Effects of non-invasive respiratory support in post-operative patients: a systematic review and network meta-analysis.

BACKGROUND: Re-intubation secondary to post-extubation respiratory failure in post-operative patients is associated with increased patient morbidity and mortality. Non-invasive respiratory support (NRS) alternative to conventional oxygen therapy (COT), i.e., high-flow nasal oxygen, continuous positive airway pressure, and non-invasive ventilation (NIV), has been proposed to prevent or treat post-extubation respiratory failure. Aim of the present study is assessing the effects of NRS application, compared to COT, on the re-intubation rate (primary outcome), and time to re-intubation, incidence of nosocomial pneumonia, patient discomfort, intensive care unit (ICU) and hospital length of stay, and mortality (secondary outcomes) in adult patients extubated after surgery. METHODS: A systematic review and network meta-analysis of randomized and non-randomized controlled trials. A search from Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science from inception until February 2, 2024 was performed. RESULTS: Thirty-three studies (11,292 patients) were included. Among all NRS modalities, only NIV reduced the re-intubation rate, compared to COT (odds ratio 0.49, 95% confidence interval 0.28; 0.87, p = 0.015, I2 = 60.5%, low certainty of evidence). In particular, this effect was observed in patients receiving NIV for treatment, while not for prevention, of post-extubation respiratory failure, and in patients at high, while not low, risk of post-extubation respiratory failure. NIV reduced the rate of nosocomial pneumonia, ICU length of stay, and ICU, hospital, and long-term mortality, while not worsening patient discomfort. CONCLUSIONS: In post-operative patients receiving NRS after extubation, NIV reduced the rate of re-intubation, compared to COT, when used for treatment of post-extubation respiratory failure and in patients at high risk of post-extubation respiratory failure.

Comparison of limited driving pressure ventilation and low tidal volume strategies in adults with acute respiratory failure on mechanical ventilation: a randomized controlled trial.

BACKGROUND: Ventilator-induced lung injury (VILI) presents a grave risk to acute respiratory failure patients undergoing mechanical ventilation. Low tidal volume (LTV) ventilation has been advocated as a protective strategy against VILI. However, the effectiveness of limited driving pressure (plateau pressure minus positive end-expiratory pressure) remains unclear. OBJECTIVES: This study evaluated the efficacy of LTV against limited driving pressure in preventing VILI in adults with respiratory failure. DESIGN: A single-centre, prospective, open-labelled, randomized controlled trial. METHODS: This study was executed in medical intensive care units at Siriraj Hospital, Mahidol University, Bangkok, Thailand. We enrolled acute respiratory failure patients undergoing intubation and mechanical ventilation. They were randomized in a 1:1 allocation to limited driving pressure (LDP; ⩽15 cmH2O) or LTV (⩽8 mL/kg of predicted body weight). The primary outcome was the acute lung injury (ALI) score 7 days post-enrolment. RESULTS: From July 2019 to December 2020, 126 patients participated, with 63 each in the LDP and LTV groups. The cohorts had the mean (standard deviation) ages of 60.5 (17.6) and 60.9 (17.9) years, respectively, and they exhibited comparable baseline characteristics. The primary reasons for intubation were acute hypoxic respiratory failure (LDP 49.2%, LTV 63.5%) and shock-related respiratory failure (LDP 39.7%, LTV 30.2%). No significant difference emerged in the primary outcome: the median (interquartile range) ALI scores for LDP and LTV were 1.75 (1.00-2.67) and 1.75 (1.25-2.25), respectively (p = 0.713). Twenty-eight-day mortality rates were comparable: LDP 34.9% (22/63), LTV 31.7% (20/63), relative risk (RR) 1.08, 95% confidence interval (CI) 0.74-1.57, p = 0.705. Incidences of newly developed acute respiratory distress syndrome also aligned: LDP 14.3% (9/63), LTV 20.6% (13/63), RR 0.81, 95% CI 0.55-1.22, p = 0.348. CONCLUSIONS: In adults with acute respiratory failure, the efficacy of LDP and LTV in averting lung injury 7 days post-mechanical ventilation was indistinguishable. CLINICAL TRIAL REGISTRATION: The study was registered with the ClinicalTrials.gov database (identification number NCT04035915).

Limited breathing pressure or low amount of air given to the lung; which one is better for adults who need breathing help by ventilator machineWe conducted this research at Siriraj Hospital in Bangkok, Thailand, aiming to compare two ways of helping patients with breathing problems. We studied 126 patients who were randomly put into two groups. One group received a method where the pressure during breathing was limited (limited driving pressure: LDP), and the other group got a method where the amount of air given to the lungs was kept low (low tidal volume: LTV). We checked how bad the lung injury was at seven days later. The results showed that there was no difference between the two methods. Both ways of helping patients breathe had similar outcomes, and neither was significantly better than the other in preventing lung problems. The study suggests that both approaches work about the same for patients who need help with breathing using a machine.

Effect of immediate initiation of invasive ventilation on mortality in acute hypoxemic respiratory failure: a target trial emulation.

PURPOSE: Invasive ventilation is a fundamental treatment in intensive care but its precise timing is difficult to determine. This study aims at assessing the effect of initiating invasive ventilation versus waiting, in patients with hypoxemic respiratory failure without immediate reason for intubation on one-year mortality. METHODS: Emulation of a target trial to estimate the benefit of immediately initiating invasive ventilation in hypoxemic respiratory failure, versus waiting, among patients within the first 48-h of hypoxemia. The eligible population included non-intubated patients with SpO2/FiO2 ≤ 200 and SpO2 ≤ 97%. The target trial was emulated using a single-center database (MIMIC-IV) which contains granular information about clinical status. The hourly probability to receive mechanical ventilation was continuously estimated. The hazard ratios for the primary outcome, one-year mortality, and the secondary outcome, 30-day mortality, were estimated using weighted Cox models with stabilized inverse probability weights used to adjust for measured confounding. RESULTS: 2996 Patients fulfilled the inclusion criteria of whom 792 were intubated within 48 h. Among the non-invasive support devices, the use of oxygen through facemask was the most common (75%). Compared to patients with the same probability of intubation but who were not intubated, intubation decreased the hazard of dying for the first year after ICU admission HR 0.81 (95% CI 0.68-0.96, p = 0.018). Intubation was associated with a 30-day mortality HR of 0.80 (95% CI 0.64-0.99, p = 0.046). CONCLUSION: The initiation of mechanical ventilation in patients with acute hypoxemic respiratory failure reduced the hazard of dying in this emulation of a target trial.

PaCO2 is nonlinearly associated with NIV failure in patients with hypoxemic respiratory failure.

OBJECTIVE: To explore the association between PaCO2 and noninvasive ventilation (NIV) failure in patients with hypoxemic respiratory failure. METHODS: A retrospective study was performed in a respiratory ICU of a teaching hospital. Patients admitted to ICU between 2011 and 2019 were screened. We enrolled the patients with hypoxemic respiratory failure. However, patients who used NIV due to acute-on-chronic respiratory failure or heart failure were excluded. Data before the use of NIV were collected. Requirement of intubation was defined as NIV failure. RESULTS: A total of 1029 patients were enrolled in final analysis. The rate of NIV failure was 45% (461/1029). A nonlinear relationship between PaCO2 and NIV failure was found by restricted cubic splines (p = 0.03). The inflection point was 32 mmHg. The rate of NIV failure was 42% (224/535) in patients with PaCO2 >32 mmHg. However, it increased to 48% (237/494) in those with PaCO2 ≤ 32 mmHg. The crude and adjusted hazard ratio (HR) for NIV failure was 1.36 (95%CI:1.13-1.64) and 1.23(1.01-1.49), respectively, if the patients with PaCO2 >32 mmHg were set as reference. In patients with PaCO2 ≤ 32 mmHg, one unit increment of PaCO2 was associated with 5% reduction of NIV failure. However, it did not associate with NIV failure in patients with PaCO2 >32 mmHg. CONCLUSIONS: PaCO2 and NIV failure was nonlinear relationship. The inflection point was 32 mmHg. Below the inflection point, lower PaCO2 was associated with higher NIV failure. However, it did not associate with NIV failure above this point.

A case of naltrexone-induced acute eosinophilic pneumonia.

Acute eosinophilic pneumonia (AEP) is a rare cause of acute respiratory failure. Clinical presentations can range from dyspnoea, fever and cough, to rapidly progressive and potentially fulminant respiratory failure. While its exact cause is often unknown, associations with inhalational injuries and exposures to new medications have been described.We report a case of a middle-aged, non-smoking man with a history of alcohol use disorder. He presented with 4 days of shortness of breath that started hours after taking injectable naltrexone (Vivitrol). The patient had rapidly worsening hypoxaemia, necessitating emergent bronchoscopy with transbronchial biopsies and bronchoalveolar lavage which showed 66% eosinophils. The patient was intubated for the procedure and unable to get extubated due to worsening hypoxaemic respiratory failure with high fractional inspired oxygen requirements. Chest radiograph showed worsening lung infiltrates and with a high index of suspicion for AEP, he was started empirically on methylprednisolone. He had rapid improvement in his respiratory status and was extubated on day 5 of admission then discharged on day 8. Histopathological examination confirmed acute/subacute eosinophilic pneumonia. A 3-week post-discharge follow-up chest radiograph confirmed the full resolution of pulmonary infiltrates.Naltrexone-induced AEP is rare, with only six other cases reported in the literature. Careful history taking and prompt evaluation for AEP are important given the potential for rapid progression to acute hypoxic respiratory failure and the excellent response to steroid treatment.

First-year outcomes of very low birth weight preterm singleton infants with hypoxemic respiratory failure treated with milrinone and inhaled nitric oxide (iNO) compared to iNO alone: A nationwide retrospective study.

BACKGROUND: Inhaled nitric oxide (iNO) has a beneficial effect on hypoxemic respiratory failure. The increased use of concurrent iNO and milrinone was observed. We aimed to report the trends of iNO use in the past 15 years in Taiwan and compare the first-year outcomes of combining iNO and milrinone to the iNO alone in very low birth weight preterm (VLBWP) infants under mechanical ventilation. METHODS: This nationwide cohort study enrolled preterm singleton infants with birth weight <1500g treated with iNO from 2004 to 2019. Infants were divided into two groups, with a combination of intravenous milrinone (Group 2, n = 166) and without milrinone (Group 1, n = 591). After propensity score matching (PSM), each group's sample size is 124. The primary outcomes were all-cause mortality and the respiratory condition, including ventilator use and duration. The secondary outcomes were preterm morbidities within one year after birth. RESULTS: After PSM, more infants in Group 2 needed inotropes. The mortality rate was significantly higher in Group 2 than in Group 1 from one month after birth till 1 year of age (55.1% vs. 13.5%) with the adjusted hazard ratio of 4.25 (95%CI = 2.42-7.47, p <0.001). For infants who died before 36 weeks of postmenstrual age (PMA), Group 2 had longer hospital stays compared to Group 1. For infants who survived after 36 weeks PMA, the incidence of moderate and severe bronchopulmonary dysplasia (BPD) was significantly higher in Group 2 than in Group 1. For infants who survived until one year of age, the incidence of pneumonia was significantly higher in Group 2 (28.30%) compared to Group 1 (12.62%) (p = 0.0153). CONCLUSION: Combined treatment of iNO and milrinone is increasingly applied in VLBWP infants in Taiwan. This retrospective study did not support the benefits of combining iNO and milrinone on one-year survival and BPD prevention. A future prospective study is warranted.

The Role of Obstructive Sleep Apnea in Hypercapnic Respiratory Failure Identified in Critical Care, Inpatient, and Outpatient Settings.

An emerging body of literature describes the prevalence and consequences of hypercapnic respiratory failure. While device qualifications, documentation practices, and previously performed clinical studies often encourage conceptualizing patients as having a single "cause" of hypercapnia, many patients encountered in practice have several contributing conditions. Physiologic and epidemiologic data suggest that sleep-disordered breathing-particularly obstructive sleep apnea (OSA)-often contributes to the development of hypercapnia. In this review, the authors summarize the frequency of contributing conditions to hypercapnic respiratory failure among patients identified in critical care, emergency, and inpatient settings with an aim toward understanding the contribution of OSA to the development of hypercapnia.

Respiratory Rate Oxygenation (ROX) index as predictor of high flow nasal cannula in pediatric patients in pediatric intensive care unit.

BACKGROUND: High-flow nasal cannula (HFNC) is often used in pediatric populations with respiratory distress. In adults, the respiratory-rate oxygenation (ROX) index is used as a predictor of HFNC therapy; however, children have age-associated differences in respiratory rate, thus may not be applicable to children. This study aims to find the reliability of ROX index and modified P-ROX index as predictors of HFNC therapy failure in pediatric patients. METHODS: Subjects in this analytical cross-sectional study were taken from January 2023 until November 2023 in Cipto Mangunkusumo Hospital. Inclusion criteria are children aged 1 month to 18 years with respiratory distress and got HFNC therapy. Receiver operating characteristics (ROC) analysis was used to find mP-ROX index cutoff value as a predictor of HFNC failure. The area under curve (AUC) score of mP-ROX index was assessed at different time point. RESULTS: A total of 102 patients, with 70% of the population with pneumonia, were included in this study. There are significant differences in the ROX index between the successful and failed HFNC group therapy (p < 0.05). This study suggests that mP-ROX index is not useful as predictor of HFNC therapy in pediatrics. While ROX index < 5.52 at 60 min and < 5.68 at 90 min after HFNC initiation have a sensitivity of 90% and specificity of 71%, sensitivity of 78% and specificity of 76%, respectively. CONCLUSION: mP-ROX index is not useful as a predictor of HFNC therapy in pediatrics. Meanwhile, ROX index at 60 min and 90 min after initiation of HFNC is useful as a predictor of HFNC failure.

Effects of extracorporeal CO2 removal on gas exchange and ventilator settings: a systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis to evaluate the impact of extracorporeal carbon dioxide removal (ECCO2R) on gas exchange and respiratory settings in critically ill adults with respiratory failure. METHODS: We conducted a comprehensive database search, including observational studies and randomized controlled trials (RCTs) from January 2000 to March 2022, targeting adult ICU patients undergoing ECCO2R. Primary outcomes were changes in gas exchange and ventilator settings 24 h after ECCO2R initiation, estimated as mean of differences, or proportions for adverse events (AEs); with subgroup analyses for disease indication and technology. Across RCTs, we assessed mortality, length of stay, ventilation days, and AEs as mean differences or odds ratios. RESULTS: A total of 49 studies encompassing 1672 patients were included. ECCO2R was associated with a significant decrease in PaCO2, plateau pressure, and tidal volume and an increase in pH across all patient groups, at an overall 19% adverse event rate. In ARDS and lung transplant patients, the PaO2/FiO2 ratio increased significantly while ventilator settings were variable. "Higher extraction" systems reduced PaCO2 and respiratory rate more efficiently. The three available RCTs did not demonstrate an effect on mortality, but a significantly longer ICU and hospital stay associated with ECCO2R. CONCLUSIONS: ECCO2R effectively reduces PaCO2 and acidosis allowing for less invasive ventilation. "Higher extraction" systems may be more efficient to achieve this goal. However, as RCTs have not shown a mortality benefit but increase AEs, ECCO2R's effects on clinical outcome remain unclear. Future studies should target patient groups that may benefit from ECCO2R. PROSPERO Registration No: CRD 42020154110 (on January 24, 2021).

Trophic Nutrition in ICU Patients Undergoing High-Flow Oxygen Therapy and/or Noninvasive Mechanical Ventilation: The Nutri-Trophic Study.

Enteral nutrition (EN) therapy in ICU patients requiring oxygen therapy with high-flow nasal cannula (HFNC) and/or noninvasive mechanical ventilation (NIMV) is controversial. A prospective, cohort, observational, and multicenter study was conducted in 10 ICUs in Spain to analyze the 90-day mortality, tolerance, side effects, and infectious complications of trophic EN in patients requiring HFNC therapy and/or NIVM. A total of 149 patients were enrolled. The mean age, severity scores, tracheobronchitis, bacteremia, and antimicrobial therapy were significantly higher in deceased than in living patients (p < 0.05), and the mortality rate was 14.8%. A total of 110 patients received oral trophic feedings, 36 patients received nasogastric tube feedings (NGFs), and 3 received mixed feedings. Trophic EN was discontinued in only ten (14.9%) patients because of feeding-related complications. The variables selected for the multivariate logistic regression on feeding discontinuation were SOFA upon admission (OR per unit = 1.461) and urea (OR per mg/dL = 1.029). There were no significant differences in the development of new infections according to the route of EN administration. Early trophic feeding administered to patients with acute respiratory failure requiring noninvasive ventilation is safe and feasible, and is associated with few dietary and infectious complications in a mortality, setting comparable to similar studies.

A First Experience of Distant Lung Preservation for Transplantation in the Russian Federation.

Lung transplant is an effective method of treating patients with end-stage respiratory diseases, but problems such as the imbalance between the number of donor organs and the number ofrecipients needing organs still play a leading role. From a transplant point of view, a multiorgan donor is considered of greatest efficiency, so that all organs that can potentially be used should be transplanted. The combination of the vast geographical territory of Russia, the shortage of actual donors, and the relatively small number of transplant centers has led to the need to transport donor lungs by air over long distances. There were already precedents in the world for remote preservation of donor organs for transplant. In this study, we have described the unique experience of remote evaluation of donor lungs with their subsequent air transportation and transplantation, which is the first such description in Russia to our knowledge. The donor lungs for lung transplant were brought from medical institutions of the Samara region to Moscow. During remote evaluation, all information was transmitted to the transplant center by providing access to the automated information system "Organ Donation," which was used at that time by the service and contained all information about a potential donor in real time. The 2 transplant candidates had end-stage cystic fibrosis and severe respiratory failure; both patients underwent organ implantation from donors located outside their regions. In conditions of shortages of donor organs, long-distance transportation is a reasonable, feasible, and safe procedure.

High-Flow Nasal Cannula Versus Noninvasive Ventilation as Initial Treatment in Acute Hypoxia: A Propensity Score-Matched Study.

IMPORTANCE: Patients presenting to the emergency department (ED) with hypoxemia often have mixed or uncertain causes of respiratory failure. The optimal treatment for such patients is unclear. Both high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) are used. OBJECTIVES: We sought to compare the effectiveness of initial treatment with HFNC versus NIV for acute hypoxemic respiratory failure. DESIGN SETTING AND PARTICIPANTS: We conducted a retrospective cohort study of patients with acute hypoxemic respiratory failure treated with HFNC or NIV within 24 hours of arrival to the University of Michigan adult ED from January 2018 to December 2022. We matched patients 1:1 using a propensity score for odds of receiving NIV. MAIN OUTCOMES AND MEASURES: The primary outcome was major adverse pulmonary events (28-d mortality, ventilator-free days, noninvasive respiratory support hours) calculated using a win ratio. RESULTS: A total of 1154 patients were included. Seven hundred twenty-six (62.9%) received HFNC and 428 (37.1%) received NIV. We propensity score matched 668 of 1154 (57.9%) patients. Patients on NIV versus HFNC had lower 28-day mortality (16.5% vs. 23.4%, p = 0.033) and required noninvasive treatment for fewer hours (median 7.5 vs. 13.5, p < 0.001), but had no difference in ventilator-free days (median [interquartile range]: 28 [26, 28] vs. 28 [10.5, 28], p = 0.199). Win ratio for composite major adverse pulmonary events favored NIV (1.38; 95% CI, 1.15-1.65; p < 0.001). CONCLUSIONS AND RELEVANCE: In this observational study of patients with acute hypoxemic respiratory failure, initial treatment with NIV compared with HFNC was associated with lower mortality and fewer composite major pulmonary adverse events calculated using a win ratio. These findings underscore the need for randomized controlled trials to further understand the impact of noninvasive respiratory support strategies.

Opioid-induced respiratory depression suspected of drug interaction in a prostate cancer patient: a case report.

BACKGROUND: Many of the drugs used for the treatment and alleviation of symptoms in cancer patients are known to inhibit or induce cytochrome P450 (CYP). Therefore, it is important to pay attention to the drug interactions of opioid analgesics that are metabolized by CYPs, because for example when using oxycodone metabolized by CYP3A4, it is possible that the effect will be attenuated or enhanced by the concomitant use of drugs that induce or inhibit CYP3A4. Aprepitant, an antiemetic drug used in many patients receiving anticancer drugs, is known as a moderate competitive inhibitor of CYP3A4. We experienced a case of respiratory depression caused by opioids, which was suspected to be caused by a drug interaction with antiemetics especially aprepitant. CASE DESCRIPTION: The patient was a 72-year-old man. He had been treated with continuous oxycodone infusion for perianal pain associated with the rectal invasion of prostate cancer. No comorbidities other than renal dysfunction were observed. Oxycodone treatment was started at 48 mg/day, and was increased to 108 mg/day, and then the pain decreased. Once the pain was controlled, chemotherapy was planned. Antiemetics (dexamethasone, palonosetron, and aprepitant) were administered before anticancer drug administration. Approximately 3 hours after antiemetics administration and before the administration of the anticancer drugs, a ward nurse noticed that oversedation and respiratory depression had occurred. When the patient was called, he immediately woke up and was able to talk normally, so the anticancer drugs were administered as scheduled. About 2 hours after the nurse noticed oversedation, the attending physician reduced the dose of oxycodone infusion to 48 mg/day. After that, his drowsiness persisted, but his respiratory condition improved. Despite reducing the dose of oxycodone to less than half, the pain remained stable at numeric rating scale (NRS) 0-1, without the use of a rescue dose. The patient was discharged from the hospital 36 days after the administration of anticancer drugs, without any problems. CONCLUSIONS: The cause of respiratory depression in this case was thought to be a combination of factors, including drug interactions between oxycodone and antiemetics, and oxycodone accumulation due to renal dysfunction.

Risk factors for COVID-19 associated pulmonary aspergillosis and outcomes in patients with acute respiratory failure in a respiratory sub-intensive care unit.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) is burdened by high mortality. Data are lacking about non-ICU patients. Aims of this study were to: (i) assess the incidence and prevalence of CAPA in a respiratory sub-intensive care unit, (ii) evaluate its risk factors and (iii) impact on in-hospital mortality. Secondary aims were to: (i) assess factors associated to mortality, and (ii) evaluate significant features in hematological patients. MATERIALS AND METHODS: This was a single-center, retrospective study of COVID-19 patients with acute respiratory failure. A cohort of CAPA patients was compared to a non-CAPA cohort. Among patients with CAPA, a cohort of hematological patients was further compared to another of non-hematological patients. RESULTS: Three hundred fifty patients were included in the study. Median P/F ratio at the admission to sub-intensive unit was 225 mmHg (IQR 155-314). 55 (15.7%) developed CAPA (incidence of 5.5%). Eighteen had probable CAPA (37.3%), 37 (67.3%) possible CAPA and none proven CAPA. Diagnosis of CAPA occurred at a median of 17 days (IQR 12-31) from SARS-CoV-2 infection. Independent risk factors for CAPA were hematological malignancy [OR 1.74 (95%CI 0.75-4.37), p = 0.0003], lymphocytopenia [OR 2.29 (95%CI 1.12-4.86), p = 0.02], and COPD [OR 2.74 (95%CI 1.19-5.08), p = 0.014]. Mortality rate was higher in CAPA cohort (61.8% vs 22.7%, p < 0.0001). CAPA resulted an independent risk factor for in-hospital mortality [OR 2.92 (95%CI 1.47-5.89), p = 0.0024]. Among CAPA patients, age > 65 years resulted a predictor of mortality [OR 5.09 (95% CI 1.20-26.92), p = 0.035]. No differences were observed in hematological cohort. CONCLUSION: CAPA is a life-threatening condition with high mortality rates. It should be promptly suspected, especially in case of hematological malignancy, COPD and lymphocytopenia.

Pro-Con Debate: Universal Versus Selective Continuous Monitoring of Postoperative Patients.

In this Pro-Con commentary article, we discuss use of continuous physiologic monitoring for clinical deterioration, specifically respiratory depression in the postoperative population. The Pro position advocates for 24/7 continuous surveillance monitoring of all patients starting in the postanesthesia care unit until discharge from the hospital. The strongest arguments for universal monitoring relate to inadequate assessment and algorithms for patient risk. We argue that the need for hospitalization in and of itself is a sufficient predictor of an individual's risk for unexpected respiratory deterioration. In addition, general care units carry the added risk that even the most severe respiratory events will not be recognized in a timely fashion, largely due to higher patient to nurse staffing ratios and limited intermittent vital signs assessments (e.g., every 4 hours). Continuous monitoring configured properly using a "surveillance model" can adequately detect patients' respiratory deterioration while minimizing alarm fatigue and the costs of the surveillance systems. The Con position advocates for a mixed approach of time-limited continuous pulse oximetry monitoring for all patients receiving opioids, with additional remote pulse oximetry monitoring for patients identified as having a high risk of respiratory depression. Alarm fatigue, clinical resource limitations, and cost are the strongest arguments for selective monitoring, which is a more targeted approach. The proponents of the con position acknowledge that postoperative respiratory monitoring is certainly indicated for all patients, but not all patients need the same level of monitoring. The analysis and discussion of each point of view describes who, when, where, and how continuous monitoring should be implemented. Consideration of various system-level factors are addressed, including clinical resource availability, alarm design, system costs, patient and staff acceptance, risk-assessment algorithms, and respiratory event detection. Literature is reviewed, findings are described, and recommendations for design of monitoring systems and implementation of monitoring are described for the pro and con positions.

Exome sequencing in extreme altitude mountaineers identifies pathogenic variants in RTEL1 and COL6A1 previously associated with respiratory failure.

Adaptation of humans to challenging environmental conditions, such as extreme temperature, malnutrition, or hypoxia, is an interesting phenomenon for both basic and applied research. Identification of the genetic factors contributing to human adaptation to these conditions enhances our understanding of the underlying molecular and physiological mechanisms. In our study, we analyzed the exomes of 22 high altitude mountaineers to uncover genetic variants contributing to hypoxic adaptation. To our surprise, we identified two putative loss-of-function variants, rs1385101139 in RTEL1 and rs1002726737 in COL6A1 in two extremely high altitude (personal record of more than 8500 m) professional climbers. Both variants can be interpreted as pathogenic according to medical geneticists' guidelines, and are linked to inherited conditions involving respiratory failure (late-onset pulmonary fibrosis and severe Ullrich muscular dystrophy for rs1385101139 and rs1002726737, respectively). Our results suggest that a loss of gene function may act as an important factor of human adaptation, which is corroborated by previous reports in other human subjects.

The role of inflammation and antithrombin supplementation on thromboelastographic parameters during veno-venous ECMO for respiratory failure.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) may act as a driver or propagator of systemic inflammation. In turn, cytokine release can modify thromboelastographic (TEG) tests which are commonly used for anticoagulation monitoring. In this context, antithrombin (AT) supplementation might further modify TEG. METHODS: This is a pre-specified sub-study of the "Randomized Controlled Trial of Antithrombin Supplementation During Extracorporeal Membrane Oxygenation" study (investigator-initiated, randomized, single-blind, two-arm trial) conducted in two Italian ECMO referral ICUs. Adult patients requiring vv-ECMO for respiratory failure and undergoing unfractioned heparin (UFH) administration were enrolled and randomized whether to receive AT supplementation. Plasma samples for cytokine assay (IL-8, IL-10, IL-6, IL-1ß, TNF-α and Pro-ADM) and heparinase TEG were collected from every patient before ECMO start, 24 h and 72 h after ECMO start, before ECMO removal, and 7 days after ECMO removal or upon ICU discharge whichever happened first. AT concentration, coagulation and clinical data were collected before ECMO start and at pre-fixed time points. RESULTS: Thirty-nine patients were enrolled (21 treatments, 18 controls). TEG-R had a weak-to-moderate positive correlation with IL-8, IL-6, IL-10 and TNF-α and a moderate positive correlation with Pro-ADM. TEG-ANG showed a weak negative correlation with IL-8, IL-6 and TNF-α, while TEG-MA negatively correlated with IL-8, TNF-α and Pro-ADM. AT supplementation seemed to modify the association between TEG-MA and IL-8, IL-10 and Pro-ADM; conversely, AT did not affect the relationship among TEG-R or TEG-ANG and the studied cytokines. CONCLUSIONS: High concentrations of systemic cytokines correlated with longer reaction times and decreased angle and amplitude at TEG, suggesting that an increase in inflammation is related with hypocoagulability as revealed by thromboelastography.