Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV): a multicentre, randomised, controlled clinical trial.

BACKGROUND: It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation. METHODS: This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age ≥18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H2O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lung-protective ventilation received combined intraoperative 4 cm H2O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT03182062, and is complete. FINDINGS: Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0·39 [95% CI 0·28 to 0·56]), with an absolute risk difference of -9·23 (95% CI -12·55 to -5·92). Recruitment manoeuvre-related adverse events were reported in five patients. INTERPRETATION: Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation. FUNDING: Instituto de Salud Carlos III and the European Regional Development Funds.

A genome-wide association study of survival in patients with sepsis.

BACKGROUND: Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units. Most genetic studies have identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome-wide association study (GWAS) of 28-day survival in adult patients with sepsis. METHODS: This study was conducted in two stages. The first stage was performed on 687 European sepsis patients from the GEN-SEP network and 7.5 million imputed variants. Association testing was conducted with Cox regression models, adjusting by sex, age, and the main principal components of genetic variation. A second stage focusing on the prioritized genetic variants was performed on 2,063 ICU sepsis patients (1362 European Americans and 701 African-Americans) from the MESSI study. A meta-analysis of results from the two stages was conducted and significance was established at p < 5.0 × 10-8. Whole-blood transcriptomic, functional annotations, and sensitivity analyses were evaluated on the identified genes and variants. FINDINGS: We identified three independent low-frequency variants associated with reduced 28-day sepsis survival, including a missense variant in SAMD9 (hazard ratio [95% confidence interval] = 1.64 [1.37-6.78], p = 4.92 × 10-8). SAMD9 encodes a possible mediator of the inflammatory response to tissue injury. INTERPRETATION: We performed the first GWAS of 28-day sepsis survival and identified novel variants associated with reduced survival. Larger sample size studies are needed to better assess the genetic effects in sepsis survival and to validate the findings.

Effect of intraoperative PEEP with recruitment maneuvers on the occurrence of postoperative pulmonary complications during general anesthesia--protocol for Bayesian analysis of three randomized clinical trials of intraoperative ventilation.

Background: Using the frequentist approach, a recent meta-analysis of three randomized clinical trials in patients undergoing intraoperative ventilation during general anesthesia for major surgery failed to show the benefit of ventilation that uses high positive end-expiratory pressure with recruitment maneuvers when compared to ventilation that uses low positive end-expiratory pressure without recruitment maneuvers. Methods: We designed a protocol for a Bayesian analysis using the pooled dataset. The multilevel Bayesian logistic model will use the individual patient data. Prior distributions will be prespecified to represent a varying level of skepticism for the effect estimate. The primary endpoint will be a composite of postoperative pulmonary complications (PPC) within the first seven postoperative days, which reflects the primary endpoint of the original studies. We preset a range of practical equivalence to assess the futility of the intervention with an interval of odds ratio (OR) between 0.9 and 1.1 and assess how much of the 95% of highest density interval (HDI) falls between the region of practical equivalence. Ethics and dissemination: The used data derive from approved studies that were published in recent years. The findings of this current analysis will be reported in a new manuscript, drafted by the writing committee on behalf of the three research groups. All investigators listed in the original trials will serve as collaborative authors.

Effects of remote ischemic postconditioning on HIF-1α and other markers in on-pump cardiac surgery.

BACKGROUND: There is a lack of data about the effects of remote ischemic postconditioning (RIPostC) on hypoxia-inducible factor-1α (HIF-1α) plasma levels after on-pump cardiac surgery (OPCS). This study aimed to measure the effects of RIPostC on postoperative HIF-1α plasma levels, cardiac markers and arterial oxygenation in patients undergoing OPCS. METHODS: This single-centre randomized, double blind, controlled trial, enrolled 70 patients (35 control and 35 RIPostC). RIPostC was performed by 3 cycles (5 min of ischemia followed by 5 min of reperfusion) administered in upper arm immediately after the pump period. The primary outcome was to measure HIF-1α plasma levels: before surgery (T0), and 2 h (T1), 8 h (T2), 24 h (T3), 36 h (T4) and 48 h (T5) after RIPostC. As secondary endpoint, Troponin T, CK-MB, CPK plasma levels and PaO2/FiO2 ratio were measured. RESULTS: HIF-1α plasma levels were increased at T1-T3 compared to T0 in both groups (P < 0.001). In the RIPostC group HIF-1α increased compared to the control group: differences between means (95% CI) were 0.034 (0.006-0.06) P = 0.019 at T1; 0.041 (0.013-0.069) P = 0.005 at T2; and 0.021 (0.001-0.042) P = 0.045 at T3. PaO2/FiO2 was higher in the RIPostC group than in the control group: at T3, T4 and T5. Moreover, Troponin T, CK-MB and CPK values decreased in the RIPostC group compared to the control group. CONCLUSIONS: HIF-1α plasma levels increased in control patients during for at least 36 h after OPCS. RIPostC resulted in even higher HIF-1α levels during at least the first 24 h and improved arterial oxygenation and cardiac markers.

Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis.

Acute respiratory distress syndrome (ARDS) is an inflammatory process of the lungs that develops primarily in response to pulmonary or systemic sepsis, resulting in a disproportionate death toll in intensive care units (ICUs). Given its role as a critical activator of the inflammatory and innate immune responses, previous studies have reported that an increase of circulating cell-free mitochondrial DNA (mtDNA) is a biomarker for fatal outcome in the ICU. Here we analyzed the association of whole-blood mtDNA (wb-mtDNA) copies with 28-day survival from sepsis and sepsis-associated ARDS. We analyzed mtDNA data from 687 peripheral whole-blood samples within 24 h of sepsis diagnosis from unrelated Spanish patients with sepsis (264 with ARDS) included in the GEN-SEP study. The wb-mtDNA copies were obtained from the array intensities of selected probes, with 100% identity with mtDNA and with the largest number of mismatches with the nuclear sequences, and normalized across the individual-probe intensities. We used Cox regression models for testing the association with 28-day survival. We observed that wb-mtDNA copies were significantly associated with 28-day survival in ARDS patients (hazard ratio = 3.65, 95% confidence interval = 1.39-9.59, p = 0.009) but not in non-ARDS patients. Our findings support that wb-mtDNA copies at sepsis diagnosis could be considered an early prognostic biomarker in sepsis-associated ARDS patients. Future studies will be needed to evaluate the mechanistic links of this observation with the pathogenesis of ARDS.

Stratification for Identification of Prognostic Categories In the Acute RESpiratory Distress Syndrome (SPIRES) Score.

OBJECTIVES: To develop a scoring model for stratifying patients with acute respiratory distress syndrome into risk categories (Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score) for early prediction of death in the ICU, independent of the underlying disease and cause of death. DESIGN: A development and validation study using clinical data from four prospective, multicenter, observational cohorts. SETTING: A network of multidisciplinary ICUs. PATIENTS: One-thousand three-hundred one patients with moderate-to-severe acute respiratory distress syndrome managed with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study followed Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines for prediction models. We performed logistic regression analysis, bootstrapping, and internal-external validation of prediction models with variables collected within 24 hours of acute respiratory distress syndrome diagnosis in 1,000 patients for model development. Primary outcome was ICU death. The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score was based on patient's age, number of extrapulmonary organ failures, values of end-inspiratory plateau pressure, and ratio of Pao2 to Fio2 assessed at 24 hours of acute respiratory distress syndrome diagnosis. The pooled area under the receiver operating characteristic curve across internal-external validations was 0.860 (95% CI, 0.831-0.890). External validation in a new cohort of 301 acute respiratory distress syndrome patients confirmed the accuracy and robustness of the scoring model (area under the receiver operating characteristic curve = 0.870; 95% CI, 0.829-0.911). The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score stratified patients in three distinct prognostic classes and achieved better prediction of ICU death than ratio of Pao2 to Fio2 at acute respiratory distress syndrome onset or at 24 hours, Acute Physiology and Chronic Health Evaluation II score, or Sequential Organ Failure Assessment scale. CONCLUSIONS: The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score represents a novel strategy for early stratification of acute respiratory distress syndrome patients into prognostic categories and for selecting patients for therapeutic trials.

Neurally adjusted ventilatory assist in acute respiratory failure: a randomized controlled trial.

PURPOSE: We hypothesized that neurally adjusted ventilatory assist (NAVA) compared to conventional lung-protective mechanical ventilation (MV) decreases duration of MV and mortality in patients with acute respiratory failure (ARF). METHODS: We carried out a multicenter, randomized, controlled trial in patients with ARF from several etiologies. Intubated patients ventilated for ≤ 5 days expected to require MV for ≥ 72 h and able to breathe spontaneously were eligible for enrollment. Eligible patients were randomly assigned based on balanced treatment assignments with a computerized randomization allocation sequence to two ventilatory strategies: (1) lung-protective MV (control group), and (2) lung-protective MV with NAVA (NAVA group). Allocation concealment was maintained at all sites during the trial. Primary outcome was the number of ventilator-free days (VFDs) at 28 days. Secondary outcome was all-cause hospital mortality. All analyses were done according to the intention-to-treat principle. RESULTS: Between March 2014 and October 2019, we enrolled 306 patients and randomly assigned 153 patients to the NAVA group and 153 to the control group. Median VFDs were higher in the NAVA than in the control group (22 vs. 18 days; between-group difference 4 days; 95% confidence interval [CI] 0 to 8 days; p = 0.016). At hospital discharge, 39 (25.5%) patients in the NAVA group and 47 (30.7%) patients in the control group had died (between-group difference - 5.2%, 95% CI - 15.2 to 4.8, p = 0.31). Other clinical, physiological or safety outcomes did not differ significantly between the trial groups. CONCLUSION: NAVA decreased duration of MV although it did not improve survival in ventilated patients with ARF.

Limb Ischemic Conditioning Induces Oxidative Stress Followed by a Correlated Increase of HIF-1α in Healthy Volunteers.

BACKGROUND: Local and remote ischemic preconditioning has been used as a protective intervention against ischemia/reperfusion (I/R) damage in several preclinical and clinical studies. However, its physiological mechanisms are not completely known. I/R increases the production of reactive oxygen species, which also serve as messengers for a variety of functions. Hypoxia-inducible factor 1 alpha (HIF-1α) is probably the most important transcription factor mediator of hypoxic signaling. OBJECTIVE: We hypothesized that limb ischemic conditioning (LIC) induces a local oxidative/nitrosative stress and a correlated increase of HIF-1α plasma levels. METHODS: An observational, prospective, and single-center study has been conducted in 27 healthy volunteers. LIC was applied: three cycles (5 min of ischemia followed by 5 min of reperfusion) using an ischemia cuff placed on the upper left arm. Time course of 8-isoprostane, nitrite, and HIF-1α levels was measured in blood plasma. Venous blood was sampled from the left arm before tourniquet inflation (basal) and after LIC: 1 min and 2 hr for 8-isoprostane and nitrite; and 1 min, 2 hr, 8 hr, 24 hr, and 48 hr for HIF-1α. RESULTS: After LIC, we have found an early increase of 8-isoprostane and nitrite. HIF-1α increased at 2 and 8 hr after LIC. We found a direct correlation between HIF-1α and 8-isoprostane and nitrite plasma levels. CONCLUSIONS: We concluded that LIC induces an early oxidative/nitrosative stress in the arm followed by an increase of HIF-1α plasma levels correlated with 8-isoprostane and nitrite levels, possibly as a local response.

A noninvasive postoperative clinical score to identify patients at risk for postoperative pulmonary complications: the Air-Test Score.

BACKGROUND: Postoperative pulmonary complications (PPCs) negatively affect morbidity, healthcare costs and postsurgical survival. Preoperative and intraoperative peripheral oxyhemoglobin saturation (SpO2) levels are independent risk factors for postoperative pulmonary complications (PPCs). The air-test assesses the value of SpO2 while breathing room-air. We aimed at building a clinical score that includes the air-test for predicting the risk for PPCs. METHODS: This is a development and validation study in patients -randomly divided into two cohorts- from a large randomized clinical trial (iPROVE) that enrolled 964 intermediate-to-high risk patients scheduled for abdominal surgery. Arterial oxygenation was assessed on room-air in the preoperative period (preoperative air-test) and 3h after admission to the postoperative care unit (postoperative air-test). The air-test was defined as positive or negative if SpO2 was ≤96% or >96%, respectively. Positive air-tests were stratified into weak (93-96%) or strong (<93%). The primary outcome was a composite of moderate-to-severe PPCs during the first seven postoperative days. RESULTS: A total of 902 patients were included in the final analysis (542 in the development cohort and 360 in the validation cohort). Regression analysis identified five independent risk factors for PPC: age, type of surgery, pre- and postoperative air-test, and atelectasis. The area under the receiver operating characteristic curve (AUC) was 0.79 (95% CI: 0.75-0.82) when including these five independent predictors. We built a simplified score termed "air-test score" by using only the pre- and postoperative SpO2, resulting in an AUC of 0.72 (95% CI: 0.67-0.76) for the derivation and 0.72 (95% CI: 0.66-0.78) for the validation cohort, respectively. The air-test score stratified patients into four levels of risk, with PPCs ranging from <15% to >75%. CONCLUSIONS: The simple, non-invasive and inexpensive bedside air-test score, evaluating pre- and postoperatively SpO2 measured on room-air, helps to predict the risk for PPCs.

Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy: a randomised controlled trial.

BACKGROUND: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. METHODS: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. RESULTS: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. CONCLUSIONS: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found. CLINICAL TRIAL REGISTRATION: NCT02776046.

Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV).

OBJECTIVE: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. DESIGN: International, multicenter, prospective, randomized controlled clinical trial. SETTING: A network of university hospitals. PARTICIPANTS: The study comprises 1,380 patients scheduled for thoracic surgery. INTERVENTIONS: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. MEASUREMENTS AND MAIN RESULTS: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients.

High-flow nasal cannula oxygenation reduces postoperative hypoxemia in morbidly obese patients: a randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPCs) are common in high-risk surgical patients. Postoperative ventilatory management may improve their outcome. Supplemental oxygen through a high-flow nasal cannula (HFNC) has become an alternative to classical oxygenation techniques, although the results published for postoperative patients are contradictory. We examined the efficacy of HFNC in postoperative morbidly obese patients who were ventilated intraoperatively with an open-lung approach (OLA). METHODS: We performed an open, two-arm, randomized controlled trial in 64 patients undergoing bariatric surgery (N.=32 in each arm) from May to November 2017 at the Hospital Clínico of Valencia. Patients were randomly assigned to receive HFNC oxygen therapy at the time of extubation or to receive conventional oxygen therapy, both applied during the first three postoperative hours. Intraoperatively, a recruitment maneuver and individualized positive end-expiratory pressure was applied in all patients. The primary outcome was postoperative hypoxemia. RESULTS: All patients were included in the final analysis. There were no significant differences between the baseline characteristics. Postoperative hypoxemia was less frequent in the HFNC group compared to those who received standard care (28.6% vs. 80.0%, relative risk [RR]: 0.35; 95%CI: 0.150-0.849, P=0.009). Prevalence of atelectasis was lower in the HFNC group (31% vs. 77%, RR: 0.39; 95%CI: 0.166-0.925, P=0.013). No severe PPCs were reported in any patient. CONCLUSIONS: Early application of HFNC in the operating room before extubation and during the immediate postoperative period decreases postoperative hypoxemia in obese patients after bariatric surgery who were intraoperatively ventilated using an OLA approach.

Individualized, perioperative, hemodynamic goal-directed therapy in major abdominal surgery (iPEGASUS trial): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative morbidity and mortality in patients undergoing surgery is high, especially in patients who are at risk of complications and undergoing major surgery. We hypothesize that perioperative, algorithm-driven, hemodynamic therapy based on individualized fluid status and cardiac output optimization is able to reduce mortality and postoperative moderate and severe complications as a major determinant of the patients' postoperative quality of life, as well as health care costs. METHODS/DESIGN: This is a multi-center, international, prospective, randomized trial in 380 patients undergoing major abdominal surgery including visceral, urological, and gynecological operations. Eligible patients will be randomly allocated to two treatment arms within the participating centers. Patients of the intervention group will be treated perioperatively following a specific hemodynamic therapy algorithm based on pulse-pressure variation (PPV) and individualized optimization of cardiac output assessed by pulse-contour analysis (ProAQT© device; Pulsion Medical Systems, Feldkirchen, Germany). Patients in the control group will be treated according to standard local care based on established basic hemodynamic treatment. The primary endpoint is a composite comprising the occurrence of moderate or severe postoperative complications or death within 28 days post surgery. Secondary endpoints are: (1) the number of moderate and severe postoperative complications in total, per patient and for each individual complication; (2) the occurrence of at least one of these complications on days 1, 3, 5, 7, and 28 in total and for every complication; (3) the days alive and free of mechanical ventilation, vasopressor therapy and renal replacement therapy, length of intensive care unit, and hospital stay at day 7 and day 28; and (4) mortality and quality of life, assessed by the EQ-5D-5L™ questionnaire, after 6 months. DISCUSSION: This is a large, international randomized controlled study evaluating the effect of perioperative, individualized, algorithm-driven ,hemodynamic optimization on postoperative morbidity and mortality. TRIAL REGISTRATION: Trial registration: NCT03021525 . Registered on 12 January 2017.

Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomised controlled trial.

BACKGROUND: The effects of individualised perioperative lung-protective ventilation (based on the open-lung approach [OLA]) on postoperative complications is unknown. We aimed to investigate the effects of intraoperative and postoperative ventilatory management in patients scheduled for abdominal surgery, compared with standard protective ventilation. METHODS: We did this prospective, multicentre, randomised controlled trial in 21 teaching hospitals in Spain. We enrolled patients who were aged 18 years or older, were scheduled to have abdominal surgery with an expected time of longer than 2 h, had intermediate-to-high-risk of developing postoperative pulmonary complications, and who had a body-mass index less than 35 kg/m2. Patients were randomly assigned (1:1:1:1) online to receive one of four lung-protective ventilation strategies using low tidal volume plus positive end-expiratory pressure (PEEP): open-lung approach (OLA)-iCPAP (individualised intraoperative ventilation [individualised PEEP after a lung recruitment manoeuvre] plus individualised postoperative continuous positive airway pressure [CPAP]), OLA-CPAP (intraoperative individualised ventilation plus postoperative CPAP), STD-CPAP (standard intraoperative ventilation plus postoperative CPAP), or STD-O2 (standard intraoperative ventilation plus standard postoperative oxygen therapy). Patients were masked to treatment allocation. Investigators were not masked in the operating and postoperative rooms; after 24 h, data were given to a second investigator who was masked to allocations. The primary outcome was a composite of pulmonary and systemic complications during the first 7 postoperative days. We did the primary analysis using the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02158923. FINDINGS: Between Jan 2, 2015, and May 18, 2016, we enrolled 1012 eligible patients. Data were available for 967 patients, whom we included in the final analysis. Risk of pulmonary and systemic complications did not differ for patients in OLA-iCPAP (110 [46%] of 241, relative risk 0·89 [95% CI 0·74-1·07; p=0·25]), OLA-CPAP (111 [47%] of 238, 0·91 [0·76-1·09; p=0·35]), or STD-CPAP groups (118 [48%] of 244, 0·95 [0·80-1·14; p=0·65]) when compared with patients in the STD-O2 group (125 [51%] of 244). Intraoperatively, PEEP was increased in 69 (14%) of patients in the standard perioperative ventilation groups because of hypoxaemia, and no patients from either of the OLA groups required rescue manoeuvres. INTERPRETATION: In patients who have major abdominal surgery, the different perioperative open lung approaches tested in this study did not reduce the risk of postoperative complications when compared with standard lung-protective mechanical ventilation. FUNDING: Instituto de Salud Carlos III of the Spanish Ministry of Economy and Competitiveness, and Grants Programme of the European Society of Anaesthesiology.

WHO Needs High FIO2?

World Health Organization and the United States Center for Disease Control have recently recommended the use of 0.8 FIO2 in all adult surgical patients undergoing general anaesthesia, to prevent surgical site infections. This recommendation has arisen several discussions: As a matter of fact, there are numerous studies with different results about the effect of FIO2 on surgical site infection. Moreover, the clinical effects of FIO2 are not limited to infection control. We asked some prominent authors about their comments regarding the recent recommendations.

Rationale and study design for an individualised perioperative open-lung ventilatory strategy with a high versus conventional inspiratory oxygen fraction (iPROVE-O2) and its effects on surgical site infection: study protocol for a randomised controlled trial.

INTRODUCTION: Surgical site infection (SSI) is a serious postoperative complication that increases morbidity and healthcare costs. SSIs tend to increase as the partial pressure of tissue oxygen decreases: previous trials have focused on trying to reduce them by comparing high versus conventional inspiratory oxygen fractions (FIO2) in the perioperative period but did not use a protocolised ventilatory strategy. The open-lung ventilatory approach restores functional lung volume and improves gas exchange, and therefore it may increase the partial pressure of tissue oxygen for a given FIO2. The trial presented here aims to compare the efficacy of high versus conventional FIO2 in reducing the overall incidence of SSIs in patients by implementing a protocolised and individualised global approach to perioperative open-lung ventilation. METHODS AND ANALYSIS: This is a comparative, prospective, multicentre, randomised and controlled two-arm trial that will include 756 patients scheduled for abdominal surgery. The patients will be randomised into two groups: (1) a high FIO2 group (80% oxygen; FIO2 of 0.80) and (2) a conventional FIO2 group (30% oxygen; FIO2 of 0.30). Each group will be assessed intra- and postoperatively. The primary outcome is the appearance of postoperative SSI complications. Secondary outcomes are the appearance of systemic and pulmonary complications. ETHICS AND DISSEMINATION: The iPROVE-O2 trial has been approved by the Ethics Review Board at the reference centre (the Hospital Clínico Universitario in Valencia). Informed consent will be obtained from all patients before their participation. If the approach using high FIO2 during individualised open-lung ventilation decreases SSIs, use of this method will become standard practice for patients scheduled for future abdominal surgery. Publication of the results is anticipated in early 2019. TRIAL REGISTRATION NUMBER: NCT02776046; Pre-results.

Remote Ischemic Preconditioning Decreases Oxidative Lung Damage After Pulmonary Lobectomy: A Single-Center Randomized, Double-Blind, Controlled Trial.

BACKGROUND: During lobectomy in patients with lung cancer, the operated lung is often collapsed and hypoperfused. Ischemia/reperfusion injury may then occur when the lung is re-expanded. We hypothesized that remote ischemic preconditioning (RIPC) would decrease oxidative lung damage and improve gas exchange in the postoperative period. METHODS: We conducted a single-center, randomized, double-blind trial in patients with nonsmall cell lung cancer undergoing elective lung lobectomy. Fifty-three patients were randomized to receive limb RIPC immediately after anesthesia induction (3 cycles: 5 minutes ischemia/5 minutes reperfusion induced by an ischemia cuff applied on the thigh) and/or control therapy without RIPC. Oxidative stress markers were measured in exhaled breath condensate (EBC) and arterial blood immediately after anesthesia induction and before RIPC and surgery (T0, baseline); during operated lung collapse, immediately before resuming two-lung ventilation (TLV) (T1); immediately after resuming TLV (T2); and 120 minutes after resuming TLV (T3). The primary outcome was 8-isoprostane levels in EBC at T1, T2, and T3. Secondary outcomes included the following: NO2+NO3, H2O2 levels, and pH in EBC and in blood (8-isoprostane, NO2+NO3) and pulmonary gas exchange variables (PaO2/FiO2, A-aDO2, a/A ratio, and respiratory index). RESULTS: Patients subjected to RIPC had lower EBC 8-isoprostane levels when compared with controls at T1, T2, and T3 (differences between means and 95% confidence intervals): -15.3 (5.8-24.8), P = .002; -20.0 (5.5-34.5), P = .008; and -10.4 (2.5-18.3), P = .011, respectively. In the RIPC group, EBC NO2+NO3 and H2O2 levels were also lower than in controls at T2 and T1-T3, respectively (all P < .05). Blood levels of 8-isoprostane and NO2+NO3 were lower in the RIPC group at T2 (P < .05). The RIPC group had better PaO2/FiO2 compared with controls at 2 hours, 8 hours, and 24 hours after lobectomy in 95% confidence intervals for differences between means: 78 (10-146), 66 (14-118), and 58 (12-104), respectively. CONCLUSIONS: Limb RIPC decreased EBC 8-isoprostane levels and other oxidative lung injury markers during lung lobectomy. RIPC also improved postoperative gas exchange as measured by PaO2/FiO2 ratio.

The accuracy of postoperative, non-invasive Air-Test to diagnose atelectasis in healthy patients after surgery: a prospective, diagnostic pilot study.

OBJECTIVE: To assess the diagnostic accuracy of peripheral capillary oxygen saturation (SpO2) while breathing room air for 5 min (the 'Air-Test') in detecting postoperative atelectasis. DESIGN: Prospective cohort study. Diagnostic accuracy was assessed by measuring the agreement between the index test and the reference standard CT scan images. SETTING: Postanaesthetic care unit in a tertiary hospital in Spain. PARTICIPANTS: Three hundred and fifty patients from 12 January to 7 February 2015; 170 patients scheduled for surgery under general anaesthesia who were admitted into the postsurgical unit were included. INTERVENTION: The Air-Test was performed in conscious extubated patients after a 30 min stabilisation period during which they received supplemental oxygen therapy via a venturi mask. The Air-Test was defined as positive when SpO2 was ≤96% and negative when SpO2 was ≥97%. Arterial blood gases were measured in all patients at the end of the Air-Test. In the subsequent 25 min, the presence of atelectasis was evaluated by performing a CT scan in 59 randomly selected patients. MAIN OUTCOME MEASURES: The primary study outcome was assessment of the accuracy of the Air-Test for detecting postoperative atelectasis compared with the reference standard. The secondary outcome was the incidence of positive Air-Test results. RESULTS: The Air-Test diagnosed postoperative atelectasis with an area under the receiver operating characteristic curve of 0.90 (95% CI 0.82 to 0.98) with a sensitivity of 82.6% and a specificity of 87.8%. The presence of atelectasis was confirmed by CT scans in all patients (30/30) with positive and in 5 patients (17%) with negative Air-Test results. Based on the Air-Test, postoperative atelectasis was present in 36% of the patients (62 out of 170). CONCLUSION: The Air-Test may represent an accurate, simple, inexpensive and non-invasive method for diagnosing postoperative atelectasis. TRIAL REGISTRATION: NCT02650037.