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Background: Disciplines involved in diagnosing transfusion-related acute lung injury (TRALI) report according to a "one-hit" theory. However, studies showed that patients with an underlying condition are at increased risk of the development of TRALI. We investigated whether accumulating evidence on the "two-hit" theory has changed the practice of reporting TRALI., Materials and Methods: Departments of haematology, haemovigilance, transfusion medicine, intensive care and anaesthesiology from all Dutch hospitals with at least five beds equipped for mechanical ventilation were invited to participate in an online survey. Using clinical vignettes with conjoint analysis we investigated the effect of patients' age, admission diagnosis, type and number of transfusions and presence of risk factors for acute lung injury on TRALI reporting. A positive β-coefficient indicated a higher likelihood of reporting TRALI., Results: We received 129 questionnaires (response rate 74%). Respondents were more likely to report TRALI in younger patients, if symptoms developed within 2 hours of transfusion and if patients had received multiple transfusions. Sepsis and the presence of a risk factor for acute lung injury reduced the inclination to report. Transfusion medicine physicians and haemovigilance staff no longer took the age of transfusion products into account in their diagnostic considerations on TRALI., Discussion: We conclude that the multidisciplinary team involved in TRALI reporting, still considers TRALI a "one-hit" event, despite accumulating evidence that supports the "two-hit" theory. These results suggest that the patients most at risk of developing TRALI are not reported to the blood bank.

A strategy of defining and checking explicitly formulated patient-specific treatments targets or "daily goals" in the intensive care unit has been associated with improved communication. We investigated the effect of incorporation of daily goals into daily care planning on length of stay in the intensive care unit. Furthermore, the type of daily goals and deviations from daily goals in daily care with or without documented reason were evaluated. Four university hospitals in the Netherlands, of which 2 study "daily goal" hospitals and 2 control hospitals, participated in a prospective before-after study. During the before phase of the study, daily goals were formulated by the attending physician but kept blinded from doctors and nurses caring for the patient. During the after phase of the study, daily goals were integrated in the care plan for patients admitted to the 2 study hospitals but not for patients admitted to the control hospitals. The implementation of daily goals was, after case-mix correction, not associated with a change in intensive care unit length of stay. However, this study showed that an improved administrative discipline, that is, the recording of the reason why a daily goal or standard protocol was not accomplished, is in favor of the daily goal implementation.

Importance: It remains uncertain whether nebulization of mucolytics with bronchodilators should be applied for clinical indication or preventively in intensive care unit (ICU) patients receiving invasive ventilation., Objective: To determine if a strategy that uses nebulization for clinical indication (on-demand) is noninferior to one that uses preventive (routine) nebulization., Design, Setting, and Participants: Randomized clinical trial enrolling adult patients expected to need invasive ventilation for more than 24 hours at 7 ICUs in the Netherlands., Interventions: On-demand nebulization of acetylcysteine or salbutamol (based on strict clinical indications, n = 471) or routine nebulization of acetylcysteine with salbutamol (every 6 hours until end of invasive ventilation, n = 473)., Main Outcomes and Measures: The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for a difference between groups of -0.5 days. Secondary outcomes included length of stay, mortality rates, occurrence of pulmonary complications, and adverse events., Results: Nine hundred twenty-two patients (34% women; median age, 66 (interquartile range [IQR], 54-75 years) were enrolled and completed follow-up. At 28 days, patients in the on-demand group had a median 21 (IQR, 0-26) ventilator-free days, and patients in the routine group had a median 20 (IQR, 0-26) ventilator-free days (1-sided 95% CI, -0.00003 to ∞). There was no significant difference in length of stay or mortality, or in the proportion of patients developing pulmonary complications, between the 2 groups. Adverse events (13.8% vs 29.3%; difference, -15.5% [95% CI, -20.7% to -10.3%]; P < .001) were more frequent with routine nebulization and mainly related to tachyarrhythmia (12.5% vs 25.9%; difference, -13.4% [95% CI, -18.4% to -8.4%]; P < .001) and agitation (0.2% vs 4.3%; difference, -4.1% [95% CI, -5.9% to -2.2%]; P < .001)., Conclusions and Relevance: Among ICU patients receiving invasive ventilation who were expected to not be extubated within 24 hours, on-demand compared with routine nebulization of acetylcysteine with salbutamol did not result in an inferior number of ventilator-free days. On-demand nebulization may be a reasonable alternative to routine nebulization., Trial Registration: clinicaltrials.gov Identifier: NCT02159196.

Background: Severe thrombocytopenia should be corrected by prophylactic platelet transfusion prior to central venous catheter (CVC) insertion, according to national and international guidelines. Even though correction is thought to prevent bleeding complications, evidence supporting the routine administration of prophylactic platelets is absent. Furthermore, platelet transfusion bears inherent risk. Since the introduction of ultrasound-guided CVC placement, bleeding complication rates have decreased. The objective of the current trial is, therefore, to demonstrate that omitting prophylactic platelet transfusion prior to CVC placement in severely thrombocytopenic patients is non-inferior compared to prophylactic platelet transfusion., Methods/design: The PACER trial is an investigator-initiated, national, multicentre, single-blinded, randomised controlled, non-inferior, two-arm trial in haematologic and/or intensive care patients with a platelet count of between 10 and 50 × 10 9 /L and an indication for CVC placement. Consecutive patients are randomly assigned to either receive 1 unit of platelet concentrate, or receive no prophylactic platelet transfusion prior to CVC insertion. The primary endpoint is WHO grades 2-4 bleeding. Secondary endpoints are any bleeding complication, costs, length of intensive care and hospital stay and transfusion requirements., Discussion: This is the first prospective, randomised controlled trial powered to test the hypothesis of whether omitting forgoing platelet transfusion prior to central venous cannulation leads to an equal occurrence of clinical relevant bleeding complications in critically ill and haematologic patients with thrombocytopenia., Trial Registration: Nederlands Trial Registry, ID: NTR5653 ( http://www.trialregister.nl/trialreg/index.asp ). Registered on 27 January 2016. Currently recruiting. Randomisation commenced on 23 February 2016.

Background: The objective of this study was to determine the incidence, risk factors, and outcome of transfusion-associated circulatory overload (TACO) in a cohort of mixed intensive care unit patients and to compare risk factors with those for cardiac overload in the absence of transfusion., Study Design and Methods: In a retrospective cohort study, patients who developed TACO were compared using multivariate analysis of two control groups: patients without pulmonary deterioration who received transfusion and patients who developed circulatory overload in the absence of transfusion., Results: TACO was diagnosed in 66 of 1140 patients who received transfusions (5.8%). A total of 585 control transfusion recipients and 76 control patients who developed circulatory overload also were identified. Risk factors were the referring specialties cardiology (odds ratio [OR], 13.6; 95% confidence interval [CI], 5.1-35.7; p ≤ 0.001) and cardiothoracic surgery (OR, 8.8; 95% CI, 3.7-20.7; p ≤ 0.001), history of cardiac failure (OR, 2.4; 95% CI, 1.2-4.6; p = 0.01), continuous veno-venous hemofiltration (OR, 3.2; 95% CI, 1.2-8.9; p = 0.03), and degree of positive fluid balance (OR, 1.15; 95% CI, 1.07-1.24; p ≤ 0.001), which was associated less with the onset of TACO compared with circulatory overload (OR, 0.89; 95% CI, 0.82-0.97; p = 0.005). Patients in the TACO group had a longer length of stay in the intensive care unit compared with the transfusion and circulatory overload controls groups (median, 7.2 vs. 4.3 vs. 4.4 days; p = 0.001 vs. p = 0.008)., Conclusions: The incidence of TACO is high in a mixed intensive care unit population. The risk factors identified for TACO are cardiac failure, renal failure, and degree of positive fluid balance. A positive fluid balance may be less essential in the onset of TACO than in the onset of circulatory overload in the absence of transfusion., (© 2017 AABB.)

Objectives: The presence of respiratory viruses and the association with outcomes were assessed in invasively ventilated ICU patients, stratified by admission diagnosis., Design: Prospective observational study., Setting: Five ICUs in the Netherlands., Patients: Between September 1, 2013, and April 30, 2014, 1,407 acutely admitted and invasively ventilated patients were included., Interventions: None., Measurements and Main Results: Nasopharyngeal swabs and tracheobronchial aspirates were collected upon intubation and tested for 14 respiratory viruses. Out of 1,407 patients, 156 were admitted because of a severe acute respiratory infection and 1,251 for other reasons (non-severe acute respiratory infection). Respiratory viruses were detected in 28.8% of severe acute respiratory infection patients and 17.0% in non-severe acute respiratory infection (p < 0.001). In one third, viruses were exclusively detected in tracheobronchial aspirates. Rhinovirus and human metapneumovirus were more prevalent in severe acute respiratory infection patients (9.6% and 2.6% vs 4.5 and 0.2%; p = 0.006 and p < 0.001). In both groups, there were no associations between the presence of viruses and the number of ICU-free days at day 28, crude mortality, and mortality in multivariate regression analyses., Conclusions: Respiratory viruses are frequently detected in acutely admitted and invasively ventilated patients. Rhinovirus and human metapneumovirus are more frequently found in severe acute respiratory infection patients. Detection of respiratory viruses is not associated with worse clinically relevant outcomes in the studied cohort of patients.

Background: Central venous catheters are frequently inserted into patients with coagulation disorders. It is unclear whether preprocedural correction of hemostasis is beneficial. We determined the incidence of bleeding complications after central venous catheter placement in patients who had severe coagulopathy and identified potential risk factors for bleeding., Study Design and Methods: The MEDLINE and Cochrane Library databases were systematically searched through November 2015. To be included, articles must have reported on hemorrhagic complications with specification of abnormal coagulation testing results. Severe coagulopathy was defined as a reduced platelet count of 50 × 10 9 /L or less, and/or an elevated international normalized ratio of 1.5 or greater, and/or a partial thromboplastin time of 45 seconds or greater., Results: We included one randomized controlled trial and 21 observational studies. In total, there were 13,256 catheter insertions, including 4213 in patients with severe coagulopathy. Before 3150 central venous catheter placements, coagulopathy was not corrected. The bleeding incidence varied from 0 to 32%. The severity of coagulopathy did not predict the risk of bleeding. No study demonstrated a beneficial effect from the prophylactic administration of platelets or fresh-frozen plasma to prevent bleeding complications. Retrospective observational studies suggested that no preprocedural correction is required up to a platelet count of 20 × 10 9 /L and an international normalized ratio of 3.0., Conclusion: The incidence of major bleeding complications after central venous catheter placement is low, even in coagulopathic patients. Based on a systematic research of the literature, strong evidence supporting the correction of hemostatic defects before central venous catheter insertion is lacking. However, well-powered randomized controlled trials will be necessary to determine the minimal platelet count, the maximal international normalized ratio, and an activated partial thromboplastin time that is safe before central venous catheter insertion., (© 2017 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.)

Background: Correction of coagulopathy prior to central venous catheter (CVC) placement is advocated by guidelines, while retrospective studies support restrictive use of transfusion products., Study Design and Methods: We conducted a mixed vignette and questionnaire web survey to investigate current practice and preferences for CVC placement. Clinical vignettes were used to quantify the tendency to administer platelet concentrate. A positive ß-coefficient is in favour of administering platelet concentrate., Results: Ninety-seven physicians answered the survey questions (36 critical care physicians, 14 haematologists, 20 radiologists and 27 anaesthesiologist). Eighty-six physicians subsequently completed the clinical vignettes (response rate 71%). Preferences in favour of correcting thrombocytopenia prior CVC placement were platelet counts of 10 × 10 9 /L and 20 × 10 9 /L (ß = 3·9; ß = 3·2, respectively), the subclavian insertion site (ß = 0·8). An elevated INR (INR = 3; ß = 0·6) and an elevated aPTT (aPTT = 60 s; ß = 0·4) showed a positive trend towards platelet transfusion. Platelet transfusion was less likely in an emergency setting (ß = -0·4). Reported transfusion thresholds for CVC placement varied from <10 × 10 9 /L to 80 × 10 9 /L for platelet count, from 1·0 to 10·0 for INR and from 25 s to 150 s for aPTT. Implementation of ultrasound guidance as standard practice was limited., Conclusion: Current transfusion practice prior to CVC placement is highly variable. Physicians adjust the decision to correct coagulopathy prior CVC placement based on clinical parameters, insertion site and technique applied., (© 2017 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Background: Goal-directed therapy (GDT) can reduce postoperative complications in high-risk surgery patients. It is uncertain whether GDT has the same benefits in patients undergoing esophageal surgery. Goal of this Quality Improvement study was to evaluate the effects of a stroke volume guided GDT on post-operative outcome., Methods and Findings: We compared the postoperative outcome of patients undergoing esophagectomy before (99 patients) and after (100 patients) implementation of GDT. There was no difference in the proportion of patients with a complication (56% vs. 54%, p = 0.82), hospital stay and mortality. The incidence of prolonged ICU stay (>48 hours) was reduced (28% vs. 12, p = .005) in patients treated with GDT. Secondary analysis of complication rate showed a decrease in pneumonia (29 vs. 15%, p = .02), mediastinal abscesses (12 vs. 3%, p = .02), and gastric tube necrosis (5% vs. 0%, p = .03) in patients treated with GDT. Patients in the GDT group received significantly less fluids but received more colloids., Conclusions: The implementation of GDT during esophagectomy was not associated with reductions in overall morbidity, mortality and hospital length of stay. However, we observed a decrease in pneumonia, mediastinal abscesses, gastric tube necrosis, and ICU length of stay.

Aim: Besides supportive care, the only recommended treatment for comatose patients after cardiac arrest is target temperature management. Helium reduces ischaemic injury in animal models, and might ameliorate neurological injury in patients after cardiac arrest. As no studies exist on the use of helium in patients after cardiac arrest we investigated whether this is safe and feasible., Methods: The study was an open-label single arm intervention study in a mixed-bed academic intensive care unit. We included 25 patients admitted after circulatory arrest, with a presenting rhythm of ventricular fibrillation or pulseless tachycardia, return of spontaneous circulation within 30min and who were treated with hypothermia. Helium was administrated in a 1:1 mix with oxygen for 3h. A safety committee reviewed all ventilation problems, complications and causes of mortality., Results: Helium ventilation was started 4:59±0:52 (mean±SD)h after circulatory arrest. In one patient, helium ventilation was discontinued prematurely due to oxygenation problems. This was caused by pre-existing pulmonary oedema, and imposed limitations to PEEP and FiO2 by the study protocol, rather than the use of helium ventilation. Sixteen (64%) patients had a favourable neurological outcome., Conclusions: We found that helium ventilation is feasible and can be used safely in patients treated with hypothermia after cardiac arrest. No adverse events related to the use of helium occurred during the three hours of administration., (Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.)

Aims: To study the impact of hypothermia upon admission to the Intensive Care Unit (ICU) on early and late mortality and to develop a prediction model for late mortality in severely injured trauma patients., Materials and Methods: A multicenter retrospective cohort study was performed in adult trauma patients admitted to the ICU of two Level-1 trauma centers between 2007 and 2012. Hypothermia was defined as a core body temperature of ≤35° Celsius. Logistic regression analyses were performed to quantify the effect of hypothermia on 24-hour and 28-day mortality and to develop a prediction model., Results: A total of 953 patients were included, of which 354 patients had hypothermia (37%) upon ICU admission. Patients were divided into a normothermic or hypothermic group. Hypothermia was associated with a significantly increased mortality at 24 hours and 28 days (OR 2.72 (1.18-6.29 and OR 2.82 (1.83-4.35) resp.). The variables included in the final prediction model were hypothermia, age, APACHE II score (corrected for temperature), INR, platelet count, traumatic brain injury and Injury Severity Score. The final prediction model discriminated between survivors and non-survivors with high accuracy (AUC = 0.871, 95% CI 0.844-0.898)., Conclusions: Hypothermia, defined as a temperature ≤35° Celsius, is common in critically ill trauma patients and is one of the most important physiological predictors for early and late mortality in trauma patients. Trauma patients admitted to the ICU may be at high risk for late mortality if the patient is hypothermic, coagulopathic, severely injured and has traumatic brain injury or an advanced age.

Objectives: To examine the effect of positive end-expiratory pressure (PEEP) on right ventricular stroke volume variation (SVV), with possible implications for the number and timing of pulmonary artery catheter thermodilution measurements., Design: Prospective, clinical pilot study., Setting: Academic medical center., Participants: Patients who underwent volume-controlled mechanical ventilation and had a pulmonary artery catheter., Intervention: PEEP was increased from 5-to-10 cmH2O and from 10-to-15 cmH2O with 10-minute intervals, with similar decreases in PEEP, from 15-to-10 cmH2O and 10-to-5 cmH2O., Measurements and Main Results: In 15 patients, right ventricular parameters were measured using thermodilution at 10% intervals of the ventilatory cycle at each PEEP level with a rapid-response thermistor. Mean right ventricular stroke volume and end-diastolic volume declined during incremental PEEP and normalized on return to 5 cmH2O PEEP (p = 0.01 and p = 0.001, respectively). Right ventricular SVV remained unaltered by changes in PEEP (p = 0.26), regardless of incremental PEEP (p = 0.15) or decreased PEEP (p = 0.12). The coefficients of variation in the ventilatory cycle of all other thermodilution-derived right ventricular parameters also were unaffected by changes in PEEP., Conclusions: This study showed that increases in PEEP did not affect right ventricular SVV in critically ill patients undergoing mechanical ventilation despite reductions in mean right ventricular stroke volume and end-diastolic volume. This could be explained by cyclic counteracting changes in right ventricular preloading and afterloading during the ventilatory cycle, independent of PEEP. Changes in PEEP did not affect the number and timing of pulmonary artery catheter thermodilution measurements., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: To determine whether a literature-based guideline, powered by educational meetings and individual feedback, improves manual hyperinflation (MH) performance by intensive care unit (ICU) nurses., Background: MH is frequently applied in intubated and mechanically ventilated ICU patients. MH is a complex intervention, and large variation in its performance has been found., Materials and Methods: First, a literature-based guideline on MH was developed. The intervention consisted of education of this guideline and individual feedback. Before and 3 months after the intervention, ICU nurses performed MH maneuvers in a skills laboratory. Data collected included applied volumes, peak inspiratory flows (PIF) and peak expiratory flows (PEF), and the use of inspiratory holds., Results: Eighty nurses participated. Decrease of PIF was not statistically significant. PEF increased from 52 ± 7 to 83 ± 23 L/min (P < 0·01). PIF to PEF ratio decreased from 1·4 [1·1-1·7] to 0·8 [0·6-1·1] (P < 0·01). Peak inspiratory pressures decreased from 40 ± 14 to 19 ± 6 cm H2 O (P < 0·01). The proportion of nurses applying inspiratory holds increased from 14% to 58%; use of rapid release of the resuscitation bag, considered mandatory, increased from 4% to 61%., Conclusion: Implementation of a literature-based guideline on MH, powered by educational meetings and individual feedback, improves MH performance by ICU nurses., Relevance to Clinical Practice: If it is decided to practice MH in the care of the intubated and mechanical ventilated patient, a standardized, uniform performed MH procedure is a prerequisite., (© 2014 British Association of Critical Care Nurses.)

Background: We retrospectively studied associations between bolus infusion of hydrocortisone and variability of the blood glucose level and changes in insulin rates in intensive care unit (ICU) patients., Methods: 'Glycemic variability' and 'insulin infusion rate variability' were calculated from and expressed as the standard deviation (SD) of all blood glucose levels and insulin infusion rates during stay in the ICU, respectively. Glycemic and insulin infusion rate variability in patients who received bolus infusion of hydrocortisone were compared to those in patients who never received bolus infusion of hydrocortisone. Multivariate analysis was performed to correct for potential covariates including disease severity., Results: We included 6409 patients over 6 years; of them 962 received bolus infusion of hydrocortisone. Compared to patients who never received bolus infusion of hydrocortisone, patients who received hydrocortisone had their blood glucose level measured more frequently, had higher glycemic variability; were more frequently treated with intravenous insulin and had higher insulin infusion rate variability. The association between hydrocortisone treatment and glycemic variability was independent of disease severity, but the effect of hydrocortisone treatment on blood glucose variability was less strong in the more severely ill patients. The association between hydrocortisone and insulin infusion rate variability was also independent of disease severity, and independent of glycemic variability., Conclusions: Bolus infusion of hydrocortisone is independently associated with higher glycemic variability and higher insulin infusion rate variability in ICU patients. Studies are needed to see if continuous infusion of hydrocortisone prevents higher glycemic variability and higher insulin infusion rate variability.

Background: Preventive nebulization of mucolytic agents and bronchodilating drugs is a strategy aimed at the prevention of sputum plugging, and therefore atelectasis and pneumonia, in intubated and ventilated intensive care unit (ICU) patients. The present trial aims to compare a strategy using the preventive nebulization of acetylcysteine and salbutamol with nebulization on indication in intubated and ventilated ICU patients., Methods/design: The preventive nebulization of mucolytic agents and bronchodilating drugs in invasively ventilated intensive care unit patients (NEBULAE) trial is a national multicenter open-label, two-armed, randomized controlled non-inferiority trial in the Netherlands. Nine hundred and fifty intubated and ventilated ICU patients with an anticipated duration of invasive ventilation of more than 24 hours will be randomly assigned to receive either a strategy consisting of preventive nebulization of acetylcysteine and salbutamol or a strategy consisting of nebulization of acetylcysteine and/or salbutamol on indication. The primary endpoint is the number of ventilator-free days and surviving on day 28. Secondary endpoints include ICU and hospital length of stay, ICU and hospital mortality, the occurrence of predefined pulmonary complications (acute respiratory distress syndrome, pneumonia, large atelectasis and pneumothorax), and the occurrence of predefined side effects of the intervention. Related healthcare costs will be estimated in a cost-benefit and budget-impact analysis., Discussion: The NEBULAE trial is the first randomized controlled trial powered to investigate whether preventive nebulization of acetylcysteine and salbutamol shortens the duration of ventilation in critically ill patients., Trial Registration: NCT02159196, registered on 6 June 2014.

Background: Recent studies show that intraoperative mechanical ventilation using low tidal volumes (VT) can prevent postoperative pulmonary complications (PPCs). The aim of this individual patient data meta-analysis is to evaluate the individual associations between VT size and positive end-expiratory pressure (PEEP) level and occurrence of PPC., Methods: Randomized controlled trials comparing protective ventilation (low VT with or without high levels of PEEP) and conventional ventilation (high VT with low PEEP) in patients undergoing general surgery. The primary outcome was development of PPC. Predefined prognostic factors were tested using multivariate logistic regression., Results: Fifteen randomized controlled trials were included (2,127 patients). There were 97 cases of PPC in 1,118 patients (8.7%) assigned to protective ventilation and 148 cases in 1,009 patients (14.7%) assigned to conventional ventilation (adjusted relative risk, 0.64; 95% CI, 0.46 to 0.88; P < 0.01). There were 85 cases of PPC in 957 patients (8.9%) assigned to ventilation with low VT and high PEEP levels and 63 cases in 525 patients (12%) assigned to ventilation with low VT and low PEEP levels (adjusted relative risk, 0.93; 95% CI, 0.64 to 1.37; P = 0.72). A dose-response relationship was found between the appearance of PPC and VT size (R2 = 0.39) but not between the appearance of PPC and PEEP level (R2 = 0.08)., Conclusions: These data support the beneficial effects of ventilation with use of low VT in patients undergoing surgery. Further trials are necessary to define the role of intraoperative higher PEEP to prevent PPC during nonopen abdominal surgery.

Background: It is uncertain whether lung-protective mechanical ventilation using low tidal volumes should be used in all critically ill patients, irrespective of the presence of the acute respiratory distress syndrome (ARDS). A low tidal volume strategy includes use of higher respiratory rates, which could be associated with increased sedation needs, a higher incidence of delirium, and an increased risk of patient-ventilator asynchrony and ICU-acquired weakness. Another alleged side-effect of low tidal volume ventilation is the risk of atelectasis. All of these could offset the beneficial effects of low tidal volume ventilation as found in patients with ARDS., Methods/design: PReVENT is a national multicenter randomized controlled trial in invasively ventilated ICU patients without ARDS with an anticipated duration of ventilation of longer than 24 hours in 5 ICUs in The Netherlands. Consecutive patients are randomly assigned to a low tidal volume strategy using tidal volumes from 4 to 6 ml/kg predicted body weight (PBW) or a high tidal volume ventilation strategy using tidal volumes from 8 to 10 ml/kg PBW. The primary endpoint is the number of ventilator-free days and alive at day 28. Secondary endpoints include ICU and hospital length of stay (LOS), ICU and hospital mortality, the incidence of pulmonary complications, including ARDS, pneumonia, atelectasis, and pneumothorax, the cumulative use and duration of sedatives and neuromuscular blocking agents, incidence of ICU delirium, and the need for decreasing of instrumental dead space., Discussion: PReVENT is the first randomized controlled trial comparing a low tidal volume strategy with a high tidal volume strategy, in patients without ARDS at onset of ventilation, that recruits a sufficient number of patients to test the hypothesis that a low tidal volume strategy benefits patients without ARDS with regard to a clinically relevant endpoint., Trial Registration: The trial is registered at www.clinicaltrials.gov under reference number NCT02153294 on 23 May 2014.

Background: Bioelectrical impedance analysis (BIA) is a method used to estimate body compartments such as fat-free mass (FFM) and fat mass (FM). Two BIA devices, a single-frequency BIA (SF-BIA) device and a bioimpedance spectroscopy (BIS) approach, were compared to evaluate their reliability and to study whether their estimations resulted in similar classifications of body composition., Materials and Methods: In a prospective observational study, body composition was estimated by SF-BIA and BIS in 123 adult patients scheduled for major abdominal surgery. Measurement agreement for the continuous variables FFM and FM were analyzed by using the intraclass correlation coefficient (ICC), the mean differences, and their limits of agreement. Measurement differences were also visualized by Bland-Altman plots. For the dichotomized FFM index (FFMI) and FM index (FMI), interobserver agreement was calculated using Cohen κ statistics; the McNemar test was performed to compare the paired proportions., Results: Agreement for the continuous variables was almost perfect for FM (.86; 95% confidence interval [CI], .80-.90) and substantial for FFM (.78; 95% CI, .70-.84). For the dichotomous variables, the agreement was substantial for FMI (.67; 95% CI, .51-.83) and slight for FFMI (.19; 95% CI, .01-.37). BIS classified a larger proportion having a low FFMI and a high FMI., Conclusion: There were good ICCs between SF-BIA and BIS for FFM and FM. However, the mean differences were substantial, whereas the classification of body composition based on FFMI and FMI was influenced by the device. Therefore, BIA devices are not interchangeable., (© 2014 American Society for Parenteral and Enteral Nutrition.)

Introduction: There is a need for continuous glucose monitoring in critically ill patients. The objective of this trial was to determine the point accuracy and reliability of a device designed for continuous monitoring of interstitial glucose levels in intensive care unit patients., Methods: We evaluated point accuracy by comparing device readings with glucose measurements in arterial blood by using blood gas analyzers. Analytical and clinical accuracy was expressed in Bland-Altman plots, glucose prediction errors, and Clarke error grids. We used a linear mixed model to determine which factors affect the point accuracy. In addition, we determined the reliability, including duration of device start-up and calibration, skips in data acquisition, and premature disconnections of sensors., Results: We included 50 patients in whom we used 105 sensors. Five patients from whom we could not collect the predefined minimum number of four consecutive comparative blood draws were excluded from the point accuracy analysis. Therefore, we had 929 comparative samples from 100 sensors in 45 patients (11 (7 to 28) samples per patient) during 4,639 hours (46 (27 to 134) hours per patient and 46 (21 to 69) hours per sensor) for the accuracy analysis. Point accuracy did not meet the International Organization for Standardization (ISO) 14971 standard for insulin dosing accuracy but did improve with increasing numbers of calibrations and was better in patients who did not have a history of diabetes. Out of 105 sensors, 60 were removed prematurely for a variety of reasons. The device start-up time was 49 (43 to 58) minutes. The number of skips in data acquisition was low, resulting in availability of real-time data during 95% (89% to 98%) of the connection time per sensor., Conclusions: The point accuracy of a device designed for continuous real-time monitoring of interstitial glucose levels was relatively low in critically ill patients. The device had few downtimes, but one third of the sensors were removed prematurely because of unresolved sensor- or device-related problems., Trial Registration: Netherlands Trial Registry number: NTR3827 . Registered 30 January 2013.

Background: Prophylactic use of fresh-frozen plasma (FFP) is common practice in patients with a coagulopathy undergoing an invasive procedure. Evidence that FFP prevents bleeding is lacking, while risks of transfusion-related morbidity after FFP have been well demonstrated. We aimed to assess whether omitting prophylactic FFP transfusion in nonbleeding critically ill patients with a coagulopathy who undergo an intervention is noninferior to a prophylactic transfusion of FFP., Study Design and Methods: A multicenter randomized open-label trial with blinded endpoint evaluation was performed in critically ill patients with a prolonged international normalized ratio (INR; 1.5-3.0). Patients undergoing placement of a central venous catheter, percutaneous tracheostomy, chest tube, or abscess drainage were eligible. Patients with clinically overt bleeding, thrombocytopenia, or therapeutic use of anticoagulants were excluded. Patients were randomly assigned to omitting or administering a prophylactic transfusion of FFP (12 mL/kg). Outcomes were occurrence of postprocedural bleeding complications, INR correction, and occurrence of lung injury., Results: Due to slow inclusion, the trial was stopped before the predefined target enrollment was reached. Eighty-one patients were randomly assigned, 40 to FFP and 41 to no FFP transfusion. Incidence of bleeding did not differ between groups, with a total of one major and 13 minor bleedings (p = 0.08 for noninferiority). FFP transfusion resulted in a reduction of INR to less than 1.5 in 54% of transfused patients. No differences in lung injury scores were observed., Conclusion: In critically ill patients undergoing an invasive procedure, no difference in bleeding complications was found regardless whether FFP was prophylactically administered or not., (© 2014 AABB.)

Background: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. In the past decade blood banks have implemented low-risk TRALI donor strategies, including a male-only donor policy for plasma-containing blood products to prevent onset of TRALI. We performed a meta-analysis to determine whether use of low-risk TRALI donor strategies for plasma indeed reduces onset of TRALI., Study Design and Methods: We searched MEDLINE and Cochrane Central Register of Controlled Trials from January 1995 up to January 2013. Two reviewers independently extracted data on study characteristics, methods, and outcomes. Primary endpoint was onset of TRALI. Subgroup analyses were performed for patient populations prone to develop TRALI and general patient populations., Results: Ten articles were included. Meta-analysis using a random-effects model taking into account all transfused products showed a significant reduction for the risk of TRALI after implementation of low-risk TRALI donor strategies (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42-0.88). Data from patient populations prone to develop TRALI showed a significant reduction of TRALI risk (OR, 0.51; 95% CI, 0.29-0.90), while data from general patient populations showed a similar nonsignificant trend (OR, 0.66; 95% CI, 0.40-1.09). Results were similar when taking only plasma products into account (OR, 0.62; 95% CI, 0.42-0.92)., Conclusion: The introduction of low-risk TRALI donor strategies for plasma-containing products results in a reduction of TRALI., (© 2014 AABB.)

Objective: Bioelectrical impedance analysis (BIA) is a commonly used method for the evaluation of body composition. However, BIA estimations are subject to uncertainties.The aim of this systematic review was to explore the variability of empirical prediction equations used in BIA estimations and to evaluate the validity of BIA estimations in adult surgical and oncological patients., Subjects: Studies developing new empirical prediction equations and studies evaluating the validity of BIA estimations compared with a reference method were included. Only studies using BIA devices measuring the entire body were included. Studies that included patients with altered body composition or a disturbed fluid balance and studies written in languages other than English were excluded.To illustrate variability between equations, fixed normal reference values of resistance values were entered into the existing empirical prediction equations of the included studies and the results were plotted in figures. The validity was expressed by the difference in means between BIA estimates and the reference method, and relative difference in %., Results: Substantial variability between equations for groups (including men and women) was found for total body water (TBW) and fat free mass (FFM). The gender-specific existing general equations assume less variability for TBW and FFM. BIA mainly underestimated TBW (range relative difference -18.8% to +7.2%) and FFM (range relative differences -15.2% to +3.8%). Estimates of the fat mass (FM) demonstrated large variability (range relative difference -15.7 to +43.1%)., Conclusions: Application of equations validated in healthy subjects to predict body composition performs less well in oncologic and surgical patients. We suggest that BIA estimations, irrespective of the device, can only be useful when performed longitudinally and under the same standard conditions.

Introduction: Data on the incidence of a hypercoagulable state in trauma, as measured by thromboelastometry (ROTEM), is limited and the prognostic value of hypercoagulability after trauma on outcome is unclear. We aimed to determine the incidence of hypercoagulability after trauma, and to assess whether early hypercoagulability has prognostic value on the occurrence of multiple organ failure (MOF) and mortality., Methods: This was a prospective observational cohort study in trauma patients who met the highest trauma level team activation. Hypercoagulability was defined as a G value of ≥ 11.7 dynes/cm(2) and hypocoagulability as a G value of <5.0 dynes/cm(2). ROTEM was performed on admission and 24 hours later., Results: A total of 1,010 patients were enrolled and 948 patients were analyzed. Median age was 38 (interquartile range (IQR) 26 to 53), 77% were male and median injury severity score was 13 (IQR 8 to 25). On admission, 7% of the patients were hypercoagulable and 8% were hypocoagulable. Altogether, 10% of patients showed hypercoagulability within the first 24 hours of trauma. Hypocoagulability, but not hypercoagulability, was associated with higher sequential organ failure assessment scores, indicating more severe MOF. Mortality in patients with hypercoagulability was 0%, compared to 7% in normocoagulable and 24% in hypocoagulable patients (P <0.001). EXTEM CT, alpha and G were predictors for occurrence of MOF and mortality., Conclusions: The incidence of a hypercoagulable state after trauma is 10% up to 24 hours after admission, which is broadly comparable to the rate of hypocoagulability. Further work in larger studies should define the clinical consequences of identifying hypercoagulability and a possible role for very early, targeted use of anticoagulants.

Background and Purpose: Median nerve somatosensory evoked potential (SEP) recordings play an important role in outcome algorithms in comatose patients after cardiopulmonary resuscitation. Knowledge of technical difficulties, clinical implications and uniform interpretation of SEP recordings is crucial. The aim of this study was to evaluate the skills of neurologists to interpret SEP recordings in post-anoxic patients., Methods: Nationwide Dutch clinical neurophysiology examinations from 2007, 2008 and 2011, containing SEP related questions, were analysed. Participants were classified as neurology residents, neurologists with less than 10 years of experience, neurologists with more than 10 years of experience and clinical neurophysiologists. End-points were the knowledge of all participants about SEP recordings per year as well as improvement in knowledge over the years, as reflected by the test scores., Results: A total of 194 participants completed the examination in 2007, 200 in 2008 and 263 in 2011. Between 2007 and 2008, all groups of respondents showed a significant increase in percentage of correct answers to SEP questions. Sixty-six participants completed all three examinations. The SEP score of this group improved in 2008 [75%, interquartile range (IQR) 50-75, P < 0.001] compared with 2007 (38%, IQR 38-50); there was no further improvement in 2011 (69%, IQR 54-77)., Conclusion: Continuing education about technical knowledge, possible pitfalls and interpretation of SEP recordings remains of utmost importance., (© 2014 The Author(s) European Journal of Neurology © 2014 EAN.)

Background: Pulmonary coagulopathy is a hallmark of lung injury following inhalation trauma. Locally applied heparin attenuates lung injury in animal models of smoke inhalation. Whether local treatment with heparin benefits patients with inhalation trauma is uncertain. The present trial aims at comparing a strategy using frequent nebulizations of heparin with standard care in intubated and ventilated burn patients with bronchoscopically confirmed inhalation trauma., Methods: The Randomized Controlled Trial Investigating the Efficacy and Safety of Nebulized HEParin versus Placebo in BURN Patients with Inhalation Trauma (HEPBURN) is an international multi-center, double-blind, placebo-controlled, two-arm study. One hundred and sixteen intubated and ventilated burn patients with confirmed inhalation trauma are randomized to nebulizations of heparin (the nebulized heparin strategy) or nebulizations of normal saline (the control strategy) every four hours for 14 days or until extubation, whichever comes first. The primary endpoint is the number of ventilator-free days, defined as days alive and breathing without assistance during the first 28 days, if the period of unassisted breathing lasts for at least 24 consecutive hours., Discussion: As far as the authors know, HEPBURN is the first randomized, placebo-controlled trial, powered to investigate whether local treatment with heparin shortens duration of ventilation of intubated and ventilated burn patients with inhalation trauma., Trial Registration: NCT01773083 (http://www.clinicaltrials.gov), registered on 16 January 2013.Recruiting. Randomisation commenced on 1 January 2014.

Purpose: To assess the sensitivity and false positive rate (FPR) of neurological examination and somatosensory evoked potentials (SSEPs) to predict poor outcome in adult patients treated with therapeutic hypothermia after cardiopulmonary resuscitation (CPR)., Methods: MEDLINE and EMBASE were searched for cohort studies describing the association of clinical neurological examination or SSEPs after return of spontaneous circulation with neurological outcome. Poor outcome was defined as severe disability, vegetative state and death. Sensitivity and FPR were determined., Results: A total of 1,153 patients from ten studies were included. The FPR of a bilaterally absent cortical N20 response of the SSEP could be calculated from nine studies including 492 patients. The SSEP had an FPR of 0.007 (confidence interval, CI, 0.001-0.047) to predict poor outcome. The Glasgow coma score (GCS) motor response was assessed in 811 patients from nine studies. A GCS motor score of 1-2 at 72 h had a high FPR of 0.21 (CI 0.08-0.43). Corneal reflex and pupillary reactivity at 72 h after the arrest were available in 429 and 566 patients, respectively. Bilaterally absent corneal reflexes had an FPR of 0.02 (CI 0.002-0.13). Bilaterally absent pupillary reflexes had an FPR of 0.004 (CI 0.001-0.03)., Conclusions: At 72 h after the arrest the motor response to painful stimuli and the corneal reflexes are not a reliable tool for the early prediction of poor outcome in patients treated with hypothermia. The reliability of the pupillary response to light and the SSEP is comparable to that in patients not treated with hypothermia.

Objectives: To improve patient safety, potential critical events should be analyzed for the existence of preventive barriers. The aim of this study was to prospectively identify existing and missing barriers using the Bow-Tie model. We expected that the analysis of these barriers would lead to feasible recommendations to improve safety in daily patient care., Methods: Multidisciplinary teams of doctors and nurses on a 28 bed ICU conducted the study. The Bow-Tie analysis was performed on intrahospital transportation, unplanned extubation, and communication, which led to 9 critical events. For each event, potential threats and consequences were defined and placed in a Bow-Tie diagram. Then, barriers were determined, ways to prevent the threat or limit the consequences. The barriers were defined as existing or missing and analyzed for feasibility., Results: Intrahospital transportation: this hazard led to 7 critical events, the Bow-Tie analysis to 52 missing but implementable barriers and 8 practical recommendations. For example, a pretransportation checklist.Unplanned extubation: this Bow-Tie analysis revealed 15 implementable missing barriers (of a total of 32) and led to 22 recommendations. One of them was optimizing treatment of delirium.Communication: this analysis showed 21 barriers, of which, 12 were missing but feasible to implement. These barriers led to 7 recommendations such as the need to cosign after the handover of a patient., Conclusions: Prospective risk analysis using the Bow-Tie model proved usable to identify existing and missing barriers for potential critical events. Many missing barriers seemed feasible to implement and led to practical recommendations and improvements in patient safety.

Background: Serum levels of N-terminal proB-type natriuretic peptide (NT-proBNP) are elevated in patients acute respiratory distress syndrome (ARDS). Recent studies showed a lower incidence of acute cor pulmonale in ARDS patients ventilated with lower tidal volumes. Consequently, serum levels of NT-proBNP may be lower in these patients. We investigated the relation between serum levels of NT-proBNP and tidal volumes in critically ill patients without ARDS at the onset of mechanical ventilation., Methods: Secondary analysis of a randomized controlled trial of lower versus conventional tidal volumes in patients without ARDS. NT-pro BNP were measured in stored serum samples. Serial serum levels of NT-pro BNP were analyzed controlling for acute kidney injury, cumulative fluid balance and presence of brain injury. The primary outcome was the effect of tidal volume size on serum levels of NT-proBNP. Secondary outcome was the association with development of ARDS., Results: Samples from 150 patients were analyzed. No relation was found between serum levels of NT-pro BNP and tidal volume size. However, NT-proBNP levels were increasing in patients who developed ARDS. In addition, higher levels were observed in patients with acute kidney injury, and in patients with a more positive cumulative fluid balance., Conclusion: Serum levels of NT-proBNP are independent of tidal volume size, but are increasing in patients who develop ARDS.

Background: Brain computer tomography (brain CT) is an important imaging tool in patients with intracranial disorders. In ICU patients, a brain CT implies an intrahospital transport which has inherent risks. The proceeds and consequences of a brain CT in a critically ill patient should outweigh these risks. The aim of this study was to critically evaluate the diagnostic and therapeutic yield of brain CT in ICU patients., Methods: In a prospective observational study data were collected during one year on the reasons to request a brain CT, expected abnormalities, abnormalities found by the radiologist and consequences for treatment. An "expected abnormality" was any finding that had been predicted by the physician requesting the brain CT. A brain CT was "diagnostically positive", if the abnormality found was new or if an already known abnormality was increased. It was "diagnostically negative" if an already known abnormality was unchanged or if an expected abnormality was not found. The treatment consequences of the brain CT, were registered as "treatment as planned", "treatment changed, not as planned", "treatment unchanged"., Results: Data of 225 brain CT in 175 patients were analyzed. In 115 (51%) brain CT the abnormalities found were new or increased known abnormalities. 115 (51%) brain CT were found to be diagnostically positive. In the medical group 29 (39%) of brain CT were positive, in the surgical group 86 (57%), p 0.01. After a positive brain CT, in which the expected abnormalities were found, treatment was changed as planned in 33%, and in 19% treatment was changed otherwise than planned., Conclusions: The results of this study show that the diagnostic and therapeutic yield of brain CT in critically ill patients is moderate. The development of guidelines regarding the decision rules for performing a brain CT in ICU patients is needed.

Introduction: Catheter-related bloodstream infections (CRBSIs) associated with short-term central venous catheters (CVCs) in intensive care unit (ICU) patients are a major clinical problem. Bacterial colonization of the skin at the CVC insertion site is an important etiologic factor for CRBSI. The aim of this study was to assess the efficacy of medical-grade honey in reducing bacterial skin colonization at insertion sites., Methods: A prospective, single-center, open-label randomized controlled trial was performed at the ICU of a university hospital in The Netherlands to assess the efficacy of medical-grade honey to reduce skin colonization of insertion sites. Medical-grade honey was applied in addition to standard CVC-site dressing and disinfection with 0.5% chlorhexidine in 70% alcohol. Skin colonization was assessed on a daily basis before CVC-site disinfection. The primary end point was colonization of insertion sites with >100 colony-forming units at the last sampling before removal of the CVC or transfer of the patient from the ICU. Secondary end points were quantitative levels of colonization of the insertion sites and colonization of insertion sites stratified for CVC location., Results: Colonization of insertion sites was not affected by the use of medical-grade honey, as 44 (34%) of 129 and 36 (34%) of 106 patients in the honey and standard care groups, respectively, had a positive skin culture (P = 0.98). Median levels of skin colonization at the last sampling were 1 (0 to 2.84) and 1 (0 to 2.70) log colony-forming units (CFUs)/swab for the honey and control groups, respectively (P = 0.94). Gender, days of CVC placement, CVC location, and CVC type were predictive for a positive skin culture. Correction for these variables did not change the effect of honey on skin-culture positivity., Conclusions: Medical-grade honey does not affect colonization of the skin at CVC insertion sites in ICU patients when applied in addition to standard disinfection with 0.5% chlorhexidine in 70% alcohol., Trial Registration: Netherlands Trial Registry, NTR1652.

Background & Aims: Low handgrip strength by dynamometry is associated with increased postoperative morbidity, higher mortality and reduced quality of life. The aim of this study was to evaluate the accuracy of four algorithms in diagnosing malnutrition by measuring handgrip strength., Methods: We included 504 consecutive preoperative outpatients. Reference standard for malnutrition was defined based on percentage involuntary weight loss and BMI. Diagnostic characteristics of the handgrip strength algorithms (Álvares-da-Silva, Klidjian, Matos, Webb) were expressed by sensitivity, specificity, positive and negative predictive value, false positive and negative rate., Results: The prevalence of malnutrition was 5.8%. Although Klidjian showed the highest sensitivity (79%, 95% CI 62%-90%), 6 out of 29 malnourished patients were falsely identified as well-nourished (false positive rate 21%, 95% CI 9%-38%). In contrast, this algorithm showed the lowest positive predictive value (8%, 95% CI 5%-13%). Matos presented the highest positive predictive value; the post-test probability increased to 13% (95% CI 8%-20%). The 1-minus negative predictive value ranged between 3% and 5% for all algorithms., Conclusions: None of the algorithms derived from handgrip strength measurements was found to have a diagnostic accuracy good enough to introduce handgrip strength as a systematic institutional screening tool to detect malnutrition in individual adult preoperative elective outpatients., (Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Acute lung injury (ALI) is characterized by a pro-coagulant state. Heparin is an anticoagulant with anti-inflammatory properties. Unfractionated heparin has been found to be protective in experimental models of ALI. We hypothesized that an intravenous therapeutic dose of unfractionated heparin would favorably influence outcome of critically ill patients diagnosed with ALI., Methods: Patients admitted to the Intensive Care Unit (ICU) of a tertiary referral center in the Netherlands between November 2004 and October 2007 were screened. Patients who developed ALI (consensus definition) were included. In this cohort, the impact of heparin use on mortality was assessed by logistic regression analysis in a propensity matched case-control design., Results: Of 5,561 admitted patients, 2,138 patients had a length of stay > 48 hours, of whom 723 were diagnosed with ALI (34%), of whom 164 received intravenous heparin. In a propensity score adjusted logistic regression analysis, heparin use did not influence 28-day mortality (odds ratio 1.23 [confidence interval 95% 0.80-1.89], nor did it affect ICU length of stay., Conclusions: Administration of therapeutic doses of intravenous unfractionated heparin was not associated with reduced mortality in critically ill patients diagnosed with ALI. Heparin treatment did not increase transfusion requirements. These results may help in the design of prospective trials evaluating the use of heparin as adjunctive treatment for ALI.

Introduction: Manual hyperinflation (MH), a frequently applied maneuver in critically ill intubated and mechanically ventilated patients, is suggested to mimic a cough so that airway secretions are mobilized toward the larger airways, where they can easily be removed. As such, MH could prevent plugging of the airways., Methods: We performed a search in the databases of Medline, Embase, and the Cochrane Library from January 1990 to April 2012. We systematically reviewed the literature on evidence for postulated benefits and risks of MH in critically ill intubated and mechanically ventilated patients., Results: The search identified 50 articles, of which 19 were considered relevant. We included 13 interventional studies and six observational studies. The number of studies evaluating physiological effects of MH is limited. Trials differed too much to permit meta-analysis. It is uncertain whether MH was applied similarly in the retrieved studies. Finally, most studies are underpowered to show clinical benefit of MH. Use of MH is associated with short-term improvements in lung compliance, oxygenation, and secretion clearance, without changes in outcomes. MH has been reported to be associated with short-term and probably clinically insignificant side effects, including decreases in cardiac output, alterations of heart rates, and increased central venous pressures., Conclusions: Studies have failed to show that MH benefits critically ill intubated and mechanically ventilated patients. MH is infrequently associated with short-term side effects.

Introduction: Treatment with hypothermia has been shown to improve outcome after cardiac arrest (CA). Current consensus is to rewarm at 0.25-0.5 °C/h and avoid fever. The aim of this study was to investigate whether active rewarming, the rate of rewarming or development of fever after treatment with hypothermia after CA was correlated with poor outcome., Methods: This retrospective cohort study included adult patients treated with hypothermia after CA and admitted to the intensive care unit between January 2006 and January 2009. The average rewarming rate from end of hypothermia treatment (passive rewarming) or start active rewarming until 36 °C was dichotomized in a high (≥ 0.5 °C/h) or normal rate (<0.5 °C/h). Fever was defined as >38 °C within 72 h after admission. Poor outcome was defined as death, vegetative state, or severe disability after 6 months., Results: From 128 included patients, 56% had a poor outcome. Actively rewarmed patients (38%) had a higher risk for poor outcome, OR 2.14 (1.01-4.57), p<0.05. However, this effect disappeared after adjustment for the confounders age and initial rhythm, OR 1.51 (0.64-3.58). A poor outcome was found in 15/21 patients (71%) with a high rewarming rate, compared to 54/103 patients (52%) with a normal rewarming rate, OR 2.61 (0.88-7.73), p = 0.08. Fever was not associated with outcome, OR 0.64 (0.31-1.30), p = 0.22., Conclusions: This study showed that patients who needed active rewarming after therapeutic hypothermia after CA did not have a higher risk for a poor outcome. In addition, neither speed of rewarming, nor development of fever had an effect on outcome., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Esophagectomy with gastric tube reconstruction results in a variety of postoperative nutrition-related complaints that can impair nutritional intake and nutritional status. The aim of this study was to determine to what extent patients reached the recommended intake of various nutrients at 6 and 12 months after esophagectomy. It was also analyzed whether a suboptimal intake could be explained by the most clinically significant nutrition-related complaints after esophagectomy. In a prospective cohort study (2002 to 2006), the nutrient intake of 96 patients, recorded in preprinted nutritional diaries, was compared with the recommended energy intake in The Netherlands and Recommended Dietary Allowance of protein and micronutrients. Energy and protein intake remained below recommendations in 24% and 7% of the patients, respectively. Less than 10% of the patients had a sufficient intake of all micronutrients. Folic acid, vitamin D, copper, calcium, and vitamin B-1 were the micronutrients most often reported to have a suboptimal intake. Multivariate logistic regression, corrected for preoperative epigastric pain and energy intake, showed that the number of nutrition-related complaints was not an independent risk factor for the presence of a suboptimal intake of nutrients (adjusted odds ratio=1.11; 95% CI: 0.94 to 1.31; P = 0.22). This study shows that the intake of micronutrients remains below recommendations in the majority of patients 12 months after esophagectomy. This problem requires special attention and care by registered dietitians., (Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac surgery-related pulmonary complications include alterations in lung mechanics and anomalies in gas exchange. Higher levels of positive end-expiratory pressure (PEEP) have been suggested to benefit cardiac surgical patients. We compared respiratory compliance, arterial oxygenation and time till tracheal extubation in 2 cohorts of patients weaned from mechanical ventilation with different levels of PEEP after elective and uncomplicated coronary artery bypass grafting (CABG). We hypothesized that higher PEEP levels improve pulmonary compliance and gas exchange in the first hours of weaning from mechanical ventilation, but not to shorten time till tracheal extubation., Methods: Secondary retrospective analysis of 2 randomized controlled trials: in the first trial patients were weaned with PEEP levels of 10 cmH2O for the first 4 hours followed by PEEP levels of 5 cmH2O until tracheal extubation (high PEEP, HP); and the second trial patients were weaned with PEEP levels of 5 cmH2O during the entire weaning phase (low PEEP, LP). The primary endpoint was pulmonary compliance. Secondary endpoints included arterial oxygenation, duration of mechanical ventilation and postoperative pulmonary complications., Results: The analysis included 121 patients; 60 HP patients and 61 LP patients. Baseline characteristics were similar. Compared to LP patients, HP patients had a better pulmonary compliance, 47.2±14.1 versus 42.7±10.2 ml/cmH2O (P<0.05), and higher levels of PaO2, 18.5±6.6 (138.75±49.5) versus 16.7±5.4 (125.25±40.5) kPa (mmHg) (P<0.05). Patients in the HP group were less frequent in need of supplementary oxygen after ICU discharge. These differences remained present during the entire weaning phase, even after reduction of PEEP. However, HP patients had a longer time till tracheal extubation, 16.9±6.1 versus 10.5±5.0 hours (P<0.001). HP patients had longer durations of postoperative infusion of propofol, 4.9 (2.6-7.4) versus 3.5 (1.8-5.8) hours (P<0.05). There were no differences in use of inotropes. Cumulative fluid balances were slightly higher in HP patients., Conclusion: Use of higher PEEP levels after elective uncomplicated CABG improves pulmonary compliance and oxygenation but seems to be associated with a delay in tracheal extubation.

Background: Blood transfusion increases the risk of nosocomial infection in trauma patients. Specific patient- and transfusion-related risk factors are largely unknown. In this study, risk factors for developing a bacterial infection after transfusion of red blood cells (RBC) or platelets were determined in a cohort of transfused critically ill trauma patients., Material and Methods: A retrospective study was conducted in a mixed medical-surgical Intensive Care Unit (ICU) of a level-1 university trauma centre, in trauma patients who received a RBC or platelet transfusion. Patients who developed a bacterial infection after transfusion were compared to transfused controls who did not develop such an infection. Multivariable logistic regression was used to determine risk factors for infection., Results: Of the 7,118 patients admitted to the ICU during the study period, 196 trauma patients met the inclusion criteria. An infection developed in 56 patients (29%). Infection occurred irrespective of the administration of antibiotics as part of selective digestive tract decontamination, surgery status or Injury Severity Score. Transfusion of RBC stored for more than 14 days was associated with infection in trauma patients (odds ratio 1.038, [95% CI: 1.01-1.07], p=0.036). Neither the amount of RBC nor that of platelets was associated with onset of infection., Conclusions: Transfusion of RBC stored for more then 14 days is a risk factor for onset of bacterial infection after trauma, irrespective of the use of prophylactic antibiotics. Transfusion of platelets was not a risk factor. These results may contribute to designing prospective studies on transfusion of fresh RBC only in trauma patients.

Background: There is evidence that percutaneous dilatational tracheotomy (PDT) can be safely performed in patients with severe coagulation disorders if these are carefully corrected immediately before the procedure. However, it is currently unclear whether PDT can be performed safely in patients in an Intensive Care Unit (ICU) with uncorrected mild coagulation disorders., Materials and Methods: In a randomised controlled trial we determined the effect of correction of mild coagulation disorders on bleeding during and after PDT. ICU patients planned for bedside PDT with: (i) a prothrombin time (PT) between 14.7-20.0 seconds, (ii) a platelet count between 40-100×10(9)/L and/or (iii) active treatment with acetylsalicylic acid were randomised to receive infusion with fresh-frozen plasma (FFP) and/or platelets ("correction") versus no transfusion ("no correction") before PDT., Results: We randomised 35 patients to the "correction" group and 37 patients to the "no correction" group. In patients who received FFP, the decrease in PT was marginal (mean decrease 0.40±0.56 seconds); the median increase in platelet counts after transfusion of platelets was 35 [11-47]x10(9)/L. The median blood loss was 3 [IQR: 1-6] grams in the "correction" group and 3 [IQR: 2-6] grams in the "no correction" group (P=0.96)., Discussion: Bleeding during and after bedside PDT in ICU patients with mild coagulation disorders is rare in our setting. Correction of subclinical coagulation disorders by transfusion of FFP and/or platelets does not affect bleeding.

Bilateral absence of cortical N20 responses of median nerve somatosensory evoked potentials (SEP) predicts poor neurological outcome in postanoxic coma after cardiopulmonary resuscitation (CPR). Although SEP is easy to perform and available in most hospitals, it is worthwhile to know how neurological signs are associated with SEP results. The aim of this study was to investigate whether specific clinical neurological signs are associated with either an absent or a present median nerve SEP in patients after CPR. Data from the previously published multicenter prospective cohort study PROPAC (prognosis in postanoxic coma, 2000-2003) were used. Neurological examination, consisting of Glasgow Coma Score (GCS) and brain stem reflexes, and SEP were performed 24, 48, and 72 h after CPR. Positive predictive values for predicting absent and present SEP, as well as diagnostic accuracy were calculated. Data of 407 patients were included. Of the 781 SEPs performed, N20 s were present in 401, bilaterally absent in 299, and 81 SEPs were technically undeterminable. The highest positive predictive values (0.63-0.91) for an absent SEP were found for absent pupillary light responses. The highest positive predictive values (0.71-0.83) for a present SEP were found for motor scores of withdrawal to painful stimuli or better. Multivariate analyses showed a fair diagnostic accuracy (0.78) for neurological examination in predicting an absent or present SEP at 48 or 72 h after CPR. This study shows that neurological examination cannot reliably predict absent or present cortical N20 responses in median nerve SEPs in patients after CPR.

Objective: This study was designed to establish the reliability of neurologic examination, neuron-specific enolase (NSE), and median nerve somatosensory-evoked potentials (SEPs) to predict poor outcome in patients treated with mild hypothermia after cardiopulmonary resuscitation (CPR)., Methods: This multicenter prospective cohort study included adult comatose patients admitted to the intensive care unit (ICU) after CPR and treated with hypothermia (32-34°C). False-positive rates (FPRs 1 - specificity) with their 95% confidence intervals (CIs) were calculated for pupillary light responses, corneal reflexes, and motor scores 72 hours after CPR; NSE levels at admission, 12 hours after reaching target temperature, and 36 hours and 48 hours after collapse; and SEPs during hypothermia and after rewarming. The primary outcome was poor outcome, defined as death, vegetative state, or severe disability (Glasgow Outcome Scale 1-3) after 6 months., Results: Of 391 patients included, 53% had a poor outcome. Absent pupillary light responses (FPR 1; 95% CI, 0-7) or absent corneal reflexes (FPR 4; 95% CI, 1-13) 72 hours after CPR, and absent SEPs during hypothermia (FPR 3; 95% CI, 1-7) and after rewarming (FPR 0; 95% CI, 0-18) were reliable predictors. Motor scores 72 hours after CPR (FPR 10; 95% CI, 6-16) and NSE levels were not., Interpretation: In patients with persisting coma after CPR and therapeutic hypothermia, use of motor score or NSE, as recommended in current guidelines, could possibly lead to inappropriate withdrawal of treatment. Poor outcomes can reliably be predicted by testing brainstem reflexes 72 hours after CPR and performing SEP., (Copyright © 2011 American Neurological Association.)

Background. Neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine have been suggested as potential early predictive biological markers of acute kidney injury (AKI) in selected critically ill patients. Methods. We performed a secondary analysis of a multicenter prospective observational cohort study of unselected critically ill patients. Results. The analysis included 140 patients, including 57 patients who did not develop AKI, 31 patients who developed AKI, and 52 patients with AKI on admission to the ICU. Levels of sNGAL and uNGAL on non-AKI days were significantly lower compared to levels of sNGAL on RIFLE(RISK) days, RIFLE(INJURY) days, and RIFLE(FAILURE) days. The AUC of sNGAL for predicting AKI was low: 0.45 (95% confidence interval (CI) 0.27-0.63) and 0.53 (CI 0.38-0.67), 2 days and 1 day before development of AKI, respectively. The AUC of uNGAL for predicting AKI was also low: 0.48 (CI 0.33-0.62) and 0.48 (CI 0.33-0.62), 2 days and 1 day before development of AKI, respectively. AUC of sNGAL and uNGAL for the prediction of renal replacement therapy requirement was 0.47 (CI 0.37-0.58) and 0.26 (CI 0.03-0.50). Conclusions. In unselected critically ill patients, sNGAL and uNGAL are poor predictors of AKI or RRT.

Introduction: Cardiac surgery is associated with post-operative reductions of functional residual capacity (FRC). Manual hyperinflation (MH) aims to prevent airway plugging, and as such could prevent the reduction of FRC after surgery. The main purpose of this study was to determine the effect of MH on post-operative FRC of cardiac surgical patients., Methods: This was a randomized controlled trial of patients after elective coronary artery bypass graft and/or valve surgery admitted to the intensive care unit (ICU) of a university hospital. Patients were randomly assigned to a "routine MH group" (MH was performed within 30 minutes after admission to the ICU and every 6 hours thereafter, and before tracheal extubation), or a "control group" (MH was performed only if perceptible (audible) sputum was present in the larger airways causing problems with mechanical ventilation, or if oxygen saturation (SpO2) dropped below 92%). The primary endpoint was the reduction of FRC from the day before cardiac surgery to one, three, and five days after tracheal extubation. Secondary endpoints were SpO2 (at similar time points) and chest radiograph abnormalities, including atelectasis (at three days after tracheal extubation)., Results: A total of 100 patients were enrolled. Patients in the routine MH group showed a decrease of FRC on the first post-operative day to 71% of the pre-operative value, versus 57% in the control group (P = 0.002). Differences in FRC became less prominent over time; differences between the two study groups were no longer statistically significant at Day 5. There were no differences in SpO2 between the study groups. Chest radiographs showed more abnormalities (merely atelectasis) in the control group compared to patients in the routine MH group (P = 0.002)., Conclusions: MH partly prevents the reduction of FRC in the first post-operative days after cardiac surgery., Trial Registration: Netherlands Trial Register (NTR): NTR1384. http://www.trialregister.nl.

Background: Post-operative pulmonary complications add to the morbidity and mortality of surgical patients, in particular after general anesthesia >2 hours for abdominal surgery. Whether a protective mechanical ventilation strategy with higher levels of positive end-expiratory pressure (PEEP) and repeated recruitment maneuvers; the "open lung strategy", protects against post-operative pulmonary complications is uncertain. The present study aims at comparing a protective mechanical ventilation strategy with a conventional mechanical ventilation strategy during general anesthesia for abdominal non-laparoscopic surgery., Methods: The PROtective Ventilation using HIgh versus LOw positive end-expiratory pressure ("PROVHILO") trial is a worldwide investigator-initiated multicenter randomized controlled two-arm study. Nine hundred patients scheduled for non-laparoscopic abdominal surgery at high or intermediate risk for post-operative pulmonary complications are randomized to mechanical ventilation with the level of PEEP at 12 cmH(2)O with recruitment maneuvers (the lung-protective strategy) or mechanical ventilation with the level of PEEP at maximum 2 cmH(2)O without recruitment maneuvers (the conventional strategy). The primary endpoint is any post-operative pulmonary complication., Discussion: The PROVHILO trial is the first randomized controlled trial powered to investigate whether an open lung mechanical ventilation strategy in short-term mechanical ventilation prevents against postoperative pulmonary complications., Trial Registration: ISRCTN: ISRCTN70332574.

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Both antibodies and bioactive lipids that have accumulated during storage of blood have been implicated in TRALI pathogenesis. In a single-center, nested, case-control study, patients were prospectively observed for onset of TRALI according to the consensus definition. Of 668 patients, 16 patients (2.4%) developed TRALI. Patient-related risk factors for onset of TRALI were age and time on the cardiopulmonary bypass. Transfusion-related risk factors were total amount of blood products (odds ratio [OR] = 1.2; 95% confidence interval [CI], 1.03-1.44), number of red blood cells stored more than 14 days (OR = 1.6; 95% CI, 1.04-2.37), total amount of plasma (OR = 1.2; 95% CI, 1.03-1.44), presence of antibodies in donor plasma (OR = 8.8; 95% CI, 1.8-44), and total amount of transfused bioactive lipids (OR = 1.0; 95% CI, 1.00-1.07). When adjusted for patient risk factors, only the presence of antibodies in the associated blood products remained a risk factor for TRALI (OR = 14.2; 95% CI, 1.5-132). In-hospital mortality of TRALI was 13% compared with 0% and 3% in transfused and nontransfused patients, respectively (P < .05). In conclusion, the incidence of TRALI is high in cardiac surgery patients and associated with adverse outcome. Our results suggest that cardiac surgery patients may benefit from exclusion of blood products containing HLA/HNA antibodies.

There is a need for insight into factors that contribute to late mortality of sepsis patients. Immunomodulatory effects have been ascribed to blood transfusion. This retrospective cohort study investigates the association between the development of nosocomial bacterial infection and transfusion of leukodepleted red blood cells (RBCs) or platelets (PLTs) in survivors of the initial phase of sepsis. Patients diagnosed with sepsis after admission to the intensive care unit of a tertiary referral hospital were included. Of 134 patients with sepsis, 67 received a blood transfusion (50%). A secondary infection developed in 19 patients (14%). A multiple logistic regression model revealed that the use of immunosuppressive medication with an odds ratio (OR) of 1.17 (95% confidence interval [CI], 1.04-1.31), but not Acute Physiology and Chronic Health Evaluation II score, malignancy, HIV infection, alcohol abuse, or diabetes mellitus, was a risk factor for nosocomial infection. In an adjusted model, the amount of transfused RBCs was associated with secondary infection with an OR of 1.18 (95% CI, 1.01-1.37). Storage time of RBCs was a relevant confounder of the effect of the amount of RBCs on infection, with an adjusted OR of 1.25 (95% CI, 1.04-1.51), P = 0.02. Also, the amount of transfused PLTs was associated with secondary infection, with an OR of 1.36 (95% CI, 1.05-1.78). In conclusion, transfusion of RBCs and PLTs is associated with the onset of secondary bacterial infection in sepsis patients. Storage time of RBCs influences this increased risk. These findings suggest that immunomodulatory effects of blood transfusion contribute to adverse outcome in the convalescent phase of sepsis.

Background: The clinical value of postoperative chest radiographs (CXRs) for surgical intensive care unit (ICU) patients is largely unknown. In the present study, we determined the diagnostic and therapeutic efficacy of postoperative CXRs for different surgical subgroups and related their efficacy to the time after ICU admission., Methods: A prospective, observational study of consecutive postoperative surgical ICU patients was performed during a 10 month period. We restricted our analysis to CXRs obtained within six hours after admission to the ICU. Diagnostic efficacy was defined by the presence of predefined major abnormalities; therapeutic efficacy was defined by predefined actions taken because of any abnormality found on postoperative CXRs., Results: Of 857 surgical ICU patients, 670 (78%) had a postoperative CXR after admission to the ICU. Of these CXRs, 80 were performed for clinical reasons, and 590 were routinely obtained (i.e., these CXRs were made without a reason other than admission to the ICU itself). The diagnostic efficacy of clinically indicated and routinely obtained CXRs was 18% (14/80) and 13% (79/590), respectively. Of all predefined abnormalities found on CXRs, 60% involved the malposition of invasive devices, such as endotracheal tubes or central venous lines. The therapeutic efficacy of clinically indicated and routinely obtained CXRs was 4% (3/80) and 4% (26/590), respectively. While the diagnostic and therapeutic efficacy of routinely obtained CXRs were not dependent on timing of admission, the diagnostic and therapeutic efficacy of clinically indicated CXRs was higher for CXRs taken closer to the time of ICU admission., Conclusion: Although the diagnostic efficacy of clinically indicated and routinely obtained postoperative CXRs in surgical ICU patients appears to be significant, their therapeutic efficacy is low.