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Intensive insulin therapy in critically ill patients.
Open accessAbstract
BACKGROUND: Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known. METHODS: We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg per deciliter [4.4 and 6.1 mmol per liter]) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter [11.9 mmol per liter] and maintenance of glucose at a level between 180 and 200 mg per deciliter [10.0 and 11.1 mmol per liter]). RESULTS: At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (P<0.04, with adjustment for sequential analyses). The benefit of intensive insulin therapy was attributable to its effect on mortality among patients who remained in the intensive care unit for more than five days (20.2 percent with conventional treatment, as compared with 10.6 percent with intensive insulin therapy, P=0.005). The greatest reduction in mortality involved deaths due to multiple-organ failure with a proven septic focus. Intensive insulin therapy also reduced overall in-hospital mortality by 34 percent, bloodstream infections by 46 percent, acute renal failure requiring dialysis or hemofiltration by 41 percent, the median number of red-cell transfusions by 50 percent, and critical-illness polyneuropathy by 44 percent, and patients receiving intensive therapy were less likely to require prolonged mechanical ventilation and intensive care. CONCLUSIONS: Intensive insulin therapy to maintain blood glucose at or below 110 mg per deciliter reduces morbidity and mortality among critically ill patients in the surgical intensive care unit.
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In the citing paper
“Inpatient hyperglycemia is associated with increased complications including surgical site infections, mortality, and increased length of hospital stay.91–93”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [92]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Overall, studies have shown that treatment including a basal insulin regimen resulted in better glycemic control compared with sliding-scale insulin alone.92,107–109”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [92]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The better glycemic control resulted in improvements in rates of postsurgical complications.92”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [92]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“RCTs have shown that treatment with a basal prandial regimen using insulin analogs improved glycemic control with fewer hospital complications in general medical and surgical persons with T2D compared with sliding-scale regular insulin alone.92,107,108,1333–1336”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [92]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Several studies have compared different basal insulin formulations, including glargine U100, insulin detemir U100, glargine U300, and degludec U100, with similar glycemic control results.92,107,1343–1346”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [92]
Experimental — accuracy not yet measured
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Reported recommendations ( 43) are based on randomized trials of hypocaloric intake performed more than 20 years ago in less than 50 patients and models based on observational data and summarized by Dickerson et al. (350).”
From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [350]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Higher protein intake reaching 1.5 to 2 g/kg/day may be considered in this population, since there are large protein losses (20-30 g/L) (350).”
From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [350]
Experimental — accuracy not yet measuredIn the citing paper
“In a single centre study, targeting blood glucose to 80-110 mg/dL reduced ICU mortality [513], however this finding was not reproduced in subsequent multi-centre RCTs [514, 515].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [513]
In the citing paper
“Observational studies in hospitalized patients with and without diabetes indicate that hyperglycemia is a predictor of poor clinical outcome and mortality.1–4”
From A comparison study of continuous insulin infusion protocols in the medical intensive care unit: Computer-guided vs. Standard column-based algorithms (2010) · cites this paper as [4]
In the citing paper
“Early randomized controlled trials of intensified insulin therapy in patients with surgical and medical acute critical illness reported a reduction on the risk of multiorgan failure and systemic infections,3–5 as well as short- and long-term mortality.1,4”
From A comparison study of continuous insulin infusion protocols in the medical intensive care unit: Computer-guided vs. Standard column-based algorithms (2010) · cites this paper as [4]
In the citing paper
“The rate of severe hypoglycemic events (<40 mg/dL) observed in both arms of our trial was significantly lower than those reported in recent international trials of intensive glycemic control.3,4,8”
From A comparison study of continuous insulin infusion protocols in the medical intensive care unit: Computer-guided vs. Standard column-based algorithms (2010) · cites this paper as [4]
In the citing paper
“The overall rate of severe hypoglycemic events in international trials ranged between 5% to 28.6%.3,4,7,8,18,19”
From A comparison study of continuous insulin infusion protocols in the medical intensive care unit: Computer-guided vs. Standard column-based algorithms (2010) · cites this paper as [4]
In the citing paper
“for protocols with intensive glucose control in critically ill patients (88), rapid glucose results are required in order to calculate the insulin dose.”
From Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus (2011) · cites this paper as [88]
In the citing paper
“A 2001 report of a seminal randomized controlled trial by van den Berghe et al. described a 34% reduction in mortality in surgical ICU patients managed according to a tight glucose-control protocol (88).”
From Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus (2011) · cites this paper as [88]
In the citing paper
“the demonstration that intensive glycemic control improved outcomes in surgical intensive care unit (ICU) patients (69)”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [69]
In the citing paper
“Intensive insulin therapy achieved a mean blood glucose of 103 mg/dl (5.7 mmol/l) and was associated with reduced mortality during the ICU stay and decreased overall in-hospital mortality (328).”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [328]
In the citing paper
“A mixed group of patients with and without diabetes admitted to a surgical ICU were randomized to receive intensive insulin therapy (target blood glucose 80–110 mg/dl [4.4–6.1 mmol/l]) or conventional therapy.”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [328]
In the citing paper
“There is relatively strong evidence from randomized controlled trials for a glycemic target of blood glucose <110 mg/dl (6.1 mmol/l) in surgical patients in critical care units (328–330).”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [328]
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Metadata
- Authors
- Van den Berghe, G., Wouters, P., Weekers, F., Verwaest, C., Bruyninckx, F., Schetz, M., Vlasselaers, D., Ferdinande, P., Lauwers, P., & Bouillon, R.
- Affiliations
- KU Leuven (BE)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2001-11-08
- Volume
- 345
- Issue
- 19
- Pages
- 1359-1367
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W1980717583
- Semantic Scholar
- fbea5f0195f44d35f827558f583cdfc44cf42cdb
- Cited by
- 9,977
- References
- 50
- Citations by year
- 2026: 118 · 2025: 142 · 2024: 175 · 2023: 149 · 2022: 142 · 2021: 191 · 2020: 212 · 2019: 226 · 2018: 245 · 2017: 296 · 2016: 283 · 2015: 384 · 2014: 468 · 2013: 419 · 2012: 549
- FWCI
- 212.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- intensive insulin therapy, critically ill patients, glycemic control, hyperglycemia, insulin resistance, mortality, multiple organ failure, bloodstream infection, acute kidney injury, critical illness polyneuropathy, mechanical ventilation, surgical intensive care unit
- MeSH terms
- Blood Glucose, Critical Care, Female, Humans, Hypoglycemic Agents, Insulin, Intensive Care Units, Length of Stay, Male, Middle Aged, Postoperative Care, Prospective Studies, Respiration, Artificial, Logistic Models, Survival Analysis, Critical Illness, Hospital Mortality, APACHE
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