Sabrine N. T. Hemmes

Protective versus Conventional Ventilation for Surgery: A Systematic Review and Individual Patient Data Meta-analysis.

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

Intraoperative ventilatory strategies to prevent postoperative pulmonary complications: a meta-analysis

Purpose of review It is uncertain whether patients undergoing short-lasting mechanical ventilation for surgery benefit from lung-protective intraoperative ventilatory settings including the use of lower tidal volumes, higher levels of positive end-expiratory pressure (PEEP) and/or recruitment maneuvers. We meta-analyzed trials testing the effect of lung-protective intraoperative ventilatory settings on the incidence of postoperative pulmonary complications. Recent findings Eight articles (1669 patients) were included. Meta-analysis showed a decrease in lung injury development [risk ratio (RR) 0.40; 95% confidence interval (CI) 0.22–0.70; I2 0%; number needed to treat (NNT) 37], pulmonary infection (RR 0.64; 95% CI 0.43–0.97; I2 0%; NNT 27) and atelectasis (RR 0.67; 95% CI 0.47–0.96; I2 48%; NNT 31) in patients receiving intraoperative mechanical ventilation with lower tidal volumes. Meta-analysis also showed a decrease in lung injury development (RR 0.29; 95% CI 0.14–0.60; I2 0%; NNT 29), pulmonary infection (RR 0.62; 95% CI 0.40–0.96; I2 15%; NNT 33) and atelectasis (RR 0.61; 95% CI 0.41–0.91; I2 0%; NNT 29) in patients ventilated with higher levels of PEEP, with or without recruitment maneuvers. Summary Lung-protective intraoperative ventilatory settings have the potential to protect against postoperative pulmonary complications.

Intraoperative protective mechanical ventilation for prevention of postoperative pulmonary complications: a comprehensive review of the role of tidal volume, positive end-expiratory pressure, and lung recruitment maneuvers.

Postoperative pulmonary complications are associated with increased morbidity, length of hospital stay, and mortality after major surgery. Intraoperative lung-protective mechanical ventilation has the potential to reduce the incidence of postoperative pulmonary complications. This review discusses the relevant literature on definition and methods to predict the occurrence of postoperative pulmonary complication, the pathophysiology of ventilator-induced lung injury with emphasis on the noninjured lung, and protective ventilation strategies, including the respective roles of tidal volumes, positive end-expiratory pressure, and recruitment maneuvers. The authors propose an algorithm for protective intraoperative mechanical ventilation based on evidence from recent randomized controlled trials.

Association between driving pressure and development of postoperative pulmonary complications in patients undergoing mechanical ventilation for general anaesthesia: a meta-analysis of individual patient data.

BACKGROUND Protective mechanical ventilation strategies using low tidal volume or high levels of positive end-expiratory pressure (PEEP) improve outcomes for patients who have had surgery. The role of the driving pressure, which is the difference between the plateau pressure and the level of positive end-expiratory pressure is not known. We investigated the association of tidal volume, the level of PEEP, and driving pressure during intraoperative ventilation with the development of postoperative pulmonary complications. METHODS We did a meta-analysis of individual patient data from randomised controlled trials of protective ventilation during general anesthaesia for surgery published up to July 30, 2015. The main outcome was development of postoperative pulmonary complications (postoperative lung injury, pulmonary infection, or barotrauma). FINDINGS We included data from 17 randomised controlled trials, including 2250 patients. Multivariate analysis suggested that driving pressure was associated with the development of postoperative pulmonary complications (odds ratio [OR] for one unit increase of driving pressure 1·16, 95% CI 1·13-1·19; p<0·0001), whereas we detected no association for tidal volume (1·05, 0·98-1·13; p=0·179). PEEP did not have a large enough effect in univariate analysis to warrant inclusion in the multivariate analysis. In a mediator analysis, driving pressure was the only significant mediator of the effects of protective ventilation on development of pulmonary complications (p=0·027). In two studies that compared low with high PEEP during low tidal volume ventilation, an increase in the level of PEEP that resulted in an increase in driving pressure was associated with more postoperative pulmonary complications (OR 3·11, 95% CI 1·39-6·96; p=0·006). INTERPRETATION In patients having surgery, intraoperative high driving pressure and changes in the level of PEEP that result in an increase of driving pressure are associated with more postoperative pulmonary complications. However, a randomised controlled trial comparing ventilation based on driving pressure with usual care is needed to confirm these findings. FUNDING None.

ESA Clinical Trials Network 2012: LAS VEGAS - Local Assessment of Ventilatory Management during General Anaesthesia for Surgery and its effects on Postoperative Pulmonary Complications A prospective, observational, international, multicentre cohort study

Mechanical ventilation is frequently used as a supportivestrategy in intensive care medicine and anaesthesiologydespite its potential to aggravate or even initiate lunginjury. Indeed, overdistension of nondependent lungregions and repetitive opening and closing of dependentlung regions may cause mechanical stress and strain,eventually worsening or causing lung damage.

Protocol for a systematic review and individual patient data meta-analysis of benefit of so-called lung-protective ventilation settings in patients under general anesthesia for surgery

BackgroundAlmost all patients under general anesthesia for surgery need mechanical ventilation. The harmful effects of short-term intra-operative ventilation on pulmonary integrity are increasingly recognized. Recent investigations suggest protection against so-called ventilation-associated lung injury with the use of lower tidal volumes and/or the use of higher levels of positive end-expiratory pressure (PEEP). This review and meta-analysis will evaluate the effects of these protective measures on pulmonary and extra-pulmonary complications, and try to discriminate the effects of lower tidal volumes from those of higher levels of PEEP.Methods/designThe Medline database will be searched for observational studies and randomized controlled trials of intra-operative ventilation. Individual patient data will be collected from databases obtained via direct contact with corresponding authors of original articles. The primary endpoint is development of postoperative acute respiratory distress syndrome, the most important postoperative pulmonary complication. Secondary endpoints include hospital length of stay and hospital mortality, and reported intra-operative and postoperative pulmonary and extra-pulmonary complications. Emphasis is put on separating the effects of lower tidal volumes from those of higher levels of PEEP.DiscussionThis will be the first meta-analysis of intra-operative ventilation using individual patient data from observational studies and randomized controlled trials. The large sample size could allow discrimination of the effect of the two most frequently used protective measures - that is, lower tidal volumes and higher levels of PEEP. The results of this review and meta-analysis can be used in designing future trials of ventilation.

Kinetics of plasma biomarkers of inflammation and lung injury in surgical patients with or without postoperative pulmonary complications.

BACKGROUND Postoperative pulmonary complications (PPCs) are common after major abdominal surgery. The kinetics of plasma biomarkers could improve identification of patients developing PPCs, but the kinetics may depend on intraoperative ventilator settings. OBJECTIVE To test whether the kinetics of plasma biomarkers are capable of identifying patients who will develop PPCs, and whether the kinetics depend on the intraoperative level of positive end-expiratory pressure (PEEP). DESIGN A preplanned substudy of a randomised controlled trial. SETTING Operation room of five centres. PATIENTS Two hundred and forty-two adult patients scheduled for abdominal surgery at risk of developing PPCs. INTERVENTIONS High (12 cmH2O) versus low (⩽2 cmH2O) levels of PEEP. MAIN OUTCOME MEASURES Individual PPCs were combined as a composite endpoint. Plasma samples were collected before surgery, directly after surgery and on the fifth postoperative day. The levels of the following were measured: tumour necrosis factor (TNF)-&agr;, interleukin (IL)-6 and IL-8, the soluble form of the Receptor for Advanced Glycation End–products (sRAGE), Surfactant Protein (SP)-D, Clara Cell protein (CC)-16 and Krebs von den Lungen 6 (KL6). RESULTS Blood sampling was complete in 242 patients: 120 patients in the high PEEP group and 122 patients in the low PEEP group. Increases in plasma levels of TNF- IL-6, IL-8 and CC-16, and a decrease in plasma levels of SP-D were greater in patients who developed PPCs; however, the area under the receiver operating characteristic curve was low for all biomarkers. CC-16 was the only biomarker whose level increased more in patients who had received high levels of PEEP. CONCLUSION In patients undergoing abdominal surgery and at risk of developing PPCs, plasma levels of biomarkers for inflammation or lung injury showed distinct kinetics with development of PPCs, but none of the biomarkers showed sufficient prognostic value. The use of high levels of PEEP was associated with increased levels of CC-16, suggesting lung overdistension. TRIAL REGISTRATION The PROVHILO trial, including this substudy, was registered at clinicaltrials.gov (NCT01441791).

Ventilation with high versus low peep levels during general anaesthesia for open abdominal surgery does not affect postoperative spirometry: A randomised clinical trial.

BACKGROUND Invasive mechanical ventilation during general anaesthesia for surgery typically causes atelectasis and impairs postoperative lung function. OBJECTIVE We investigated the effect of intraoperative ventilation with high positive end-expiratory pressure (PEEP) and recruitment manoeuvres (RMs) on postoperative spirometry. DESIGN This was a preplanned, single-centre substudy of an international multicentre randomised controlled trial, the PROVHILO trial. SETTING University hospital from November 2011 to January 2013. PATIENTS Nonobese patients scheduled for major abdominal surgery at a high risk of postoperative pulmonary complications (PPCs). INTERVENTION Intraoperative low tidal volume ventilation with PEEP levels of 12 cmH2O and RM (the high PEEP group) or with PEEP levels of 2 cmH2O or less without RM (the low PEEP group). MAIN OUTCOME MEASURES Time-weighted averages (TWAs) of the forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC) up to postoperative day five. RESULTS Thirty-one patients were allocated to the high PEEP group and 32 to the low PEEP group. No postoperative spirometry test results were available for 6 patients. In both groups, TWA of FEV1 and FVC until postoperative day five were lower than preoperative values. Postoperative spirometry test results were not different between the high and low PEEP group; Data are median [interquartile range], TWA FVC 1.8 [1.6 to 2.4] versus 1.7 [1.2 to 2.4] l (P = NS) and TWA FEV1 1.2 [1.1 to 2.5] versus 1.2 [0.9 to 1.9] l (P = NS). Patients who developed PPCs had lower FEV1 and FVC on postoperative day five; 1.1 [0.9 to 1.6] versus 1.6 [1.4 to 1.9] l (P = 0.001) and 1.6 [1.2 to 2.6] versus 2.3 [1.7 to 2.6] l (P = 0.036), respectively. CONCLUSION Postoperative spirometry is not affected by PEEP and RM during intraoperative ventilation for open abdominal surgery in nonobese patients at a high risk of PPCs, but rather is associated with the development of PPCs. TRIAL REGISTRATION ClinicalTrials.gov NCT01441791.

Rationale and Study Design of Provent-An International Multicenter Observational Study on Practice of Ventilation in Critically Ill Patients without ARDS

Background: Use of lower tidal volumes during mechanical ventilation is associated with reduced morbidity and mortality of Intensive Care Unit (ICU) patients with the Acute Respiratory Distress Syndrome (ARDS). Use of lower tidal volumes could also protect ICU patients without ARDS. While use of higher tidal volumes is strongly discouraged in ARDS patients, guidelines do not yet recommend on tidal volume size in patients not suffering from this complication, resulting in unwanted variable mechanical ventilation settings amongst ICU patients. Purpose: The present study aims to determine ventilation characteristics, including tidal volume size in intubated and mechanically ventilated patients in ICUs in Europe, Australia and the Americas. Ventilation characteristics and outcomes are compared among patients without ARDS, patients at risk for ARDS and patients with mild, moderate or severe ARDS. Methods: The ‘PRatice of VENTilation in critically ill patients without ARDS’ study (PRoVENT) is an international multicenter observational study in critically ill intubated and ventilated ICU patients by the PROVENet (PROtective VENtilation Network) investigators (http://www.provenet.eu/). At least 1,000 patients under invasive mechanical ventilation are included in a time window of 7 days, and followed up to the end of stay in ICU. The primary endpoint is the variability of tidal volume size in ventilated patients in ICUs in Europe, Australia and the Americas. Conclusion: PRoVENT is designed to investigate and compare tidal volume settings in patients without ARDS, patients at risk for ARDS, and patients with mild, moderate or severe ARDS, and to determine the impact of tidal volume size on important clinical endpoints, in particular patients without ARDS. PRoVENT shall provide information on ventilator settings that could be used in future trials of ventilation, especially in ICU patients without or at risk for ARDS (Trial Registration: NCT01868321).

The LAS VEGAS risk score for prediction of postoperative pulmonary complications : an observational study

BACKGROUND Currently used pre-operative prediction scores for postoperative pulmonary complications (PPCs) use patient data and expected surgery characteristics exclusively. However, intra-operative events are also associated with the development of PPCs. OBJECTIVE We aimed to develop a new prediction score for PPCs that uses both pre-operative and intra-operative data. DESIGN This is a secondary analysis of the LAS VEGAS study, a large international, multicentre, prospective study. SETTINGS A total of 146 hospitals across 29 countries. PATIENTS Adult patients requiring intra-operative ventilation during general anaesthesia for surgery. INTERVENTIONS The cohort was randomly divided into a development subsample to construct a predictive model, and a subsample for validation. MAIN OUTCOME MEASURES Prediction performance of developed models for PPCs. RESULTS Of the 6063 patients analysed, 10.9% developed at least one PPC. Regression modelling identified 13 independent risk factors for PPCs: six patient characteristics [higher age, higher American Society of Anesthesiology (ASA) physical score, pre-operative anaemia, pre-operative lower SpO2 and a history of active cancer or obstructive sleep apnoea], two procedure-related features (urgent or emergency surgery and surgery lasting ≥ 1 h), and five intra-operative events [use of an airway other than a supraglottic device, the use of intravenous anaesthetic agents along with volatile agents (balanced anaesthesia), intra-operative desaturation, higher levels of positive end-expiratory pressures > 3 cmH2O and use of vasopressors]. The area under the receiver operating characteristic curve of the LAS VEGAS risk score for prediction of PPCs was 0.78 [95% confidence interval (95% CI), 0.76 to 0.80] for the development subsample and 0.72 (95% CI, 0.69 to 0.76) for the validation subsample. CONCLUSION The LAS VEGAS risk score including 13 peri-operative characteristics has a moderate discriminative ability for prediction of PPCs. External validation is needed before use in clinical practice. TRIAL REGISTRATION The study was registered at Clinicaltrials.gov, number NCT01601223.