Invasive mechanical ventilation in patients with acute respiratory distress syndrome receiving extracorporeal support: a narrative review of strategies to mitigate lung injury.

Veno-venous extracorporeal membrane oxygenation is indicated in patients with acute respiratory distress syndrome and severely impaired gas exchange despite evidence-based lung protective ventilation, prone positioning and other parts of the standard algorithm for treating such patients. Extracorporeal support can facilitate ultra-lung-protective ventilation, meaning even lower volumes and pressures than standard lung-protective ventilation, by directly removing carbon dioxide in patients needing injurious ventilator settings to maintain sufficient gas exchange. Injurious ventilation results in ventilator-induced lung injury, which is one of the main determinants of mortality in acute respiratory distress syndrome. Marked reductions in the intensity of ventilation to the lowest tolerable levels under extracorporeal support may be achieved and could thereby potentially mitigate ventilator-induced lung injury and theoretically patient self-inflicted lung injury in spontaneously breathing patients with high respiratory drive. However, the benefits of this strategy may be counterbalanced by the use of continuous deep sedation and even neuromuscular blocking drugs, which may impair physical rehabilitation and impact long-term outcomes. There are currently a lack of large-scale prospective data to inform optimal invasive ventilation practices and how to best apply a holistic approach to patients receiving veno-venous extracorporeal membrane oxygenation, while minimising ventilator-induced and patient self-inflicted lung injury. We aimed to review the literature relating to invasive ventilation strategies in patients with acute respiratory distress syndrome receiving extracorporeal support and discuss personalised ventilation approaches and the potential role of adjunctive therapies in facilitating lung protection.

How doctors actually (do not) involve families in decisions to continue or discontinue life-sustaining treatment in neonatal, pediatric, and adult intensive care: A qualitative study.

BACKGROUND: Intensive care doctors have to find the right balance between sharing crucial decisions with families of patients on the one hand and not overburdening them on the other hand. This requires a tailored approach instead of a model based approach. AIM: To explore how doctors involve families in the decision-making process regarding life-sustaining treatment on the neonatal, pediatric, and adult intensive care. DESIGN: Exploratory inductive thematic analysis of 101 audio-recorded conversations. SETTING/PARTICIPANTS: One hundred four family members (61% female, 39% male) and 71 doctors (60% female, 40% male) of 36 patients (53% female, 47% male) from the neonatal, pediatric, and adult intensive care of a large university medical center participated. RESULTS: We identified eight relevant and distinct communicative behaviors. Doctors' sequential communicative behaviors either reflected consistent approaches-a shared approach or a physician-driven approach-or reflected vacillating between both approaches. Doctors more often displayed a physician-driven or a vacillating approach than a shared approach, especially in the adult intensive care. Doctors did not verify whether their chosen approach matched the families' decision-making preferences. CONCLUSIONS: Even though tailoring doctors' communication to families' preferences is advocated, it does not seem to be integrated into actual practice. To allow for true tailoring, doctors' awareness regarding the impact of their communicative behaviors is key. Educational initiatives should focus especially on improving doctors' skills in tactfully exploring families' decision-making preferences and in mutually sharing knowledge, values, and treatment preferences.

Effect of an individualized versus standard pneumoperitoneum pressure strategy on postoperative recovery: a randomized clinical trial in laparoscopic colorectal surgery.

BACKGROUND: It remains uncertain whether individualization of pneumoperitoneum pressures during laparoscopic surgery improves postoperative recovery. This study compared an individualized pneumoperitoneum pressure (IPP) strategy with a standard pneumoperitoneum pressure (SPP) strategy with respect to postoperative recovery after laparoscopic colorectal surgery. METHODS: This was a multicentre RCT. The IPP strategy comprised modified patient positioning, deep neuromuscular blockade, and abdominal wall prestretching targeting the lowest intra-abdominal pressure (IAP) that maintained acceptable workspace. The SPP strategy comprised patient positioning according to the surgeon's preference, moderate neuromuscular blockade and a fixed IAP of 12 mmHg. The primary endpoint was physiological postoperative recovery, assessed by means of the Postoperative Quality of Recovery Scale. Secondary endpoints included recovery in other domains and overall recovery, the occurrence of intraoperative and postoperative complications, duration of hospital stay, and plasma markers of inflammation up to postoperative day 3. RESULTS: Of 166 patients, 85 received an IPP strategy and 81 an SPP strategy. The IPP strategy was associated with a higher probability of physiological recovery (odds ratio (OR) 2·77, 95 per cent c.i. 1·19 to 6·40, P = 0·017; risk ratio (RR) 1·82, 1·79 to 1·87, P = 0·049). The IPP strategy was also associated with a higher probability of emotional (P = 0·013) and overall (P = 0·011) recovery. Intraoperative adverse events were less frequent with the IPP strategy (P < 0·001) and the plasma neutrophil-lymphocyte ratio was lower (P = 0·029). Other endpoints were not affected. CONCLUSION: In this cohort of patients undergoing laparoscopic colorectal surgery, an IPP strategy was associated with faster recovery, fewer intraoperative complications and less inflammation than an SPP strategy. Registration number: NCT02773173 ( http://www.clinicaltrials.gov).

ANTECEDENTES: No se sabe con certeza si individualizar las presiones del neumoperitoneo durante la cirugía laparoscópica mejora la recuperación postoperatoria. Comparamos una estrategia con individualización de la presión del neumoperitoneo (individualised pneumoperitoneum pressure, IPP) frente a una estrategia con presión estándar del neumoperitoneo (standard pneumoperitoneum pressure, SPP) respecto a la recuperación postoperatoria tras cirugía colorrectal laparoscópica. MÉTODOS: Ensayo clínico aleatorizado multicéntrico. La estrategia IPP consistió en una modificación de la posición, bloqueo neuromuscular profundo, y una distensión de la pared abdominal conseguida con la presión intraabdominal (intra-abdominal pressure, IAP) más baja en la que el espacio quirúrgico operativo siguiera siendo aceptable. La estrategia SPP consistió en una posición de acuerdo con la preferencia del cirujano, bloqueo neuromuscular moderado, e IAP fija de 12 mm Hg. El resultado primario fue la recuperación fisiológica postoperatoria, evaluada mediante la escala de calidad en la recuperación postoperatoria (Postoperative Quality of Recovery Scale, PQRS). Los resultados secundarios incluyeron la recuperación en otros dominios y la recuperación global, la aparición de complicaciones intraoperatorias y postoperatorias, duración de la estancia hospitalaria, y los valores de los marcadores inflamatorios séricos durante tres días postoperatorios. RESULTADOS: De un total de 166 pacientes, 85 recibieron una estrategia IPP y 81 una estrategia SPP. La estrategia IPP se asoció con una elevada probabilidad de recuperación fisiológica (razón de oportunidades, odds ratio OR, 2,8 (i.c. del 95% 1,2-6,4); P = 0,017, razón de riesgo, 1,8 (i.c. del 95% 1,7-1,9), P = 0,05)). La estrategia IPP también se asoció con una elevada probabilidad de recuperación emotiva (P = 0,013) y global (P = 0,011). Los eventos adversos intraoperatorios fueron menos frecuentes con la estrategia IPP (P < 0,001) y la tasa neutrófilo-linfocito fue más baja (P = 0,029). No se observaron cambios en otras variables. CONCLUSIÓN: En esta cohorte de pacientes sometidos a cirugía colorrectal laparoscópica, una estrategia IPP se asoció con una recuperación más rápida, menos complicaciones intraoperatorias y menos inflamación en comparación con una estrategia SPP.

Association between night-time surgery and occurrence of intraoperative adverse events and postoperative pulmonary complications.

BACKGROUND: The aim of this post hoc analysis of a large cohort study was to evaluate the association between night-time surgery and the occurrence of intraoperative adverse events (AEs) and postoperative pulmonary complications (PPCs). METHODS: LAS VEGAS (Local Assessment of Ventilatory Management During General Anesthesia for Surgery) was a prospective international 1-week study that enrolled adult patients undergoing surgical procedures with general anaesthesia and mechanical ventilation in 146 hospitals across 29 countries. Surgeries were defined as occurring during 'daytime' when induction of anaesthesia was between 8:00 AM and 7:59 PM, and as 'night-time' when induction was between 8:00 PM and 7:59 AM. RESULTS: Of 9861 included patients, 555 (5.6%) underwent surgery during night-time. The proportion of patients who developed intraoperative AEs was higher during night-time surgery in unmatched (43.6% vs 34.1%; P<0.001) and propensity-matched analyses (43.7% vs 36.8%; P=0.029). PPCs also occurred more often in patients who underwent night-time surgery (14% vs 10%; P=0.004) in an unmatched cohort analysis, although not in a propensity-matched analysis (13.8% vs 11.8%; P=0.39). In a multivariable regression model, including patient characteristics and types of surgery and anaesthesia, night-time surgery was independently associated with a higher incidence of intraoperative AEs (odds ratio: 1.44; 95% confidence interval: 1.09-1.90; P=0.01), but not with a higher incidence of PPCs (odds ratio: 1.32; 95% confidence interval: 0.89-1.90; P=0.15). CONCLUSIONS: Intraoperative adverse events and postoperative pulmonary complications occurred more often in patients undergoing night-time surgery. Imbalances in patients' clinical characteristics, types of surgery, and intraoperative management at night-time partially explained the higher incidence of postoperative pulmonary complications, but not the higher incidence of adverse events. CLINICAL TRIAL REGISTRATION: NCT01601223.

Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial.

Importance: An intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain. Objective: To determine whether a higher level of PEEP with alveolar recruitment maneuvers decreases postoperative pulmonary complications in obese patients undergoing surgery compared with a lower level of PEEP. Design, Setting, and Participants: Randomized clinical trial of 2013 adults with body mass indices of 35 or greater and substantial risk for postoperative pulmonary complications who were undergoing noncardiac, nonneurological surgery under general anesthesia. The trial was conducted at 77 sites in 23 countries from July 2014-February 2018; final follow-up: May 2018. Interventions: Patients were randomized to the high level of PEEP group (n = 989), consisting of a PEEP level of 12 cm H2O with alveolar recruitment maneuvers (a stepwise increase of tidal volume and eventually PEEP) or to the low level of PEEP group (n = 987), consisting of a PEEP level of 4 cm H2O. All patients received volume-controlled ventilation with a tidal volume of 7 mL/kg of predicted body weight. Main Outcomes and Measures: The primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including respiratory failure, acute respiratory distress syndrome, bronchospasm, new pulmonary infiltrates, pulmonary infection, aspiration pneumonitis, pleural effusion, atelectasis, cardiopulmonary edema, and pneumothorax. Among the 9 prespecified secondary outcomes, 3 were intraoperative complications, including hypoxemia (oxygen desaturation with Spo2 ≤92% for >1 minute). Results: Among 2013 adults who were randomized, 1976 (98.2%) completed the trial (mean age, 48.8 years; 1381 [69.9%] women; 1778 [90.1%] underwent abdominal operations). In the intention-to-treat analysis, the primary outcome occurred in 211 of 989 patients (21.3%) in the high level of PEEP group compared with 233 of 987 patients (23.6%) in the low level of PEEP group (difference, -2.3% [95% CI, -5.9% to 1.4%]; risk ratio, 0.93 [95% CI, 0.83 to 1.04]; P = .23). Among the 9 prespecified secondary outcomes, 6 were not significantly different between the high and low level of PEEP groups, and 3 were significantly different, including fewer patients with hypoxemia (5.0% in the high level of PEEP group vs 13.6% in the low level of PEEP group; difference, -8.6% [95% CI, -11.1% to 6.1%]; P < .001). Conclusions and Relevance: Among obese patients undergoing surgery under general anesthesia, an intraoperative mechanical ventilation strategy with a higher level of PEEP and alveolar recruitment maneuvers, compared with a strategy with a lower level of PEEP, did not reduce postoperative pulmonary complications. Trial Registration: ClinicalTrials.gov Identifier: NCT02148692.

The fragility of statistically significant findings in randomised controlled anaesthesiology trials: systematic review of the medical literature.

The fragility index (FI), the number of events the statistical significance a result depends on, and the number of patients lost to follow-up are important parameters for interpreting randomised clinical trial results. We evaluated these two parameters in randomised controlled trials in anaesthesiology. For this, we performed a systematic search of the medical literature, seeking articles reporting on anaesthesiology trials with a statistically significant difference in the primary outcome and published in the top five general medicine journals, or the top 15 anaesthesiology journals. We restricted the analysis to trials reporting clinically important primary outcome measures. The search identified 139 articles, 35 published in general medicine journals and 104 in anaesthesiology journals. The median (inter-quartile range) sample size was 150 (70-300) patients. The FI was 4 (2-17) and 3 (2-7), and the number of patients lost to follow-up was 0 (0-18) and 0 (0-6) patients in trials published in general medicine and anaesthesiology journals, respectively. The number of patients lost to follow-up exceeded the FI in 41 and 27% in trials in general medicine journals and anaesthesiology journals, respectively. The FI positively correlated with sample size and number of primary outcome events, and negatively correlated with the reported P-values. The results of this systematic review suggest that statistically significant differences in randomised controlled anaesthesiology trials are regularly fragile, implying that the primary outcome status of patients lost to follow-up could possibly have changed the reported effect.

Intraoperative ventilation settings and their associations with postoperative pulmonary complications in obese patients.

BACKGROUND: There is limited information concerning the current practice of intraoperative mechanical ventilation in obese patients, and the optimal ventilator settings for these patients are debated. We investigated intraoperative ventilation parameters and their associations with the development of postoperative pulmonary complications (PPCs) in obese patients. METHODS: We performed a secondary analysis of the international multicentre Local ASsessment of VEntilatory management during General Anesthesia for Surgery' (LAS VEGAS) study, restricted to obese patients, with a predefined composite outcome of PPCs as primary end-point. RESULTS: We analysed 2012 obese patients from 135 hospitals across 29 countries in Europe, North America, North Africa, and the Middle East. Tidal volume was 8.8 [25th-75th percentiles: 7.8-9.9] ml kg-1 predicted body weight, PEEP was 4 [1-5] cm H2O, and recruitment manoeuvres were performed in 7.7% of patients. PPCs occurred in 11.7% of patients and were independently associated with age (P<0.001), body mass index ≥40 kg m-2 (P=0.033), obstructive sleep apnoea (P=0.002), duration of anaesthesia (P<0.001), peak airway pressure (P<0.001), use of rescue recruitment manoeuvres (P<0.05) and routine recruitment manoeuvres performed by bag squeezing (P=0.021). PPCs were associated with an increased length of hospital stay (P<0.001). CONCLUSIONS: Obese patients are frequently ventilated with high tidal volume and low PEEP, and seldom receive recruitment manoeuvres. PPCs increase hospital stay, and are associated with preoperative conditions, duration of anaesthesia and intraoperative ventilation settings. Randomised trials are warranted to clarify the role of different ventilatory parameters in obese patients. CLINICAL TRIAL REGISTRATION: NCT01601223.

A systematic review and consensus definitions for standardised end-points in perioperative medicine: pulmonary complications.

BACKGROUND: There is a need for robust, clearly defined, patient-relevant outcome measures for use in randomised trials in perioperative medicine. Our objective was to establish standard outcome measures for postoperative pulmonary complications research. METHODS: A systematic literature search was conducted using MEDLINE, Web of Science, SciELO, and the Korean Journal Database. Definitions were extracted from included manuscripts. We then conducted a three-stage Delphi consensus process to select the optimal outcome measures in terms of methodological quality and overall suitability for perioperative trials. RESULTS: From 2358 records, the full texts of 81 manuscripts were retrieved, of which 45 met the inclusion criteria. We identified three main categories of outcome measure specific to perioperative pulmonary outcomes: (i) composite outcome measures of multiple pulmonary outcomes (27 definitions); (ii) pneumonia (12 definitions); and (iii) respiratory failure (six definitions). These were rated by the group according to suitability for routine use. The majority of definitions were given a low score, and many were imprecise, difficult to apply consistently, or both, in large patient populations. A small number of highly rated definitions were identified as appropriate for widespread use. The group then recommended four outcome measures for future use, including one new definition. CONCLUSIONS: A large number of postoperative pulmonary outcome measures have been used, but most are poorly defined. Our four recommended outcome measures include a new definition of postoperative pulmonary complications, incorporating an assessment of severity. These definitions will meet the needs of most clinical effectiveness trials of treatments to improve postoperative pulmonary outcomes.

Variable versus conventional lung protective mechanical ventilation during open abdominal surgery (PROVAR): a randomised controlled trial.

BACKGROUND: Experimental studies showed that controlled variable ventilation (CVV) yielded better pulmonary function compared to non-variable ventilation (CNV) in injured lungs. We hypothesized that CVV improves intraoperative and postoperative respiratory function in patients undergoing open abdominal surgery. METHODS: Fifty patients planned for open abdominal surgery lasting >3 h were randomly assigned to receive either CVV or CNV. Mean tidal volumes and PEEP were set at 8 ml kg-1 (predicted body weight) and 5 cm H2O, respectively. In CVV, tidal volumes varied randomly, following a normal distribution, on a breath-by-breath basis. The primary endpoint was the forced vital capacity (FVC) on postoperative Day 1. Secondary endpoints were oxygenation, non-aerated lung volume, distribution of ventilation, and pulmonary and extrapulmonary complications until postoperative Day 5. RESULTS: FVC did not differ significantly between CVV and CNV on postoperative Day 1, 61.5 (standard deviation 22.1) % vs 61.9 (23.6) %, respectively; mean [95% confidence interval (CI)] difference, -0.4 (-13.2-14.0), P=0.95. Intraoperatively, CVV did not result in improved respiratory function, haemodynamics, or redistribution of ventilation compared to CNV. Postoperatively, FVC, forced expiratory volume at the first second (FEV1), and FEV1/FVC deteriorated, while atelectasis volume and plasma levels of interleukin-6 and interleukin-8 increased, but values did not differ between groups. The incidence of postoperative pulmonary and extrapulmonary complications was comparable in CVV and CNV. CONCLUSIONS: In patients undergoing open abdominal surgery, CVV did not improve intraoperative and postoperative respiratory function compared with CNV. CLINICAL TRIAL REGISTRATION: NCT 01683578.

Identification and validation of distinct biological phenotypes in patients with acute respiratory distress syndrome by cluster analysis.

RATIONALE: We hypothesised that patients with acute respiratory distress syndrome (ARDS) can be clustered based on concentrations of plasma biomarkers and that the thereby identified biological phenotypes are associated with mortality. METHODS: Consecutive patients with ARDS were included in this prospective observational cohort study. Cluster analysis of 20 biomarkers of inflammation, coagulation and endothelial activation provided the phenotypes in a training cohort, not taking any outcome data into account. Logistic regression with backward selection was used to select the most predictive biomarkers, and these predicted phenotypes were validated in a separate cohort. Multivariable logistic regression was used to quantify the independent association with mortality. RESULTS: Two phenotypes were identified in 454 patients, which we named 'uninflamed' (N=218) and 'reactive' (N=236). A selection of four biomarkers (interleukin-6, interferon gamma, angiopoietin 1/2 and plasminogen activator inhibitor-1) could be used to accurately predict the phenotype in the training cohort (area under the receiver operating characteristics curve: 0.98, 95% CI 0.97 to 0.99). Mortality rates were 15.6% and 36.4% (p<0.001) in the training cohort and 13.6% and 37.5% (p<0.001) in the validation cohort (N=207). The 'reactive phenotype' was independent from confounders associated with intensive care unit mortality (training cohort: OR 1.13, 95% CI 1.04 to 1.23; validation cohort: OR 1.18, 95% CI 1.06 to 1.31). CONCLUSIONS: Patients with ARDS can be clustered into two biological phenotypes, with different mortality rates. Four biomarkers can be used to predict the phenotype with high accuracy. The phenotypes were very similar to those found in cohorts derived from randomised controlled trials, and these results may improve patient selection for future clinical trials targeting host response in patients with ARDS.

Transient versus persistent acute kidney injury and the diagnostic performance of fractional excretion of urea in critically ill patients.

AIMS: To evaluate the performance of fractional excretion of urea (FeU) for differentiating transient (T) from persistent (P) acute kidney injury (AKI) and to assess performance of FeU in predicting AKI in patients admitted to the ICU. METHODS: We performed secondary analysis of a multicenter prospective observational cohort study on the predictive performance of biological markers for AKI in critically ill patients. AKI was diagnosed according to RIFLE staging. RESULTS: Of 150 patients, 51 and 41 patients were classified as having T-AKI and P-AKI, respectively. The diagnostic performance for FeU to discriminate T-AKI from P-AKI on the day of AKI was poor (AUC-ROC = 0.61; 95% CI: 0.49-0.73). The diagnostic performance of FeU to predict AKI 1 and 2 days prior to AKI was poor as well (AUC-ROC = 0.61; 95% CI: 0.47-0.74, and 0.58; 95% CI: 0.43-0.73, respectively). CONCLUSIONS: FeU does not seem to be helpful in differentiating T- from P-AKI in critically ill patients and it is a poor predictor of AKI.

Risk factors for PPCs in laparoscopic non-robotic vs. laparoscopic robotic abdominal surgery (LapRas): rationale and protocol for a patient-level analysis of LAS VEGAS and AVATaR.

INTRODUCTION: Postoperative pulmonary complications (PPCs) vary amongst different surgical techniques. We aim to compare the incidence of PPCs after laparoscopic non-robotic versus laparoscopic robotic abdominal surgery. METHODS AND ANALYSIS: LapRas (Risk Factors for PPCs in Laparoscopic Non-robotic vs Laparoscopic robotic abdominal surgery) incorporates harmonized data from 2 observational studies on abdominal surgery patients and PPCs: 'Local ASsessment of VEntilatory management during General Anaesthesia for Surgery' (LAS VEGAS), and 'Assessment of Ventilation during general AnesThesia for Robotic surgery' (AVATaR). The primary endpoint is the occurrence of one or more PPCs in the first five postoperative days. Secondary endpoints include the occurrence of each individual PPC, hospital length of stay and in-hospital mortality. Logistic regression models will be used to identify risk factors for PPCs in laparoscopic non-robotic versus laparoscopic robotic abdominal surgery. We will investigate whether differences in the occurrence of PPCs between the two groups are driven by differences in duration of anesthesia and/or the intensity of mechanical ventilation. ETHICS AND DISSEMINATION: This analysis will address a clinically relevant research question comparing laparoscopic and robotic assisted surgery. No additional ethical committee approval is required for this metanalysis. Data will be shared with the scientific community by abstracts and original articles submitted to peer-reviewed journals. REGISTRATION: The registration of this post-hoc analysis is pending; individual studies that were merged into the used database were registered at clinicaltrials.gov: LAS VEGAS with identifier NCT01601223, AVATaR with identifier NCT02989415.

Cardiopulmonary interactions during mechanical ventilation in critically ill patients.

Cardiopulmonary interactions induced by mechanical ventilation are complex and only partly understood. Applied tidal volumes and/or airway pressures largely mediate changes in right ventricular preload and afterload. Effects on left ventricular function are mostly secondary to changes in right ventricular loading conditions. It is imperative to dissect the several causes of haemodynamic compromise during mechanical ventilation as undiagnosed ventricular dysfunction may contribute to morbidity and mortality.

Basic concepts of fluid responsiveness.

Predicting fluid responsiveness, the response of stroke volume to fluid loading, is a relatively novel concept that aims to optimise circulation, and as such organ perfusion, while avoiding futile and potentially deleterious fluid administrations in critically ill patients. Dynamic parameters have shown to be superior in predicting the response to fluid loading compared with static cardiac filling pressures. However, in routine clinical practice the conditions necessary for dynamic parameters to predict fluid responsiveness are frequently not met. Passive leg raising as a means to alter biventricular preload in combination with subsequent measurement of the change in stroke volume can provide a fast and accurate way to guide fluid management in a broad population of critically ill patients.

Epidemiology, ventilation management and outcome in patients receiving intensive care after non-thoracic surgery - Insights from the LAS VEGAS study.

INTRODUCTION AND OBJECTIVES: Information about epidemiology, ventilation management and outcome in postoperative intensive care unit (ICU) patients remains scarce. The objective was to test whether postoperative ventilation differs from that in the operation room. MATERIAL AND METHODS: This was a substudy of the worldwide observational LAS VEGAS study, including patients undergoing non-thoracic surgeries. Of 146 study sites participating in the LAS VEGAS study, 117 (80%) sites reported on the postoperative ICU course, including ventilation and complications. The coprimary outcomes were two key elements of ventilator management, i.e., tidal volume (VT) and positive end-expiratory pressure (PEEP). Secondary outcomes included the proportion of patients receiving low VT ventilation (LTVV, defined as ventilation with a median VT < 8.0 ml/kg PBW), and the proportion of patients developing postoperative pulmonary complications (PPC), including ARDS, pneumothorax, pneumonia and need for escalation of ventilatory support, ICU and hospital length of stay, and mortality at day 28. RESULTS: Of 653 patients who were admitted to the ICU after surgery, 274 (42%) patients received invasive postoperative ventilation. Median postoperative VT was 8.4 [7.3-9.8] ml/kg predicted body weight (PBW), PEEP was 5 [5-5] cm H2O, statistically significant but not meaningfully different from median intraoperative VT (8.1 [7.3-8.9] ml/kg PBW; P < 0.001) and PEEP (4 [2-5] cm H2O; P < 0.001). The proportion of patients receiving LTVV after surgery was 41%. The PPC rate was 10%. Length of stay in ICU and hospital was independent of development of a PPC, but hospital mortality was higher in patients who developed a PPC (24 versus 4%; P < 0.001). CONCLUSIONS: In this observational study of patients undergoing non-thoracic surgeries, postoperative ventilation was not meaningfully different from that in the operating room. Like in the operating room, there is room for improved use of LTVV. Development of PPC is associated with mortality.

Hyperoxemia in invasively ventilated COVID-19 patients-Insights from the PRoVENT-COVID study.

OBJECTIVE: We determined the prevalences of hyperoxemia and excessive oxygen use, and the epidemiology, ventilation characteristics and outcomes associated with hyperoxemia in invasively ventilated patients with coronavirus disease 2019 (COVID-19). METHODS: Post hoc analysis of a national, multicentre, observational study in 22 ICUs. Patients were classified in the first two days of invasive ventilation as 'hyperoxemic' or 'normoxemic'. The co-primary endpoints were prevalence of hyperoxemia (PaO2 > 90 mmHg) and prevalence of excessive oxygen use (FiO2 ≥ 60% while PaO2 > 90 mmHg or SpO2 > 92%). Secondary endpoints included ventilator settings and ventilation parameters, duration of ventilation, length of stay (LOS) in ICU and hospital, and mortality in ICU, hospital, and at day 28 and 90. We used propensity matching to control for observed confounding factors that may influence endpoints. RESULTS: Of 851 COVID-19 patients, 225 (26.4%) were classified as hyperoxemic. Excessive oxygen use occurred in 385 (45.2%) patients. Acute respiratory distress syndrome (ARDS) severity was lowest in hyperoxemic patients. Hyperoxemic patients were ventilated with higher positive end-expiratory pressure (PEEP), while rescue therapies for hypoxemia were applied more often in normoxemic patients. Neither in the unmatched nor in the matched analysis were there differences between hyperoxemic and normoxemic patients with regard to any of the clinical outcomes. CONCLUSION: In this cohort of invasively ventilated COVID-19 patients, hyperoxemia occurred often and so did excessive oxygen use. The main differences between hyperoxemic and normoxemic patients were ARDS severity and use of PEEP. Clinical outcomes were not different between hyperoxemic and normoxemic patients.

Awake prone positioning in nonintubated spontaneous breathing ICU patients with acute hypoxemic respiratory failure (PRONELIFE)-protocol for a randomized clinical trial.

BACKGROUND: It is uncertain whether awake prone positioning can prevent intubation for invasive ventilation in spontaneous breathing critically ill patients with acute hypoxemic respiratory failure. Awake prone positioning could benefit these patients for various reasons, including a reduction in direct harm to lung tissue, and prevention of tracheal intubation-related complications. DESIGN AND METHODS: The PRONELIFE study is an investigator-initiated, international, multicenter, randomized clinical trial in patients who may need invasive ventilation because of acute hypoxemic respiratory failure. Consecutive patients admitted to participating ICUs are randomly assigned to standard care with awake prone positioning, versus standard care without awake prone positioning. The primary endpoint is a composite of tracheal intubation and all-cause mortality in the first 14 days after enrolment. Secondary endpoints include time to tracheal intubation and effects of awake prone positioning on oxygenation parameters, dyspnea sensation, and complications. Other endpoints are the number of days free from ventilation and alive at 28 days, total duration of use of noninvasive respiratory support, total duration of invasive ventilation, length of stay in ICU and hospital, and mortality in ICU and hospital, and at 28, 60, and 90 days. We will also collect data regarding the tolerance of prone positioning. DISCUSSION: The PRONELIFE study is among the first randomized clinical trials investigating the effect of awake prone positioning on intubation rate in ICU patients with acute hypoxemic failure from any cause. The PRONELIFE study is sufficiently sized to determine the effect of awake prone positioning on intubation for invasive ventilation-patients are eligible in case of acute hypoxemic respiratory failure without restrictions regarding etiology. The PRONELIFE study is a pragmatic trial in which blinding is impossible-however, as around 35 ICUs worldwide will participate in this study, its findings will be highly generalizable. The findings of the PRONELIFE study have the potential to change clinical management of patients who may need invasive ventilation because of acute hypoxemic respiratory failure. TRIAL REGISTRATION: ISRCTN ISRCTN11536318 . Registered on 17 September 2021. The PRONELIFE study is registered at clinicaltrials.gov with reference number NCT04142736 (October, 2019).

Practice of tracheostomy in patients with acute respiratory failure related to COVID-19 - Insights from the PRoVENT-COVID study.

OBJECTIVE: Invasively ventilated patients with acute respiratory failure related to coronavirus disease 2019 (COVID-19) potentially benefit from tracheostomy. The aim of this study was to determine the practice of tracheostomy during the first wave of the pandemic in 2020 in the Netherlands, to ascertain whether timing of tracheostomy had an association with outcome, and to identify factors that had an association with timing. METHODS: Secondary analysis of the 'PRactice of VENTilation in COVID-19' (PRoVENT-COVID) study, a multicenter observational study, conducted from March 1, 2020 through June 1, 2020 in 22 Dutch intensive care units (ICU) in the Netherlands. The primary endpoint was the proportion of patients receiving tracheostomy; secondary endpoints were timing of tracheostomy, duration of ventilation, length of stay in ICU and hospital, mortality, and factors associated with timing. RESULTS: Of 1023 patients, 189 patients (18.5%) received a tracheostomy at median 21 [17 to 28] days from start of ventilation. Timing was similar before and after online publication of an amendment to the Dutch national guidelines on tracheostomy focusing on COVID-19 patients (21 [17-28] vs. 21 [17-26] days). Tracheostomy performed ≤ 21 days was independently associated with shorter duration of ventilation (median 26 [21 to 32] vs. 40 [34 to 47] days) and higher mortality in ICU (22.1% vs. 10.2%), hospital (26.1% vs. 11.9%) and at day 90 (27.6% vs. 14.6%). There were no patient demographics or ventilation characteristics that had an association with timing of tracheostomy. CONCLUSIONS: Tracheostomy was performed late in COVID-19 patients during the first wave of the pandemic in the Netherlands and timing of tracheostomy possibly had an association with outcome. However, prospective studies are needed to further explore these associations. It remains unknown which factors influenced timing of tracheostomy in COVID-19 patients.

ICONIC study-conservative versus conventional oxygenation targets in intensive care patients: study protocol for a randomized clinical trial.

BACKGROUND: Oxygen therapy is a widely used intervention in acutely ill patients in the intensive care unit (ICU). It is established that not only hypoxia, but also prolonged hyperoxia is associated with poor patient-centered outcomes. Nevertheless, a fundamental knowledge gap remains regarding optimal oxygenation for critically ill patients. In this randomized clinical trial, we aim to compare ventilation that uses conservative oxygenation targets with ventilation that uses conventional oxygen targets with respect to mortality in ICU patients. METHODS: The "ConservatIve versus CONventional oxygenation targets in Intensive Care patients" trial (ICONIC) is an investigator-initiated, international, multicenter, randomized clinical two-arm trial in ventilated adult ICU patients. The ICONIC trial will run in multiple ICUs in The Netherlands and Italy to enroll 1512 ventilated patients. ICU patients with an expected mechanical ventilation time of more than 24 h are randomized to a ventilation strategy that uses conservative (PaO2 55-80 mmHg (7.3-10.7 kPa)) or conventional (PaO2 110-150 mmHg (14.7-20 kPa)) oxygenation targets. The primary endpoint is 28-day mortality. Secondary endpoints are ventilator-free days at day 28, ICU mortality, in-hospital mortality, 90-day mortality, ICU- and hospital length of stay, ischemic events, quality of life, and patient opinion of research and consent in the emergency setting. DISCUSSION: The ICONIC trial is expected to provide evidence on the effects of conservative versus conventional oxygenation targets in the ICU population. This study may guide targeted oxygen therapy in the future. TRIAL REGISTRATION: Trialregister.nl NTR7376 . Registered on 20 July, 2018.

Pre-clinical validation of a turbine-based ventilator for invasive ventilation-The ACUTE-19 ventilator.

BACKGROUND: The Severe Acute Respiratory Syndrome (SARS)-Coronavirus 2 (CoV-2) pandemic pressure on healthcare systems can exhaust ventilator resources, especially where resources are restricted. Our objective was a rapid preclinical evaluation of a newly developed turbine-based ventilator, named the ACUTE-19, for invasive ventilation. METHODS: Validation consisted of (a) testing tidal volume (VT) delivery in 11 simulated models, with various resistances and compliances; (b) comparison with a commercial ventilator (VIVO-50) adapting the United Kingdom Medicines and Healthcare products Regulatory Agency-recommendations for rapidly manufactured ventilators; and (c) in vivo testing in a sheep before and after inducing acute respiratory distress syndrome (ARDS) by saline lavage. RESULTS: Differences in VT in the simulated models were marginally different (largest difference 33ml [95%-confidence interval (CI) 31-36]; P<.001ml). Plateau pressure (Pplat) was not different (-0.3cmH2O [95%-CI -0.9 to 0.3]; P=.409), and positive end-expiratory pressure (PEEP) was marginally different (0.3 cmH2O [95%-CI 0.2 to 0.3]; P<.001) between the ACUTE-19 and the commercial ventilator. Bland-Altman analyses showed good agreement (mean bias, -0.29, [limits of agreement, 0.82 to -1.42], and mean bias 0.56 [limits of agreement, 1.94 to -0.81], at a Pplat of 15 and 30cmH2O, respectively). The ACUTE-19 achieved optimal oxygenation and ventilation before and after ARDS induction. CONCLUSIONS: The ACUTE-19 performed accurately in simulated and animal models yielding a comparable performance with a VIVO-50 commercial device. The acute 19 can provide the basis for the development of a future affordable commercial ventilator.