[Pre-clinical validation of a turbine-based ventilator for invasive ventilation-The ACUTE-19 ventilator]. / Validación preclínica de un respirador de turbina para la ventilación invasiva: el respirador ACUTE-19.

Background: The severe acute respiratory syndrome-coronavirus 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 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 by saline lavage. Results: Differences in tidal volume in the simulated models were marginally different (largest difference 33 ml [95% CI 31 to 36]; P < .001). Plateau pressure was not different (-0.3 cmH2O [95% CI -0.9 to 0.3]; P = .409), and positive end-expiratory pressure 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 plateau pressure of 15 and 30 cmH2O, respectively). The ACUTE-19 achieved optimal oxygenation and ventilation before and after acute respiratory distress syndrome 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.

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.

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.

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.

Toxicological aspects of cannabinoid, pesticide and metal levels detected in light Cannabis inflorescences grown in Italy.

Recently, the cultivation of light Cannabis, with a total THC content less than 0.6%, has been encouraged due to its industrial and therapeutic potential. This has increased the consumption of hemp for both smoking purposes and food preparation. Even so, Cannabis inflorescences are not subject to EU regulations and standards provided for food and tobacco products. A study was carried out on thirty-one inflorescences samples, collected in different Italian regions, in order to determine cannabinoids, pesticides and metals and to evaluate the exposure of consumers to contaminants and ensure a safe consumption. Contents of THC were always below 0.5%, while CBD ranged between 0.3 and 8.64%. The determination of 154 pesticides showed that 87% of the samples contained fungicides and insecticides in the range 0.01-185 µg/g. The most found are spinosad and cyprodinil. The concentration of metals ranged from 1 to more than 100 µg/g and As, Cd, Co, Cr, Hg, Cu, Mo, Ni and V exceeded the regulatory US limits for inhaled Cannabis products, while Pb exceeded them for both oral and inhaled products. These contaminants are intrinsically toxic and may affect public health. Actions are needed to establish regulatory measures and reduce the adverse effects caused by contaminants in Cannabis.

Video vs. direct laryngoscopy for adult surgical and intensive care unit patients requiring tracheal intubation: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis aimed to determine whether a specific videolaryngoscopy technique is superior to standard direct laryngoscopy using a Macintosh blade to reduce the risk of difficult intubation in surgical and intensive care unit patients. MATERIALS AND METHODS: We identified all randomized controlled trials comparing videolaryngoscopes (VLSs) to direct laryngoscopy in the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE (from inception to April 2020). The primary outcome was difficult intubation in adult surgical and intensive care unit patients. Secondary outcomes were successful intubation at the first attempt, airway trauma, sore throat, hoarseness, hypoxia, and mortality. RESULTS: We included 97 randomized controlled trials to evaluate 12775 patients. A high risk of bias was found in at least 50% of the included studies for each outcome. VLSs reduced the risk of difficult intubation compared to direct Macintosh laryngoscopy (RR 0.48, 95% CI from 0.35 to 0.65). VLSs increased the rate of successful intubation at the first attempt when compared to direct Macintosh laryngoscopy (RR 1.03, 95% CI from 1.00 to 1.07). Lower risks of airway trauma were found with VLSs (RR 0.69, 95% CI from 0.55 to 0.86). A decreased risk of hoarseness was associated with the use of VLSs (RR 0.67, 95% CI from 0.54 to 0.83). In addition, VLSs did not significantly reduce the risk of hypoxia compared with direct laryngoscopy (RR 0.83, 95% CI from 0.60 to 1.16). CONCLUSIONS: In this systematic review and meta-analysis, we found that the use of VLSs reduced the risk of difficult intubation and slightly increased the ratio of successful intubation at the first attempt among adult patients.

An international multidisciplinary consensus statement on the prevention of opioid-related harm in adult surgical patients.

This international multidisciplinary consensus statement was developed to provide balanced guidance on the safe peri-operative use of opioids in adults. An international panel of healthcare professionals evaluated the literature relating to postoperative opioid-related harm, including persistent postoperative opioid use; opioid-induced ventilatory impairment; non-medical opioid use; opioid diversion and dependence; and driving under the influence of prescription opioids. Recommended strategies to reduce harm include pre-operative assessment of the risk of persistent postoperative opioid use; use of an assessment of patient function rather than unidimensional pain scores alone to guide adequacy of analgesia; avoidance of long-acting (modified-release and transdermal patches) opioid formulations and combination analgesics; limiting the number of tablets prescribed at discharge; providing deprescribing advice; avoidance of automatic prescription refills; safe disposal of unused medicines; reducing the risk of opioid diversion; and better education of healthcare professionals, patients and carers. This consensus statement provides a framework for better prescribing practices that could help reduce the risk of postoperative opioid-related harm in adults.

Efficacy of Telavancin in Comparison to Linezolid in a Porcine Model of Severe Methicillin-Resistant Staphylococcus aureus Pneumonia.

Current guidelines recommend vancomycin and linezolid as first-line agents against methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Telavancin is a potential new therapeutic alternative, specifically in monomicrobial MRSA pneumonia. This study compared the efficacies of telavancin versus linezolid in a porcine model of severe MRSA pneumonia. In 18 mechanically ventilated pigs (32.11 ± 1.18 kg), 75 ml of 106 CFU/ml of MRSA was administered into each pulmonary lobe. After the onset of pneumonia, pigs were randomized into three groups: a control group, a group receiving 22.5 mg/kg of body weight every 24 h (q24h) of telavancin, and a group receiving 10 mg/kg q12h of linezolid intravenously. Tracheal aspirate and bronchoalveolar lavage (BAL) fluids were cultured every 24 h. After 48 h of treatment, tissue samples were collected from the ventral and dorsal sections of each lobe. Microbiological and histopathological analyses were performed. Lung tissue concentrations differed among the groups (P = 0.019), with the lowest MRSA lung burden in the telavancin group (P < 0.05 versus the control). MRSA was detected in 46.7%, 40.0%, and 21.7% of the lung tissue samples from the control, linezolid, and telavancin groups, respectively (P < 0.001). MRSA concentrations differed among the groups in tracheal aspirate fluid (P = 0.011) but not in BAL fluid. Furthermore, there was no increased risk of kidney injury during telavancin use. Thus, telavancin has higher bactericidal efficacy than linezolid during the first 48 h of treatment in a porcine model of severe MRSA pneumonia. However, studies are needed to confirm the benefits of telavancin in treating MRSA nosocomial pneumonia.

Reevaluación de los efectos de PEEP alta con maniobras de reclutamiento vs. PEEP baja sin maniobras de reclutamiento durante la anestesia general para cirugía: protocolo y plan de análisis estadístico para un metaanálisis de los datos de pacientes individuales de PROVHILO, iPROVE y PROBESE / Re-evaluation of the effects of high PEEP with recruitment manoeuvres versus low PEEP without recruitment manoeuvres during general anaesthesia for surgery -Protocol and statistical analysis plan for an individual patient data meta-analysis of PROVHILO, iPROVE and PROBESE

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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.

Correction to: Protective ventilation with high versus low positive end-expiratory pressure during one-lung ventilation for thoracic surgery (PROTHOR): study protocol for a randomized controlled trial.

After publication of the original article [1], the authors have notified us that two of the collaborator first and last names have been inverted in the "PROTHOR Investigators" table.

Protective ventilation with high versus low positive end-expiratory pressure during one-lung ventilation for thoracic surgery (PROTHOR): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPC) may result in longer duration of in-hospital stay and even mortality. Both thoracic surgery and intraoperative mechanical ventilation settings add considerably to the risk of PPC. It is unclear if one-lung ventilation (OLV) for thoracic surgery with a strategy of intraoperative high positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM) reduces PPC, compared to low PEEP without RM. METHODS: PROTHOR is an international, multicenter, randomized, controlled, assessor-blinded, two-arm trial initiated by investigators of the PROtective VEntilation NETwork. In total, 2378 patients will be randomly assigned to one of two different intraoperative mechanical ventilation strategies. Investigators screen patients aged 18 years or older, scheduled for open thoracic or video-assisted thoracoscopic surgery under general anesthesia requiring OLV, with a maximal body mass index of 35 kg/m2, and a planned duration of surgery of more than 60 min. Further, the expected duration of OLV shall be longer than two-lung ventilation, and lung separation is planned with a double lumen tube. Patients will be randomly assigned to PEEP of 10 cmH2O with lung RM, or PEEP of 5 cmH2O without RM. During two-lung ventilation tidal volume is set at 7 mL/kg predicted body weight and, during OLV, it will be decreased to 5 mL/kg. The occurrence of PPC will be recorded as a collapsed composite of single adverse pulmonary events and represents the primary endpoint. DISCUSSION: PROTHOR is the first randomized controlled trial in patients undergoing thoracic surgery with OLV that is adequately powered to compare the effects of intraoperative high PEEP with RM versus low PEEP without RM on PPC. The results of the PROTHOR trial will support anesthesiologists in their decision to set intraoperative PEEP during protective ventilation for OLV in thoracic surgery. TRIAL REGISTRATION: The trial was registered in clinicaltrials.gov ( NCT02963025 ) on 15 November 2016.

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.

In-vitro analysis of a novel 'add-on' silicone cuff to improve sealing properties of tracheal tubes.

Leakage of colonised oropharyngeal secretions across the tracheal tube cuff may cause iatrogenic pulmonary infection. We studied a novel 'add-on' cuff, which can be inserted over an existing tracheal tube and advanced into the subglottic region. The physical properties of the novel silicone cuff (BronchoGuard, Ciel Medical, USA) were evaluated in comparison with the Hi-Lo® tracheal tube. In a bench study, we identified saline inflation volumes required to transmit pressures between 15 and 30 cmH2 O against artificial tracheas of 18, 20 and 22 mm internal diameter. We computed cuff compliance, and minimal inflation volume to achieve air sealing during mechanical ventilation. Finally, we compared the leakage flow rate of artificial saliva across the novel cuff. On average, the mean (SD) inflation volumes necessary to transmit tracheal pressures of 15, 20, 25 and 30 cmH2 O were 4.1 (2.2), 4.4 (2.3), 4.6 (2.4) and 4.8 (2.4) ml for the novel cuff and 7.7 (2.5), 8.0 (2.6), 8.4 (2.6) and 8.7 (2.7) ml for the Hi-Lo tube, respectively (p < 0.001). The minimal inflation volumes to achieve air sealing were 3.8 (0.9) and 10.5 (2.1) ml (p < 0.001), which resulted in transmitted tracheal pressures of 8.3 (9.8) and 27.6 (34.8) cmH2 O (p < 0.001). Compliance was 0.026 (0.004) and 0.616 (0.324) ml.cmH2 0-1 , respectively (p < 0.001). Although massive leak was found when the novel cuff transmitted pressures ≤ 20 cmH2 O against the trachea, leakage was avoided with pressures ≥ 25 cmH2 O, owing to optimal contact between the cuff and the tracheal wall. In contrast, the standard cuff consistently leaked irrespective of the pressure. We conclude that the novel cuff has advantageous properties that warrant clinical corroboration.

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.

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.

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.

Role of the extracellular matrix in the genesis of ventilator-induced lung injury.

The extracellular matrix represents the three-dimensional scaffold of the alveolar wall, which is composed of a layer of epithelial and endothelial cells, their basal membrane, and a thin interstitial layer containing fibrous proteins, glycoproteins, glycosaminoglycans, and proteoglycans. Mechanical ventilation with low and high tidal volumes can induce proteoglycan fragmentation, which may cause activation of the inflammatory cascade, leading to the main features of ventilator-induced lung injury (VILI): alveolar edema and collagen deposition. The purpose of this article is to describe VILI pathophysiology with a special focus on the effects of mechanical ventilation on the extracellular matrix. A more complete understanding of the molecular effects induced by physical forces is required to better assess the impact of existing mechanical ventilation strategies, as well as to develop new therapeutic strategies to reduce lung damage.