mitochondrial function? Yes! Innate immunity? Yes! Endothelial dysfunction? Coagulation & Fibrinolysis? Studies ongoing...
It works! Strict glycemic control < 110 mg/dl (and/or the other effects mimicked by glycemic control) with exogenous insulin Reduces ICU and hospital mortality of surgical ICU patients Prevents typical ICU complications : Sepsis and excessive inflammation Multiple organ failure Ventilator dependency Prolonged ICU stay Improves outcome of patients with or without sepsis
And it saved a median 2.916 $ per patient... Parameter Costs ($) (median) Intensive Therapy (n=765) Conventional Therapy (n=783) ICU stay 4.284.150 5.674.175 Mechanical Ventilation 1.113.075 1.576.347 Dialysis 260.736 644.448 Inotropic Support 98.615 118.855 Vasopressor Support 52.318 83.324 Antibiotic Treatment 426.496 615.680 Blood Transfusions 151.976 234.244 Insulin Administration / 188.397 65.775 Blood Glucose Monitoring TOTALS $ 6.575.753 $ 9.012.848 $ 8.595/pt $ 11.511/pt Van den Berghe G & Hilleman D, 2004 in submission
Conclusions Intensive insulin therapy saves lives and money in ICU Several mechanisms involved; both glucose control and other effects of insulin are important BG control is feasible in ICU, taking a few crucial recommendations into account Benefits clearly outweigh the risks Whether the benefits of BG control can be extrapolated to medical ICU patients, pediatric ICU patients or to patients on regular wards remains to be investigated
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Results : side effects? Brief hypoglycemia (< 40 mg/dl ) in total group (N = 1548) : 0.8 % --- > 5.2 % P < 0.0001 Occurred in stable phase : on median (IQR) ICU day 11 (2-20) --- > 6 (2-14) P = NS Van den Berghe G et al. Crit Care Med 2003, 31: 359-366
How to maintain strict normoglycemia in the SICU?
How? standard feeding regimen, started on admission Insulin (Actrapid HM ) by continuous infusion 50 ml syringe pump 1 IU / ml (exceptionally 2 IU / ml) whole blood glucose systematically monitored / 1-4 hours Nurse controlled, physician supervised
Non-protein calories : average 19 kcal / kg BW / day 30 Conventional Intensive kcal / kg / day 25 20 15 10 5 7 22 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 22 29 P = NS Days in ICU M ± SEM Van den Berghe G et al. N Engl J Med 2001 Van den Berghe G et al. Crit Care Med 2003
Carbohydrates : started with 110 g IV glucose the first 24h 300 250 Conventional Intensive gram / 24h 200 150 100 50 0 Van den Berghe G et al. N Engl J Med 2001 Van den Berghe G et al. Crit Care Med 2003 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 22 29 Days in ICU P = NS M ± SEM
How? standard feeding regimen, started on admission Insulin (Actrapid HM ) by continuous infusion 50 ml syringe pump 1 IU / ml (exceptionally 2 IU / ml) whole blood glucose systematically monitored / 1-4 hours Nurse controlled, physician supervised
Insulin requirements Insulin Treatment Conventional Intensive P Patients receiving insulin Mean daily insulin dose, when given (IU/d) (N = 783) (N = 765) 39% 33 99% <0.0001 71 <0.0001 Duration of insulin requirement (% ICU stay) 67 100 <0.0001 Mean 06:00h blood glucose (mg/dl) (when on insulin) 173 ± 33 103 ± 18 <0.0001 Van den Berghe G et al. N Engl J Med. 2001; 345: 1359-1367
Insulin dose : on average 3 to 4 U per hour 6 All P < 0.0001 Units / h 4 2 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 22 29 M ± SEM Conventional Intensive Van den Berghe G et al. CCM 2003, 31: 359-366
Independent determinants of insulin requirements IU insulin/h per Cal/kg.6.5.4.3.2.1 0 *** *** No Diabetes Diabetes Adm BG < 200 mg/dl IU insulin/h per Cal/kg.5.4.3.2.1 0 *** *** ***.4 *** Adm BG > 200 mg/dl IU insulin/h per Cal/kg.3.2.1 0 BMI < 25 BMI > 25 Conventional Intensive Van den Berghe G et al. Crit Care Med 2003, 31: 359-366
Independent determinants of insulin requirements.6 P 0.0001.5.4.3.2.1 0 Conventional **** Intensive ** abdominal other vascular thoracic multiple trauma cerebral cardiac transplantation IU insulin/h per Cal/kg Van den Berghe G et al. Crit Care Med 2003, 31: 359-366
Guidelines Van den Berghe G et al. N Engl J Med 2002; 346: 1586-1588 Crit Care Med 2003, 31: 359-366 Available upon e-mail request to : greta.vandenberghe@med.kuleuven.ac.be
Guidelines To apply with common sense...
Recommendations to avoid hypoglycemia (1) Regarding the insulin drip : Use a syringe-driven insulin pump (50 ml) Do not concentrate more than 1(-2) IU/ml Connect the insulin drip as close as possible to the patient (no T-connections!!)
Recommendations to avoid hypoglycemia (2) Special concerns regarding alterations of caloric intake : Use infusion pumps to administer glucose-containing solutions Rule of thumb : insulin follows caloric intake During pause of enteral feeding : reduce insulin proportionately to reduction of caloric intake! At extubation (limited oral food intake is planned) : reduce insulin! At times of patient transportation : reduce insulin proportionately to reduction of caloric intake!
Recommendations to avoid hypoglycemia (3) Special concerns regarding concomitant drugs : e. g. Glucocorticoids : doses > equivalent of 90 mg hydrocortisone : administer as a continuous infusion Special concerns regarding patients at risk of acute renal failure : Hourly substitution of urinary volume loss add 16, 12 or 10 IU insulin / liter substitution fluid of glucose 5%, glucose 3.3%+sodium 0.3%, or glucose 2.5%, respectively
Recommendations to avoid hypoglycemia (4) Regarding the blood glucose measuring : Use a point of care measurement Use an accurate measurement : e.g. ABL,...
Discharge from ICU to regular ward Previously diabetic : restart oral drugs or half of home dose of insulin Previously not diabetic : When BG < 6.1 mm (110 mg / dl) on less than 2 IU / h insulin : attempt to stop insulin check BG within 1 h when BG < 11.1 mm (200 mg/dl) : discharge without insulin infusion When insulin is required to maintain BG < 11.1 mm (200 mg/dl) : patients likely has undiagnosed diabetes call diabetologist for follow up on ward start IV insulin as for diabetic patients