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Background: Exploring clinical trial data using alternative methods may enhance original study's findings and provide new insights. The SOAP II trial has been published more than 10 years ago; but there is still some speculation that some patients may benefit from dopamine administration for shock management. We aimed to reanalyse the trial under different approaches and evaluate for heterogeneity in treatment effect (HTE). Methods: All patients enrolled in SOAP II were eligible for reanalysis. We used a variety of methods including the win-ratio (WR), a Bayesian reanalysis stratified according to shock type, and both a risk-based and effect-based explorations for HTE. The methods were applied to different endpoints, including a hierarchy of death, new use of renal-replacement therapy (RRT), and new-onset arrhythmia; 28-day mortality; a composite endpoint (mortality, new use of RRT, and new-onset arrhythmia), and days alive and free of ICU at 28-days (DAFICU28). Results: A total of 1679 patients were included (average age was 64.9 years, 57% male, 62% with septic and 17% with cardiogenic shock). All analysis favoured norepinephrine over dopamine. Under the WR approach, dopamine had fewer wins compared to norepinephrine (WR 0.79; 95% confidence intervals [CI] 0.68–0.92; p = 0.003), evident in both cardiogenic and septic shock subgroups. The Bayesian reanalysis for type of shock showed, for dopamine, a probability of harm of 0.95 for mortality, > 0.99 probability of harm for composite endpoint, and 0.91 probability of harm for DAFICU28. The fewer DAFICU28 with dopamine was more apparent in those with cardiogenic shock (0.92). Under the risk-based HTE, there was a high probability that dopamine resulted fewer DAFICU28 in the highest quartile of predicted mortality risk. The effect-based HTE assessment model did not recommended dopamine over norepinephrine for any combination of possible modifiers including age, type of shock, presence of cardiomyopathy, and SOFA score. Receiving dopamine when the effect-based model recommended norepinephrine was associated with an absolute increase in composite endpoint of 6%. Conclusion: The harm associated with the use of dopamine for the management of shock appears to be present in both septic and cardiogenic shock patients. There was no suggestion of any subgroup in which dopamine was found to be favourable over norepinephrine. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Copyright © 2009 National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Unlabelled: 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 < 10(9) /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)., (© 2016 by the American Association for the Study of Liver Diseases.)

Introduction: Hyperchloremic acidosis is frequent in critically ill patients. Renal tubular acidosis (RTA) may contribute to acidemia in the state of hyperchloremic acidosis, but the prevalence of RTA has never been studied in critically ill patients. Therefore, we aimed to investigate the prevalence, type, and possible risk factors of RTA in critically ill patients using a physical-chemical approach., Methods: This prospective, observational trial was conducted in a medical ICU of a university hospital. One hundred consecutive critically ill patients at the age ≥18, expected to stay in the ICU for ≥24 h, with the clinical necessity for a urinary catheter and the absence of anuria were included. Base excess (BE) subset calculation based on a physical-chemical approach on the first 7 days after ICU admission was used to compare the effects of free water, chloride, albumin, and unmeasured anions on the standard base excess. Calculation of the urine osmolal gap (UOG)--as an approximate measure of the unmeasured urine cation NH4(+)--served as determinate between renal and extrarenal bicarbonate loss in the state of hyperchloremic acidosis., Results: During the first week of ICU stay 43 of the patients presented with hyperchloremic acidosis on one or more days represented as pronounced negative BEChloride. In 31 patients hyperchloremic acidosis was associated with RTA characterized by a UOG ≤150 mosmol/kg in combination with preserved renal function. However, in 26 of the 31 patients with RTA metabolic acidosis was neutralized by other acid-base disturbances leading to a normal arterial pH., Conclusions: RTA is highly prevalent in critically ill patients with hyperchloremic acidosis, whereas it is often neutralized by the simultaneous occurrence of other acid-base disturbances., Trial Registration: Clinicaltrials.gov NCT02392091. Registered 17 March 2015.

The 'renal threshold for glucose' has never been evaluated in critically ill patients. Therefore, we aimed to investigate the renal glucose threshold in this patient group using high-sensitivity urine glucose assays. In this retrospective analysis of prospectively collected data, we analysed 100 consecutive critically ill patients from a medical intensive care unit (ICU). Arterial blood glucose and spot urine glucose were simultaneously quantified daily during the first week after ICU admission. Three hundred seventy-three pairs of blood/urine glucose were plotted in five pre-defined categories of blood glucose (<80, 80-109, 110-139, 140-179 and ≥180 mg/dL). Urine glucose values of the five categories were compared using the Kruskal-Wallis test to assess the relation with blood glucose. Urine glucose was detected in virtually all of the urine samples. Urine glucose showed a positive nonlinear correlation with blood glucose and was significantly elevated at blood glucose levels of 140-179 and ≥180 mg/dL compared with lower blood glucose ranges. Basal glucosuria is ubiquitous in critically ill patients. A 'soft' renal threshold for glucose is present at blood glucose levels in the range of 140-179 mg/dL., (© 2015 Asian Pacific Society of Nephrology.)

Introduction: Targeted temperature management improves outcome after cardiopulmonary resuscitation. Reduction of resting energy expenditure might be one mode of action. The aim of this study was to correlate resting energy expenditure and substrate oxidation rates with targeted temperature management at 33°C and outcome in patients after cardiac arrest., Methods: This prospective, observational cohort study was performed at the department of emergency medicine and a medical intensive care unit of a university hospital. Patients after successful cardiopulmonary resuscitation undergoing targeted temperature management at 33°C for 24 hours with subsequent rewarming to 36°C and standardized sedation, analgesic and paralytic medication were included. Indirect calorimetry was performed five times within 48 h after cardiac arrest. Measurements were correlated to outcome with repeated measures ANOVA, linear and logistic regression analysis., Results: In 25 patients resting energy expenditure decreased 20 (18 to 27) % at 33°C compared to 36°C without differences between outcome groups (favourable vs. unfavourable: 25 (21 to 26) vs. 21 (16 to 26); P = 0.5). In contrast to protein oxidation rate (favourable vs. unfavourable: 35 (11 to 68) g/day vs. 39 (7 to 75) g/day, P = 0.8) patients with favourable outcome had a significantly higher fat oxidation rate (139 (104 to 171) g/day vs. 117 (70 to 139) g/day, P <0.05) and a significantly lower glucose oxidation rate (30 (-34 to 88) g/day vs. 77 (19 to 138) g/day; P < 0.05) as compared to patients with unfavourable neurological outcome., Conclusions: Targeted temperature management at 33°C after cardiac arrest reduces resting energy expenditure by 20% compared to 36°C. Glucose and fat oxidation rates differ significantly between patients with favourable and unfavourable neurological outcome., Trial Registration: Clinicaltrials.gov NCT00500825. Registered 11 July 2007.

Objective: Mortality on medical intensive care units (ICU) is approximately 25%. It is associated with age, severity of illness, and comorbidities. Preexisting depression is a risk factor for worse outcome in many diseases. The impact of depression on outcome of ICU patients has not been investigated. We assessed a possible association between mortality and preexisting depressive mood at the time of ICU admission. The primary end point was 28-day mortality., Methods: This single-center cohort study was conducted in a tertiary medical ICU. Two hundred patients were evaluated for preexisting depressive mood at ICU admission, determined by Hospital Anxiety and Depression Scale (HADS) score ≥8 in the depression dimension in patients with appropriate cognitive function. Patients with insufficient cognitive function were assessed using observer rating by next of kin by Hammond scale (cutoff ≥4) and/or a modified version of the Hospital Anxiety and Depression Scale for observer rating (cutoff ≥10)., Results: In total, 66 (33%) of 200 patients were classified with preexisting depressive mood. Forty-nine (24.5%) of 200 patients had died by day 28. Of these, 23 (47%) had preexisting depressive mood as compared with 43 of 151 (29%) 28-day survivors (p = .017). Multiple logistic regression analysis revealed that preexisting depressive mood at the time of ICU admission is an independent risk factor for 28-day (odds ratio = 2.2, 95% confidence interval = 1.08-4.5, p = .030) and in-hospital mortality (median time till death = 20.5 [2-186] days, odds ratio = 2.58, 95% confidence interval = 1.31-5.1, p = .006)., Conclusion: Preexisting depressive mood might be an independent risk factor for 28-day mortality in medical ICU patients. This could have diagnostic and therapeutic implications for critically ill patients.

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.

Background & Aims: Hypoxic hepatitis (HH) is a frequent and life-threatening complication associated with states of oxygen depletion in critically ill patients. Ischemia and reperfusion contribute to liver injury in HH. Experimental data suggest beneficial effects of statins in hepatic ischemia/reperfusion injury. This study was conducted to investigate whether statin treatment prior to intensive care unit (ICU) admission affects incidence rates and severity of HH., Methods: Eight hundred fifty-one patients admitted consecutively to three medical ICUs between December 2008 and December 2009 were prospectively screened for new occurrence of HH within 48 h following ICU admission. Statin treatment prior to ICU admission was assessed. 28-day-, 90-day-, and 1-year-survival as well as new-onset of complications in HH patients were prospectively documented., Results: Eighty-seven patients (10%) developed HH. Statin treatment prior to ICU admission was significantly associated with decreased incidence of HH within 48 h after ICU admission in the multivariate analysis (adjusted OR=0.42 (95% CI 0.19-0.95); p<0.05). Cardiogenic shock (p<0.001), septic shock (p<0.001) and active alcohol consumption (p<0.01) were identified as independent risk factors for development of HH. 28-day-, 90-day-, and 1-year-mortality rates in HH were 58%, 67%, and 74%, respectively. Statins were associated with improved 28-day-survival in the total study cohort (p<0.05), but did not affect 90-day- and 1-year-mortality, respectively., Conclusions: Cardiogenic shock, septic shock, and active alcohol consumption were independent factors predisposing patients to new onset of HH. Statin treatment prior to ICU admission was the only protective factor regarding the new occurrence of HH in critically ill patients., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Introduction: Critical illness polyneuropathy and/or myopathy (CIPNM) is a severe complication of critical illness. Retrospective data suggest that early application of IgM-enriched intravenous immunoglobulin (IVIG) may prevent or mitigate CIPNM. Therefore, the primary objective was to assess the effect of early IgM-enriched IVIG versus placebo to mitigate CIPNM in a prospective setting., Methods: In this prospective, randomized, double-blinded and placebo-controlled trial, 38 critically ill patients with multiple organ failure (MOF), systemic inflammatory response syndrome (SIRS)/sepsis, and early clinical signs of CIPNM were included. Patients were randomly assigned to be treated either with IgM-enriched IVIG or placebo over a period of three days. CIPNM was measured by the CIPNM severity sum score based on electrophysiological stimulation of the median, ulnar, and tibial nerves on days 0, 4, 7, 14 and on the histological evaluation of muscle biopsies on days 0 and 14 and ranged from 0 (no CIPNM) to 8 (very severe CIPNM)., Results: A total of 38 critically ill patients were included and randomized to receive either IgM-enriched IVIG (n = 19) or placebo (n = 19). Baseline characteristics were similar between the two groups. CIPNM could not be improved by IVIG treatment, represented by similar CIPNM severity sum scores on day 14 (IVIG vs. placebo: 4.8 ± 2.0 vs. 4.5 ± 1.8; P = 0.70). CIPNM severity sum score significantly increased from baseline to day 14 (3.5 ± 1.6 vs. 4.6 ± 1.9; P = 0.002). After an interim analysis the study was terminated early due to futility in reaching the primary endpoint., Conclusions: Early treatment with IVIG did not mitigate CIPNM in critically ill patients with MOF and SIRS/sepsis., Trial Registration: Clinicaltrials.gov: NCT01867645.

The functional integrity of the gastrointestinal tract is an essential prerequisite in intensive care patients for the sufficient administration of enteral nutrition. Up to 65% of patients in intensive care units develop symptoms of gastrointestinal dysfunction with high residual gastric volume, vomiting and abdominal distension. The pathophysiological alterations of gastrointestinal intolerance and the subsequent effect on the tolerance of enteral nutrition can affect the whole gastrointestinal tract. Gastroduodenal motility disorders in particular, with increased gastroesophageal reflux lead to intolerance. In more than 90% of intensive care patients with gastrointestinal motility disorders an adequate postpyloric enteral nutrition can be carried out using a jejunal tube. In addition to improved tolerance of enteral nutrition this leads to a reduction of gastroesophageal reflux and the incidence of ventilation-associated pneumonia. Apart from the possibility of endoscopic application of the jejunal tube, alternative techniques were developed which allow a faster positioning of the jejunal tube with less complications. Furthermore, there are therapeutic options for improvement of gastrointestinal motility disorders and apart from general measures, also medicinal options for treatment of gastrointestinal intolerance which allow a sufficient enteral nutrition for intensive care patients.

Background: Adequate anticoagulation is essential to achieve efficient and cost-effective continuous renal replacement therapy (CRRT). However, in critically ill patients with advanced liver cirrhosis, this goal is challenging because of the concomitant bleeding disorder. Therefore, the evaluation of alternative anticoagulants is necessary., Methods: In this retrospective study, we analyzed data of 37 CRRTs in 16 critically ill patients with advanced liver cirrhosis and acute kidney injury admitted to a medical intensive care unit between 2006 and 2008 and included patients undergoing CRRT with either single doses of antithrombin (AT) or continuous low-dose heparin as a sole anticoagulant. The primary outcome measure was lifetime of single CRRT filters., Results: Data were available for 13 CRRT filters for patients anticoagulated with single doses of AT (n = 6), and 24 CRRT filters for patients anticoagulated continuously with low-dose heparin (n = 10). Means of single-filter lifetimes were significantly higher in the AT group compared with the heparin group (45 ± 29 hours [95% confidence interval 27-62 hours] vs 26 ± 23 hours [95% confidence interval 16-36 hours]; P = 0.03), whereas mean filter lifetimes of individual patients were comparable (median [25th-75th percentile] 30 hours [21-59 hours] vs 28 hours [17-70 hours]; P = 0.79)., Conclusions: Our data suggest that anticoagulation with single doses of AT may be an alternative to continuously administered low-dose heparin in critically ill patients with advanced liver cirrhosis during CRRT. However, additional controlled trials are necessary to confirm our findings.

Introduction: 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., Methods: 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., Results: 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., Conclusions: 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.

Introduction: Glycemic 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., Methods: Retrospective 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., Results: Glycemic 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)., Conclusions: IIT 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.

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.

Objective: Head-to-head comparison of the success rate of jejunal placement of a new electromagnetically visualized jejunal tube with that of the endoscopic technique in critically ill patients., Design: : Prospective, randomized clinical trial., Setting: Two intensive care units at a university hospital., Patients: : A total of 66 critically ill patients not tolerating intragastric nutrition., Interventions: Patients were randomly assigned (2:1 ratio) to receive an electromagnetically visualized jejunal feeding tube or an endoscopically placed jejunal tube. The success rate of correct jejunal placement after 24 hrs was the main outcome parameter., Measurements and Main Results: The correct jejunal tube position was reached in 21 of 22 patients using the endoscopic technique and in 40 of 44 patients using the electromagnetically visualized jejunal tube (95% vs. 91%; relative risk 0.9524, confidence interval 0.804-1.127, p = .571). In the remaining four patients, successful endoscopic jejunal tube placement was performed subsequently. The implantation times, times in the right position, and occurrences of nose bleeding were not different between the two groups. The electromagnetically visualized technique resulted in the correct jejunal position more often at the first attempt. Factors associated with successful placement at the first attempt of the electromagnetically visualized jejunal tube seem to be a higher body mass index and absence of emesis. This trial is registered at ClinicalTrials.gov, number NCT00500851., Conclusions: In a head-to-head comparison correct jejunal tube placement using the new electromagnetically visualized method was as fast, safe, and successful as the endoscopic method in a comparative intensive care unit patient population.

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 >10(4) 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 degrees. 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.

Objective: To compare the success rate of correct jejunal placement of a new self-advancing jejunal tube with the gold standard, the endoscopic guided technique, in a comparative intensive care unit (ICU) patient population., Design: Prospective, randomized study., Setting: Two medical ICUs at a university hospital., Patients: Forty-two mechanically ventilated patients with persisting intolerance of intragastric enteral nutrition despite prokinetic therapy., Methods: Patients were randomly assigned to receive an unguided self-advancing jejunal feeding tube (Tiger Tube) or an endoscopic guided jejunal tube (Freka Trelumina). Primary outcome measure was the success rate of correct jejunal placement after 24 h., Results: Correct jejunal tube placement was reached in all 21 patients using the endoscopic guided technique whereas the unguided self-advancing jejunal tube could be placed successfully in 14 out of 21 patients (100% versus 67%; P = 0.0086). In the remaining seven patients, successful endoscopic jejunal tube placement was performed subsequently. Duration of tube placement was longer in the unguided self-advancing tube group (20 +/- 12 min versus 597 +/- 260 min; P < 0.0001). Secondary outcome parameters (complication rate, number of attempts, days in correct position with accurate functional capability, days with high gastric residual volume, length of ICU stay, ICU mortality) were not statistically different between the two groups. No potentially relevant parameter predicting the failure of correct jejunal placement of the self-advancing tube could be identified., Conclusions: Success rate of correct jejunal placement of the new unguided self-advancing tube was significantly lower than the success rate of the endoscopic guided technique.

Background & Aims: Ionized ammonia (NH(3)) and partial pressure of the gaseous ammonia (pNH(3)) are associated with hepatic encephalopathy and intracranial hypertension in patients with acute liver failure; NH(3) is also believed to contribute to extrahepatic organ failure. We investigated whether the severity of organ failure was associated with intracranial hypertension and evaluated the correlation between NH(3) and pNH(3) and grade of hepatic encephalopathy., Methods: In 87 patients with acute liver failure admitted to the intensive care unit, we simultaneously evaluated arterial ammonia, pNH(3), clinical grade of hepatic encephalopathy, the sequential organ failure assessment score (SOFA score), and evidence of intracranial hypertension., Results: In comparing patients with intracranial hypertension (n = 37) with patients without intracranial hypertension (n = 50), the highest NH(3) and pNH(3) levels and SOFA scores before onset of intracranial hypertension were independent predictors of intracranial hypertension (P < .001). Among patients with NH(3) levels less than 146 mumol/L, those with intracranial hypertension had a higher SOFA score than those without intracranial hypertension (median, 10 vs 5.5; P = .004), despite the patients' similar levels of NH(3). NH(3) (r = 0.68, P < .0001) and pNH(3) (r = 0.78, P < .0001) both correlated with grade of hepatic encephalopathy. However, in multiple regression analysis, only pNH(3) (P < .0001) was shown to be a significant independent parameter for predicting grade of hepatic encephalopathy (P = .27)., Conclusions: SOFA score and ammonia levels are independent predictors of intracranial hypertension. In patients with acute liver failure admitted to the intensive care unit, pNH(3) level is a better predictor of clinical grade of hepatic encephalopathy than arterial NH(3) level.

Purpose: Hypoxic hepatitis (HH) is a frequent cause of acute hepatocellular damage at the intensive care unit. Although mortality is reported to be high, risk factors for mortality in this population are unknown., Methods: One-hundred and seventeen consecutive patients with HH were studied prospectively at three medical intensive care units of a university hospital., Results: The main causes of hypoxic hepatitis were low cardiac output and septic shock, and most patients (74%) had more than one underlying factor. Peak aspartate transaminase (P = 0.02), lactate dehydrogenase (P = 0.03), INR (P < 0.001) and lactate (P < 0.01) were higher in non-survivors. Prolonged duration of HH caused higher overall mortality rate (P = 0.03). INR > 2 (P = 0.02), septic shock (P = 0.01) and SOFA score >10 (P = 0.04) were risk factors of mortality in the regression model., Conclusions: Hypoxic hepatitis is the consequence of multiorgan injury. Outcome is influenced by the severity of liver impairment and the etiology and severity of the basic disease.

Objective: To evaluate the impact of circulatory shock requiring norepinephrine therapy on the accuracy and reliability of a subcutaneous continuous glucose monitoring system (CGMS) in critically ill patients., Design and Setting: A prospective, validation study of a medical intensive care unit at a university hospital was carried out., Methods: Continuous glucose monitoring was performed subcutaneously in 50 consecutive patients on intensive insulin therapy (IIT), who were assessed according to the a priori strata of circulatory shock requiring norepinephrine therapy or not., Results: A total of 736 pairs of sensor glucose (SG)/blood glucose (BG) values were analysed (502 without and 234 with norepinephrine therapy). For all values, repeated measures Bland-Altman analysis showed a mean difference of 0.08 mmol/l (limits of agreement: -1.26 and 1.43 mmol/l). Circulatory shock requiring norepinephrine therapy did not influence the relation of arterial BG with SG in a multivariable random effects linear regression analysis. The covariates norepinephrine dose, body mass index (BMI), glucose level and severity of illness also had no influence. Insulin titration grid analysis showed that 98.6% of the data points were in the acceptable treatment zone. No data were in the life-threatening zone., Conclusions: Circulatory shock requiring norepinephrine therapy, as well as other covariates, had no influence on the accuracy and reliability of the CGMS in critically ill patients.

Background: Strict glycemic control in critically ill patients is challenging for both physicians and nurses., Objectives: To determine the effect of focused education of intensive care staff followed by implementation of a glucose control protocol., Methods: A prospective observational study in a medical intensive care unit in a university hospital. After intensive education of nurses and physicians, a glucose control protocol with a nurse-managed insulin therapy algorithm was developed and implemented. Every measured blood glucose value and insulin dose per hour and per day were documented in 36 patients before and 44 patients after implementation of the protocol., Results: Median blood glucose levels decreased after implementation of the protocol (133 vs 110 mg/dL; P < .001). The amounts of time when patients' blood glucose levels were less than 110 mg/dL and less than 150 mg/dL increased after implementation of the protocol (8% vs 44%; 75% vs 96%; P<.001). The median use of insulin increased after implementation of the protocol (28 vs 35 IU/day; P=.002). Diabetic patients had higher median blood glucose levels than did nondiabetic patients both before (138 vs 131 mg/dL) and after (115 vs 108 mg/dL; P<.001) implementation, although median insulin use also increased (before implementation, 33 vs 26 IU/day; P=.04; after implementation, 46 vs 30 IU/day; P < .001)., Conclusions: Use of a collaboratively developed glucose control protocol led to decreased median blood glucose levels and to longer periods of normoglycemia. Despite increased insulin use, glucose control was worse in diabetic patients.

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., Patients and Method: One-hundred and eighty-one consecutive patients with cirrhosis were investigated in a prospective observational cohort study on admission to a medical intensive care unit (ICU) of a university hospital. Arterial acid-base state was assessed according to the Gilfix methodology. Clinical data, ICU mortality and hospital mortality were recorded., Main Results: Patients had net metabolic acidosis owing to unmeasured anions and owing to hyperchloraemic, dilutional and lactic acidosis. Lactic acidosis, acidemia and acute renal failure on ICU admission were associated with increased mortality. Lactate and pH discriminated survivors from non-survivors. The presence of lactic acidosis could not always be recognized by customary acid-base parameters., Conclusion: The stable equilibrium of acid-base disorders is lost when patients with cirrhosis become critically ill. Lactic acidosis and acidaemia are associated with increased ICU mortality caused by severe underlying organ dysfunction.

Objective: To establish whether prolonged lateral steep position during continuous rotation therapy leads to improvement on pulmonary gas exchange, respiratory mechanics and hemodynamics., Design: Prospective observational study., Setting: Intensive care unit of a university hospital., Patients: Twelve consecutive patients suffering from acute lung injury or adult respiratory distress syndrome undergoing continuous rotation therapy., Interventions: Blood gas analysis, static lung compliance, blood pressure, cardiac index and pulmonary shunt fraction were measured in supine as well as in left and right lateral steep position at 62 degrees during continuous rotation therapy (phase I). Rotation was then stopped for 30 min with the patients in supine position, left and right lateral steep position, and the same measurements were performed every 10 min (phase II)., Measurements and Results: Phase I and II revealed no significant changes in PaO(2)/FiO(2) ratio, mean arterial blood pressure, pulmonary shunt fraction, or cardiac index. Significantly lower static compliance was observed in lateral steep position than in supine position (p<0.001). Concomitantly, PaCO(2) was significantly lower in supine position than in left and right lateral steep position (p<0.01)., Conclusions: Lateral steep positioning impairs the compliance of the respiratory system. Prolonged lateral steep position does not lead to benefits with respect to oxygenation or hemodynamics. Individual response to the different positions is unpredictable. The pauses in "extreme" positions should be as short as possible.

Background/aims: Hyperlactatemia with unexplained absence of metabolic acidosis is observed in acute liver failure. In chronic liver disease offsetting metabolic acid-base disorders could be revealed by means of physical-chemical acid-base analysis. The purpose of this study was to determine whether the acidifying effect of lactate is neutralized by the alkalinizing effect of hypoalbuminemia in acute liver failure., Methods: Serial arterial blood samples of 46 consecutive patients with non-paracetamol-induced acute liver failure were studied after admission to a medical ICU in a prospective investigation and compared to healthy controls. Acid-base state was assessed by quantitative physical-chemical analysis., Results: Lactate was increased and albumin was decreased in patients with acute liver failure compared to healthy controls resulting in normal net metabolic acid-base state. The alkalinizing effect of hypoalbuminemia was neutralized by the acidifying effect of elevated lactate. This observation was confirmed in serial analysis during 5 days after admission., Conclusions: The acidifying effect of lactate is neutralized by the alkalinizing effect of hypoalbuminemia in non-paracetamol-induced acute liver failure. The absence of apparent metabolic acidosis in the presence of elevated lactate can be explained by means of the physical-chemical acid-base model.

Background & Aims: The hepatopulmonary syndrome (HPS) is defined as the triad of liver disease, arterial deoxygenation, and widespread pulmonary vasodilatation. Hypoxic hepatitis, also known as ischemic hepatitis, is the leading cause of acute liver impairment in hospitals. It is unknown whether HPS occurs in hypoxic hepatitis. We assessed the prevalence and clinical consequences of HPS in patients with hypoxic hepatitis., Methods: Forty-four patients with hypoxic hepatitis were screened prospectively for HPS using established criteria: (1) presence of hepatic disease, (2) increased alveolar-arterial difference for the partial pressure of oxygen greater than the age-related threshold, and (3) intrapulmonary vasodilatation detected via contrast-enhanced echocardiography. Sixty-two critically ill patients with different cardiopulmonary diseases but without hepatic disease were screened for prevalence of intrapulmonary vasodilatation as a control group., Results: Criteria of HPS were fulfilled in 18 patients with hypoxic hepatitis. HPS-positive patients had a significantly decreased partial pressure of arterial oxygen (P = .001) and partial pressure of arterial oxygen/fraction of inspired oxygen ratio (P = .034) at the time of diagnosis of HPS, a significant decreased area under the curve of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio during the first 48 hours after diagnosis of hypoxic hepatitis (P = .009), and a significantly increased peak serum aspartate transaminase level (P = .028), compared with patients without HPS. Complete resolution of intrapulmonary vasodilatation was observed during follow-up evaluation. Contrast-enhanced echocardiography was negative for intrapulmonary vasodilatation in all 62 control patients., Conclusions: Intrapulmonary vasodilatation indicating HPS frequently occurs in patients with hypoxic hepatitis. It is reversible after normalization of the hepatic dysfunction. Clinicians should consider intrapulmonary vasodilatation and HPS in patients with hypoxic hepatitis.

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., Materials and Methods: We report the effect of the administration of a human protein C concentrate (Ceprotin, Baxter, Vienna, Austria) in eight adult patients with purpura fulminans. Five patients received the concentrate as level-adjusted continuous infusion (10 U/kg/h, target protein C activity 100%) and three patients received the concentrate as bolus infusions (100 U/kg every 6 h) in addition to standard sepsis therapy. Heparin, fresh-frozen plasma, antithrombin- and fibrinogen concentrates, low-dose rtPA, and platelet transfusions were given when appropriate., Results: Six patients had overt disseminated intravascular coagulation: platelets, 19 g/l; fibrinogen, 60 mg/dl; antithrombin, 47%; prothrombin time, 32%; activated partial thromboplastin time (APTT), 88 s; d-dimer, 66 microg/ml; protein C activity, 29% (medians). Five patients had septic shock, six renal failure and four respiratory failure. Patients received between 5000 and 77,000 U of protein C concentrate over 2.5 days (median); the protein C activity increased to 184% (median) and coagulopathy resolved within 3 days in seven of the eight patients. Six patients survived, one died early from fulminant sepsis, and one died after 14 days from candida sepsis., Conclusions: Our data suggest that treatment with a plasma-derived protein C zymogen concentrate might be a useful support in adult patients with purpura fulminans.

Objective: Hyperglycemia and protein catabolism frequently occur in critically ill patients and both are associated with increased complication rates. These metabolic alterations can be improved by insulin administered exogenously. Since a wide range of insulin dosages have been used, this randomized, placebo-controlled, investigator-blinded, clinical study tests the hypothesis that a low-dose insulin regimen improves hyperglycemia and protein catabolism in critically ill medical patients., Patients and Methods: The day after their admission to a medical intensive care unit, forty consecutive, critically ill medical patients were randomized for receiving either a low-dose insulin regimen (i.e. 1 IU/h) (treatment group, n = 20) or placebo (control group, n = 20) continuously over 24 hours. The primary endpoint was the efficacy of the low-dose insulin regimen to decrease serum glucose concentrations; the secondary endpoint was its influence on protein catabolism. Serum glucose concentrations and protein catabolism, which was assessed by the urea nitrogen appearance rate, were determined at baseline and at 8 and 24 hours thereafter. Serum insulin concentrations were measured at baseline and after 24 hours., Results: After 24 hours the low-dose insulin regimen increased serum insulin concentrations compared with baseline (16.8+/-13.3 microU/ml and 11.5+/-16.9 microU/ml, respectively; p<0.05). Hyperglycemia and the urea nitrogen appearance rate did not change within the two groups of patients and there was no difference between the groups at the different time points., Conclusions: Administration of the low-dose insulin regimen was safe. However, the short-term low-dose insulin regimen was inefficient in influencing mild hyperglycemia and protein catabolism in critically ill medical patients.