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Purpose: Although noninvasive ventilation (NIV) may reduce reintubation in patients with acute hypoxemic respiratory failure following abdominal surgery, this strategy has not been specifically assessed in patients with obesity., Methods: We conducted a post hoc analysis of a multicenter randomized controlled trial comparing NIV delivered via facial mask to standard oxygen therapy among patients with obesity and acute hypoxemic respiratory failure within 7 days after abdominal surgery. The primary outcome was reintubation within 7 days. Secondary outcomes were invasive ventilation-free days at day 30, intensive care unit (ICU)-acquired pneumonia and 30-day survival., Results: Among 293 patients with hypoxemic respiratory failure following abdominal surgery, 76 (26%) patients had obesity and were included in the intention-to-treat analysis. Reintubation rate was significantly lower with NIV (13/42, 31%) than with standard oxygen therapy (19/34, 56%) within 7 days (absolute difference: - 25%, 95% confidence interval (CI) - 49 to - 1%, p = 0.03). NIV was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (27.1 ± 8.6 vs 22.7 ± 11.1 days; p = 0.02), while fewer patients developed ICU-acquired pneumonia (1/42, 2% vs 6/34, 18%; p = 0.04). The 30-day survival was 98% in the NIV group (41/42) versus 85% in the standard oxygen therapy (p = 0.08). In patients with body mass index (BMI) < 30 kg/m 2 , no significant difference was observed between NIV (36/105, 34%) and standard oxygen therapy (47/109, 43%, p = 0.03). An interaction test showed no statistically significant difference between the two subsets (BMI ≥ 30 kg/m 2 and BMI < 30 kg/m 2 )., Conclusions: Among patients with obesity and hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of reintubation within 7 days, contrary to patients without obesity. However, no interaction was found according to the presence of obesity or not, suggesting either a lack of power to conclude in the non-obese subgroup despite existing differences, or that the statistical difference found in the overall sample was driven by a large effect in the obese subsets., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: "Macintosh"-videolaryngoscopes (VLs) are VLs that allow both direct and indirect laryngoscopy for intubation. We describe the decision-making and implementation-processes that our hospital used regarding the choice of device. We compared the performances of 4 Macintosh-VLs both in direct and indirect laryngoscopy., Methods: A quality-improvement-project for airway management aiming at implementing Macintosh-VL for all intubation procedures performed in the operating room, involving 4 Macintosh-VLs (McGrath-Mac, C-MAC-S, C-MAC-S-Pocket-Monitor [PM], and APA). Three consecutive steps were described: (1) direct laryngoscopy with Macintosh-VL, (2) indirect laryngoscopy with Macintosh-VL (intubation attempt with Macintosh-style blade in case of Cormack I or II), (3) intubation attempt with hyperangulated blade in case of Cormack III/IV or failure of Macintosh-style blade. The main end point was the need to move to step III and use a hyperangulated blade. A mixed-effects multivariable logistic regression analysis was performed to compare devices on the main end point while considering site as a random effect. Comparison of means was performed using analysis of variance and Tukey's test for multiple comparisons (number of laryngoscopy attempts, numeric rate scale [NRS] difficulty of intubation and NRS user-friendliness). Comparison of percentages was performed using a χ2 test for the need to move to step III and a Kruskal-Wallis test for the quality of image (bad, passable, good, very good, excellent). A P value ≤.008 was considered statistically significant., Results: From May to September 2017, 589 patients were included. Using the McGrath-Mac (22/180 [12%]) was associated with less use of hyperangulated blade than using the C-MAC-S (39/132 [30%], odds ratio [OR] [99.2% confidence interval {CI}] 0.34 [0.16-0.77], P = .0005), the APA (35/138 [25%], OR [99.2% CI] 0.42 [0.19-0.93]; P = .004), but not the C-MAC-S-PM (29/139 [21%], OR [99.2% CI] 0.53 [0.23-1.2]; P = .04).Overall, the number of intubation attempts was significantly lower using the McGrath Mac than the C-MAC-S or the C-MAC-S-PMVLs. Subjective appreciation of intubation difficulty and user-friendliness of the devices showed respectively lower and higher NRS scores for the McGrath-Mac compared to the other devices, whereas subjective assessment of image quality showed higher quality for the C-MAC-S and C-MAC-S-PM compared to the APA or McGrath-Mac., Conclusions: Among 4 single-use Macintosh-VLs, glottic visualization in direct and indirect laryngoscopy with the Macintosh-style blade was significantly improved with the McGrath-Mac compared to other Macintosh-VLs, leading to a less frequent need to resort to the hyperangulated blade and reduced overall number of intubation attempts., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2020 International Anesthesia Research Society.)

Introduction: Hypoxaemia and hyperoxaemia may occur after surgery, with related complications. This multicentre randomised trial evaluated the impact of automated closed-loop oxygen administration after high-risk abdominal or thoracic surgeries in terms of optimising the oxygen saturation measured by pulse oximetry time within target range., Methods: After extubation, patients with an intermediate to high risk of post-operative pulmonary complications were randomised to "standard" or "automated" closed-loop oxygen administration. The primary outcome was the percentage of time within the oxygenation range, during a 3-day frame. The secondary outcomes were the time with hypoxaemia and hyperoxaemia under oxygen., Results: Among the 200 patients, time within range was higher in the automated group, both initially (≤3 h; 91.4±13.7% versus 40.2±35.1% of time, difference +51.0% (95% CI -42.8-59.2%); p<0.0001) and during the 3-day period (94.0±11.3% versus 62.1±23.3% of time, difference +31.9% (95% CI 26.3-37.4%); p<0.0001). Periods of hypoxaemia were reduced in the automated group (≤3 days; 32.6±57.8 min (1.2±1.9%) versus 370.5±594.3 min (5.0±11.2%), difference -10.2% (95% CI -13.9--6.6%); p<0.0001), as well as hyperoxaemia under oxygen (≤3 days; 5.1±10.9 min (4.8±11.2%) versus 177.9±277.2 min (27.0±23.8%), difference -22.0% (95% CI -27.6--16.4%); p<0.0001). Kaplan-Meier analysis depicted a significant difference in terms of hypoxaemia (p=0.01) and severe hypoxaemia (p=0.0003) occurrence between groups in favour of the automated group. 25 patients experienced hypoxaemia for >10% of the entire monitoring time during the 3 days within the standard group, as compared to the automated group (p<0.0001)., Conclusion: Automated closed-loop oxygen administration promotes greater time within the oxygenation target, as compared to standard manual administration, thus reducing the occurrence of hypoxaemia and hyperoxaemia., Competing Interests: Conflict of interest: E. L'Her reports other from Oxynov, during the conduct of the study; personal fees from Smiths Medical, personal fees and other from GE Healthcare, grants and personal fees from Sedana Medical, outside the submitted work. In addition, E. L'Her has a patent Method and device for delivering oxygen licensed to Oxynov. Conflict of interest: S. Jaber reports personal fees from Drager, Fisher-Paykel, Baxter, Fresenius-Xenios and Medtronic, during the conduct of the study. Conflict of interest: D. Verzilli has nothing to disclose. Conflict of interest: C. Jacob has nothing to disclose. Conflict of interest: B. Huiban has nothing to disclose. Conflict of interest: E. Futier reports consulting fees from Drager Medical, GE Healthcare, Orion Pharma and Edwards Lifesciences, lecture fees from Fresenius Kabi and Getinge, and non-financial support from Fisher and Paykel Healthcare, during the conduct of the study. Conflict of interest: T. Kerforne has nothing to disclose. Conflict of interest: V. Pateau reports other from OxyNov, during the conduct of the study. Conflict of interest: P-A. Bouchard has nothing to disclose. Conflict of interest: M. Consigny has nothing to disclose. Conflict of interest: F. Lellouche reports other from Oxynov, during the conduct of the study., (Copyright ©ERS 2021.)

The obese patient is at risk of perioperative complications including difficult airway access (intubation, difficult or impossible ventilation), and postextubation acute respiratory failure due to the formation of atelectases or to airway obstruction. The association of obstructive sleep apnoea syndrome (OSA) with obesity is very common, and induces a high risk of per and postoperative complications. Preoperative OSA screening is crucial in the obese patient, as well as its specific management: use of continuous positive pre-, per- and postoperative pressure. For any obese patient, the implementation of difficult intubation protocols and the use of protective ventilation (low tidal volume 6-8mL/kg of ideal body weight, moderate positive end-expiratory pressure of 10cmH20, recruitment manoeuvres in absence of contra-indications), with morphine sparing and semi-seated positioning as much as possible are recommended, associated with a close postoperative monitoring. The dosage of anaesthetic drugs is usually based on the ideal body weight or the adjusted body weight and then titrated, except for succinylcholine that is dosed according to the total body weight. Monitoring of neuromuscular blockers should be used where appropriate, as well as monitoring of the depth of anaesthesia, especially when total intravenous anaesthesia is used in association with neuromuscular blockers. The occurrence of intraoperative awareness is indeed more frequent in the obese patient than in the non-obese patient. Appropriate prophylaxis against venous thromboembolism and early mobilisation are recommended, if possible included in an early rehabilitation protocol, to further reduce postoperative complications., (Copyright © 2020 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Importance: It is not known if use of colloid solutions containing hydroxyethyl starch (HES) to correct for intravascular deficits in high-risk surgical patients is either effective or safe., Objective: To evaluate the effect of HES 130/0.4 compared with 0.9% saline for intravascular volume expansion on mortality and postoperative complications after major abdominal surgery., Design, Setting, and Participants: Multicenter, double-blind, parallel-group, randomized clinical trial of 775 adult patients at increased risk of postoperative kidney injury undergoing major abdominal surgery at 20 university hospitals in France from February 2016 to July 2018; final follow-up was in October 2018., Interventions: Patients were randomized to receive fluid containing either 6% HES 130/0.4 diluted in 0.9% saline (n = 389) or 0.9% saline alone (n = 386) in 250-mL boluses using an individualized hemodynamic algorithm during surgery and for up to 24 hours on the first postoperative day, defined as ending at 7:59 am the following day., Main Outcomes and Measures: The primary outcome was a composite of death or major postoperative complications at 14 days after surgery. Secondary outcomes included predefined postoperative complications within 14 days after surgery, durations of intensive care unit and hospital stays, and all-cause mortality at postoperative days 28 and 90., Results: Among 826 patients enrolled (mean age, 68 [SD, 7] years; 91 women [12%]), 775 (94%) completed the trial. The primary outcome occurred in 139 of 389 patients (36%) in the HES group and 125 of 386 patients (32%) in the saline group (difference, 3.3% [95% CI, -3.3% to 10.0%]; relative risk, 1.10 [95% CI, 0.91-1.34]; P = .33). Among 12 prespecified secondary outcomes reported, 11 showed no significant difference, but a statistically significant difference was found in median volume of study fluid administered on day 1: 1250 mL (interquartile range, 750-2000 mL) in the HES group and 1500 mL (interquartile range, 750-2150 mL) in the saline group (median difference, 250 mL [95% CI, 83-417 mL]; P = .006). At 28 days after surgery, 4.1% and 2.3% of patients had died in the HES and saline groups, respectively (difference, 1.8% [95% CI, -0.7% to 4.3%]; relative risk, 1.76 [95% CI, 0.79-3.94]; P = .17)., Conclusions and Relevance: Among patients at risk of postoperative kidney injury undergoing major abdominal surgery, use of HES for volume replacement therapy compared with 0.9% saline resulted in no significant difference in a composite outcome of death or major postoperative complications within 14 days after surgery. These findings do not support the use of HES for volume replacement therapy in such patients., Trial Registration: ClinicalTrials.gov Identifier: NCT02502773.

The obese patient is at an increased risk of perioperative complications. Most importantly, these include difficult access to the airways (intubation, difficult or impossible ventilation), and post-extubation respiratory distress secondary to the development of atelectasis or obstruction of the airways, sometimes associated with the use of morphine derivatives. The association of obstructive sleep apnea syndrome (OSA) with obesity is very common, and induces a high risk of peri- and postoperative complications. Preoperative OSA screening is crucial in the obese patient, as well as its specific management: use of continuous positive pre, per and postoperative pressure. For any obese patient, the implementation of protocols for mask ventilation and/or difficult intubation and the use of protective ventilation, morphine-sparing strategies and a semi-seated positioning throughout the care, is recommended, combined with close monitoring postoperatively. The dosage of anesthetic drugs should be based on the theoretical ideal weight and then titrated, rather than dosed to the total weight. Monitoring of neuromuscular blocking should be used where appropriate, as well as monitoring of the depth of anesthesia. The occurrence of intraoperative recall is indeed more frequent in the obese patient than in the non-obese patient. Appropriate prophylaxis against venous thromboembolic disease and early mobilization are recommended, as thromboembolic disease is increased in the obese patient. The use of non-invasive ventilation to prevent the occurrence of acute post-operative respiratory failure and for its treatment is particularly effective in obese patients. In case of admission to ICU, an individualized ventilatory management based on pathophysiology and careful monitoring should be initiated., (Copyright © 2019 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2019. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2019 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

Introduction: Hypoxemia and hyperoxia may occur after surgery with potential related complications. The FreeO 2 PostOp trial is a prospective, multicentre, randomised controlled trial that evaluates the clinical impact of automated O 2 administration versus conventional O 2 therapy after major abdominal or thoracic surgeries. The study is powered to demonstrate benefits of automated oxygen titration and weaning in term of oxygenation, which is an important surrogate for complications after such interventions., Methods and Analysis: After extubation, patients are randomly assigned to the Standard (manual O 2 administration) or FreeO 2 group (automated closed-loop O 2 administration). Stratification is performed for the study centre and a medical history of chronic obstructive pulmonary disease (COPD). Primary outcome is the percentage of time spent in the target zone of oxygen saturation, during a 3-day time frame. In both groups, patients will benefit from continuous oximetry recordings. The target zone of oxygen saturation is SpO 2 =88%-92% for patients with COPD and 92%-96% for patients without COPD. Secondary outcomes are the nursing workload assessed by the number of manual O 2 flow adjustments, the time spent with severe desaturation (SpO 2 <85%) and hyperoxia area (SpO 2 >98%), the time spent in a hyperoxia area (SpO 2 >98%), the VO 2 , the duration of oxygen administration during hospitalisation, the frequency of use of mechanical ventilation (invasive or non-invasive), the duration of the postrecovery room stay, the hospitalisation length of stay and the survival rate., Ethics and Dissemination: The FreeO 2 PostOp study is conducted in accordance with the declaration of Helsinki and was registered on 11 September 2015 (http://www.clinicaltrials.gov). First patient inclusion was performed on 14 January 2016. The results of the study will be presented at academic conferences and submitted to peer-reviewed journals., Trial Registration Number: NCT02546830., Competing Interests: Competing interests: EL’h reports lecture fees and travel expenses for lectures given at academic meetings from GE Healthcare, Sedana Medical, Smiths Medical, Air Liquide Medical Systems. EL’h and FL are the inventors of the FreeO2 device and founded Oxynov Inc. to develop the commercial device. The firm Oxynov Inc. provides the automated oxygen therapy equipment to all the participating centres but has no other involvement in the study., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The targeting of hepatocellular carcinomas (HCC) in the hepatic dome can be challenging during percutaneous thermal ablation (PTA). The aims of this study were (1) to evaluate the safety and efficacy of PTA of HCC in the hepatic dome that cannot be visualized under US, using artificial CO2 pneumothorax and CT-guidance and (2) to compare the results with US-visible HCC located in the liver dome treated under US-guidance., Materials: Over a 32-month period, 56 HCC located in the hepatic dome were extracted from a prospectively maintained database. Twenty-eight cases (US-guidance group) were treated under US-guidance, while the others (n = 28, CT-CO2 group) were treated under CT-guidance using artificial CO2 pneumothorax after lipiodol tagging of the tumor. The primary technical success and complications rates of this technique were retrospectively assessed. Local tumor progression (LTP), intrahepatic distant recurrence (IDR), local recurrence-free survival (LRFS) and overall survival (OS) were also compared between both groups., Results: Primary technical success was 100% in both groups. No major complications occurred. After a median follow-up of 13.8 months (range, 1-33.4 months), LTP occurred in 10.7% (3/28) in CT-CO2 vs. 25% (7/28) in the US-guidance group (p = NS). IDR occurred in 39.3% (11/28) in CT-CO2 vs. 28.6% (8/28) in the US-guidance group (p = NS). Death occurred in 17.9% (5/28) of patients in both groups. LRFS and OS did not significantly differ using Kaplan-Meier survival estimates., Conclusion: CT-guided PTA after artificially induced CO2 pneumothorax is a safe and efficient technique to treat HCC located in the hepatic dome.

Purpose: The relation between driving pressure (plateau pressure-positive end-expiratory pressure) and mortality has never been studied in obese ARDS patients. The main objective of this study was to evaluate the relationship between 90-day mortality and driving pressure in an ARDS population ventilated in the intensive care unit (ICU) according to obesity status., Methods: We conducted a retrospective single-center study of prospectively collected data of all ARDS patients admitted consecutively to a mixed medical-surgical adult ICU from January 2009 to May 2017. Plateau pressure, compliance of the respiratory system (Crs) and driving pressure of the respiratory system within 24 h of ARDS diagnosis were compared between survivors and non-survivors at day 90 and between obese (body mass index ≥ 30 kg/m 2 ) and non-obese patients. Cox proportional hazard modeling was used for mortality at day 90., Results: Three hundred sixty-two ARDS patients were included, 262 (72%) non-obese and 100 (28%) obese patients. Mortality rate at day 90 was respectively 47% (95% CI, 40-53) in the non-obese and 46% (95% CI, 36-56) in the obese patients. Driving pressure at day 1 in the non-obese patients was significantly lower in survivors at day 90 (11.9 ± 4.2 cmH 2 O) than in non-survivors (15.2 ± 5.2 cmH 2 O, p < 0.001). Contrarily, in obese patients, driving pressure at day 1 was not significantly different between survivors (13.7 ± 4.5 cmH 2 O) and non-survivors (13.2 ± 5.1 cmH 2 O, p = 0.41) at day 90. After three multivariate Cox analyses, plateau pressure [HR = 1.04 (95% CI 1.01-1.07) for each point of increase], Crs [HR = 0.97 (95% CI 0.96-0.99) for each point of increase] and driving pressure [HR = 1.07 (95% CI 1.04-1.10) for each point of increase], respectively, were independently associated with 90-day mortality in non-obese patients, but not in obese patients., Conclusions: Contrary to non-obese ARDS patients, driving pressure was not associated with mortality in obese ARDS patients.

Obesity is often associated with obstructive sleep apnea (OSA), which increases the risk of intraoperative and postoperative complications. The role of preoperative screening of OSA is crucial, with adequate management based on continuous positive pressure before, during and after surgery. The obese patient is at risk of postoperative complications: difficult airway management, acute respiratory failure following extubation due to atelectasis and airway obstruction, added to morphine overdosing. Optimal management of difficult mask ventilation and intubation, protective ventilation, combined to the reduction of sedatives and analgesics and the sitting position as soon as possible with a postoperative monitoring should decrease the occurrence of complications. Cardiovascular risk is also increased in the obese patient. Preoperative screening of cardiovascular complications with appropriate therapy, combined to per- and postoperative hemodynamic optimization with a close monitoring allow to limit the cardiovascular risk. Drug dosing titration is fundamental due to unknown pharmacokinetic and pharmacodynamics properties in obese patients. Neuromuscular monitoring should always be used whenever neuromuscular blocking drugs are used, as depth of anaesthesia monitoring, especially when total intravenous anaesthesia is used in conjunction with neuromuscular blocking drugs. Appropriate prophylaxis against venous thromboembolism (VTE) after assessment of risk benefit ratio and early mobilisation are recommended since the incidence of venous thromboembolism is increased in the obese., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objectives: To determine the short- and long-term mortality of obese ICU patients following medical as opposed to surgical admission and the relation between obesity and mortality., Design: Retrospective analysis of prospectively collected data, using a propensity score-matched analysis of patients with medical or surgical admission., Setting: One French mixed medical-surgical ICU., Patients: Critically ill obese patients (body mass index ≥ 30 kg/m) and nonobese patients admitted during a 14-year period., Interventions: None., Measurements and Main Results: Seven-hundred ninety-one obese patients and 4,644 nonobese patients were included, 338 (43%) and 2,367 (51%) medical and 453 (57%) and 2,277 (49%) surgical obese and nonobese patients, respectively. Mortality was significantly higher in medical than in surgical obese patients in ICU (25% vs 12%; p < 0.001) and up to 365 days (36% vs 18%; p < 0.001) post ICU admission. One-to-one propensity score matching generated 260 pairs with well-balanced baseline characteristics. After matching on propensity score, mortality was still significantly higher in medical patients both in the ICU (21% vs 13%; p = 0.03) and up to 365 days (30% vs 20%; p = 0.01) post ICU admission. Obesity was not significantly associated with mortality both in univariate analysis (140 obese patients [15%] in the dead group vs 651 [14%] in the alive group; p = 0.72) and multivariate analysis (odds ratio, 1.09 [95% CI, 0.86-1.38]; p = 0.49) after adjustment for Simplified Acute Physiology Score II, age, category of admission, history of cardiac disease, and history of respiratory disease., Conclusions: After careful matching, the data suggest that ICU mortality in obese population was higher in the medical group than in the surgical group and remains significantly higher 365 days post ICU admission.

Objective: The aim of this study was to assess the safety and efficacy of extended liver venous deprivation (eLVD), i.e. combination of right portal vein embolisation and right (accessory right) and middle hepatic vein embolisation before major hepatectomy for future remnant liver (FRL) functional increase., Methods: eLVD was performed in non-cirrhotic patients referred for major hepatectomy in a context of small FRL (baseline FRL <25% of the total liver volume or FRL function <2.69%/min/m 2 ). All patients underwent 99m Tc-mebrofenin hepatobiliary scintigraphy (HBS) and computed tomographic evaluations., Results: Ten consecutive patients underwent eLVD before surgery for liver metastases (n = 8), Klatskin tumour (n = 1) and gallbladder carcinoma (n = 1). FRL function increased by 64.3% (range = 28.1-107.5%) at day 21. In patients with serial measurements, maximum FRL function was at day 7 (+65.7 ± 16%). The FRL volume increased by +53.4% at 7 days (+25 ± 8 cc/day). Thirty-one days (range = 22-45 days) after eLVD, 9/10 patients were resected. No post-hepatectomy liver failure was reported. Two grade II and one grade III complications (Dindo-Clavien classification) occurred. No patient died with-in 90 days following surgery., Conclusions: eLVD is safe and provides a marked and very rapid increase in liver function, unprecedented for an interventional radiology procedure., Key Points: • eLVD is safe • eLVD provides a marked and very rapid increase in liver function • After eLVD, the FRL-F increased by 64.3% (28.1-107.5%) at day 21 • After eLVD, the maximum FRL-F was obtained at day 7 (+65.7 ± 16%) • After eLVD, the FRL volume increased by +53.4% at 7 days (+25 ± 8 cc/day).

Head and neck paragangliomas (HNPGLs) are rare tumors that may cause important morbidity, because of their tendency to infiltrate the skull base. At present, surgery is the only therapeutic option, but radical removal may be difficult or impossible. Thus, effective targets and molecules for HNPGL treatment need to be identified. However, the lack of cellular models for this rare tumor hampers this task. PPARα receptor activation was reported in several tumors and this receptor appears to be a promising therapeutic target in different malignancies. Considering that the role of PPARα in HNPGLs was never studied before, we analyzed the potential of modulating PPARα in a unique model of HNPGL cells. We observed an intense immunoreactivity for PPARα in HNPGL tumors, suggesting that this receptor has an important role in HNPGL. A pronounced nuclear expression of PPARα was also confirmed in HNPGL-derived cells. The specific PPARα agonist WY14643 had no effect on HNPGL cell viability, whereas the specific PPARα antagonist GW6471 reduced HNPGL cell viability and growth by inducing cell cycle arrest and caspase-dependent apoptosis. GW6471 treatment was associated with a marked decrease of CDK4, cyclin D3 and cyclin B1 protein expression, along with an increased expression of p21 in HNPGL cells. Moreover, GW6471 drastically impaired clonogenic activity of HNPGL cells, with a less marked effect on cell migration. Notably, the effects of GW6471 on HNPGL cells were associated with the inhibition of the PI3K/GSK3β/β-catenin signaling pathway. In conclusion, the PPARα antagonist GW6471 reduces HNPGL cell viability, interfering with cell cycle and inducing apoptosis. The mechanisms affecting HNPGL cell viability involve repression of the PI3K/GSK3β/β-catenin pathway. Therefore, PPARα could represent a novel therapeutic target for HNPGL.

Purpose: High-flow nasal cannula (HFNC) oxygen therapy is attracting increasing interest in acute medicine as an alternative to standard oxygen therapy; however, its use to prevent hypoxaemia after major abdominal surgery has not been evaluated. Our trial was designed to close this evidence gap., Methods: A multicentre randomised controlled trial was carried out at three university hospitals in France. Adult patients at moderate to high risk of postoperative pulmonary complications who had undergone major abdominal surgery using lung-protective ventilation were randomly assigned using a computer-generated sequence to receive either HFNC oxygen therapy or standard oxygen therapy (low-flow oxygen delivered via nasal prongs or facemask) directly after extubation. The primary endpoint was absolute risk reduction (ARR) for hypoxaemia at 1 h after extubation and after treatment discontinuation. Secondary outcomes included occurrence of postoperative pulmonary complications within 7 days after surgery, the duration of hospital stay, and in-hospital mortality. The analysis was performed on data from the modified intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT01887015)., Results: Between 6 November 2013 and 1 March 2015, 220 patients were randomly assigned to receive either HFNC (n = 108) or standard oxygen therapy (n = 112); all of these patients completed follow-up. The median duration of the allocated treatment was 16 h (interquartile range 14-18 h) with standard oxygen therapy and 15 h (interquartile range 12-18) with HFNC therapy. Twenty-three (21 %) of the 108 patients treated with HFNC 1 h after extubation and 29 (27 %) of the 108 patients after treatment discontinuation had postextubation hypoxaemia, compared with 27 (24 %) and 34 (30 %) of the 112 patients treated with standard oxygen (ARR 4, 95 % CI -8 to 15 %; p = 0.57; adjusted relative risk [RR] 0.87, 95 % CI 0.53-1.43; p = 0.58). Over the 7-day postoperative follow-up period, there was no statistically significant difference between the groups in the proportion of patients who remained free of any pulmonary complication (ARR 7, 95 % CI -6 to 20 %; p = 0.40). Other secondary outcomes also did not differ significantly between the two groups., Conclusions: Among patients undergoing major abdominal surgery, early preventive application of high-flow nasal cannula oxygen therapy after extubation did not result in improved pulmonary outcomes compared with standard oxygen therapy.

Background: Genome-wide association studies have identified more than 60 single nucleotide polymorphisms associated with Body Mass Index (BMI). Additional genetic variants, such as copy number variations (CNV), have also been investigated in relation to BMI. Recently, the highly polymorphic CNV in the salivary amylase (AMY1) gene, encoding an enzyme implicated in the first step of starch digestion, has been associated with obesity in adults and children. We assessed the potential association between AMY1 copy number and a wide range of BMI in a population of Italian school-children., Methods: 744 children (354 boys, 390 girls, mean age (±SD): 8.4±1.4years) underwent anthropometric assessments (height, weight) and collection of saliva samples for DNA extraction. AMY1 copies were evaluated by quantitative PCR., Results: A significant increase of BMI z-score by decreasing AMY1 copy number was observed in boys (β: -0.117, p = 0.033), but not in girls. Similarly, waist circumference (β: -0.155, p = 0.003, adjusted for age) was negatively influenced by AMY1 copy number in boys. Boys with 8 or more AMY1 copy numbers presented a significant lower BMI z-score (p = 0.04) and waist circumference (p = 0.01) when compared to boys with less than 8 copy numbers., Conclusions: In this pediatric-only, population-based study, a lower AMY1 copy number emerged to be associated with increased BMI in boys. These data confirm previous findings from adult studies and support a potential role of a higher copy number of the salivary AMY1 gene in protecting from excess weight gain.

Importance: It has not been established whether noninvasive ventilation (NIV) reduces the need for invasive mechanical ventilation in patients who develop hypoxemic acute respiratory failure after abdominal surgery., Objective: To evaluate whether noninvasive ventilation improves outcomes among patients developing hypoxemic acute respiratory failure after abdominal surgery., Design, Setting, and Participants: Multicenter, randomized, parallel-group clinical trial conducted between May 2013 and September 2014 in 20 French intensive care units among 293 patients who had undergone abdominal surgery and developed hypoxemic respiratory failure (partial oxygen pressure <60 mm Hg or oxygen saturation [SpO2] ≤90% when breathing room air or <80 mm Hg when breathing 15 L/min of oxygen, plus either [1] a respiratory rate above 30/min or [2] clinical signs suggestive of intense respiratory muscle work and/or labored breathing) if it occurred within 7 days after surgical procedure., Interventions: Patients were randomly assigned to receive standard oxygen therapy (up to 15 L/min to maintain SpO2 of 94% or higher) (n = 145) or NIV delivered via facial mask (inspiratory pressure support level, 5-15 cm H2O; positive end-expiratory pressure, 5-10 cm H2O; fraction of inspired oxygen titrated to maintain SpO2 ≥94%) (n = 148)., Main Outcomes and Measures: The primary outcome was tracheal reintubation for any cause within 7 days of randomization. Secondary outcomes were gas exchange, invasive ventilation-free days at day 30, health care-associated infections, and 90-day mortality., Results: Among the 293 patients (mean age, 63.4 [SD, 13.8] years; n=224 men) included in the intention-to-treat analysis, reintubation occurred in 49 of 148 (33.1%) in the NIV group and in 66 of 145 (45.5%) in the standard oxygen therapy group within+ 7 days after randomization (absolute difference, -12.4%; 95% CI, -23.5% to -1.3%; P = .03). Noninvasive ventilation was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (25.4 vs 23.2 days; absolute difference, -2.2 days; 95% CI, -0.1 to 4.6 days; P = .04), while fewer patients developed health care-associated infections (43/137 [31.4%] vs 63/128 [49.2%]; absolute difference, -17.8%; 95% CI, -30.2% to -5.4%; P = .003). At 90 days, 22 of 148 patients (14.9%) in the NIV group and 31 of 144 (21.5%) in the standard oxygen therapy group had died (absolute difference, -6.5%; 95% CI, -16.0% to 3.0%; P = .15). There were no significant differences in gas exchange., Conclusions and Relevance: Among patients with hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of tracheal reintubation within 7 days. These findings support use of NIV in this setting., Trial Registration: clinicaltrials.gov Identifier: NCT01971892.

Background: Intubation procedure in obese patients is a challenging issue both in the intensive care unit (ICU) and in the operating theatre (OT). The objectives of the study were (i) to compare the incidence of difficult intubation and (ii) its related complications in obese patients admitted to ICU and OT., Methods: We conducted a multicentre prospective observational cohort study in ICU and OT in obese (BMI≥30 kg m(-2)) patients. The primary endpoint was the incidence of difficult intubation. Secondary endpoints were the risk factors for difficult intubation, the use of difficult airway management techniques, and severe life-threatening complications related to intubation (death, cardiac arrest, severe hypoxaemia, severe cardiovascular collapse)., Results: In cohorts of 1400 and 11 035 consecutive patients intubated in ICU and in the OT, 282 (20%) and 2103 (19%) were obese. In obese patients, the incidence of difficult intubation was twice more frequent in ICU than in the OT (16.3% vs 8.2%, P<0.01). In both cohorts, risk factors for difficult intubation were Mallampati score III/IV, obstructive sleep apnoea syndrome, and reduced mobility of cervical spine, while limited mouth opening, severe hypoxaemia, and coma appeared only in ICU. Specific difficult airway management techniques were used in 66 (36%) cases of difficult intubation in obese patients in the OT and in 10 (22%) cases in ICU (P=0.04). Severe life-threatening complications were significantly more frequent in ICU than in the OT (41.1% vs 1.9%, relative risk 21.6, 95% confidence interval 15.4-30.3, P<0.01)., Conclusions: In obese patients, the incidence of difficult intubation was twice more frequent in ICU than in the OT and severe life-threatening complications related to intubation occurred 20-fold more often in ICU., Clinical Trial Registration: Current controlled trials. Identifier: NCT01532063., (© The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

During the past few years, many manufacturers have developed a new generation anesthesia ventilators or anesthesia workstations with innovative technology and introduced so-called new ventilatory modes in the operating room. The aim of this article is to briefly explain how an anesthesia ventilator works, to describe the main differences between the technologies used, to describe the main criteria for evaluating technical and pneumatic performances and to list key elements not to be forgotten during the process of acquiring an anesthesia ventilator., (Copyright © 2014. Published by Elsevier SAS.)

Background: Lung-protective ventilation with the use of low tidal volumes and positive end-expiratory pressure is considered best practice in the care of many critically ill patients. However, its role in anesthetized patients undergoing major surgery is not known., Methods: In this multicenter, double-blind, parallel-group trial, we randomly assigned 400 adults at intermediate to high risk of pulmonary complications after major abdominal surgery to either nonprotective mechanical ventilation or a strategy of lung-protective ventilation. The primary outcome was a composite of major pulmonary and extrapulmonary complications occurring within the first 7 days after surgery., Results: The two intervention groups had similar characteristics at baseline. In the intention-to-treat analysis, the primary outcome occurred in 21 of 200 patients (10.5%) assigned to lung-protective ventilation, as compared with 55 of 200 (27.5%) assigned to nonprotective ventilation (relative risk, 0.40; 95% confidence interval [CI], 0.24 to 0.68; P=0.001). Over the 7-day postoperative period, 10 patients (5.0%) assigned to lung-protective ventilation required noninvasive ventilation or intubation for acute respiratory failure, as compared with 34 (17.0%) assigned to nonprotective ventilation (relative risk, 0.29; 95% CI, 0.14 to 0.61; P=0.001). The length of the hospital stay was shorter among patients receiving lung-protective ventilation than among those receiving nonprotective ventilation (mean difference, -2.45 days; 95% CI, -4.17 to -0.72; P=0.006)., Conclusions: As compared with a practice of nonprotective mechanical ventilation, the use of a lung-protective ventilation strategy in intermediate-risk and high-risk patients undergoing major abdominal surgery was associated with improved clinical outcomes and reduced health care utilization. (IMPROVE ClinicalTrials.gov number, NCT01282996.).

Objective: To determined whether the implementation of an intubation management protocol leads to the reduction of intubation-related complications in the intensive care unit (ICU)., Design: Two-phase, prospective, multicenter controlled study., Setting: Three medical-surgical ICUs in two university hospitals., Patients: Two hundred three consecutive ICU patients required 244 intubations., Interventions: All intubations performed during two consecutive phases (a 6-month quality control phase followed by a 6-month intervention phase based on the implementation of an ICU intubation bundle management protocol) were evaluated. The ten bundle components were: preoxygenation with noninvasive positive pressure ventilation, presence of two operators, rapid sequence induction, cricoid pressure, capnography, protective ventilation, fluid loading, preparation and early administration of sedation and vasopressor use if needed., Measurements and Main Results: The primary end points were the incidence of life-threatening complications occurring within 60 min after intubation (cardiac arrest or death, severe cardiovascular collapse and hypoxemia). Other complications (mild to moderate) were also evaluated. Baseline characteristics, including demographic data and reason for intubation (mainly acute respiratory failure), were similar in the two phases. The intubation procedure in the intervention phase (n = 121) was associated with significant decreases in both life-threatening complications (21 vs. 34%, p = 0.03) and other complications (9 vs. 21%, p = 0.01) compared to the control phase (n = 123)., Conclusions: The implementation of an intubation management protocol can reduce immediate severe life-threatening complications associated with intubation of ICU patients.

Introduction: To examine the effects of positive end-expiratory pressure (PEEP) on intra-abdominal pressure (IAP) in patients with acute lung injury (ALI)., Methods: Thirty sedated and mechanically ventilated patients with ALI or acute respiratory distress syndrome (ARDS) admitted to a sixteen-bed surgical medical ICU were included. All patients were studied with sequentially increasing PEEP (0, 6 and 12 cmH2O) during a PEEP-trial., Results: Age was 55 ± 17 years, weight was 70 ± 17 kg, SAPS II was 44 ± 14 and PaO2/FIO2 was 192 ± 53 mmHg. The IAP was 12 ± 5 mmHg at PEEP 0 (zero end-expiratory pressure, ZEEP), 13 ± 5 mmHg at PEEP 6 and 15 ± 6 mmHg at PEEP 12 (P < 0.05 vs ZEEP). In the patients with intra-abdominal hypertension defined as IAP ≥ 12 mmHg (n = 15), IAP significantly increased from 15 ± 3 mmHg at ZEEP to 20 ± 3 mmHg at PEEP 12 (P < 0.01). Whereas in the patients with IAP < 12 mmHg (n = 15), IAP did not significantly change from ZEEP to PEEP 12 (8 ± 2 vs 10 ± 3 mmHg). In the 13 patients in whom cardiac output was measured, increase in PEEP from 0 to 12 cmH2O did not significantly change cardiac output, nor in the 8 out of 15 patients of the high-IAP group. The observed effects were similar in both ALI (n = 17) and ARDS (n = 13) patients., Conclusions: PEEP is a contributing factor that impacts IAP values. It seems necessary to take into account the level of PEEP whilst interpreting IAP values in patients under mechanical ventilation.

Objective: To measure (1) the discomfort in non-intubated patients under high-flow oxygen therapy (HFOT) humidified with bubble (BH) or heated humidifiers (HH), and (2) the hygrometric properties of oxygen with a BH and an HH., Design and Setting: This was a randomized cross-over study in critically ill patients during a 3-day period. The humidification device used at days 1 and 3 was changed for the other at day 2. (2) It was also an experimental bench study using the psychrometric method with five randomized flows (3, 6, 9, 12 and 15 l/min) and different humidification techniques., Methods: Discomfort, particularly dryness of the mouth and throat, was measured for two humidification conditions (BH and HH) using a 0-10 numerical rating scale (NRS) by patients requiring HFOT with a face mask at a flow >/=5 l/min, in a double-blinded condition., Results: (1) In this clinical study, 30 patients treated by HFOT at a median flow of 7.8 l/min (5.1-10.9) were included. The global incidence of moderate (NRS = 4-6) and severe discomfort (NRS = 7-10) was 25 and 29%, respectively. The median intensities of both mouth and throat dryness were significantly lower with the HH than with the BH [7.8 (5.0-9.4) vs. 5.0 (3.1-7.0), P = 0.001 and 5.8 (2.3-8.5) vs. 4.3 (2.0-5.0), P = 0.005, respectively]. (2) In the bench study, the mean absolute humidity measured at an ambient temperature of 26 degrees C with the HH was two times greater than with the BH (30 +/- 1 vs. 16 +/- 2 mg/l, P < 0.05) regardless of the flow rate., Conclusions: Compared to bubble humidifiers, the use of a heated-humidifier in patients with high-flow oxygen therapy is associated with a decrease of dryness symptoms mediated by increased humidity delivered to the patient.

Background: Dual-control modes of ventilation adapt the pressure delivery to keep a volume target in response to changes in respiratory mechanics, but they may respond poorly to changes in ventilatory demand. Adaptive support ventilation (ASV), a complex minute volume-targeted pressure-regulated ventilation, was compared to adaptive pressure ventilation (APV), a dual-mode in which the pressure level is adjusted to deliver a preset tidal volume, and to pressure support ventilation (PSV) when facing an increase in ventilatory demand., Methods: A total of 14 intensive care unit patients being weaned off mechanical ventilation were included in this randomized crossover study. The effect of adding a heat-and-moisture exchanger to augment circuit dead space was assessed with a same fixed level of ASV, PSV, and APV., Results: Arterial blood gases, ventilator response, and patient respiratory effort parameters were evaluated at the end of the six periods. Adding dead space significantly increased minute ventilation and PaCO2 values with the three modes. Indexes of respiratory effort (pressure-time index of respiratory muscles and work of breathing) increased with all ventilatory modes after dead-space augmentation. This increase was significantly greater with APV than with PSV or ASV (P < 0.05). The assistance delivered during APV decreased significantly with dead-space from 12.7 +/- 2.6 to 6.7 +/- 1.4 cm H2O, whereas no change occurred with ASV and PSV., Conclusions: ASV and PSV behaved differently but ended up with similar pressure level facing acute changes in ventilatory demand, by contrast to APV (a simple volume-guaranteed pressure-control mode), in which an increase in ventilatory demand results in a decrease in the pressure support provided by the ventilator.

Objectives: Any delay in adequate antibiotic treatment compromises the outcome of ventilator-associated pneumonia (VAP). However, the diagnosis and optimal treatment of VAP remain a challenge for intensivists. We assessed the potential impact of using results of routine weekly endotracheal aspirate (EA) cultures to guide initial antibiotic treatment for VAP., Design and Setting: Retrospective analysis of prospectively collected data in a medical-surgical intensive care unit (ICU) of a university hospital., Patients and Methods: We studied 113 VAP episodes and evaluated the concordance between the latest EA and the broncho-alveolar lavage (BAL). We stratified patients into three groups: concordant EA-BAL (concordant group), discordant EA-BAL (discordant group) and EA not performed group. We then compared the adequacy of the antibiotic prescribed initially and outcomes between the three groups., Measurements and Main Results: Ninety assessable EA-BAL samples were evaluated. When guided by EA, the initial antibiotic regimen was adequate in 85% of situations, a proportion significantly superior (P < 0.05) to that resulting from application of the ATS guidelines (73%). When clinicians did not have a pre-VAP EA to guide their treatment (EA not performed group), only 61% of treatments were adequate. No significant difference was observed between the three groups for length of mechanical ventilation, length of ICU stay, nonpulmonary nosocomial infections and mortality., Conclusion: Once-a-week routine quantitative EA cultures may help to improve the adequacy of empiric antibiotic therapy for VAP.

Background: Noninvasive positive-pressure ventilation (NPPV) with pressure support-ventilation and positive end-expiratory pressure are effective in providing oxygenation during intubation in hypoxemic patients. We hypothesized administration of oxygen (O2) using NPPV would more rapidly increase the end-tidal O2 concentration (ETO2) than preoxygenation using spontaneous ventilation (SV) in morbidly obese patients., Methods: Twenty-eight morbidly obese patients were enrolled in this prospective randomized study. Administration of O2 for 5 min was performed either with SV group or with NPPV (pressure support = 8 cm H2O, positive end-expiratory pressure = 6 cm H2O) (NPPV group). ETO2 was measured using the anesthesia breathing circuit, and is expressed as a fraction of atmospheric concentration. The primary end-point was the number of patients with an ETo(2) >95% at the end of O2 administration. Secondary end-points included the time to reach the maximal ETO2 and the ETO2 at the conclusion of O2 administration., Results: A larger proportion of patients achieved a 95% ETO2 at 5 min with NPPV than SV (13/14 vs 7/14, P = 0.01). The time to reach the maximal ETO2 was significantly less in the NPPV than in the SV group (185 +/- 46 vs 222 +/- 42 s, P = 0.02). The mean ETO2 at the conclusion of O2 administration was larger in the NPPV group than the SV group (96.9 +/- 1.3 vs 94.1 +/- 2.0%, P < 0.001). A modest, although significant, increase in gastric distension was observed in the NPPV group. No adverse effects were observed in either group., Conclusion: Administration of O2 via a facemask with NPPV in the operating room is safe, feasible, and efficient in morbidly obese patients. In this population NPPV provides a more rapid O2 administration, achieving a higher ETO2.