Ulrike Holzinger

Real-Time Continuous Glucose Monitoring in Critically Ill Patients: A prospective randomized trial

OBJECTIVE To evaluate the impact of real-time continuous glucose monitoring (CGM) on glycemic control and risk of hypoglycemia in critically ill patients. RESEARCH DESIGN AND METHODS A total 124 patients receiving mechanical ventilation were randomly assigned to the real-time CGM group (n = 63; glucose values given every 5 min) or to the control group (n = 61; selective arterial glucose measurements according to an algorithm; simultaneously blinded CGM) for 72 h. Insulin infusion rates were guided according to the same algorithm in both groups. The primary end point was percentage of time at a glucose level <110 mg/dl. Secondary end points were mean glucose levels and rate of severe hypoglycemia (<40 mg/dl). RESULTS Percentage of time at a glucose level <110 mg/dl (59.0 ± 20 vs. 55.0 ± 18% in the control group, P = 0.245) and the mean glucose level (106 ± 18 vs. 111 ± 10 mg/dl in the control group, P = 0.076) could not be improved using real-time CGM. The rate of severe hypoglycemia was lower in the real-time CGM group (1.6 vs. 11.5% in the control group, P = 0.031). CGM reduced the absolute risk of severe hypoglycemia by 9.9% (95% CI 1.2–18.6) with a number needed to treat of 10.1 (95% CI 5.4–83.3). CONCLUSIONS In critically ill patients, real-time CGM reduces hypoglycemic events but does not improve glycemic control compared with intensive insulin therapy guided by an algorithm.

Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study.

IntroductionHyperglycemia, hypoglycemia, and increased glycemic variability have each beenindependently associated with increased risk of mortality in critically illpatients. The role of diabetic status on modulating the relation of these threedomains of glycemic control with mortality remains uncertain. The purpose of thisinvestigation was to determine how diabetic status affects the relation ofhyperglycemia, hypoglycemia, and increased glycemic variability with the risk ofmortality in critically ill patients.MethodsThis is a retrospective analysis of prospectively collected data involving 44,964patients admitted to 23 intensive care units (ICUs) from nine countries, betweenFebruary 2001 and May 2012. We analyzed mean blood glucose concentration (BG),coefficient of variation (CV), and minimal BG and created multivariable models toanalyze their independent association with mortality. Patients were stratifiedaccording to the diagnosis of diabetes.ResultsAmong patients without diabetes, mean BG bands between 80 and 140 mg/dl wereindependently associated with decreased risk of mortality, and mean BG bands> 140 mg/dl, with increased risk of mortality. Among patients withdiabetes, mean BG from 80 to 110 mg/dl was associated with increased risk ofmortality and mean BG from 110 to 180 mg/dl with decreased risk of mortality. Aneffect of center was noted on the relation between mean BG and mortality.Hypoglycemia, defined as minimum BG <70 mg/dl, was independently associatedwith increased risk of mortality among patients with and without diabetes andincreased glycemic variability, defined as CV > 20%, was independentlyassociated with increased risk of mortality only among patients without diabetes.Derangements of more than one domain of glycemic control had a cumulativeassociation with mortality, especially for patients without diabetes.ConclusionsAlthough hyperglycemia, hypoglycemia, and increased glycemic variability is eachindependently associated with mortality in critically ill patients, diabeticstatus modulates these relations in clinically important ways. Our findingssuggest that patients with diabetes may benefit from higher glucose target rangesthan will those without diabetes. Additionally, hypoglycemia is independentlyassociated with increased risk of mortality regardless of the patients diabeticstatus, and increased glycemic variability is independently associated withincreased risk of mortality among patients without diabetes.See related commentary by Krinsley,http://ccforum.com/content/17/2/131See related commentary by Finfer and Billot,http://ccforum.com/content/17/2/134

Accuracy and reliability of a subcutaneous continuous glucose-monitoring system in critically ill patients.

Background:Continuous glucose monitoring has been proposed to optimize glucose control in critically ill patients. To achieve strict glucose regulation, accurate and reliable continuous glucose-monitoring systems are essential. Objective:Evaluation of a subcutaneous continuous glucose-monitoring system for use in critically ill patients. Design:Pooled-data analysis of two prospective, randomized, controlled trials. Setting:An eight-bed medical intensive care unit of a university hospital. Patients:A total of 174 critically ill patients on intensive insulin therapy. Interventions:Subcutaneous continuous glucose monitoring. Measurements:Two thousand forty-five continuous glucose-monitoring system sensor glucose values were compared with arterial reference blood glucose levels, determined by a blood gas analyzer. Continuous glucose monitoring data were recorded continuously for up to 72 hrs by using a subcutaneous continuous glucose-monitoring sensor. The correlation of both methods and differences between continuous glucose-monitoring systems and reference values were calculated, as well as the conformity of continuous glucose-monitoring values with the International Organization for Standardization criteria (<0.83 mmol/L [15 mg/dL] difference for glucose values ≤4.12 mmol/L [≤75 mg/dL] and <20% difference for glucose values >4.12 mmol/L [>75 mg/dL]). Results:The Pearson correlation coefficient was 0.92, showing strong correlation between the two methods. The intraclass correlation coefficient was 0.92, indicating that 92% of the variability is due to subjects and measurement occasions. Mean difference between continuous glucose-monitoring system and reference values was −0.10 mmol/L (confidence interval: −0.13 to −0.07) (−2 mg/dL [confidence interval: −2 to −1]) (continuous glucose-monitoring system minus reference) and absolute difference 0.44 mmol/L (confidence interval: 0.41–0.47) (8 mg/dL [confidence interval: 7–8]). According to the insulin titration error grid analysis, 99.1% of continuous glucose-monitoring system values were in the acceptable treatment zone. No continuous glucose-monitoring system measurements were found in the life-threatening zone, and 92.9% of the continuous glucose-monitoring system glucose values met the International Organization for Standardization criteria. Conclusion:The subcutaneous continuous glucose-monitoring system is reliable for use in critically ill patients and showed glucose values with a strong correlation to arterial reference blood glucose levels, determined by a blood gas analyzer.

Tonicity Balance in Patients With Hypernatremia Acquired in the Intensive Care Unit

BACKGROUND Hypernatremia is a serious electrolyte disturbance and an independent risk factor for mortality in critically ill patients. In many cases, hypernatremia is an iatrogenic problem that develops in the intensive care unit (ICU). STUDY DESIGN Case series. SETTING & PARTICIPANTS 45 patients were studied in a medical ICU. For inclusion in the study, patients needed to show an increase in serum sodium concentration to greater than 149 mEq/L from an initial concentration of less than 146 mEq/L. OUTCOMES Solute balance, fluid balance, and both. Causes of hypernatremia. MEASUREMENTS The daily mass balance of sodium, potassium, and water over 1- to 3-day intervals was measured while serum sodium levels were increasing. RESULTS During the study period, 69 of 981 patients (7%) acquired hypernatremia after admission to the ICU. Of these, 45 had sufficient data for evaluation. Maximum serum sodium levels were 150 to 164 mEq/L. The average duration of hypernatremia was 2 days (range, 1 to 10 days), with an average onset on day 5.9 +/- 4.3 of the ICU stay. Patients were classified as having a positive solute balance (n = 17; 38%), negative fluid balance (n = 20; 44%), or both (n = 8; 18%). The most important extrarenal factors contributing to hypernatremia were fever (45%) and diarrhea (18%). Polyuria was observed in 38% of patients and 35% had acute renal failure. Hypertonic solutions were administered to 27% of patients. LIMITATIONS Retrospective analysis; lack of daily measurement of body weight. CONCLUSION ICU-acquired hypernatremia is associated with multiple factors associated with negative fluid and positive solute balance.

Glycemic variability and glucose complexity in critically ill patients: a retrospective analysis of continuous glucose monitoring data

IntroductionGlycemic variability as a marker of endogenous and exogenous factors, and glucose complexity as a marker of endogenous glucose regulation are independent predictors of mortality in critically ill patients. We evaluated the impact of real time continuous glucose monitoring (CGM) on glycemic variability in critically ill patients on intensive insulin therapy (IIT), and investigated glucose complexity - calculated using detrended fluctuation analysis (DFA) - in ICU survivors and non-survivors.MethodsRetrospective analysis were conducted of two prospective, randomized, controlled trials in which 174 critically ill patients either received IIT according to a real-time CGM system (n = 63) or according to an algorithm (n = 111) guided by selective arterial blood glucose measurements with simultaneously blinded CGM for 72 hours. Standard deviation, glucose lability index and mean daily delta glucose as markers of glycemic variability, as well as glucose complexity and mean glucose were calculated.ResultsGlycemic variability measures were comparable between the real time CGM group (n = 63) and the controls (n = 111). Glucose complexity was significantly lower (higher DFA) in ICU non-survivors (n = 36) compared to survivors (n = 138) (DFA: 1.61 (1.46 to 1.68) versus 1.52 (1.44 to 1.58); P = 0.003). Diabetes mellitus was significantly associated with a loss of complexity (diabetic (n = 33) versus non-diabetic patients (n = 141) (DFA: 1.58 (1.48 to 1.65) versus 1.53 (1.44 to 1.59); P = 0.01).ConclusionsIIT guided by real time CGM did not result in significantly reduced glycemic variability. Loss of glucose complexity was significantly associated with mortality and with the presence of diabetes mellitus.

Continuous glucose control in the ICU: report of a 2013 round table meeting

Achieving adequate glucose control in critically ill patients is a complex but important part of optimal patient management. Until relatively recently, intermittent measurements of blood glucose have been the only means of monitoring blood glucose levels. With growing interest in the possible beneficial effects of continuous over intermittent monitoring and the development of several continuous glucose monitoring (CGM) systems, a round table conference was convened to discuss and, where possible, reach consensus on the various aspects related to glucose monitoring and management using these systems. In this report, we discuss the advantages and limitations of the different types of devices available, the potential advantages of continuous over intermittent testing, the relative importance of trend and point accuracy, the standards necessary for reporting results in clinical trials and for recognition by official bodies, and the changes that may be needed in current glucose management protocols as a result of a move towards increased use of CGM. We close with a list of the research priorities in this field, which will be necessary if CGM is to become a routine part of daily practice in the management of critically ill patients.

Acid–base disturbances in critically ill patients with cirrhosis

Background/Aims: The equilibrium of offsetting metabolic acid–base disorders in stable cirrhosis might be lost during episodes of hepatic decompensation, haemorrhage or sepsis. The purpose of this study was to determine whether the acid–base state is destabilized in critically ill patients with cirrhosis and whether this is associated with mortality.

Continuous lateral rotation therapy to prevent ventilator-associated pneumonia

Objective: To investigate the impact of prophylactic continuous lateral rotation therapy on the prevalence of ventilator-associated pneumonia, duration of mechanical ventilation, length of stay, and mortality in critically ill medical patients. Design: Prospective, randomized, clinical study. Setting: Three medical intensive care units of an university tertiary care hospital. Patients: Patients were randomized to continuous lateral rotation therapy or standard care if they were mechanically ventilated for <48 hrs and free from pneumonia. Primary study end point was development of ventilator-associated pneumonia. Ventilator-associated pneumonia was defined as infiltrate on the chest radiograph plus newly developed purulent tracheal secretion plus increasing signs of inflammation. The diagnosis had to be confirmed microbiologically and required the growth of a pathogen >104 colony-forming units/mL in bronchoalveolar lavage. Radiologists were blinded to randomization whereas clinical outcome assessors were not. Interventions: Rotation therapy was performed continuously in a specially designed bed over an arc of 90°. Additional measures to prevent ventilator-associated pneumonia were equally standardized in both groups including semirecumbent position. Measurements and Main Results: Ventilator-associated pneumonia frequency during the intensive care unit stay was 11% in the rotation group and 23% in the control group (p = .048), respectively. Duration of ventilation (8 ± 5 vs. 14 ± 23 days, p = .02) and length of stay (25 ± 22 days vs. 39 ± 45 days, p = .01) were significantly shorter in the rotation group. In a forward stepwise logistic regression model including the continuous lateral rotation therapy, gender, Lung Injury Score, and Simplified Acute Physiology Score II, continuous lateral rotation therapy just failed to reach statistical significance with respect to development of ventilator-associated pneumonia (p = .08). Intolerance to continuous lateral rotation therapy during the weaning phase was observed in 29 patients (39%). Mortality was comparable in both groups. Conclusions: Ventilator-associated pneumonia prevalence was significantly reduced by continuous lateral rotation therapy. Continuous lateral rotation therapy led to shorter ventilation time and length of stay. Continuous lateral rotation therapy should be considered in ventilated patients at risk for ventilator-associated pneumonia as a feasible method exerting additive effects to other preventive measures.

Coagulation parameters and major bleeding in critically ill patients with cirrhosis

Disturbances of coagulation and hemostasis are common in patients with liver cirrhosis. The typical laboratory pattern mimics disseminated intravascular coagulation (DIC). The aim of this study was to assess the impact of routine coagulation parameters in critically ill cirrhosis patients with regard to new onset of major bleeding and outcome. A total of 1,493 critically ill patients were studied prospectively. Routine coagulation parameters were assessed, and the DIC score was calculated based on platelets, fibrinogen, d‐dimer, and prothrombin index. New onset of major bleeding during the stay at the intensive care unit and mortality were assessed. Patients were followed for 1 year. Two hundred eleven patients of the cohort had liver cirrhosis. Platelets, fibrinogen, prothrombin index, activated partial thromboplastin time, and d‐dimer as well as the DIC score differed significantly between patients with and without cirrhosis (P < 0.001 for all). Moreover, fibrinogen, platelets, and activated partial thromboplastin time (but not prothrombin index) differed significantly between cirrhosis patients with and without major bleeding (P < 0.01 for all). Bleeding on admission, platelet count <30 < 109/L, fibrinogen level <60 mg/dL, and activated partial thromboplastin time values >100 seconds were the strongest independent predictors for new onset of major bleeding in multivariate regression analysis. One‐year mortality in cirrhosis patients with and without major bleeding was 89% and 68%, respectively (P < 0.05 between groups). Conclusion: Abnormal coagulation parameters and high DIC scores (primarily due to fibrinogen and platelets) correspond to increased bleeding risk in patients with liver cirrhosis in the intensive care unit, and fibrinogen and platelet count were identified as the best routine coagulation parameters for prediction of new onset of major bleeding; however, further studies are required to evaluate the potential therapeutic implications of these findings. (Hepatology 2016;64:556‐568)

Treatment of adult patients with sepsis-induced coagulopathy and purpura fulminans using a plasma-derived protein C concentrate (Ceprotin®)

Background and Objectives  The aim of this study was to document the effects of supplementation with a plasma‐derived protein C concentrate in adult patients with infectious purpura fulminans.