Acute Hypoxemic Respiratory Failure Research Articles

Dysregulated Coagulation and Fibrinolysis Are Present in Patients Admitted to the Emergency Department with Acute Hypoxemic Respiratory Failure: A Prospective Study

Acute hypoxemic respiratory failure (AHRF) is defined as acute and progressive, and patients are at a greater risk of developing acute respiratory distress syndrome (ARDS). Until now, most studies have focused on prognostic and diagnostic biomarkers in ARDS. Since there is evidence supporting a connection between dysregulated coagulant and fibrinolytic pathways in ARDS progression, it is plausible that this dysregulation also exists in AHRF. The aim of this study was to explore whether levels of soluble endothelial protein C receptor (sEPCR) and plasminogen differentiate patients admitted to the emergency department (ED) with AHRF. sEPCR and plasminogen levels were measured in 130 AHRF patients upon ED presentation by ELISA. Our results demonstrated that patients presenting to the ED with AHRF had elevated levels of sEPCR and plasminogen. It seems that dysregulation of coagulation and fibrinolysis occur in the early stages of respiratory failure requiring hospitalisation. Further research is needed to fully comprehend the contribution of sEPCR and plasminogen in AHRF.

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

PurposeInvasive 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.MethodsEmulation 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.Results2996 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).ConclusionThe initiation of mechanical ventilation in patients with acute hypoxemic respiratory failure reduced the hazard of dying in this emulation of a target trial.

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

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. We sought to compare the effectiveness of initial treatment with HFNC versus NIV for acute hypoxemic respiratory failure. 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. The primary outcome was major adverse pulmonary events (28-d mortality, ventilator-free days, noninvasive respiratory support hours) calculated using a win ratio. 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). 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.

Abstract PO1-05-04: CDK4/6 inhibitor-induced Interstitial Lung Disease (ILD) - A Case Series

Abstract Introduction: CDK4/6 inhibitors interrupt cell cycle by inhibiting intracellular and hormonal signals responsible for proliferation of malignant cells, making them an effective treatment for patients with HR+ advanced breast cancer. Pre-clinical data demonstrates that CDK4/6 inhibitors allow for inflammatory cell recruitment, inducing pulmonary inflammation and thereby increasing the risk of ILD. The overall risk of ILD was 1.6% in a meta-analysis of over 16,000 patients treated with CDK4/6 inhibitors while individual reported risk was 1%, 1.6% and 3% for palbociclib, ribociclib, and abemaciclib respectively. Objective: The aim of this case series is to add to the body of literature about this rare but possibly serious side effect of CDK4/6 inhibitor associated ILD. Early detection and prompt management are essential for improved patient outcomes. Case 1 A 61 year-old female was diagnosed with metastatic breast cancer to brain and bones after being admitted for evaluation of acute vision loss. She started on palbociclib and letrozole and subsequently had 2 hospitalizations for acute hypoxemic respiratory failure with unremarkable infectious workup. CT scan was significant for bilateral pulmonary infiltrates raising suspicion for CDK4/6 inhibitor-induced pneumonitis; subsequently palbociclib was discontinued and the patient was started on steroid taper resulting in improvement of her respiratory status. Case 2 A 71 year-old female with a remote history of left breast cancer and sarcoidosis presented with respiratory symptoms. She was found to have metastatic breast cancer with CT scan revealing hilar and mediastinal adenopathy. The patient initially received taxol with near resolution of disease on imaging. The patient was subsequently started on palbociclib + letrozole. After 9 months of treatment, the patient was admitted for pneumonia and discharged home with oxygen. PFTs at the time were suggestive of restrictive pathology related to obesity hypoventilation. Six months later, the patient was admitted for worsening respiratory failure; CT scan revealed interstitial changes likely due to multifactorial etiologies including palbociclib-induced pneumonitis. The patient subsequently passed away. Case 3 An 81 year-old female diagnosed with remote history of L. breast cancer presented with shortness of breath and weakness. CT scan revealed a nodule and lymphadenopathy; biopsy of nodule was consistent with breast primary. The patient was initially started on ribociclib which was discontinued after 4 cycles due to transaminitis. She was switched to palbociclib, however 2 months after initiation, the patient presented with flu-like symptoms. CT revealed scattered subpleural ground-glass opacities. Infectious workup was negative; pulmonary consultation believed this was likely due to drug-induced pneumonitis and palbociclib was discontinued and she was treated with a steroid taper. Patient was switched to fulvestrant; and after 9 months she was diagnosed with stage IV tongue cancer and her breast cancer therapy was discontinued. Discussion CDK4/6 inhibitors have improved survival in patients with metastatic breast cancer, however they are associated with rare but serious adverse effects like ILD. ILD is a challenging clinical diagnosis as it refers to a cluster of disorders of varying presentation and pathophysiology, and as a result can be missed. Conclusion This case series demonstrates that CDK4/6 inhibitor-associated ILD may be more prevalent than originally reported. It is important to identify early by performing a thorough workup, including a detailed history and physical exam, medication list review, infectious work-up, chest imaging, PFTs and pulmonology consultation. Publishing a set of standardized guidelines to diagnose and treat CDK4/6 inhibitor-induced ILD is necessary as more cases are identified. Citation Format: Ami Chitalia, Krishna Shah. CDK4/6 inhibitor-induced Interstitial Lung Disease (ILD) - A Case Series [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-05-04.

Designing a Bayesian adaptive clinical trial to evaluate novel mechanical ventilation strategies in acute respiratory failure using integrated nested Laplace approximations

BackgroundAdaptive trials usually require simulations to determine values for design parameters, demonstrate error rates, and establish the sample size. We designed a Bayesian adaptive trial comparing ventilation strategies for patients with acute hypoxemic respiratory failure using simulations. The complexity of the analysis would usually require computationally expensive Markov Chain Monte Carlo methods but this barrier to simulation was overcome using the Integrated Nested Laplace Approximations (INLA) algorithm to provide fast, approximate Bayesian inference. MethodsWe simulated two-arm Bayesian adaptive trials with equal randomization that stratified participants into two disease severity states. The analysis used a proportional odds model, fit using INLA. Trials were stopped based on pre-specified posterior probability thresholds for superiority or futility, separately for each state. We calculated the type I error and power across 64 scenarios that varied the probability thresholds and the initial minimum sample size before commencing adaptive analyses. Two designs that maintained a type I error below 5%, a power above 80%, and a feasible mean sample size were evaluated further to determine the optimal design. ResultsPower generally increased as the initial sample size and the futility threshold increased. The chosen design had an initial recruitment of 500 and a superiority threshold of 0.9925, and futility threshold of 0.95. It maintained high power and was likely to reach a conclusion before exceeding a feasible sample size. ConclusionsWe designed a Bayesian adaptive trial to evaluate novel strategies for ventilation using the INLA algorithm to efficiently evaluate a wide range of designs through simulation.

The role of electrical impedance tomography in predicting the failure of non-invasive ventilation in patients with COVID-19-associated hypoxemic acute respiratory failure: a prospective observational study

INTRODUCTION: Data on prediction of the failure of non-invasive lung ventilation (NIV) in patients with respiratory failure associated with COVID-19, based on electrical impedance tomography (EIT) patterns are limited. OBJECTIVE: To identify predictors of non-invasive lung ventilation failure in patients with respiratory insufficiency associated with COVID-19, using electrical impedance tomography data. MATERIALS AND METHODS: A monocenter prospective cohort observational study was conducted in patients with moderate-to-severe COVID-19-associated acute respiratory failure, who underwent NIV in the ICU (n = 43). EIT was used to measure the actual ventilation area (SVENT), hyperinflation area (SHYPER), ventilation delay zone (SRVD), and calculate the proportion of ventilated lungs (AVENT), proportion of hyperinflation area (ZHYPER), proportion of RVD area (ZRVD), as well as the duration of hyperinflation during one respiratory cycle (THYPER), and the ratio of hyperinflation time to inhalation time. RESULTS: The study included 43 patients admitted 15 (10–22) days after the onset of COVID-19. Patients with NIV failure (n = 34) had higher ZHYPER values on the first day (19.5 (16.3–30.5) in the NIV success group and 35.2 (25.0–45.0) in the failure group, AUROC 0.80, p = 0.004, Cut-off 39.7, Se 85 %, Sp 89 %) and the last day (20.6 (10.4–28.5) in the success group and 32.7 (26.4–43.3) in the failure group, AUROC 0.92, p = 0.003, Cut-off 32.7, Se 50 %, Sp 100 %), as well as a higher THYPER/TINSP ratio on the last day of NIV (37.5 (31.0–47.9) in the success group and 65.3 (43.7–88.4) in the failure group, AUROC 0.87, p = 0.001, Cut-off 52.7, Se 71 %, Sp 100 %). AVENT, ZRVD, and inhalation time did not show prognostic significance. CONCLUSIONS: EIT can predict the NIV failure in moderate-to-severe ARDS associated with COVID-19, based on the assessment of alveolar overdistention zones. Further research are needed to investigate this theory.

Case study observational research: inflammatory cytokines in the bronchial epithelial lining fluid of COVID-19 patients with acute hypoxemic respiratory failure

BackgroundIn this study, the concentrations of inflammatory cytokines were measured in the bronchial epithelial lining fluid (ELF) and plasma in patients with acute hypoxemic respiratory failure (AHRF) secondary to severe coronavirus disease 2019 (COVID-19).MethodsWe comprehensively analyzed the concentrations of 25 cytokines in the ELF and plasma of 27 COVID-19 AHRF patients. ELF was collected using the bronchial microsampling method through an endotracheal tube just after patients were intubated for mechanical ventilation.ResultsCompared with those in healthy volunteers, the concentrations of interleukin (IL)-6 (median 27.6 pmol/L), IL-8 (1045.1 pmol/L), IL-17A (0.8 pmol/L), IL-25 (1.5 pmol/L), and IL-31 (42.3 pmol/L) were significantly greater in the ELF of COVID-19 patients than in that of volunteers. The concentrations of MCP-1 and MIP-1β were significantly greater in the plasma of COVID-19 patients than in that of volunteers. The ELF/plasma ratio of IL-8 was the highest among the 25 cytokines, with a median of 737, and the ELF/plasma ratio of IL-6 (median: 218), IL-1β (202), IL-31 (169), MCP-1 (81), MIP-1β (55), and TNF-α (47) were lower.ConclusionsThe ELF concentrations of IL-6, IL-8, IL-17A, IL-25, and IL-31 were significantly increased in COVID-19 patients. Although high levels of MIP-1 and MIP-1β were also detected in the blood samples collected simultaneously with the ELF samples, the results indicated that lung inflammation was highly compartmentalized. Our study demonstrated that a comprehensive analysis of cytokines in the ELF is a feasible approach for understanding lung inflammation and systemic interactions in patients with severe pneumonia.

Using the ROX Index to Predict Treatment Outcome for High-Flow Nasal Cannula and/or Noninvasive Ventilation in Patients With COPD Exacerbations.

The ratio of oxygen saturation index (ROX index; or SpO2 /FIO2 /breathing frequency) has been shown to predict risk of intubation after high-flow nasal cannula (HFNC) support among adults with acute hypoxemic respiratory failure primarily due to pneumonia. However, its predictive value for other subtypes of respiratory failure is unknown. This study investigated whether the ROX index predicts liberation from HFNC or noninvasive ventilation (NIV), intubation with mechanical ventilation, or death in adults admitted for respiratory failure due to an exacerbation of COPD. We performed a retrospective study of 260 adults hospitalized with a COPD exacerbation and treated with HFNC and/or NIV (continuous or bi-level). ROX index scores were collected at treatment initiation and predefined time intervals throughout HFNC and/or NIV treatment or until the subject was intubated or died. A ROX index score of ≥ 4.88 was applied to the cohort to determine if the same score would perform similarly in this different cohort. Accuracy of the ROX index was determined by calculating the area under the receiver operator curve. A total of 47 subjects (18%) required invasive mechanical ventilation or died while on HFNC/NIV. The ROX index at treatment initiation, 1 h, and 6 h demonstrated the best prediction accuracy for avoidance of invasive mechanical ventilation or death (area under the receiver operator curve 0.73 [95% CI 0.66-0.80], 0.72 [95% CI 0.65-0.79], and 0.72 [95% CI 0.63-0.82], respectively). The optimal cutoff value for sensitivity (Sn) and specificity (Sp) was a ROX index score > 6.88 (sensitivity 62%, specificity 57%). The ROX index applied to adults with COPD exacerbations treated with HFNC and/or NIV required higher scores to achieve similar prediction of low risk of treatment failure when compared to subjects with hypoxemic respiratory failure/pneumonia. ROX scores < 4.88 did not accurately predict intubation or death.

Transbronchial Lung Cryobiopsies, Transbronchial Forceps Lung Biopsies, and Surgical Lung Biopsies in Mechanically Ventilated Patients with Acute Hypoxemic Respiratory Failure: A Retrospective Cohort Study.

Lung biopsies are sometimes performed in mechanically ventilated patients with acute hypoxemic respiratory failure (AHRF) of unknown etiology to guide patient management. While surgical lung biopsies (SLB) offer high diagnostic rates, they may also cause significant complications. Transbronchial forceps lung biopsies (TBLB) are less invasive but often produce non-contributive specimens. Transbronchial lung cryobiopsies (TBLC) yield specimens of potentially better quality than TBLB, but due to their novel implementation in the intensive care unit (ICU), their accuracy and safety are still unclear. Our main objective was to evaluate the risk of adverse events in patients with AHRF following the three biopsy techniques. Our secondary objectives were to assess the diagnostic yield and associated modifications of patient management of each technique. We conducted a retrospective cohort study comparing TBLC, TBLB, and SLB in mechanically ventilated patients with AHRF. The primary outcome was the proportion of patients with at least one complication, and secondary outcomes included complication rates, diagnostic yields, treatment modifications, and mortality. Of the 26 patients who underwent lung biopsies from 2018 to 2022, all TBLC and SLB patients and 60% of TBLB patients had at least one complication. TBLC patients had higher unadjusted numbers of total and severe complications, but also worse Sequential Organ Failure Assessment scores and P/F ratios. A total of 25 biopsies (25/26, 96%) provided histopathological diagnoses, 88% (22/25) of which contributed to patient management. ICU mortality was high for all modalities (63% for TBLC, 60% for TBLB and 50% for SLB). All biopsy methods had high diagnostic yields and the great majority contributed to patient management; however, complication rates were elevated. Further research is needed to determine which patients may benefit from lung biopsies and to determine the best biopsy modality.

Severe pulmonary hypertension and circulatory failure associated with Congenital syphilis. Case report.

Congenital syphilis is a vertical infection caused by Treponema pallidum. Despite the implementation of preventive strategies during pregnancy, its incidence is increasing, and it constitutes an important public health problem. Most patients with congenital syphilis are asymptomatic; however, a small group may develop severe disease at birth with the need of advanced resuscitation in the delivery room, acute hypoxemic respiratory failure, and hemodynamic instability. Therefore, awareness is needed. This series describes the clinical course of two late preterm infants with congenital syphilis who developed acute hypoxemic respiratory failure, pulmonary hypertension, and circulatory collapse early after birth. Integrated hemodynamic evaluation with neonatologist-performed echocardiography (NPE) and therapeutic management is provided. A comprehensive hemodynamic evaluation including early and serial functional echocardiography in these patients is needed to address the underlying complex pathophysiology and to help to establish accurate treatment.

Respiratory alkalosis in the acute hypoxemic patient during non-invasive mechanical ventilation: troubleshooting and prognostic relevance

Respiratory alkalosis is one of the four basic disturbances to the acid-base equilibrium. Persistent primary respiratory alkalosis during non-invasive mechanical ventilation in patients with hypoxemic respiratory failure could be a risk factor for NIV failure. A 69-year-old man with acute hypoxemic respiratory failure caused by severe COVID-19 pneumonia demonstrated progressive worsening of gas exchange and clinical conditions. Despite a positive response to noninvasive mechanical ventilation, a therapeutic increase in respiratory support was required.

High-flow nasal oxygen in resource-constrained, non-intensive, high-care wards for COVID-19 acute hypoxaemic respiratory failure: Comparing outcomes of the first v. third waves at a tertiary centre in South Africa

Background. High-flow nasal oxygen (HFNO) is an accepted treatment for severe COVID-19-related acute hypoxaemic respiratory failure (AHRF). Objectives. To determine whether treatment outcomes at Groote Schuur Hospital, Cape Town, South Africa, during the third COVID-19 wave would be affected by increased institutional experience and capacity for HNFO and more restrictive admission criteria for respiratory high-care wards and intensive care units. Methods. We included consecutive patients with COVID-19-related AHRF treated with HFNO during the first and third COVID-19 waves. The primary endpoint was comparison of HFNO failure (composite of the need for intubation or death while on HFNO) between waves. Results. A total of 744 patients were included: 343 in the first COVID-19 wave and 401 in the third. Patients treated with HFNO in the first wave were older (median (interquartile range) age 53 (46 - 61) years v. 47 (40 - 56) years; p&lt;0.001), and had higher prevalences of diabetes (46.9% v. 36.9%; p=0.006), hypertension (51.0% v. 35.2%; p&lt;0.001), obesity (33.5% v. 26.2%; p=0.029) and HIV infection (12.5% v. 5.5%; p&lt;0.001). The partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio at HFNO initiation and the ratio of oxygen saturation/FiO2 to respiratory rate within 6 hours (ROX-6 score) after HFNO commencement were lower in the first wave compared with the third (median 57.9 (47.3 - 74.3) mmHg v. 64.3 (51.2 - 79.0) mmHg; p=0.005 and 3.19 (2.37 - 3.77) v. 3.43 (2.93 - 4.00); p&lt;0.001, respectively). The likelihood of HFNO failure (57.1% v. 59.6%; p=0.498) and mortality (46.9% v. 52.1%; p=0.159) did not differ significantly between the first and third waves. Conclusion. Despite differences in patient characteristics, circulating viral variant and institutional experience with HFNO, treatment outcomes were very similar in the first and third COVID-19 waves. We conclude that once AHRF is established in COVID-19 pneumonia, the comorbidity profile and HFNO provider experience do not appear to affect outcome.

High-flow nasal oxygen in infants and children for early respiratory management of pneumonia-induced acute hypoxemic respiratory failure: the CENTURI randomized clinical trial

ObjectiveTo compare the effectiveness of early high-flow nasal cannula (HFNC) and low-flow oxygen support (LFOS) in children under 5 years with acute hypoxemic respiratory failure (AHRF) due to severe community-acquired pneumonia in low-middle-income countries.MethodsAn open-label randomized clinical trial enrolled children aged 2–59 months with AHRF due to severe community-acquired pneumonia and randomized into HFNC and LFOS. In the LFOS group, the patient received cold wall oxygen humidified by bubbling through sterile water administered through simple nasal prongs at a fixed flow rate of 2 L/min. In the HFNC group, the patient received humidified, heated (37 °C), high-flow oxygen at a flow rate assigned based on weight range, with a titratable oxygen fraction. The primary outcome was treatment failure in 72 h (escalating the respiratory support method using any modality other than primary intervention).ResultsData was analyzed intention-to-treat (HFNC = 124; LFOS = 120). Median (IQR) age was 12 (6–20) and 11 (6–27) months, respectively. Treatment failure occurred in a significantly lower proportion in the HFNC group (7.3%, n = 9/124) as compared to the LFOS group (20%, n = 24/120) (relative risk = 0.36, 95% CI 0.18 to 0.75; p = 0.004; adjusted hazard ratio 0.34, 95% CI 0.16 to 0.73; p = 0.006). The intubation rate was significantly lower in the HFNC group (7.3%, n = 9/124 vs. 16.7%, n = 20/120; relative risk = 0.44, 95% CI 0.21 to 0.92, p = 0.023). There were no significant differences noted in other secondary outcomes. No mortality occurred.ConclusionHigh-flow nasal cannula oxygen therapy used as early respiratory support in children under 5 years with acute hypoxemic respiratory failure due to severe community-acquired pneumonia was associated with significantly lower treatment failure compared with standard low-flow oxygen support.Trial registration CTRI/2016/04/006788. Registered 01 April 2016, https://ctri.nic.in/Clinicaltrials/advsearch.php.

Switches in non-invasive respiratory support strategies during acute hypoxemic respiratory failure: Need to monitoring from a retrospective observational study

ObjectiveTo explore combined non-invasive-respiratory-support (NIRS) patterns, reasons for NIRS switching, and their potential impact on clinical outcomes in acute-hypoxemic-respiratory-failure (AHRF) patients. DesignRetrospective, single-center observational study. SettingIntensive Care Medicine. PatientsAHRF patients (cardiac origin and respiratory acidosis excluded) underwent combined NIRS therapies such as non-invasive-ventilation (NIV) and High-Flow-Nasal-Cannula (HFNC). InterventionsPatients were classified based on the first NIRS switch performed (HFNC-to-NIV or NIV-to-HFNC), and further specific NIRS switching strategies (NIV trial-like vs. Non-NIV trial-like and single vs. multiples switches) were independently evaluated. Main variables of interestReasons for switching, NIRS failure and mortality rates. ResultsA total of 63 patients with AHRF were included, receiving combined NIRS, 58.7% classified in the HFNC-to-NIV group and 41.3% in the NIV-to-HFNC group. Reason for switching from HFNC to NIV was AHRF worsening (100%), while from NIV to HFNC was respiratory improvement (76.9%). NIRS failure rates were higher in the HFNC-to-NIV than in NIV-to-HFNC group (81% vs. 35%, p < 0.001). Among HFNC-to-NIV patients, there was no difference in the failure rate between the NIV trial-like and non-NIV trial-like groups (86% vs. 78%, p = 0.575) but the mortality rate was significantly lower in NIV trial-like group (14% vs. 52%, p = 0.02). Among NIV to HFNC patients, NIV failure was lower in the single switch group compared to the multiple switches group (15% vs. 53%, p = 0.039), with a shorter length of stay (5 [2–8] vs. 12 [8–30] days, p = 0.001). ConclusionsNIRS combination is used in real life and both switches’ strategies, HFNC to NIV and NIV to HFNC, are common in AHRF management. Transitioning from HFNC to NIV is suggested as a therapeutic escalation and in this context performance of a NIV-trial could be beneficial. Conversely, switching from NIV to HFNC is suggested as a de-escalation strategy that is deemed safe if there is no NIRS failure.

Severe Community-Acquired Pneumonia: Noninvasive Mechanical Ventilation, Intubation, and HFNT.

Severe acute respiratory failure (ARF) is a major issue in patients with severe community-acquired pneumonia (CAP). Standard oxygen therapy is the first-line therapy for ARF in the less severe cases. However, respiratory supports may be delivered in more severe clinical condition. In cases with life-threatening ARF, invasive mechanical ventilation (IMV) will be required. Noninvasive strategies such as high-flow nasal therapy (HFNT) or noninvasive ventilation (NIV) by either face mask or helmet might cover the gap between standard oxygen and IMV. The objective of all the supporting measures for ARF is to gain time for the antimicrobial treatment to cure the pneumonia. There is uncertainty regarding which patients with severe CAP are most likely to benefit from each noninvasive support strategy. HFNT may be the first-line approach in the majority of patients. While NIV may be relatively contraindicated in patients with excessive secretions, facial hair/structure resulting in air leaks or poor compliance, NIV may be preferable in those with increased work of breathing, respiratory muscle fatigue, and congestive heart failure, in which the positive pressure of NIV may positively impact hemodynamics. A trial of NIV might be considered for select patients with hypoxemic ARF if there are no contraindications, with close monitoring by an experienced clinical team who can intubate patients promptly if they deteriorate. In such cases, individual clinician judgement is key to choose NIV, interface, and settings. Due to the paucity of studies addressing IMV in this population, the protective mechanical ventilation strategies recommended by guidelines for acute respiratory distress syndrome can be reasonably applied in patients with severe CAP.

A randomised clinical trial of awake prone positioning in COVID-19 suspects with acute hypoxemic respiratory failure

BackgroundAwake prone position (APP) has been reported to improve oxygenation in patients with COVID-19 disease and to reduce the requirement for invasive mechanical ventilation for patients requiring support with high flow nasal cannula.There is conflicting data for patients requiring lower-level oxygen support. Research questionDoes APP reduce escalation of oxygen support in COVID-19 patients requiring supplementary oxygen?The primary outcome was defined as an escalation of oxygen support from simple supplementary oxygen (NP, HM, NRB) to NIV (CPAP or BiPAP), HFNC or IMV; OR from NIV (CPAP or BiPAP) or HFNC to IMV by day30. Study designTwo center, prospective, non-blind, randomised controlled trial.Patients with confirmed or suspected COVID-19 pneumonia requiring ≥ 5 liters/minute oxygen to maintain saturations ≥ 94 % were randomised to either APP or control group.The APP group received a three-hour APP session three times per day for three days. ResultsBetween 9 May and 13 July 2021, 89 adults were screened and 61 enrolled, 31 to awake prone position and 30 controls.There was no difference in the primary outcome, 7 (22.6 %) patients randomised to APP and 9 (30.0 %) controls required escalation of oxygen support (OR 0.68 (0.22–2.14), P = 0.51).There were no differences in any secondary outcomes, in APP did not improve oxygenation. InterpretationIn COVID-19 patients, the use of APP did not prevent escalation of oxygen support from supplementary to invasive or non-invasive ventilation or improve patient respiratory physiology. Trial registrationNCT04853979 (clinicaltrials.gov).

Clinical implementation of automated O2 titration in a tertiary care hospital.

Background: When treating acute respiratory failure, both hypoxemia and hyperoxemia should be avoided. SpO2 should be monitored closely and O2 flows adjusted accordingly. Achieving this goal might be easier with automated O2 titration compared to manual titration of fixed-flow O2 We evaluated the feasibility of using an automated O2 titration device in subjects treated for acute hypoxemic respiratory failure in a tertiary care hospital.Methods: Healthcare workers received education and training about oxygen therapy and were familiarized with an automated O2 titration device (FreeO2, Oxynov, Quebec City, Canada). A coordinator was available from 8 am to 5 pm during week days to provide technical assistance. The ability of the device to maintain SpO2 within the prescribed therapeutic window was recorded. Basic clinical information was recorded.Results: Subjects were enrolled from November 2020 to August 2022. We trained 508 healthcare workers on use of automated O2 titration which was finally used on 872 occasions in 763 subjects, distributed on the respiratory, COVID-19 and thoracic surgery wards and the emergency room. Clinical information could be retrieved for 609 (80%) subjects who were on the system for a median of 3 days (interquartile range: 2 to 6 days) representing 2567 subject-days of clinical experience with the device. In the 82 (14%) subjects for whom this information was available, the system maintained SpO2 within the prescribed targets 89% of the time. Ninety-six subjects experienced clinical deterioration as defined by the need to be transferred to the intensive care unit and/or requirement of high nasal flow oxygen but none of these events were judged to be related to the O2 device.Conclusions: Automated O2 titration could be successfully implemented in hospitalized subjects with hypoxemic respiratory failure from various causes. This experience should foster further improvement of the device and recommendations for an optimized utilization.

Sedation-Ventilation Interaction in Acute Hypoxemic Respiratory Failure: Secondary Analysis of the LANDMARK Trial

BackgroundVentilation and sedation are used for the management of acute hypoxemic respiratory failure (AHRF), but their optimal combination to minimize the risks of ventilation is not well understood. Research questionWhat are the individual effects and interactions of inspiratory and end-expiratory pressure (PEEP), sedation, and venovenous extracorporeal membrane oxygenation (VV-ECMO) on respiratory drive, effort, and lung-distending pressure in patients with AHRF triggering the ventilator? Study designand methods: Secondary exploratory analysis of a trial of lung and diaphragm protection in AHRF. Inspiratory pressure, sedation, PEEP, and VV-ECMO were titrated while respiratory drive (airway pressure in the first 100 milliseconds, P0.1), effort (esophageal pressure swing, |ΔPes|), and lung-distending pressure (dynamic transpulmonary driving pressure, ΔPL,dyn) were recorded. Associations were evaluated using linear mixed effects regression models including pre-specified terms for potential interactions. ResultsThe study included 223 individual measurements of P0.1 and 235 individual measurements of |ΔPes| and ΔPL,dyn from 30 patients. Propofol attenuated P0.1 (–0.4 cm H2O, 95% CI –0.3, –0.1 per 10 mcg/kg/min increase), |ΔPes| (–2.5 cm H2O, 95% CI –3.4, –1.7 per 10 mcg/kg/min increase) and ΔPL,dyn (–1.6 cm H2O, 95% CI –2.3, –0.8 per 10 mcg/kg/min increase). The effect of inspiratory pressure on |ΔPes| varied depending on propofol dose: with higher propofol dose, inspiratory pressure resulted in higher ΔPL,dyn. Under VV-ECMO, patients (n=16) had significantly lower |ΔPes| (–10 cm H2O, 95% CI –17.5, –2.5) and required less sedation to reduce |ΔPes| than without VV-ECMO (n=14). InterpretationMechanical ventilation, sedation, and VV-ECMO exert interdependent effects on respiratory drive, effort, and lung-distending pressure in AHRF. Patients under VV-ECMO require less sedation to control respiratory effort.

A Prospective Observational Study Comparing Oxygen Saturation/Fraction of Inspired Oxygen Ratio with Partial Pressure of Oxygen in Arterial Blood/Fraction of Inspired Oxygen Ratio among Critically Ill Patients Requiring Different Modes of Oxygen Supplementation in Intensive Care Unit.

Intensive care unit (ICU) patients face a significant rise in mortality rates due to acute hypoxemic respiratory failure (AHRF). The diagnosis of AHRF is based on the PF ratio, but it has limitations in resource-constrained settings. Instead, the Kigali modification suggests using the oxygen saturation/fraction of inspired oxygen (SF) ratio. This study aims to correlate SF ratio and arterial oxygen pressure (PF) ratio in critically ill adults with hypoxemic respiratory failure, who required O2 therapy through different modes of oxygen supplementation. In an ICU, a prospective observational study included 125 adult AHRF patients receiving oxygen therapy, with data collected on FiO2, PaO2, and SpO2. The SF ratio and PF ratio were calculated, and their correlation was assessed using statistical analysis. The receiver operator characteristics (ROC) curve analysis was conducted to assess the diagnostic precision of the SF ratio in identifying AHRF. Data from a total of 250 samples were collected. The study showed a positive correlation (r = 0.622) between the SF ratio and the PF ratio. The SF threshold values of 252 and 321 were established for PF values of 200 and 300, respectively, featuring a sensitivity of 69% and specificity of 95%. Furthermore, it is worth noting that the PF ratio and SF ratio are interchangeable, regardless of the type of oxygen therapy, as the median values of both the PF ratio and SF ratio displayed statistical significance (p < 0.01) in both acidosis and alkalosis conditions. For patients with AHRF, the noninvasive SF ratio can effectively serve as a substitute for the invasive PF ratio across all oxygen supplementation modes. Alur TR, Iyer SS, Shah JN, Kulkarni S, Jedge P, Patil V. A Prospective Observational Study Comparing Oxygen Saturation/Fraction of Inspired Oxygen Ratio with Partial Pressure of Oxygen in Arterial Blood/Fraction of Inspired Oxygen Ratio among Critically Ill Patients Requiring Different Modes of Oxygen Supplementation in Intensive Care Unit. Indian J Crit Care Med 2024; 28(3):251-255.

Comparison of Oxygen Delivery Devices in Postoperative Patients with Hypoxemia: An Open-labeled Randomized Controlled Study.

Acute hypoxemic respiratory failure is among the more commonly occurring complications in postoperative patients. Supplemental oxygen and addressing the primary etiology form the basis of its treatment. We conducted an open-labeled randomized control trial with 90 adult patients and compared three oxygen delivery vehicles (ODV), i.e., noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and venturi mask (VM) in postoperative hypoxemic patients. The primary outcome variable was a change in the P/F ratio after 2 hours of use of ODV. It was observed that the change in P/F ratio after 2 hours was similar in all three ODV groups (p = 0.274). The mean values of the post-ODV P/F ratio were comparable with the pre-ODV P/F ratio in all three modalities. The P/F ratio after HFNC was 358.08 ± 117.95; after NIV was 357.60 ± 220.67; and after VM was 355.47 ± 101.90 (p = 0.997). Among HFNC, NIV, and VM, none of the devices proved superior to the other for use in postoperative hypoxemia. Mishra S, Kothari N, Sharma A, Goyal S, Rathod D, Meshram T, et al. Comparison of Oxygen Delivery Devices in Postoperative Patients with Hypoxemia: An Open-labeled Randomized Controlled Study. Indian J Crit Care Med 2024;28(3):294-298.