The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis
Open accessAbstract
BACKGROUND: The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids. METHODS: In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer's lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points. RESULTS: The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], P<0.001). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P=0.01). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer's lactate. CONCLUSIONS: The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials.gov number, NCT00135473.)
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The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Though effective, the basal-bolus regimen is labor intensive, requires several injections per day, and is associated with risk of hypoglycemia, affecting up to 10% to 30% of noncritically ill persons.102,1333”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [102]
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
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly beneficial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70–74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [70]
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 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 [8]
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
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly bene fi cial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70 -74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [70]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly beneficial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70–74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [70]
The cited source says what the claim attributes to it.
In the citing paper
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly beneficial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70–74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [70]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Two randomised controlled trials conducted in critically ill patients in the intensive care unit setting also identified severe hypoglycaemia as an independent risk factor for mortality.25 26”
From The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: Retrospective epidemiological analysis of the ACCORD study (2010) · cites this paper as [25]
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In the citing paper
“Those without preexisting DM or stress hyperglycemia have a higher incidence of more postheart surgery complications.91,100–103”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [102]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The transition of persons from the hospital to ambulatory or subacute settings is a high-risk period for medication errors, but also an opportunity to improve glycemic control, avoiding what is often termed clinical inertia.102,1285,1286,1380”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [102]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Adipose tissue utilizes 4.5 kcal/kg/day and muscle 13 kcal/kg/day.(352).”
From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [352]
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 [514]
In the citing paper
“In addition, intensified insulin therapy in critically-ill patients has been shown to be associated with a higher rate of severe hypoglycemic events than less aggressive glycemic control protocols.7–10”
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 [8]
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 [8]
In the citing paper
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly bene fi cial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70 -74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [70]
In the citing paper
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly bene fi cial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70 -74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [70]
In the citing paper
“However, in several studies of critically ill medical patients (330,331,333), the incidence of severe hypoglycemia (blood glucose <40 mg/dl) was approximately threefold greater in intensively treated patients.”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [331]
In the citing paper
“In another study using a similar intervention targeting a blood glucose range of 4.4–6.1 mmol in patients admitted with sepsis, no difference in mortality from the conventionally treated group was observed.”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [331]
In the citing paper
“There were more episodes of hypoglycemia, defined as a blood glucose <40 mg/dl (2.2 mmol/l), and more serious adverse events in the group receiving intensive insulin therapy (331).”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [331]
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Citations
Cites
Bone, R. C., BALK, R. A., Cerra, F. B., Dellinger, R. P., Fein, A. M., Knaus, W. A., Schein, R. M. H., & Sibbald, W. J. (1992) · CHEST Journal · doi:10.1378/chest.101.6.1644 · Cited by 13,317
Intensive insulin therapy in critically ill patients.
Van den Berghe, G., Wouters, P., Weekers, F., Verwaest, C., Bruyninckx, F., Schetz, M., Vlasselaers, D., Ferdinande, P., Lauwers, P., & Bouillon, R. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011300 · Cited by 9,977
American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference
(1992) · Critical Care Medicine · doi:10.1097/00003246-199206000-00025 · Cited by 5,134
Intensive insulin therapy in the medical ICU
Van den Berghe, G., Wilmer, A., Hermans, G., Meersseman, W., Wouters, P. J., Milants, I., Van Wijngaerden, E., Bobbaers, H., & Bouillon, R. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052521 · Cited by 3,639
Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock
Dellinger, R. P., Carlet, J. M., Masur, H., Gerlach, H., Calandra, T., Cohen, J., Gea‐Banacloche, J., Keh, D., Marshall, J. C., Parker, M. M., et al. (2004) · Intensive Care Medicine · doi:10.1007/s00134-004-2210-z · Cited by 3,309
Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock
Dellinger, R. P., Carlet, J. M., Masur, H., Gerlach, H., Calandra, T., Cohen, J., Gea‐Banacloche, J., Keh, D., Marshall, J. C., Parker, M. M., et al. (2004) · Critical Care Medicine · doi:10.1097/01.ccm.0000117317.18092.e4 · Cited by 3,038
den Berghe, G. V., Wouters, P. J., Bouillon, R., Weekers, F., Verwaest, C., Schetz, M., Vlasselaers, D., Ferdinande, P., & Lauwers, P. (2003) · Critical Care Medicine · doi:10.1097/01.ccm.0000045568.12881.10 · Cited by 1,441
Thadhani, R., Pascual, M. A., & Bonventre, J. V. (1996) · New England Journal of Medicine · doi:10.1056/nejm199605303342207 · Cited by 1,426
Colloids versus crystalloids for fluid resuscitation in critically ill patients
Perel, P., Roberts, I., & Ker, K. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd000567.pub6 · Cited by 1,154
Moreno, R. P., Vincent, J., Matos, R., de Mendonça, A., Cantraine, F. R. L., THIJS, L. G., Takala, J., Sprung, C. L., Antonelli, M. M., Bruining, H. A., et al. (1999) · Intensive Care Medicine · doi:10.1007/s001340050931 · Cited by 1,050
Research works printed but not linked: 3
- Roberts I, 2004, Cochrane Database Syst Rev, 4, CD000567
- Brunkhorst FM, 2005, Infection, 33, 19
- Wiesen P, 2005, Acta Anaesthesiol Belg, 56, 257
Cited by
Sorted by citations
Items 1,001–1,002 of 1,002
Regulatory effect of insulin on the structure, function and metabolism of Na+/K+‑ATPase (Review)
Wen, X.-P., & Wan, Q.-Q. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.10678 · Cited by 11
The association of glucose control on in-hospital mortality in the cardiac intensive care unit
Adie, S. K., Ketcham, S. W., Marshall, V. D., Farina, N., & Sukul, D. (2023) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2023.108453 · Cited by 3
Metadata
- Authors
- Brunkhorst, F. M., Engel, C., Bloos, F., Meier-Hellmann, A., Ragaller, M., Weiler, N., Moerer, O., Gruendling, M., Oppert, M., Grond, S., Olthoff, D., Jaschinski, U., John, S., Rossaint, R., Welte, T., Schaefer, M., Kern, P., Kuhnt, E., Kiehntopf, M., Hartog, C., Natanson, C., Loeffler, M., & Reinhart, K.
- Affiliations
- Friedrich Schiller University Jena (DE)
- Leipzig University (DE)
- Technische Universität Dresden (DE)
- University Hospital Schleswig-Holstein (DE)
- University of Göttingen (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Martin Luther University Halle-Wittenberg (DE)
- University Hospital Leipzig (DE)
- Otto-von-Guericke-Universität Magdeburg (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Universitätsklinikum Aachen (DE)
- Medizinische Hochschule Hannover (DE)
- Krankenhaus Dresden-Friedrichstadt (DE)
- National Institutes of Health (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2008-01-10
- Volume
- 358
- Issue
- 2
- Pages
- 125-139
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2148706741
- Cited by
- 2,921
- References
- 37
- Citations by year
- 2026: 30 · 2025: 47 · 2024: 47 · 2023: 70 · 2022: 68 · 2021: 95 · 2020: 75 · 2019: 85 · 2018: 116 · 2017: 114 · 2016: 158 · 2015: 195 · 2014: 218 · 2013: 245 · 2012: 251
- FWCI
- 265.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- OPUS (Augsburg University) (submittedVersion)
- Funders
- Massachusetts Medical Society
- Friedrich-Schiller-Universität Jena
- Bundesministerium für Bildung und Forschung (01KI0106)
- Hebrew University of Jerusalem
- Novo Nordisk
- 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 › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- intensive insulin therapy, pentastarch, hydroxyethyl starch, fluid resuscitation, severe sepsis, septic shock, normoglycemia, hypoglycemia, lactated Ringer's solution, acute kidney injury, organ failure, mortality
- MeSH terms
- Ringer's Solution, Aged, Combined Modality Therapy, Dose-Response Relationship, Drug, Female, Fluid Therapy, Humans, Hydroxyethyl Starch Derivatives, Hypoglycemia, Hypoglycemic Agents, Infusions, Intravenous, Insulin, Isotonic Solutions, Male, Middle Aged, Risk Factors, Multivariate Analysis, Critical Illness, Treatment Failure, Sepsis, Kaplan-Meier Estimate, Acute Kidney Injury
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