Colin Hegarty

Hypoglycemia and Outcome in Critically Ill Patients

OBJECTIVE To determine whether mild or moderate hypoglycemia that occurs in critically ill patients is independently associated with an increased risk of death. PATIENTS AND METHODS Of patients admitted to 2 hospital intensive care units (ICUs) in Melbourne and Sydney, Australia, from January 1, 2000, to October 14, 2004, we analyzed all those who had at least 1 episode of hypoglycemia (glucose concentration, <81 mg/dL). The independent association between hypoglycemia and outcome was statistically assessed. RESULTS Of 4946 patients admitted to the ICUs, a cohort of 1109 had at least 1 episode of hypoglycemia (blood glucose level, <81 mg/dL). Of these 1109 patients (22.4% of all admissions to the intensive care unit), hospital mortality was 36.6% compared with 19.7% in the 3837 nonhypoglycemic control patients (P<.001). Even patients with a minimum blood glucose concentration between 72 and 81 mg/dL had a greater unadjusted mortality rate than did control patients (25.9% vs 19.7%; unadjusted odds ratio, 1.42; 95% confidence interval, 1.12-1.80; P=.004.) Mortality increased significantly with increasing severity of hypoglycemia (P<.001). After adjustment for insulin therapy, hypoglycemia was independently associated with increased risk of death, cardiovascular death, and death due to infectious disease. CONCLUSION In critically ill patients, an association exists between even mild or moderate hypoglycemia and mortality. Even after adjustment for insulin therapy or timing of hypoglycemic episode, the more severe the hypoglycemia, the greater the risk of death.

Blood glucose concentration and outcome of critical illness: the impact of diabetes.

Objective:To study the impact of diabetes mellitus on the relationship between glycemia and mortality in critically ill patients. Design:Retrospective observational study. Setting:Intensive care units of two university hospitals. Patients:Cohort of 4946 critically ill patients including 728 patients with diabetes mellitus. Intervention:None. Measurements and Main Results:We assessed and compared the relationship between glycemia during intensive care unit stay and mortality in diabetic and nondiabetic patients. There were 125,036 blood glucose measurements (5.7 measurements/day on average). Intensive care unit mortality increased significantly with increasing mean blood glucose concentration in nondiabetes mellitus patients but not in diabetes mellitus patients. Nondiabetes mellitus patients with a time-weighted glucose concentration (GluTw) between 8.0 and 10.0 mmol/L were found to be 1.74 times more likely to die in intensive care unit as diabetes mellitus patients in the same range (odds ratio = 1.74 [1.13–2.68] p = 0.01). They were also more than three times more likely to die in the intensive care unit compared with diabetes mellitus patients when the Glutw was between 10.0 and 11.1 mmol/L (odds ratio = 3.34 [1.35–8.23] p = 0.009). Using multivariate logistic regression analysis, hyperglycemia was strongly and independently associated with outcome in nondiabetic patients (p < 0.001) but showed no significant association with outcome in diabetic patients. Conclusions:Unlike nondiabetic patients, diabetic patients show no clear association between hyperglycemia during intensive care unit stay and mortality and markedly lower odds ratios of death at all levels of hyperglycemia. These findings suggest that, in critically patients with diabetes mellitus, hyperglycemia may have different biological and/or clinical implications. LEARNING OBJECTIVESOn completion of this article, the reader should be able to: Explain the impact of blood glucose monitoring on outcomes. Describe the impact of the diagnosis of diabetes on outcomes in patients with hyperglycemia. Use this information in a clinical setting. Dr. French has disclosed that he was the recipient of grant/research funds from Novartis and is currently receiving grant/research funds from Novartis, Wyeth, Lilly, and Takeda. Dr. French has disclosed that he was a consultant/advisor for Wyeth. The remaining authors have disclosed that they have no financial relationships with or interests in any commercial companies pertaining to this educational activity. All faculty and staff in a position to control the content of this CME activity have disclosed that they have no financial relationship with, or financial interests in, any commercial companies pertaining to this educational activity. Lippincott CME Institute, Inc., has identified and resolved all faculty conflicts of interest regarding this educational activity. Visit the Critical Care Medicine Web Site (www.ccmjournal.org) for information on obtaining continuing medical education credit.

The interaction of chronic and acute glycemia with mortality in critically ill patients with diabetes.

Objectives:The relationship between hyperglycemia and mortality is altered by the presence of diabetes mellitus. Biological adjustment to preexisting hyperglycemia might explain this phenomenon. We tested whether the degree of preexisting hyperglycemia would modulate the association between glycemia and outcome during critical illness in patients with diabetes mellitus. Design:Retrospective observational study. Setting:Two tertiary intensive care units. Patients:Four hundred fifteen critically ill diabetic patients with HbA1c levels measured within 3 months of intensive care unit admission. Interventions:None. Measurements and Main Results:There were 9,946 blood glucose measurements in this study cohort (glucose measured 6.7 times per day; every 3.6 hrs on average). The median preadmission HbA1c level was 7.0%. There was no significant difference in HbA1c levels (p = .17) or time-weighted average of blood glucose concentrations (p = .49) between survivors and nonsurvivors. The time-weighted average of blood glucose concentrations during intensive care unit stay for nonsurvivors was lower than that of survivors when the HbA1c was >6.8%. In multivariate analysis, we found that there was a significant interaction between HbA1c and the time-weighted glucose level, indicating that the relationship between HbA1c and mortality changed according to the levels of time-weighted average of blood glucose concentrations (p = .008). As a consequence, in patients with higher (>7%) preadmission levels of HbA1c, the higher the time-weighted acute glucose concentration during intensive care unit stay (>10 mmol/L), the lower the hospital mortality compared with the lower HbA1c cohort (<7%). Conclusions:In patients with diabetes mellitus admitted to intensive care units, there was a significant interaction between preexisting hyperglycemia and the association between acute glycemia and mortality. These observations generate the hypothesis that glucose levels that are considered safe and desirable in other patients might be undesirable in diabetic patients with chronic hyperglycemia. Further studies are required to confirm or refute our findings.

Ionized calcium concentration and outcome in critical illness

Objective:To assess the association of abnormalities of ionized calcium levels with mortality in a heterogeneous cohort of critically ill patients. Design:Retrospective, combined clinical and biochemical study. Setting:Four combined medical/surgical intensive care units. Patients:Cohort of 7,024 adult critically ill patients. Interventions:None. Measurements and Main Results:We studied 177,578 ionized calcium measurements, from 7024 patients, with a mean value of 1.11 mmol/L (ionized calcium measured every 4.5 hrs on average). The unadjusted lowest and highest ionized calcium reported during intensive care unit stay were significantly different between intensive care unit survivors and nonsurvivors (p < .001). If hypocalcemia occurred at least once during the intensive care unit stay, the probability of intensive care unit mortality increased by 46%, 108%, and 150% for ionized calcium levels <1.15, 0.90, and 0.80 mmol/L, respectively. If hypercalcemia occurred at least once during the intensive care unit stay, the probability of intensive care unit mortality increased by 100%, 162%, and 190% for ionized calcium levels >1.25, 1.35, and 1.45 mmol/L, respectively. Similar trends were seen for hospital mortality. However, from multivariate logistic regression analysis, only an ionized calcium <0.8 mmol/L or an ionized calcium >1.4 mmol/L were independently associated with intensive care unit and hospital mortality. Conclusions:Within a broad range of values, ionized calcium concentration has no independent association with hospital or intensive care unit mortality. Only extreme abnormalities of ionized calcium concentrations are independent predictors of mortality.

Hypophosphatemia in critically ill patients

PURPOSE The aim of this study was to assess the association of phosphate concentration with key clinical outcomes in a heterogeneous cohort of critically ill patients. MATERIALS AND METHODS This was a retrospective observational study at a general intensive care unit (ICU) of an Australian university teaching hospital enrolling 2730 adult critically ill patients. RESULTS We studied 10504 phosphate measurements with a mean value of 1.17 mmol/L (measurements every 28.8 hours on average). Hyperphosphatemia (inorganic phosphate [iP] concentration > 1.4 mmol/L) occurred in 45% and hypophosphatemia (iP ≤ 0.6 mmol/L) in 20%. Among patients without any episodes of hyperphosphatemia, patients with at least 1 episode of hypophosphatemia had a higher ICU mortality than those without hypophosphatemia (P = .004). In addition, ICU nonsurvivors had lower minimum phosphate concentrations than did survivors (P = .009). Similar results were seen for hospital mortality. However, on multivariable logistic regression analysis, hypophosphatemia was not independently associated with ICU mortality (adjusted odds ratio, 0.86 [95% confidence interval, 0.66-1.10]; P = .24) and hospital mortality (odds ratio, 0.89 [0.73-1.07]; P = .21). Even when different cutoff points were used for hypophosphatemia (iP ≤ 0.5, 0.4, 0.3, or 0.2 mmol/L), hypophosphatemia was not an independent risk factor for ICU and hospital morality. In addition, timing of onset and duration of hypophosphatemia were not independent risk factor for ICU and hospital mortality. CONCLUSIONS Hypophosphatemia behaves like a general marker of illness severity and not as an independent predictor of ICU or in-hospital mortality in critically ill patients.

Duration of red blood cells storage and outcome in critically ill patients.

PURPOSE There is conflicting evidence on the effect of red blood cells (RBC) storage duration and clinical outcomes. We aimed to investigate the association between RBC storage duration and clinical outcomes in patients admitted to the intensive care unit (ICU). MATERIALS AND METHODS We retrospectively (2001-2011) studied adults admitted to the ICUs of 2 hospitals who received RBC. Using the mean, maximum and minimum age of RBC units transfused, we evaluated the association between RBC storage duration and mortality. We also analyzed the association between mean age of RBC units and length of stay (LOS) in survivors. We performed sensitivity analyses in patients who only received RBC in ICU and who only received leukodepleted RBC. RESULTS We studied 8416 patients who received a median of 4 (interquartile range, 2-7) RBC units. After multivariate analysis, age of RBC was not independently associated with mortality, including in the subgroup analyses. Furthermore, there was no clinically relevant relationship between mean RBC age and LOS. CONCLUSIONS RBC storage duration was not associated with increased mortality nor ICU and hospital LOS. These results support the view that the effect of RBC storage duration on outcomes in critically ill patients is uncertain.

Common laboratory tests predict imminent death in ward patients.

OBJECTIVE To estimate the ability of commonly measured laboratory variables to predict an imminent (within the same or next calendar day) death in ward patients. DESIGN Retrospective observational study. SETTING Two university affiliated hospitals. PATIENTS Cohort of 42,701 patients admitted for more than 24 hours and external validation cohort of 13,137 patients admitted for more than 24 hours. INTERVENTION We linked commonly measured laboratory tests with event databases and assessed the ability of each laboratory variable or combination of variables together with patient age to predict imminent death. MEASUREMENTS AND MAIN RESULTS In the inception teaching hospital, we studied 418,897 batches of tests in 42,701 patients (males 55%; average age 65.8 ± 17.6 years), for a total of >2.5 million individual measurements. Among these patients, there were 1596 deaths. Multivariable logistic modelling achieved an AUC-ROC of 0.87 (95% CI: 0.85-0.89) for the prediction of imminent death. Using an additional 105,074 batches from a cohort of 13,137 patients from a second teaching hospital, the multivariate model achieved an AUC-ROC of 0.88 (95% CI: 0.85-0.90). CONCLUSIONS Commonly performed laboratory tests can help predict imminent death in ward patients. Prospective investigations of the clinical utility of such predictions appear justified.

Common laboratory tests predict imminent medical emergency team calls, intensive care unit admission or death in emergency department patients

To estimate the ability of commonly measured laboratory variables to predict imminent (within the same or next calendar day) medical emergency team (MET) calls, ICU admission or death.

Is platelet transfusion associated with hospital-acquired infections in critically ill patients?

BackgroundPlatelets are commonly transfused to critically ill patients. Reports suggest an association between platelet transfusion and infection. However, there is no large study to have determined whether platelet transfusion in critically ill patients is associated with hospital-acquired infection.MethodsWe conducted a multi-centre study using prospectively maintained databases of two large academic intensive care units (ICUs) in Australia. Characteristics of patients who received platelets in ICUs between 2008 and 2014 were compared to those of patients who did not receive platelets. Association between platelet administration and infection (bacteraemia and/or bacteriuria) was modelled using multiple logistic regression and Cox regression, with blood components as time-varying covariates. A propensity covariate adjustment was also performed to verify results.ResultsOf the 18,965 patients included, 2250 (11.9%) received platelets in ICU with a median number of 1 platelet unit (IQR 1–3) administered. Patients who received platelets were more severely ill at ICU admission (mean Acute Physiology and Chronic Health Evaluation III score 65 (SD 29) vs 52 (SD 25), p < 0.01) and had more comorbidities (31% vs 19%, p < 0.01) than patients without platelet transfusion. Invasive mechanical ventilation (87% vs 57%, p < 0.01) and renal replacement therapy (20% vs 4%, p < 0.01) were more frequently administered in patients receiving platelets than in patients without platelets. On univariate analysis, platelet transfusion was associated with hospital-acquired infection in the ICU (7.7% vs 1.4%, p < 0.01). After adjusting for confounders, including other blood components administered, patient severity, centre, year, and diagnosis category, platelet transfusions were independently associated with infection (adjusted OR 2.56 95% CI 1.98–3.31, p < 0.001). This association was also found in survival analysis with blood components as time-varying covariates (adjusted HR 1.85, 95% CI 1.41–2.41, p < 0.001) and when only bacteraemia was considered (adjusted OR 3.30, 95% CI 2.30–4.74, p <0.001). Platelet transfusions remained associated with infection after propensity covariate adjustment.ConclusionsAfter adjustment for confounders, including patient severity and other blood components, platelet transfusion was independently associated with ICU-acquired infection. Further research aiming to better understand this association and to prevent this complication is warranted.

Duration of platelet storage and outcomes of critically ill patients

The storage duration of platelet (PLT) units is limited to 5 to 7 days. This study investigates whether PLT storage duration is associated with patient outcomes in critically ill patients.