Hypoglycemia and risk of death in critically ill patients
Open accessAbstract
BACKGROUND: Whether hypoglycemia leads to death in critically ill patients is unclear. METHODS: We examined the associations between moderate and severe hypoglycemia (blood glucose, 41 to 70 mg per deciliter [2.3 to 3.9 mmol per liter] and ≤40 mg per deciliter [2.2 mmol per liter], respectively) and death among 6026 critically ill patients in intensive care units (ICUs). Patients were randomly assigned to intensive or conventional glucose control. We used Cox regression analysis with adjustment for treatment assignment and for baseline and postrandomization covariates. RESULTS: Follow-up data were available for 6026 patients: 2714 (45.0%) had moderate hypoglycemia, 2237 of whom (82.4%) were in the intensive-control group (i.e., 74.2% of the 3013 patients in the group), and 223 patients (3.7%) had severe hypoglycemia, 208 of whom (93.3%) were in the intensive-control group (i.e., 6.9% of the patients in this group). Of the 3089 patients who did not have hypoglycemia, 726 (23.5%) died, as compared with 774 of the 2714 with moderate hypoglycemia (28.5%) and 79 of the 223 with severe hypoglycemia (35.4%). The adjusted hazard ratios for death among patients with moderate or severe hypoglycemia, as compared with those without hypoglycemia, were 1.41 (95% confidence interval [CI], 1.21 to 1.62; P<0.001) and 2.10 (95% CI, 1.59 to 2.77; P<0.001), respectively. The association with death was increased among patients who had moderate hypoglycemia on more than 1 day (>1 day vs. 1 day, P=0.01), those who died from distributive (vasodilated) shock (P<0.001), and those who had severe hypoglycemia in the absence of insulin treatment (hazard ratio, 3.84; 95% CI, 2.37 to 6.23; P<0.001). CONCLUSIONS: In critically ill patients, intensive glucose control leads to moderate and severe hypoglycemia, both of which are associated with an increased risk of death. The association exhibits a dose-response relationship and is strongest for death from distributive shock. However, these data cannot prove a causal relationship. (Funded by the Australian National Health and Medical Research Council and others; NICE-SUGAR ClinicalTrials.gov number, NCT00220987.).
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In the surgical ICU, earlier studies found that intensive glucose control at 80 to 110 mg/dL inconsistently reduced length of stay.
“In the surgical ICU, earlier studies have indicated that intensive glucose control (80 to 110 mg/dL) inconsistently resulted in decreased length of stay.94–96”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [95]
The Study Participants section describes an intensive glucose target of 81–108 mg/dL, close to the cited 80–110 mg/dL range. The introductory passage on p. 1109 says initial trials suggested a mortality benefit in surgical ICU patients that subsequent trials did not confirm, but it does not say earlier studies found inconsistent reductions in length of stay. The Clinical Course and Hypoglycemia section discusses length of stay by hypoglycemia status, not that claimed treatment effect. (LLM, conf=0.78)
Experimental — accuracy not yet measuredThe NICE-SUGAR study showed that more aggressive ICU glucose targets of 81 to 108 mg/dL compared with a conventional target below 180 mg/dL did not change length of stay, days needing mechanical ventilation, or need for renal replacement therapy.
“The Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation study showed that more aggressive glucose targets of 81 to 108 mg/dL compared with a conventional glucose target (<180 mg/dL) in the ICU did not change length of stay, number of days needing mechanical ventilation, or need for renal replacement therapy.95”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [95]
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Experimental — accuracy not yet measuredIn NICE-SUGAR, the intensively controlled group had increased mortality and higher rates of hypoglycemia.
“However, the intensively controlled group had increased mortality and higher rates of hypoglycemia.95,97”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [95]
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- Authors
- The NICE-SUGAR Study Investigators
- Affiliations
- The George Institute for Global Health (AU)
- Corresponding author
- The NICE-SUGAR Study Investigators
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2012-09-20
- Volume
- 367
- Issue
- 12
- Pages
- 1108-1118
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W1708450707
- Cited by
- 1,009
- References
- 34
- Citations by year
- 2026: 41 · 2025: 42 · 2024: 50 · 2023: 64 · 2022: 49 · 2021: 71 · 2020: 64 · 2019: 74 · 2018: 84 · 2017: 77 · 2016: 89 · 2015: 86 · 2014: 100 · 2013: 97 · 2012: 17
- FWCI
- 76.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- Medical Research Council
- National Health and Medical Research Council
- Health Research Council of New Zealand
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Keywords
- hypoglycemia, critically ill patients, mortality, tight glycemic control, blood glucose, insulin therapy, sepsis, intensive care unit, glucose-lowering therapy, septic shock, distributive shock, mortality risk factors, randomized controlled trials, sepsis mortality, vasopressor requirement
- MeSH terms
- Follow-Up Studies, Humans, Hyperglycemia, Hypoglycemia, Hypoglycemic Agents, Risk, Proportional Hazards Models, Critical Illness
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