Edward Stachowski

Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients

Background:Intensive insulin therapy may reduce mortality and morbidity in selected surgical patients. Intensive insulin therapy also reduced the SD of blood glucose concentration, an accepted measure of variability. There is no information on the possible significance of variability in glucose concentration. Methods:The methods included extraction of blood glucose values from electronically stored biochemical databases and of data on patients characteristics, clinical features, and outcome from electronically stored prospectively collected patient databases; calculation of SD of glucose as a marker of variability and of several indices of glucose control in each patient; and statistical assessment of the relation between these variables and intensive care unit mortality. Results:There were 168,337 blood glucose measurements in the study cohort of 7,049 critically ill patients (4.2 hourly measurements on average). The mean ± SD of blood glucose concentration was 1.7 ± 1.3 mm in survivors and 2.3 ± 1.6 mm in nonsurvivors (P < 0.001). Using multiple variable logistic regression analysis, both mean and SD of blood glucose were significantly associated with intensive care unit mortality (P < 0.001; odds ratios [per 1 mm] 1.23 and 1.27, respectively) and hospital mortality (P < 0.001 and P = 0.013; odds ratios [per 1 mm] 1.21 and 1.18, respectively). Conclusions:The SD of glucose concentration is a significant independent predictor of intensive care unit and hospital mortality. Decreasing the variability of blood glucose concentration might be an important aspect of glucose management.

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.

Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multi-centre study

IntroductionHigher lactate concentrations within the normal reference range (relative hyperlactatemia) are not considered clinically significant. We tested the hypothesis that relative hyperlactatemia is independently associated with an increased risk of hospital death.MethodsThis observational study examined a prospectively obtained intensive care database of 7,155 consecutive critically ill patients admitted to the Intensive Care Units (ICUs) of four Australian university hospitals. We assessed the relationship between ICU admission lactate, maximal lactate and time-weighted lactate levels and hospital outcome in all patients and also in those patients whose lactate concentrations (admission n = 3,964, maximal n = 2,511, and time-weighted n = 4,584) were under 2 mmol.L-1 (i.e. relative hyperlactatemia).ResultsWe obtained 172,723 lactate measurements. Higher admission and time-weightedlactate concentration within the reference range was independently associated with increased hospital mortality (admission odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3 to 3.5, P = 0.01; time-weighted OR 3.7, 95% CI 1.9 to 7.00, P < 0.0001). This significant association was first detectable at lactate concentrations > 0.75 mmol.L-1. Furthermore, in patients whose lactate ever exceeded 2 mmol.L-1, higher time-weighted lactate remained strongly associated with higher hospital mortality (OR 4.8, 95% CI 1.8 to 12.4, P < 0.001).ConclusionsIn critically ill patients, relative hyperlactataemia is independently associated with increased hospital mortality. Blood lactate concentrations > 0.75 mmol.L-1 can be used by clinicians to identify patients at higher risk of death. The current reference range for lactate in the critically ill may need to be re-assessed.

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.

Arterial carbon dioxide tension and outcome in patients admitted to the intensive care unit after cardiac arrest

BACKGROUND Arterial carbon dioxide tension (PaCO2) affects neuronal function and cerebral blood flow. However, its association with outcome in patients admitted to intensive care unit (ICU) after cardiac arrest (CA) has not been evaluated. METHODS AND RESULTS Observational cohort study using data from the Australian New Zealand (ANZ) Intensive Care Society Adult-Patient-Database (ANZICS-APD). Outcomes analyses were adjusted for illness severity, co-morbidities, hypothermia, treatment limitations, age, year of admission, glucose, source of admission, PaO2 and propensity score. We studied 16,542 consecutive patients admitted to 125 ANZ ICUs after CA between 2000 and 2011. Using the APD-PaCO2 (obtained within 24 h of ICU admission), 3010 (18.2%) were classified into the hypo- (PaCO2<35 mmHg), 6705 (40.5%) into the normo- (35-45 mmHg) and 6827 (41.3%) into the hypercapnia (>45 mmHg) group. The hypocapnia group, compared with the normocapnia group, had a trend toward higher in-hospital mortality (OR 1.12 [95% CI 1.00-1.24, p=0.04]), lower rate of discharge home (OR 0.81 [0.70-0.94, p<0.01]) and higher likelihood of fulfilling composite adverse outcome of death and no discharge home (OR 1.23 [1.10-1.37, p<0.001]). In contrast, the hypercapnia group had similar in-hospital mortality (OR 1.06 [0.97-1.15, p=0.19]) but higher rate of discharge home among survivors (OR 1.16 [1.03-1.32, p=0.01]) and similar likelihood of fulfilling the composite outcome (OR 0.97 [0.89-1.06, p=0.52]). Cox-proportional hazards modelling supported these findings. CONCLUSIONS Hypo- and hypercapnia are common after ICU admission post-CA. Compared with normocapnia, hypocapnia was independently associated with worse clinical outcomes and hypercapnia a greater likelihood of discharge home among survivors.

Plasma-Lyte 148 vs 0.9% saline for fluid resuscitation in diabetic ketoacidosis.

PURPOSE The purpose of the study was to determine the effects of Plasma-Lyte 148 (PL) vs 0.9% saline (NS) fluid resuscitation in diabetic ketoacidosis (DKA). METHODS A multicenter retrospective analysis of adults admitted for DKA to the intensive care unit, who received almost exclusively PL or NS infusion up until 12 hours, was performed. RESULTS Nine patients with PL and 14 patients with NS were studied. Median serum bicarbonate correction was higher in the PL vs NS groups at 4 to 6 hours (8.4 vs 1.7 mEq/L) and 6 to 12 hours (12.8 vs 6.2 mEq/L) from baseline (P < .05). Median standard base excess improved by 10.5 vs 4.2 mEq/L at 4 to 6 hours and by 16.0 vs 9.1 mEq/L at 6 to 12 hours in the PL and NS groups, respectively (P < .05). Chloride levels increased significantly in the NS vs PL groups over 24 hours. Potassium levels were lower at 6 to 12 hours in the PL group. Mean arterial blood pressure was higher at 2 to 4 hours in the PL group, whereas cumulative urine output was lower at 4 to 6 hours in the NS group. There were no differences in glycemic control or duration of intensive care unit stay. CONCLUSION Patients with DKA resuscitated with PL instead of NS had faster initial resolution of metabolic acidosis and less hyperchloremia, with a transiently improved blood pressure profile and urine output.

Dynamic lactate indices as predictors of outcome in critically ill patients

IntroductionDynamic changes in lactate concentrations in the critically ill may predict patient outcome more accurately than static indices. We aimed to compare the predictive value of dynamic indices of lactatemia in the first 24 hours of intensive care unit (ICU) admission with the value of more commonly used static indices.MethodsThis was a retrospective observational study of a prospectively obtained intensive care database of 5,041 consecutive critically ill patients from four Australian university hospitals. We assessed the relationship between dynamic lactate values collected in the first 24 hours of ICU admission and both ICU and hospital mortality.ResultsWe obtained 36,673 lactate measurements in 5,041 patients in the first 24 hours of ICU admission. Both the time weighted average lactate (LACTW24) and the change in lactate (LACΔ24) over the first 24 hours were independently predictive of hospital mortality with both relationships appearing to be linear in nature. For every one unit increase in LACTW24 and LACΔ24 the risk of hospital death increased by 37% (OR 1.37, 1.29 to 1.45; P < 0.0001) and by 15% (OR 1.15, 1.10 to 1.20; P < 0.0001) respectively. Such dynamic indices, when combined with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, improved overall outcome prediction (P < 0.0001) achieving almost 90% accuracy. When all lactate measures in the first 24 hours were considered, the combination of LACTW24 and LACΔ24 significantly outperformed (P < 0.0001) static indices of lactate concentration, such as admission lactate, maximum lactate and minimum lactate.ConclusionsIn the first 24 hours following ICU admission, dynamic indices of hyperlactatemia have significant independent predictive value, improve the performance of illness severity score-based outcome predictions and are superior to simple static indices of lactate concentration.

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.

Circadian rhythm of blood glucose values in critically ill patients

Objective:To test whether there is a circadian rhythm of blood glucose control in critically ill patients and whether morning blood glucose is an accurate surrogate of overall blood glucose control. Design:Retrospective multiple-center observational study. Setting:Intensive care units of three tertiary hospitals and one affiliated private hospital. Patients:Cohort of 8,307 consecutive critically ill patients. Interventions:Extraction of blood glucose values from electronically stored measurements. Extraction of demographic and outcome data from unit and hospital databases. Statistical assessment of variations in blood glucose control over each 24-hr cycle. Measurements and Main Results:We studied 208,362 blood glucose measurements in 8,307 patients (5.5 measurements/day/person). In each hospital, there was a circadian rhythm of blood glucose control (p < .0001). The differences between highest and lowest blood glucose concentration in different time periods in each hospital were 0.27, 0.28, 0.95, and 0.22 mmol/L. There was also significant variation in the incidence and notional duration of hyperglycemia. The differences between the lowest and highest incidence of hyperglycemia in different time periods were 3.3, 2.7, 9.9, and 2.6% in each hospital. In all four hospitals, the average blood glucose value from 5:30 am to 6:30 am was significantly lower than the 24-hr average. Conclusions:Blood glucose values and the incidence of hyperglycemia have a circadian rhythm in critically ill patients. Morning blood glucose may not be an accurate surrogate of blood glucose control over the daily cycle.