Glycemic Control, Diabetic Status, and Mortality in a Heterogeneous Population of Critically Ill Patients Before and During the Era of Intensive Glycemic Management: Six and One-Half Years Experience at a University-Affiliated Community Hospital
Hyperglycemia occurs commonly in acutely and critically ill patients and has been associated with adverse clinical consequences. An emerging body of literature describes the beneficial effects of intensive glycemic monitoring and treatment (tight glycemic control, or "TGC"). This manuscript reviews the experience of a cohort of 5365 non-cardiac surgery patients admitted to the adult intensive care unit of a university-affiliated community hospital before and after implementation of TGC. Significant decreases in mortality occurred among medical and surgical patients during the TGC era, but not among trauma patients. Non-diabetics who sustained hyperglycemia had an especially high risk of mortality, and benefited greatly from treatment. Further investigations will be needed to identify the most appropriate glycemic targets for different populations of patients.
Available from: Alan H Morris
- "We believe it necessary to stratify analysis upon diabetic status. Diabetic patients behave differently than non-diabetic patients regarding intravenous insulin therapy [16-19,30-33]. Although prior studies also demonstrated that hypoglycemia and glycemic variability contribute to mortality, many do not demonstrate that the association of glycemic variability to mortality is independent of hypoglycemia [12,14,16,29,34]. "
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Both patient- and context-specific factors may explain the conflicting evidence regarding glucose control in critically ill patients. Blood glucose variability appears to correlate with mortality, but this variability may be an indicator of disease severity, rather than an independent predictor of mortality. We assessed blood glucose coefficient of variation as an independent predictor of mortality in the critically ill.
We used eProtocol-Insulin, an electronic protocol for managing intravenous insulin with explicit rules, high clinician compliance, and reproducibility. We studied critically ill patients from eight hospitals, excluding patients with diabetic ketoacidosis and patients supported with eProtocol-insulin for < 24 hours or with < 10 glucose measurements. Our primary clinical outcome was 30-day all-cause mortality. We performed multivariable logistic regression, with covariates of age, gender, glucose coefficient of variation (standard deviation/mean), Charlson comorbidity score, acute physiology score, presence of diabetes, and occurrence of hypoglycemia < 60 mg/dL.
We studied 6101 critically ill adults. Coefficient of variation was independently associated with 30-day mortality (odds ratio 1.23 for every 10% increase, P < 0.001), even after adjustment for hypoglycemia, age, disease severity, and comorbidities. The association was higher in non-diabetics (OR = 1.37, P < 0.001) than in diabetics (OR 1.15, P = 0.001).
Blood glucose variability is associated with mortality and is independent of hypoglycemia, disease severity, and comorbidities. Future studies should evaluate blood glucose variability.
Available from: S. E. Siegelaar
- "Some studies found the opposite, with higher mortality rates for DM patients
in the low-normal mean glucose range. However, these findings were unadjusted results
only [18,20] and this relation was not significant after adjustment for severity of
disease . Furthermore, high glucose variability in ICU patients with DM seems to be
less harmful than in patients without DM [21,22] although data are limited. "
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In critical illness, four measures of glycaemic control are associated with ICU mortality: mean glucose concentration, glucose variability, the incidence of hypoglycaemia (≤2.2 mmol/l) or low glucose (2.3 to 4.7 mmol/l). Underlying diabetes mellitus (DM) might affect these associations. Our objective was to study whether the association between these measures of glycaemic control and ICU mortality differs between patients without and with DM and to explore the cutoff value for detrimental low glucose in both cohorts.
This retrospective database cohort study included patients admitted between January 2004 and June 2011 to a 24-bed medical/surgical ICU in a teaching hospital. We analysed glucose and outcome data from 10,320 patients: 8,682 without DM and 1,638 with DM. The cohorts were subdivided into quintiles of mean glucose and quartiles of glucose variability. Multivariable regression models were used to examine the independent association between the four measures of glycaemic control and ICU mortality, and for defining the cutoff value for detrimental low glucose.
Regarding mean glucose, a U-shaped relation was observed in the non-DM cohort with an increased ICU mortality in the lowest and highest glucose quintiles (odds ratio=1.4 and 1.8, P<0.001). No clear pattern was found in the DM cohort. Glucose variability was related to ICU mortality only in the non-DM cohort, with highest ICU mortality in the upper variability quartile (odds ratio=1.7, P<0.001). Hypoglycaemia was associated with ICU mortality in both cohorts (odds ratio non-DM=2.5, P<0.001; odds ratio DM=4.2, P=0.001), while low-glucose concentrations up to 4.9 mmol/l were associated with an increased risk of ICU mortality in the non-DM cohort and up to 3.5 mmol/l in the DM cohort.
Mean glucose and high glucose variability are related to ICU mortality in the non-DM cohort but not in the DM cohort. Hypoglycaemia (≤2.2 mmol/l) was associated with ICU mortality in both. The cutoff value for detrimental low glucose is higher in the non-DM cohort (4.9 mmol/l) than in the DM cohort (3.5 mmol/l). While hypoglycaemia (≤2.2 mmol/l) should be avoided in both groups, DM patients seem to tolerate a wider glucose range than non-DM patients.
Available from: Roosmarijn T.M. Van Hooijdonk
- "Finally, the independent impact of diabetic status, without reference to glycemic
control, on the mortality of critically ill patients has been the subject of recent
observational studies that concluded that patients with diabetes did not experience
higher mortality, and diabetes may, in fact, be protective [30-36]. We demonstrated here that diabetes is independently associated with
decreased risk of mortality. "
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Hyperglycemia, hypoglycemia, and increased glycemic variability have each been independently associated with increased risk of mortality in critically ill patients. The role of diabetic status on modulating the relation of these three domains of glycemic control with mortality remains uncertain. The purpose of this investigation was to determine how diabetic status affects the relation of hyperglycemia, hypoglycemia, and increased glycemic variability with the risk of mortality in critically ill patients.
This is a retrospective analysis of prospectively collected data involving 44,964 patients admitted to 23 intensive care units (ICUs) from nine countries, between February 2001 and May 2012. We analyzed mean blood glucose concentration (BG), coefficient of variation (CV), and minimal BG and created multivariable models to analyze their independent association with mortality. Patients were stratified according to the diagnosis of diabetes.
Among patients without diabetes, mean BG bands between 80 and 140 mg/dl were independently associated with decreased risk of mortality, and mean BG bands>or=140 mg/dl, with increased risk of mortality. Among patients with diabetes, mean BG from 80 to 110 mg/dl was associated with increased risk of mortality and mean BG from 110 to 180 mg/dl with decreased risk of mortality. An effect of center was noted on the relation between mean BG and mortality. Hypoglycemia, defined as minimum BG<70 mg/dl, was independently associated with increased risk of mortality among patients with and without diabetes and increased glycemic variability, defined as CV>or=20%, was independently associated with increased risk of mortality only among patients without diabetes. Derangements of more than one domain of glycemic control had a cumulative association with mortality, especially for patients without diabetes.
Although hyperglycemia, hypoglycemia, and increased glycemic variability is each independently associated with mortality in critically ill patients, diabetic status modulates these relations in clinically important ways. Our findings suggest that patients with diabetes may benefit from higher glucose target ranges than will those without diabetes. Additionally, hypoglycemia is independently associated with increased risk of mortality regardless of the patient's diabetic status, and increased glycemic variability is independently associated with increased risk of mortality among patients without diabetes.
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