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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.)

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.)

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.

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.

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.)

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.

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.

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.