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Purpose: Hyperoxia may induce pulmonary injury and may increase oxidative stress. In this retrospective database study we aimed to evaluate the response to hyperoxia by intensivists in a Dutch academic intensive care unit.Methods: All arterial blood gas (ABG) data from mechanically ventilated patients from 2005 until 2009 were extracted from an electronic storage database of a mixed 32-bed intensive care unit in a university hospital in Amsterdam. Mechanical ventilation settings at the time of the ABG tests were retrieved.Results: The results of 126,778 ABG tests from 5,498 mechanically ventilated patients were retrieved including corresponding ventilator settings. In 28,222 (22%) of the ABG tests the arterial oxygen tension (PaO(2)) was >16 kPa (120 mmHg). In only 25% of the tests with PaO(2) >16 kPa (120 mmHg) was the fraction of inspired oxygen (FiO(2)) decreased. Hyperoxia was accepted without adjustment in ventilator settings if FiO(2) was 0.4 or lower.Conclusion: Hyperoxia is frequently seen but in most cases does not lead to adjustment of ventilator settings if FiO(2) <0.41. Implementation of guidelines concerning oxygen therapy should be improved and further research is needed concerning the effects of frequently encountered hyperoxia. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the incidence, risk factors, and outcome of transfusion-related acute lung injury in a cohort of critically ill patients. DESIGN: In a retrospective cohort study, patients with transfusion-related acute lung injury were identified using the consensus criteria of acute lung injury within 6 hrs after transfusion. Inclusion criterion was a length of intensive care unit admission >48 hrs. Patients developing transfusion-related acute lung injury were matched (on age, sex, and admission diagnosis) to transfused control subjects and patients developing acute lung injury from another origin. SETTING: Tertiary referral hospital. PATIENTS: All first-admitted patients from November 1, 2004, until October 1, 2007, to the intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 5208 admitted patients, 2024 patients had a length of stay >48 hrs, of whom 109 were suspected transfusion-related acute lung injury cases. Compared with transfused control subjects, risk factors for transfusion-related acute lung injury were emergency cardiac surgery (odds ratio, 17.6 [1.8-168.5]), hematologic malignancy (odds ratio, 13.1 [2.7-63.8]), massive transfusion (odds ratio, 4.5 [2.1-9.8]), sepsis (odds ratio, 2.5 [1.2-5.2]), mechanical ventilation (odds ratio, 3.0 [1.3-7.1], and high Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1 [1.0-1.1]; p < .03 for all). The volume of platelets and plasma transfused was associated with transfusion-related acute lung injury in the univariate analysis. However, this association disappeared in the multivariate analysis. Compared with acute lung injury control subjects, risk factors for transfusion-related acute lung injury were sepsis (odds ratio, 2.4 [1.1-5.3]) and high Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1 [1.0-1.1]), whereas pneumonia (odds ratio, 0.4 [0.2-0.7]) was a negative predictive factor. Patients with transfusion-related acute lung injury had a longer duration of mechanical ventilation compared with transfused control subjects and acute lung injury control subjects (231 [138-472] vs. 71 [46-163] and 70 [42-121] hrs, p < .001). Also, 90-day survival of patients with transfusion-related acute lung injury was lower compared with transfused control subjects and acute lung injury control subjects (53% vs. 75% and 83%, p < .02). CONCLUSIONS: Transfusion-related acute lung injury is common in critically ill patients. Transfusion-related acute lung injury may contribute to an adverse outcome associated with transfusion. This study identifies transfusion-related acute lung injury risk factors, which may aid in assessing the risks and benefits of transfusion in critically ill patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the daily bedside routine of the intensive care, potentially hazardous interventions that lack evidence need critical consideration. Therefore we examined current practice and knowledge of basic principles of manual hyperinflation (MH) in intubated and mechanically ventilated patients among intensive care unit nurses in the Netherlands. METHODS: A written survey method was used, questionnaires were sent to ICU nurses specialised in mechanical ventilation in 115 Dutch hospitals. The questions related to following domains: (1) demographics; (2) use of MH; (3) presumed benefits; (4) essential elements of the MH procedure; (5) equipment and safety. RESULTS: The response rate was 77%. From responding ICUs the majority (96%) stated they performed MH; 27% as a daily routine procedure, 69% performed MH on indication only. MH was mainly performed by ICU nurses. Half of ICUs reported to have a MH guideline available. Improved oxygenation and better removal of sputum were presumed benefits of MH. While slow inspiration and rapid expiration are considered to be essential elements of MH procedures, the majority of respondents stated to use rapid inspiration and slow expiration. CONCLUSIONS: This survey indicates that MH is widely used as an important item of airway management. Importantly, there is no uniformity in the performance of the procedure. Before definitive research can be developed, standards for the MH procedure should be established. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine tracheostomy-management practices in Dutch intensive care units (ICUs) and post-ICU step-down facilities. METHODS: We surveyed the physician medical directors of all Dutch nonpediatric ICUs that have >/= 5 beds suitable for mechanical ventilation. The survey asked for demographic information about the hospital and ICU setting, and for information and opinions about tracheostomy management in the ICU and step-down facilities, and the use of tracheostomy-management guidelines. RESULTS: Forty-four of the 69 ICUs responded. Sixty-four percent of the respondent ICUs only deflate the cuff when the patient is breathing spontaneously, without assistance from the ventilator. Fifty-nine percent do not routinely change the tracheostomy tube. Almost half use inner cannulas in tracheostomy tubes. Overall, intensivists were most often involved in the follow-up of discharged tracheostomized patients. In the nonacademic hospitals, specialized ICU nurses were more often involved (P = .05). Sixty-four percent indicated they have no guideline for managing discharged tracheostomized patients. There was a diversity of opinion (median visual-analog-scale score 5.0, 95% confidence interval 3.0 to 8.0) on whether the tracheostomy tube should be removed 'at once' or after 'down-sizing.' CONCLUSIONS: There were large differences in tracheostomy management among Dutch ICUs. ICU and post-ICU tracheostomy-management guidelines are lacking and needed. [ABSTRACT FROM AUTHOR]

What is the efficacy and safety of enteral nutrition (EN) compared with total parenteral nutrition (PN) for patients with acute pancreatitis (AP)?METHODSData sources: Medline (1966 to January 2004), EMBASE/ Excerpta Medica, Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews; bibliographies of relevant studies; and experts in the field.Study selection and assessment: randomised controlled trials (RCTs) that compared EN with PN in patients admitted to hospital with AP, and included >/=1 of the outcomes listed below. Methodological quality of individual studies was assessed using the 5 point Jadad composite scale.Outcomes: infections (pneumonia, abdominal abscess, pancreatic abscess, wound infection, or bloodstream infection), non-infectious complications (adult respiratory distress syndrome, multiorgan failure, acute pseudocysts, and pancreatic fistula), need for surgical intervention, length of hospital stay, and hospital mortality.MAIN RESULTS6 trials (n = 263) met the selection criteria. 4 studies had poor quality (Jadad score 2 out of 5). Meta-analysis was completed using a random effects model and intention to treat data from individual studies. Patients who received EN had a lower risk of infection than those who received PN, less need for surgical intervention, fewer septic complications, and shorter hospital stays (mean reduction 2.9 days, 95% CI 1.6 to 4.3) (table). The EN and PN groups did not differ for complications other than infections or hospital mortality (table).CONCLUSIONEvidence from primarily low quality trials shows that in patients with acute pancreatitis, enteral nutrition reduces infections, septic complications, need for surgical intervention, and length of hospital stay compared with total parenteral nutrition but does not affect non-infectious complications or hospital mortality. [ABSTRACT FROM AUTHOR]

In critically ill patients, does implementation of an evidence based algorithm for nutritional support improve the provision of nutritional support and patient outcomes?METHODSDesign: cluster randomised controlled trial.Allocation: {concealed}.Blinding: {unblinded}.Follow up period: until hospital discharge.Setting: intensive care units (ICUs) of 11 community and 3 teaching hospitals in Ontario, Canada.Patients: 499 patients aged >/=16 years (mean age 66 y, 61% men) with an expected ICU stay of >/=48 hours. Exclusion criteria: expected to be receiving sufficient oral nutrition within 24 hours after ICU' admission, admitted for palliative care, moribund and not expected to survive >6 hours, or suspected brain death.Intervention: 7 intervention ICUs were allocated to an evidence-based algorithm for nutritional support, with a multifaceted implementation strategy including opinion leader led education sessions, educational outreach visits, and audit and feedback. The algorithm emphasised early nutrition, preference for the enteral route, frequent re-evaluation; and management of adverse outcomes. 7 ICUs were allocated to the control arm, which included care by a dietitian who had not been given specific guidance on provision of feedback.Outcomes: hospital mortality, length of hospital stay, length of ICU stay, and receipt of nutritional support.Patient follow up: 99% (intention to treat analysis).MAIN RESULTSThe intervention ICUs did not differ from control ICUs for hospital mortality rates (27% v 37%, p=0.06). Patients in intervention ICUs had a shorter mean length of hospital stay than those in control ICUs(25 v 35 d, p = 0.003), but the groups did not differ for mean length of ICU stay (10.9 v 11.8 d, p=0.7). Patients in intervention ICUs received more days of enteral nutrition than those in control ICUs (6.7 v 5.4/10 patient d, p=0.04).CONCLUSIONIn critically ill patients, multifaceted implementation of an evidence-based algorithm for nutritional support improved provision of enteral nutrition and reduced length of hospital stay. [ABSTRACT FROM AUTHOR]

QUESTION: In patients who are critically ill, does normalisation of blood glucose concentrations with intensive insulin treatment reduce mortality and morbidity?DesignRandomised (allocation concealed), blinded (patients, outcome assessors), controlled trial (with mean follow up of 23 days}*.SettingSurgical intensive care unit (ICU) at the university hospital in Leuven, Belgium.Patients1548 patients (mean age 63 y, 71% men) admitted to the ICU who were receiving mechanical ventilation. Patients were excluded if they were participating in other trials, were moribund, or had 'do not resuscitate' orders. Follow up was 100%.InterventionPatients were assigned to receive intensive (n=765) or conventional (n=783) insulin treatment Intensive treatment was insulin infusion that was started if the blood glucose concentration was > 6.1 mmol/l, and was adjusted to maintain a blood glucose concentration of 4.4-6.1 mmol/l (maximum insulin dose 50 IU/h). Conventional treatment was continuous insulin infusion by a pump that was started if the blood glucose concentration was > 11.9 mmol/l and adjusted to maintain a blood glucose concentration between 10.0 and 11.1 mmol/l. All patients were fed continuous intravenous glucose upon ICU admission. Total parenteral, combined parenteral and cnteral, or total enteral feeding was started the next day. Total enteral feeding was attempted as early as possible.Main outcome measuresThe primary outcome measure was all cause death in the ICU. Secondary outcome measures included in hospital death, length of ICU stay, need for ICU care or ventilatory support > 14 days, and various complications of the critical illness.Main resultsAnalysis was by intention to treat. Intensive insulin treatment had reduced rates of all cause ICU deaths among all patients (p < 0.04) and among those who were in the ICU > 5 days (p=0.005); in hospital deaths (p=0.01); ICU care > 14 days (p=0.01); ventilatory support > 14 days (p=0.003); renal failure requiring dialysis or haemofiltration (p=0.007); bloodstream infections in the ICU (p=0.003); and critical illness polyneuropathy (p < 0.001) (table). The groups did not differ for length of ICU stay (median 3 d in both groups, p=0.2).ConclusionIn patients who were critically ill, normalisation of blood glucose concentrations with intensive insulin treatment reduced mortality and morbidity.*Information provided by author. [ABSTRACT FROM AUTHOR]

Background: Transfusion guidelines regarding platelet-count thresholds before the placement of a central venous catheter (CVC) offer conflicting recommendations because of a lack of good-quality evidence. The routine use of ultrasound guidance has decreased CVC-related bleeding complications., Methods: In a multicenter, randomized, controlled, noninferiority trial, we randomly assigned patients with severe thrombocytopenia (platelet count, 10,000 to 50,000 per cubic millimeter) who were being treated on the hematology ward or in the intensive care unit to receive either one unit of prophylactic platelet transfusion or no platelet transfusion before ultrasound-guided CVC placement. The primary outcome was catheter-related bleeding of grade 2 to 4; a key secondary outcome was grade 3 or 4 bleeding. The noninferiority margin was an upper boundary of the 90% confidence interval of 3.5 for the relative risk., Results: We included 373 episodes of CVC placement involving 338 patients in the per-protocol primary analysis. Catheter-related bleeding of grade 2 to 4 occurred in 9 of 188 patients (4.8%) in the transfusion group and in 22 of 185 patients (11.9%) in the no-transfusion group (relative risk, 2.45; 90% confidence interval [CI], 1.27 to 4.70). Catheter-related bleeding of grade 3 or 4 occurred in 4 of 188 patients (2.1%) in the transfusion group and in 9 of 185 patients (4.9%) in the no-transfusion group (relative risk, 2.43; 95% CI, 0.75 to 7.93). A total of 15 adverse events were observed; of these events, 13 (all grade 3 catheter-related bleeding [4 in the transfusion group and 9 in the no-transfusion group]) were categorized as serious. The net savings of withholding prophylactic platelet transfusion before CVC placement was $410 per catheter placement., Conclusions: The withholding of prophylactic platelet transfusion before CVC placement in patients with a platelet count of 10,000 to 50,000 per cubic millimeter did not meet the predefined margin for noninferiority and resulted in more CVC-related bleeding events than prophylactic platelet transfusion. (Funded by ZonMw; PACER Dutch Trial Register number, NL5534.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28)., Methods: This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume ( V T ) was defined as V T  ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma., Results: A total of 160 patients from 28 ICUs in 16 countries were included. Low V T was used in 74% of patients, median V T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma ( p  = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V T ( p  = 0.98). All patients were ventilated with PEEP levels ≥5 cmH 2 O; 80% of patients had maximum airway pressures <30 cmH 2 O., Conclusion: In this international cohort study we found that lung-protective ventilation is used in the majority of burn patients, irrespective of the presence of inhalation trauma. Use of low V T was not associated with a reduction in VFD-28., Trial Registration: Clinicaltrials.gov NCT02312869. Date of registration: 9 December 2014., (© The Author(s) 2021. Published by Oxford University Press.)

Background: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients., Objectives: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference., Design, Patients and Setting: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries., Main Outcome Measures: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation., Results: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT., Conclusion: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV., Trial Registration: The study was registered at Clinicaltrials.gov, NCT01601223., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: To examine whether venoarterial extracorporeal membrane oxygenation (VA-ECMO) improves survival of patients with acute pulmonary embolism (PE)., Methods: Following the PRISMA guidelines, a systematic search was conducted up to August 2019 of the databases: PubMed/MEDLINE, EMBASE and Cochrane. All studies reporting the survival of adult patients with acute PE treated with VA-ECMO and including four patients or more were included. Exclusion criteria were: correspondences, reviews and studies in absence of a full text, written in other languages than English or Dutch, or dating before 1980. Short-term (hospital or 30-day) survival data were pooled and presented with relative risks (RR) and 95% confidence intervals (95% CI). Also, the following pre-defined factors were evaluated for their association with survival in VA-ECMO treated patients: age > 60 years, male sex, pre-ECMO cardiac arrest, surgical embolectomy, catheter directed therapy, systemic thrombolysis, and VA-ECMO as single therapy., Results: A total of 29 observational studies were included (N = 1947 patients: VA-ECMO N = 1138 and control N = 809). There was no difference in short-term survival between VA-ECMO treated patients and control patients (RR 0.91, 95% CI 0.71-1.16). In acute PE patients undergoing VA-ECMO, age > 60 years was associated with lower survival (RR 0.72, 95% CI 0.52-0.99), surgical embolectomy was associated with higher survival (RR 1.96, 95% CI 1.39-2.76) and pre-ECMO cardiac arrest showed a trend toward lower survival (RR 0.88, 95% CI 0.77-1.01). The other evaluated factors were not associated with a difference in survival., Conclusions: At present, there is insufficient evidence that VA-ECMO treatment improves short-term survival of acute PE patients. Low quality evidence suggest that VA-ECMO patients aged ≤60 years or who received SE have higher survival rates. Considering the limited evidence derived from the present data, this study emphasizes the need for prospective studies., Protocol Registration: PROSPERO CRD42019120370., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Anaemia is frequently recorded during preoperative screening and has been suggested to affect outcomes after surgery negatively., Objectives: The objectives were to assess the frequency of moderate to severe anaemia and its association with length of hospital stay., Design: Post hoc analysis of the international observational prospective 'Local ASsessment of VEntilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study., Patients and Setting: The current analysis included adult patients requiring general anaesthesia for non-cardiac surgery. Preoperative anaemia was defined as a haemoglobin concentration of 11 g dl-1 or lower, thus including moderate and severe anaemia according to World Health Organisation criteria., Main Outcome Measures: The primary outcome was length of hospital stay. Secondary outcomes included hospital mortality, intra-operative adverse events and postoperative pulmonary complications (PPCs)., Results: Haemoglobin concentrations were available for 8264 of 9864 patients. Preoperative moderate to severe anaemia was present in 7.7% of patients. Multivariable analysis showed that preoperative moderate to severe anaemia was associated with an increased length of hospital stay with a mean difference of 1.3 ((95% CI 0.8 to 1.8) days; P < .001). In the propensity-matched analysis, this association remained present, median 4.0 [IQR 1.0 to 5.0] vs. 2.0 [IQR 0.0 to 5.0] days, P = .001. Multivariable analysis showed an increased in-hospital mortality (OR 2.9 (95% CI 1.1 to 7.5); P  = .029), and higher incidences of intra-operative hypotension (36.3 vs. 25.3%; P < .001) and PPCs (17.1 vs. 10.5%; P = .001) in moderately to severely anaemic patients. However, this was not confirmed in the propensity score-matched analysis., Conclusions: In this international cohort of non-cardiac surgical patients, preoperative moderate to severe anaemia was associated with a longer duration of hospital stay but not increased intra-operative complications, PPCs or in-hospital mortality., Trial Registration: The LAS VEGAS study was registered at Clinicaltrials.gov, NCT01601223., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: Intraoperative hypotension, with varying definitions in literature, may be associated with postoperative complications. The aim of this meta-analysis was to assess the association of intraoperative hypotension with postoperative morbidity and mortality., Methods: MEDLINE, Embase and Cochrane databases were searched for studies published between January 1990 and August 2018. The primary endpoints were postoperative overall morbidity and mortality. Secondary endpoints were postoperative cardiac outcomes, acute kidney injury, stroke, delirium, surgical outcomes and combined outcomes. Subgroup analyses, sensitivity analyses and a meta-regression were performed to test the robustness of the results and to explore heterogeneity., Results: The search identified 2931 studies, of which 29 were included in the meta-analysis, consisting of 130 862 patients. Intraoperative hypotension was associated with an increased risk of morbidity (odds ratio (OR) 2.08, 95 per cent confidence interval 1.56 to 2.77) and mortality (OR 1.94, 1.32 to 2.84). In the secondary analyses, intraoperative hypotension was associated with cardiac complications (OR 2.44, 1.52 to 3.93) and acute kidney injury (OR 2.69, 1.31 to 5.55). Overall heterogeneity was high, with an I2 value of 88 per cent. When hypotension severity, outcome severity and study population variables were added to the meta-regression, heterogeneity was reduced to 50 per cent., Conclusion: Intraoperative hypotension during non-cardiac surgery is associated with postoperative cardiac and renal morbidity, and mortality. A universally accepted standard definition of hypotension would facilitate further research into this topic., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Objectives: Previous studies demonstrated that extensive fluid loading and consequently positive fluid balances during sepsis resuscitation are associated with adverse outcome. Yet, the association between fluid balance and mortality after reversal of shock, that is, during deresuscitation, is largely unappreciated. Our objective was to investigate the effects of fluid balance on mortality in the days after septic shock reversal., Design: Retrospective observational cohort study., Setting: ICUs of two university-affiliated hospitals in The Netherlands., Patients: Adult patients admitted with septic shock followed by shock reversal. Reversal of septic shock was defined based on Sepsis-3 criteria as the first day that serum lactate was less than or equal to 2 mmol/L without vasopressor requirement., Interventions: None., Measurements and Main Results: Reversal of septic shock occurred in 636 patients, of whom 20% died in the ICU. Mixed-effects logistic regression modeling, adjusted for possible confounders, showed that fluid balance in the days after reversal of septic shock (until discharge or death) was an independent predictor of ICU mortality: odds ratio 3.18 (1.90-5.32) per 10 mL/kg increase in daily fluid balance. Similar results were found for 30-day, 90-day, hospital, and 1-year mortality: odds ratios 2.09 (1.64-2.67); 1.79 (1.38-2.32); 1.70 (1.40-2.07); and 1.53 (1.17-2.01), respectively. Positive cumulative fluid balances vs. neutral or negative fluid balances on the final day in the ICU were associated with increased ICU, hospital, 30-day, and 90-day mortality: odds ratios 3.46 (2.29-5.23); 3.39 (2.35-4.9); 5.33 (3.51-8.08); and 3.57 (2.49-5.12), respectively. Using restricted cubic splines, we found a dose-response relationship between cumulative fluid balance after shock reversal and ICU mortality., Conclusions: A higher fluid balance in the days after septic shock reversal was associated with increased mortality. This stresses the importance of implementing restrictive and deresuscitative fluid management strategies after initial hemodynamic resuscitation. Prospective interventional studies are needed to confirm our results., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Pulmonary hypercoagulopathy is intrinsic to inhalation trauma. Nebulized heparin could theoretically be beneficial in patients with inhalation injury, but current data are conflicting. We aimed to investigate the safety, feasibility, and effectiveness of nebulized heparin., Methods: International multicenter, double-blind, placebo-controlled randomized clinical trial in specialized burn care centers. Adult patients with inhalation trauma received nebulizations of unfractionated heparin (25,000 international unit (IU), 5 mL) or placebo (0.9% NaCl, 5 mL) every four hours for 14 days or until extubation. The primary outcome was the number of ventilator-free days at day 28 post-admission. Here, we report on the secondary outcomes related to safety and feasibility., Results: The study was prematurely stopped after inclusion of 13 patients (heparin N = 7, placebo N = 6) due to low recruitment and high costs associated with the trial medication. Therefore, no analyses on effectiveness were performed. In the heparin group, serious respiratory problems occurred due to saturation of the expiratory filter following nebulizations. In total, 129 out of 427 scheduled nebulizations were withheld in the heparin group (in 3 patients) and 45 out of 299 scheduled nebulizations were withheld in the placebo group (in 2 patients). Blood-stained sputum or expected increased bleeding risks were the most frequent reasons to withhold nebulizations., Conclusion: In this prematurely stopped trial, we encountered important safety and feasibility issues related to frequent heparin nebulizations in burn patients with inhalation trauma. This should be taken into account when heparin nebulizations are considered in these patients., Competing Interests: The authors declare no conflict of interest.

Background: Anemia of inflammation (AI) is the most common cause of anemia in the critically ill, but its diagnosis is a challenge. New therapies specific to AI are in development, and they require accurate detection of AI. This study explores the potential of parameters of iron metabolism for the diagnosis of AI during an ICU stay., Methods: In a nested case-control study, 30 patients developing AI were matched to 60 controls. The iron parameters were determined in plasma samples during an ICU stay. Receiver operating characteristic curves were used to determine the iron parameter threshold with the highest sensitivity and specificity to predict AI. Likelihood ratios as well as positive and negative predictive values were calculated as well., Results: The sensitivity of iron parameters for diagnosing AI ranges between 62 and 76%, and the specificity between 57 and 72%. Iron and transferrin show the greatest area under the curve. Iron shows the highest sensitivity, and transferrin and transferrin saturation display the highest specificity. Hepcidin and ferritin show the lowest specificity. At an actual anemia prevalence of 53%, the diagnostic accuracy of iron, transferrin, and transferrin saturation was fair, with a positive predictive value between 71 and 73%. Combining iron, transferrin, transferrin saturation, hepcidin, and/or ferritin levels did not increase the accuracy of the AI diagnosis., Conclusions: In this explorative study on the use of different parameters of iron metabolism for diagnosing AI during an ICU stay, low levels of commonly measured markers such as plasma iron, transferrin, and transferrin saturation have the highest sensitivity and specificity and outperform ferritin and hepcidin., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2019 by S. Karger AG, Basel.)

Introduction: Acute respiratory distress syndrome (ARDS) is characterized by acute, diffuse, inflammatory lung injury leading to increased pulmonary vascular permeability, pulmonary oedema and loss of aerated tissue. Previous literature showed that restrictive fluid therapy in ARDS shortens time on mechanical ventilation and length of ICU-stay. However, the effect of intravenous fluid use on mortality remains uncertain. We investigated the relationship between cumulative fluid balance (FB), time on mechanical ventilation and mortality in ARDS patients., Materials and Methods: Retrospective observational study. Patients were divided in four cohorts based on cumulative FB on day 7 of ICU-admission: ≤0 L (Group I); 0-3.5 L (Group II); 3.5-8 L (Group III) and ≥8 L (Group IV). In addition, we used cumulative FB on day 7 as continuum as a predictor of mortality. Primary outcomes were 28-day mortality and ventilator-free days. Secondary outcomes were 90-day mortality and ICU length of stay., Results: Six hundred ARDS patients were included, of whom 156 (26%) died within 28 days. Patients with a higher cumulative FB on day 7 had a longer length of ICU-stay and fewer ventilator-free days on day 28. Furthermore, after adjusting for severity of illness, a higher cumulative FB was associated with 28-day mortality (Group II, adjusted OR (aOR) 2.1 [1.0-4.6], p = 0.045; Group III, aOR 3.3 [1.7-7.2], p = 0.001; Group IV, aOR 7.9 [4.0-16.8], p<0.001). Using restricted cubic splines, a non-linear dose-response relationship between cumulative FB and probability of death at day 28 was found; where a more positive FB predicted mortality and a negative FB showed a trend towards survival., Conclusions: A higher cumulative fluid balance is independently associated with increased risk of death, longer time on mechanical ventilation and longer length of ICU-stay in patients with ARDS. This underlines the importance of implementing restrictive fluid therapy in ARDS patients., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Deep neuromuscular blockade (NMB) can improve surgical conditions and possibly pain after low-risk laparoscopic surgery. We hypothesized that targeting a deep level of NMB by a continuous compared with an on-demand infusion of rocuronium could improve surgical conditions in patients undergoing thoraco-laparoscopic esophagectomy., Methods: In this single-centre, randomized-controlled, double-blind trial, patients received either a continuous infusion of rocuronium 0.6 mg·kg -1 ·hr -1 (intervention) or NaCl 0.9% (control). Both surgeon and anesthesiologist were blinded to group assignment and the train-of-four measurements. Open-label rocuronium was given if requested (i.e., on-demand) by the surgeon. At the end of surgery, sugammadex was given if necessary to reverse the NMB. The primary outcome was the quality of surgical conditions during the abdominal phase of the operation as measured by the surgical rating scale (SRS). Secondary outcomes included the thoracic SRS, number of on-demand boluses, intraoperative surgical events, pain scores (up to 12 hr postoperatively), and duration of surgery., Results: The median [interquartile range] abdominal SRS was not different between the intervention (4 [4-5]) and control (4 [4-5]) groups (median difference, 0; 95% confidence interval, 0 to 0; P = 0.45). The thoracic SRS was 4 [4-4] in both groups (P = 0.23). The median number of rocuronium bolus requests was higher in the control group compared with the intervention group (3 [3-6] vs 1 [0-2], respectively; P < 0.01). There were no between-group differences in intraoperative surgical events (P = 0.05), pain scores (overall P > 0.05), or duration of surgery (P = 0.95)., Conclusions: Continuous rocuronium infusion did not improve surgical conditions when boluses of rocuronium were available on-demand. No major benefits in other outcomes were seen., Trial Registration: EUDRACT (2014-002147-18); registered 19 May, 2014 and clinicaltrials.gov (NCT02320734); registered 18 December, 2014.

Importance: It remains uncertain whether invasive ventilation should use low tidal volumes in critically ill patients without acute respiratory distress syndrome (ARDS)., Objective: To determine whether a low tidal volume ventilation strategy is more effective than an intermediate tidal volume strategy., Design, Setting, and Participants: A randomized clinical trial, conducted from September 1, 2014, through August 20, 2017, including patients without ARDS expected to not be extubated within 24 hours after start of ventilation from 6 intensive care units in the Netherlands., Interventions: Invasive ventilation using low tidal volumes (n = 477) or intermediate tidal volumes (n = 484)., Main Outcomes and Measures: The primary outcome was the number of ventilator-free days and alive at day 28. Secondary outcomes included length of ICU and hospital stay; ICU, hospital, and 28- and 90-day mortality; and development of ARDS, pneumonia, severe atelectasis, or pneumothorax., Results: In total, 961 patients (65% male), with a median age of 68 years (interquartile range [IQR], 59-76), were enrolled. At day 28, 475 patients in the low tidal volume group had a median of 21 ventilator-free days (IQR, 0-26), and 480 patients in the intermediate tidal volume group had a median of 21 ventilator-free days (IQR, 0-26) (mean difference, -0.27 [95% CI, -1.74 to 1.19]; P = .71). There was no significant difference in ICU (median, 6 vs 6 days; 0.39 [-1.09 to 1.89]; P = .58) and hospital (median, 14 vs 15 days; -0.60 [-3.52 to 2.31]; P = .68) length of stay or 28-day (34.9% vs 32.1%; hazard ratio [HR], 1.12 [0.90 to 1.40]; P = .30) and 90-day (39.1% vs 37.8%; HR, 1.07 [0.87 to 1.31]; P = .54) mortality. There was no significant difference in the percentage of patients developing the following adverse events: ARDS (3.8% vs 5.0%; risk ratio [RR], 0.86 [0.59 to 1.24]; P = .38), pneumonia (4.2% vs 3.7%; RR, 1.07 [0.78 to 1.47]; P = .67), severe atelectasis (11.4% vs 11.2%; RR, 1.00 [0.81 to 1.23]; P = .94), and pneumothorax (1.8% vs 1.3%; RR, 1.16 [0.73 to 1.84]; P = .55)., Conclusions and Relevance: In patients in the ICU without ARDS who were expected not to be extubated within 24 hours of randomization, a low tidal volume strategy did not result in a greater number of ventilator-free days than an intermediate tidal volume strategy., Trial Registration: ClinicalTrials.gov Identifier: NCT02153294.

Objectives: This study aims at identifying factors that disciplines consider when diagnosing and reporting transfusion-associated circulatory overload ('TACO')., Background: TACO is a clinical diagnosis based mainly on subjective factors. Therefore, TACO could be an underreported complication of blood transfusion., Methods: A survey was conducted among critical care physicians, anaesthesiologists, haematologists, transfusion medicine physicians and haemovigilance officers using case vignettes and a questionnaire. Factors that may affect diagnosing TACO were investigated using conjoint analysis. A positive B-coefficient indicates a positive preference for diagnosing TACO. Participants rated factors influencing reporting TACO on a 0- to 100-point scale., Results: One hundred and seven surveys were returned (62%). Vignettes showed preferences in favour of diagnosing TACO with the onset of symptoms within 2 h [β 0·4(-0·1-1·0)], positive fluid balance [β 0·9(0·4-1·5)] and history of renal failure [β 0·6(0·1-1·2)]. Compared with transfusion of a single unit of red blood cells (RBC), respondents showed a preference for diagnosing TACO following a single unit of solvent/detergent (S/D) plasma or pooled platelet concentrate (PPC) [β 0·3(-0·2-0·7) resp. 0·5(-0·1-1·2)]. Multiple transfusion (6 RBC + 4 S/D plasma) was a strong preference for diagnosing TACO compared to 1 RBC and 1 S/D plasma [β 0·3(-0·8-1·3)]. Respondents did not fully take into account new hypertension and tachycardia when reporting TACO [median 70 (IQR 50-80) resp. 60 (IQR 50-80)]. No differences were observed between disciplines involved., Conclusion: When diagnosing and reporting TACO, physicians and haemovigilance officers do consider known risk factors for TACO. Reporting could be improved by increasing the awareness of haemodynamic variables in future education programmes., (© 2017 British Blood Transfusion Society.)

Aims: Mechanical ventilation practices in patients with cardiac arrest are not well described. Also, the effect of temperature on mechanical ventilation settings is not known. The aims of this study were 1) to describe practice of mechanical ventilation and its relation with outcome 2) to determine effects of different target temperatures strategies (33 °C versus 36 °C) on mechanical ventilation settings., Methods: This is a substudy of the TTM-trial in which unconscious survivors of a cardiac arrest due to a cardiac cause were randomized to two TTM strategies, 33 °C (TTM33) and 36 °C (TTM36). Mechanical ventilation data were obtained at three time points: 1) before TTM; 2) at the end of TTM (before rewarming) and 3) after rewarming. Logistic regression was used to determine an association between mechanical ventilation variables and outcome. Repeated-measures mixed modelling was performed to determine the effect of TTM on ventilation settings., Results: Mechanical ventilation data was available for 567 of the 950 TTM patients. Of these, 81% was male with a mean (SD) age of 64 (12) years. At the end of TTM median tidal volume was 7.7 ml/kg predicted body weight (PBW)(6.4-8.7) and 60% of patients were ventilated with a tidal volume ≤ 8 ml/kg PBW. Median PEEP was 7.7cmH 2 O (6.4-8.7) and mean driving pressure was 14.6 cmH 2 O (±4.3). The median FiO 2 fraction was 0.35 (0.30-0.45). Multivariate analysis showed an independent relationship between increased respiratory rate and 28-day mortality. TTM33 resulted in lower end-tidal CO 2 (Pgroup = 0.0003) and higher alveolar dead space fraction (Pgroup = 0.003) compared to TTM36, while PCO 2 levels and respiratory minute volume were similar between groups., Conclusions: In the majority of the cardiac arrest patients, protective ventilation settings are applied, including low tidal volumes and driving pressures. High respiratory rate was associated with mortality. TTM33 results in lower end-tidal CO 2 levels and a higher alveolar dead space fraction compared to TTTM36., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Anemia occurring as a result of inflammatory processes (anemia of inflammation, AI) has a high prevalence in critically ill patients. Knowledge on changes in iron metabolism during the course of AI is limited, hampering the development of strategies to counteract AI. This case control study aimed to investigate iron metabolism during the development of AI in critically ill patients., Methods: Iron metabolism in 30 patients who developed AI during ICU stay was compared with 30 septic patients with a high Hb and 30 non-septic patients with a high Hb. Patients were matched on age and sex. Longitudinally collected plasma samples were analyzed for levels of parameters of iron metabolism. A linear mixed model was used to assess the predictive values of the parameters., Results: In patients with AI, levels of iron, transferrin and transferrin saturation showed an early decrease compared to controls with a high Hb, already prior to the development of anemia. Ferritin, hepcidin and IL-6 levels were increased in AI compared to controls. During AI development, erythroferrone decreased. Differences in iron metabolism between groups were not influenced by APACHE IV score., Conclusions: The results show that in critically ill patients with AI, iron metabolism is already altered prior to the development of anemia. Levels of iron regulators in AI differ from septic controls with a high Hb, irrespective of disease severity. AI is characterized by high levels of hepcidin, ferritin and IL-6 and low levels of iron, transferrin and erythroferrone.