Noninvasive positive pressure ventilation (NIV) is a positive pressure ventilation method employed across various disease processes, utilizing noninvasive interfaces such as helmets and facemasks rather than invasive methods such as endotracheal intubation. The benefits of NIV are significant in both the acute care setting, such as improving work of breathing and avoiding the need for endotracheal intubation, as well as in the chronic care setting, improving quality of life and mortality. While new guidelines broaden the application of NIV across various disease areas and introduce emerging modalities, uncertainty persists regarding the appropriate timing and circumstances for NIV utilization. We present a detailed review of the literature with up-to-date studies assessing the indications and limitations of NIV in a variety of conditions associated with acute and chronic respiratory failure. The review also summarizes the current guidelines on the use of NIV in the acute care setting. Although primarily targeted towards the acute indications of NIV, we believe this review will aid in better understanding and managing noninvasive ventilation for clinicians across both the inpatient and outpatient settings.

The Sequential Organ Failure Assessment (SOFA) score originated as a tool for assessing organ dysfunction in critical illness but has expanded to become an outcome measure in clinical trials. We aimed to assess how the SOFA score was used as the primary or secondary endpoint of major randomized controlled trials (RCTs).

Independent reviewers searched MEDLINE/PubMed, Scopus, and Embase databases.

Articles were selected when they fulfilled: 1) RCT; 2) SOFA score was primary or secondary endpoint; and 3) published in the Lancet , New England Journal of Medicine , or Journal of the American Medical Association .

Data collection included study details, outcomes, statistical differences in SOFA score, choice of score statistics, timepoints of SOFA reporting, and how missing data and competing risks analysis were managed.

Twenty-three RCTs had SOFA score as outcome measure, eight used it as primary endpoint. Daily maximum SOFA was the key statistic in 11 RCTs, delta SOFA was used in eight, and mean SOFA in four. Mean SOFA was most frequently chosen as primary endpoint (4/8, 50%). There were 18 different outcome assessment timepoints, ranging from 1 to 28 days. Three RCTs reported statistically significant difference in SOFA between groups. Handling of missing SOFA scores was not described in ten of 23 RCTs. When described, it varied from study to study with variable imputation methods and variable accounting for the competing risk of mortality and ICU discharge.

There is major variability in the choice of summary statistic for SOFA score analysis and assessment timepoints, when using it as outcome measure in RCTs. There was either no information or great variability in the handling of missing values, use of imputation, and accounting for competing risk. The current use of SOFA scores in RCTs lacks sufficient reproducibility and statistical and methodological robustness.

Acute hypoxemic respiratory failure in immunocompromised patients remains the leading cause of admission to the ICU, with high case fatality. The response to the initial oxygenation strategy may be predictive of outcome. This study aims to assess the response to the evolutionary profiles of oxygenation strategy and the association with survival.

Post hoc analysis of EFRAIM study with a nonparametric longitudinal clustering technique (longitudinal K-mean).

Multinational, observational prospective cohort study performed in critically ill immunocompromised patients admitted for an acute respiratory failure.

None.

A total of 1547 patients who did not require invasive mechanical ventilation (iMV) at ICU admission were included. Change in ventilatory support was assessed and three clusters of change in oxygenation modality over time were identified. Cluster A: 12.3% iMV requirement and high survival rate, n = 717 patients (46.3%); cluster B: 32.9% need for iMV, 97% ICU mortality, n = 499 patients (32.3%); and cluster C: 37.5% need for iMV, 0.3% ICU mortality, n = 331 patients (21.4%). These clusters demonstrated a high discrimination. After adjustment for confounders, clusters B and C were independently associated with need for iMV (odds ratio [OR], 9.87; 95% CI, 7.26-13.50 and OR, 19.8; 95% CI, 13.7-29.1).

This study identified three distinct highly performing clusters of response to initial oxygenation strategy, which reliably predicted the need for iMV requirement and hospital mortality.

Significant advancements have been made in the care of the allogeneic hematopoietic stem cell (HCT) recipient. However, they remain one of the most vulnerable groups of patients who may be admitted to the ICU. On the one hand, they have been administered treatment with the goal of achieving cure for their underlying disease, yet their unique immunocompromised trajectory and treatment-associated toxicities continue to challenge the intensivist from a diagnostic and management perspective. While infectious disease, allogeneic HCT and critical care research have improved outcomes, there remain significant areas to advance critical care management to further increase the likelihood of bridging to an acceptable quality of life. This review focuses on care of the critically ill patient undergoing allogeneic HCT for hematologic malignancies, critical care conditions that may arise, contemporary practices in their management, and areas to focus future research.

This study evaluates the impact of different initial ventilation strategies on in-hospital mortality among sepsis patients.

We included hospitalized sepsis patients who underwent mechanical ventilation from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and categorized them into groups based on their initial ventilation strategy: non-invasive ventilation (NIV) and invasive mechanical ventilation (IMV). The main endpoint analyzed was in-hospital mortality. A propensity score matching model was employed to address confounding factors, and Cox survival analysis was performed in the matched cohort. Subgroup analyses were conducted to evaluate population heterogeneity.

Among 19,796 patients who received mechanical ventilation, 10,073 (50.8%) initially received NIV. The analysis included 2935 matched pairs. Patients initially receiving NIV exhibited a higher survival rate (P = 0.009) and a 24% lower risk of in-hospital mortality compared to those initially receiving IMV (P < 0.001). Subgroup analysis indicated significant survival benefits with initial NIV for patients without malignant tumor (MT), or lower Sequential Organ Failure Assessment (SOFA) scores and higher PO2/FiO2.

Among sepsis patients, initial NIV is linked to increased in-hospital survival rates and reduced mortality risk, particularly in patients without concurrent MT, lower SOFA scores, and higher PO2/FiO2.

Managing acute myeloid leukemia (AML) and its critical complications requires understanding the complex interplay between disease biology, treatment strategies, and patient characteristics. Complications like sepsis, acute respiratory failure (ARF), hyperleukocytosis, coagulopathy, tumor lysis syndrome (TLS) and central nervous system (CNS) involvement present unique challenges needing precise evaluation and tailored interventions. Venetoclax-induced TLS and differentiation syndrome (DS) from IDH1/IDH2 or menin inhibitors highlight the need for ongoing research and innovative approaches. As the microbiological landscape evolves and new therapeutic agents emerge, adapting strategies to mitigate harmful pharmacological interactions is crucial. Advances in understanding the genetic profiles of patients with hyperleukocytosis contribute to better-targeted therapeutic strategies. Effective AML management relies on collaborative efforts from hematologists, specialized services, and intensive care units (ICUs). This review analyzes recent data on critical AML complications, identifies areas for further investigation, and proposes ways to advance clinical research and enhance patient care strategies.

Multidrug resistant (MDR) Gram-negative bacterial infections are considered a major public health threat. The objectives of this study were to describe the epidemiology, potential contributing factors, and antimicrobial resistance patterns associated with infections caused by MDR Gram-negative bacteria (GNB) in non-immunocompromised children and adolescents.

This was a retrospective observational study conducted at the American University of Beirut Medical Center (AUBMC) from 2009 to 2017. The study included non-immunocompromised patients 18 years of age or younger with infections caused by GNB isolated from a sterile site or nonsterile site in the setting of clinical infection.

A total of 810 episodes of infection with GNB in 674 pediatric patients were identified. The most common pathogens were Enterobacterales followed by Pseudomonas. MDR GNB infections represented 47.8% of the episodes, with alarming MDR rates among Escherichia coli (64.3%), Klebsiella pneumoniae (59.1%) and Acinetobacter species (70.6%). Previous infection with the same organism during the previous 12 months, urinary catheter or cardiac catheterization in the past 30 days had high percentages of infections with MDR GNB. The carbapenem resistance rates were 1.7% in Enterobacterales, 19.8% in Pseudomonas species and 64.7% in Acinetobacter species.

High prevalence of infections with MDR GNB was detected in non-immunocompromised pediatric patients in Lebanon. This poses a significant threat to the pediatric population and underscores the importance of implementing antimicrobial stewardship programs and infection control policies, which are crucial to cope with the burden of these infections, especially in the presence of other ongoing challenges such as the current economic collapse and ongoing war leading to severe antimicrobial shortages.

To describe the use of life-sustaining therapies and mortality in patients with acute leukemia admitted to the intensive care unit (ICU).

The PubMed database was searched from January 1st, 2000 to July 1st, 2023. All studies including adult critically ill patients with acute leukemia were included. Two reviewers independently selected the studies, assessed bias using the Newcastle-Ottawa scale for cohort studies, and performed data extraction from full-text reading. We performed a proportional meta-analysis using a random effects model. The primary outcome was all-cause ICU mortality. Secondary outcomes included reasons for ICU admission, use of organ support therapies (mechanical ventilation, vasopressors and renal replacement therapy), hospital, day-90 and one-year mortality rates.

Of the 1,331 studies screened, 136 (24,861 patients) met the inclusion criteria and were included in the meta-analysis. Acute myeloid leukemia affected 16,269 (66%) patients, acute lymphoblastic leukemia affected 835 (3%) patients, and the type of leukemia was not specified in 7,757 (31%) patients. Acute respiratory failure (70%) and acute circulatory failure (25%) were the main reasons for ICU admission. Invasive mechanical ventilation, vasopressors and renal replacement therapy, were needed in 65%, 53%, and 23% of the patients, respectively. ICU mortality was available in 51 studies (6,668 patients, of whom 2,956 died throughout their ICU stay), resulting in a metanalytical proportion of 52% (95% CI [47%; 57%]; I2 93%). In a meta-regression, variables that influenced ICU mortality included year of publication, and intubation rate.

Acute respiratory failure is the main reason for ICU admission in patients with acute leukemia. Mechanical ventilation is the first life-sustaining therapy to be used, and also a strong predictor of mortality.

This study's protocol was preregistered on PROSPERO (CRD42023439630).

Multidrug resistant Gram-negative bacterial infections are considered a major public health threat. Immunocompromised pediatric patients are at a great risk of severe or overwhelming infections. The aim of this study was to describe the frequency of infections with multidrug resistant (MDR) Gram-negative bacteria (GNB) in immunocompromised pediatric patients and to determine the risk factors. In addition, we aimed to identify the antimicrobial resistance patterns of these isolates.

This was a retrospective observational study conducted at the American University of Beirut Medical Center (AUBMC) from 2009 to 2017. The study included immunocompromised patients 18 years of age or younger with infections caused by Gram-negative bacteria isolated from a sterile site, or nonsterile site in the setting of clinical infection.

A total of 381 episodes of infection with GNB in 242 immunocompromised pediatric patients were identified. The mean age was 7.7 years. The most common pathogens were Enterobacterales followed by Pseudomonas and Acinetobacter spp. MDR GNB infections predominated causing 72% of the episodes, with alarming MDR rates among Escherichia coli (95.7%) and Klebsiella pneumoniae (82.7%). The overall rate of MDR GNB isolated increased from 62.7% in 2015 to 90% in 2017. Thrombocytopenia, chemotherapy and previous colonization or infection with the same organism during the past 12 months were found to be independent risk factors for infection with MDR GNB.

This study provides data on the epidemiology of infections with MDR GNB in immunocompromised pediatric patients and illustrates the alarmingly high prevalence of these infections. This necessitates the frequent revisiting of treatment guidelines in these high-risk patients and the implementation of judicious antimicrobial stewardship programs and infection control policies to stabilize or decrease the prevalence of these infections.

Cancer patients who are exposed to sepsis and had previous chemotherapy may have increased severity. Among chemotherapeutic agents, anthracyclines have been associated with cardiac toxicity. Like other chemotherapeutic agents, they may cause endothelial toxicity. The aim of this study was to evaluate the effect of anthracycline treatment on the outcome of cancer patients with sepsis.

Data from cancer patients admitted to intensive care units (ICUs) for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique database (1994-2015). Comparison between patients who received anthracycline and those who did not was performed using a propensity score, including confounding variables (age and underlying diseases). A competing risk adjusted for severity of illness (Sequential Organ Failure Assessment [SOFA] score) was used to analyze the duration of vasopressor requirement.

Among 2046 patients, 1070 (52.3%) patients who received anthracycline were compared with 976 (47.7%) who did not. The underlying disease was mostly acute hematological malignancy (49.2%). Sepsis, mostly pneumonia (47.7%), had developed 2 days (interquartile range [IQR]:1-4 days) prior to ICU admission. Most patients (n=1156/1980,58.4%) required vasopressors for 3 days (IQR: 2-6 days). Factors associated with the need for vasopressors were aplasia (hazard ratio [HR]=1.72, 95% confidence interval [CI]: 1.21 to 2.47, P=0.002) and day 1 respiratory SOFA score (HR=7.07, 95% CI: 2.75 to 22.1, P <0.001). Previous anthracycline treatment was not associated with an increased risk of vasopressor use. The duration of vasopressors was not different between patients who received anthracycline and those who did not (P=0.79). Anthracycline was not associated with ICU mortality.

Previous anthracycline treatment did not alter the course of sepsis in a cohort of cancer patients admitted to intensive care with sepsis.

Improving short- and long-term outcomes in immunosuppressed patients, including patients with cancer, solid-organ transplant recipients, and patients with short- and long-term steroid treatment, has led to a paradigm shift in intensive care unit admission policies. Approximately 20% of patients currently admitted to the ICU carry a diagnosis of immune deficiency. In this population, acute respiratory failure and acute respiratory distress syndrome are the most frequent causes of ICU admission. Intensivists should therefore be aware of etiologies, diagnostics, and management strategies unique to this population.

The understanding of acute respiratory distress syndrome (ARDS) has evolved greatly since it was first described in a 1967 case series, with several subsequent updates to the definition of the syndrome. Basic science advances and clinical trials have provided insight into the mechanisms of lung injury in ARDS and led to reduced mortality through comprehensive critical care interventions. This review summarizes the current understanding of the epidemiology, pathophysiology, and management of ARDS. Key highlights include a recommended new global definition of ARDS and updated guidelines for managing ARDS on a backbone of established interventions such as low tidal volume ventilation, prone positioning, and a conservative fluid strategy. Future priorities for investigation of ARDS are also highlighted.

This narrative review was written by an expert panel to the members of the jury to help in the development of clinical practice guidelines on oxygen therapy.

According to the expert panel, acute hypoxemic respiratory failure was defined as PaO2 < 60 mm Hg or SpO2 < 90% on room air, or PaO2/FiO2 ≤ 300 mm Hg. Supplemental oxygen should be administered according to the monitoring of SpO2, with the aim at maintaining SpO2 above 92% and below 98%. Noninvasive respiratory supports are generally reserved for the most hypoxemic patients with the aim of relieving dyspnea. High-flow nasal cannula oxygen (HFNC) seems superior to conventional oxygen therapy (COT) as a means of avoiding intubation and may therefore be should probably be used as a first-line noninvasive respiratory support in patients requiring more than 6 L/min of oxygen or PaO2/FiO2 ≤ 200 mm Hg and a respiratory rate above 25 breaths/minute or clinical signs of respiratory distress, but with no benefits on mortality. Continuous positive airway pressure (CPAP) cannot currently be recommended as a first-line noninvasive respiratory support, since its beneficial effects on intubation remain uncertain. Despite older studies favoring noninvasive ventilation (NIV) over COT, recent clinical trials fail to show beneficial effects with NIV compared to HFNC. Therefore, there is no evidence to support the use of NIV or CPAP as first-line treatment if HFNC is available. Clinical trials do not support the hypothesis that noninvasive respiratory supports may lead to late intubation. The potential benefits of awake prone positioning on the risk of intubation in patients with COVID-19 cannot be extrapolated to patients with another etiology.

Whereas oxygen supplementation should be initiated for patients with acute hypoxemic respiratory failure defined as PaO2 below 60 mm Hg or SpO2 < 90% on room air, HFNC should be the first-line noninvasive respiratory support in patients with PaO2/FiO2 ≤ 200 mm Hg with increased respiratory rate. Further studies are needed to assess the potential benefits of CPAP, NIV through a helmet and awake prone position in patients with acute hypoxemic respiratory failure not related to COVID-19.

Although largely used, the place of oxygen therapy and its devices in patients with acute hypoxemic respiratory failure (ARF) deserves to be clarified. The French Intensive Care Society (Société de Réanimation de Langue Française, SRLF) and the French Emergency Medicine Society (Société Française de Médecine d'Urgence, SFMU) organized a consensus conference on oxygen therapy in ARF (excluding acute cardiogenic pulmonary oedema and hypercapnic exacerbation of chronic obstructive diseases) in December 2023.

A committee without any conflict of interest (CoI) with the subject defined 7 generic questions and drew up a list of sub questions according to the population, intervention, comparison and outcomes (PICO) model. An independent work group reviewed the literature using predefined keywords. The quality of the data was assessed using the GRADE methodology. Fifteen experts in the field from both societies proposed their own answers in a public session and answered questions from the jury (a panel of 16 critical-care and emergency medicine physicians, nurses and physiotherapists without any CoI) and the public. The jury then met alone for 48 h to write its recommendations.

The jury provided 22 statements answering 11 questions: in patients with ARF (1) What are the criteria for initiating oxygen therapy? (2) What are the targets of oxygen saturation? (3) What is the role of blood gas analysis? (4) When should an arterial catheter be inserted? (5) Should standard oxygen therapy, high-flow nasal cannula oxygen therapy (HFNC) or continuous positive airway pressure (CPAP) be preferred? (6) What are the indications for non-invasive ventilation (NIV)? (7) What are the indications for invasive mechanical ventilation? (8) Should awake prone position be used? (9) What is the role of physiotherapy? (10) Which criteria necessarily lead to ICU admission? (11) Which oxygenation device should be preferred for patients for whom a do-not-intubate decision has been made?

These recommendations should optimize the use of oxygen during ARF.

The guideline update outlines the advantages as well as the limitations of NIV in the treatment of acute respiratory failure in daily clinical practice and in different indications.Non-invasive ventilation (NIV) has a high value in therapy of hypercapnic acute respiratory failure, as it significantly reduces the length of ICU stay and hospitalization as well as mortality.Patients with cardiopulmonary edema and acute respiratory failure should be treated with continuous positive airway pressure (CPAP) and oxygen in addition to necessary cardiological interventions. This should be done already prehospital and in the emergency department.In case of other forms of acute hypoxaemic respiratory failure with only mild or moderately disturbed gas exchange (PaO2/FiO2 > 150 mmHg) there is no significant advantage or disadvantage compared to high flow nasal oxygen (HFNO). In severe forms of ARDS NIV is associated with high rates of treatment failure and mortality, especially in cases with NIV-failure and delayed intubation.NIV should be used for preoxygenation before intubation. In patients at risk, NIV is recommended to reduce extubation failure. In the weaning process from invasive ventilation NIV essentially reduces the risk of reintubation in hypercapnic patients. NIV is regarded useful within palliative care for reduction of dyspnea and improving quality of life, but here in concurrence to HFNO, which is regarded as more comfortable. Meanwhile NIV is also recommended in prehospital setting, especially in hypercapnic respiratory failure and pulmonary edema.With appropriate monitoring in an intensive care unit NIV can also be successfully applied in pediatric patients with acute respiratory insufficiency.

Dyspnea is a key symptom of de novo acute hypoxemic respiratory failure. This study explores dyspnea and its association with intubation and mortality in this population.

This was a secondary analysis of a multicenter, randomized, controlled trial. Dyspnea was quantified by a visual analog scale (dyspnea-VAS) from zero to 100 mm. Dyspnea was measured in 259 of the 310 patients included. Factors associated with intubation were assessed with a competing risks model taking into account ICU discharge. The Cox model was used to evaluate factors associated with 90-day mortality.

At baseline (randomization in the parent trial), median dyspnea-VAS was 46 (interquartile range, 16-65) mm and was ≥ 40 mm in 146 patients (56%). The intubation rate was 45%. Baseline variables independently associated with intubation were moderate (dyspnea-VAS 40-64 mm) and severe (dyspnea-VAS ≥ 65 mm) dyspnea at baseline (sHR 1.96 and 2.61, p = 0.023), systolic arterial pressure (sHR 2.56, p < 0.001), heart rate (sHR 1.94, p = 0.02) and PaO2/FiO2 (sHR 0.34, p = 0.028). 90-day mortality was 20%. The cumulative probability of survival was lower in patients with baseline dyspnea-VAS ≥ 40 mm (logrank test, p = 0.049). Variables independently associated with mortality were SAPS 2 ≥ 25 (p < 0.001), moderate-to-severe dyspnea at baseline (p = 0.073), PaO2/FiO2 (p = 0.118), and treatment arm (p = 0.046).

In patients admitted to the ICU for de novo acute hypoxemic respiratory failure, dyspnea is associated with a higher risk of intubation and with a higher mortality.

clinicaltrials.gov Identifier # NCT01320384.

Acute respiratory failure (ARF) is a leading cause, along with sepsis, of admission to the intensive care unit (ICU) of patients with active cancer. Presenting variable clinical severity, ARF in onco-hematological patients has differing etiologies, primarily represented by possibly opportunistic acute infectious pneumonia (de novo hypoxemic ARF), and decompensation in chronic cardiac or respiratory diseases (e.g., acute pulmonary edema or exacerbated chronic obstructive pulmonary disease). In these patients, orotracheal intubation is associated with a doubled risk of in-hospital mortality. Consequently, over the last three decades, numerous researchers have attempted to demonstrate and pinpoint the precise role of non-invasive ventilation (NIV) in the specific context of ARF in onco-hematological patients. While the benefits of NIV in the management of acute pulmonary edema or alveolar hypoventilation (hypercapnic ARF) are well-demonstrated, its positioning in de novo hypoxemic ARF is debatable, and has recently been called into question. In the early 2000s, based on randomized controlled trials, NIV was recommended as first-line treatment, one reason being that it allowed significantly reduced use of orotracheal intubation. In the latest randomized studies, however, the benefits of NIV in terms of survival orotracheal intubation have not been observed; as a result, it is no longer recommended in the management of de novo hypoxemic ARF in onco-haematological patients.

Patients with hematological malignancies are at high risk for life-threatening complications. To date, little attention has been paid to the impact of hyperoxemia and excess oxygen use on mortality. The aim of this study was to investigate the association between partial pressure of arterial oxygen (PaO2) and 28-day mortality in critically ill patients with hematologic malignancies.

Data from three international cohorts (Europe, Canada, Oceania) of patients who received respiratory support (noninvasive ventilation, high-flow nasal cannula, invasive mechanical ventilation) were obtained. We used mixed-effect Cox models to investigate the association between day one PaO2 or excess oxygen use (inspired fraction of oxygen ≥ 0.6 with PaO2 > 100 mmHg) on day-28 mortality.

11,249 patients were included. On day one, 5716 patients (50.8%) had normoxemia (60 ≤ PaO2 ≤ 100 mmHg), 1454 (12.9%) hypoxemia (PaO2 < 60 mmHg), and 4079 patients (36.3%) hyperoxemia (PaO2 > 100 mmHg). Excess oxygen was used in 2201 patients (20%). Crude day-28 mortality rate was 40.6%. There was a significant association between PaO2 and day-28 mortality with a U-shaped relationship (p < 0.001). Higher PaO2 levels (> 100 mmHg) were associated with day-28 mortality with a dose-effect relationship. Subgroup analyses showed an association between hyperoxemia and mortality in patients admitted with neurological disorders; however, the opposite relationship was seen across those admitted with sepsis and neutropenia. Excess oxygen use was also associated with subsequent day-28 mortality (adjusted hazard ratio (aHR) [95% confidence interval (CI)]: 1.11[1.04-1.19]). This result persisted after propensity score analysis (matched HR associated with excess oxygen:1.31 [1.20-1.1.44]).

In critically-ill patients with hematological malignancies, exposure to hyperoxemia and excess oxygen use were associated with increased mortality, with variable magnitude across subgroups. This might be a modifiable factor to improve mortality.

In 2023, the new European guidelines on severe community-acquired pneumonia, providing clinical practice recommendations for the management of this life-threatening infection, characterized by a high burden of mortality, morbidity, and costs for the society. This review article aims to summarize the principal evidence related to eight different questions covered in the guidelines, by also highlighting the future perspectives for research activity.

Due to higher survival rates with good quality of life, related to new treatments in the fields of oncology, hematology, and transplantation, the number of immunocompromised patients is increasing. But these patients are at high risk of intensive care unit admission because of numerous complications. Acute respiratory failure due to severe community-acquired pneumonia is one of the leading causes of admission. In this setting, the need for invasive mechanical ventilation is up to 60%, associated with a high hospital mortality rate of around 40 to 50%. A wide range of pathogens according to the reason of immunosuppression is associated with severe pneumonia in those patients: documented bacterial pneumonia represents a third of cases, viral and fungal pneumonia both account for up to 15% of cases. For patients with an undetermined etiology despite comprehensive diagnostic workup, the hospital mortality rate is very high. Thus, a standardized diagnosis strategy should be defined to increase the diagnosis rate and prescribe the appropriate treatment. This review focuses on the benefit-to-risk ratio of invasive or noninvasive strategies, in the era of omics, for the management of critically ill immunocompromised patients with severe pneumonia in terms of diagnosis and oxygenation.

Severe community-acquired pneumonia (sCAP) remains one of the leading causes of admission to the intensive care unit, thus consuming a large share of resources and is associated with high mortality rates worldwide. The evidence generated by clinical studies in the last decade was translated into recommendations according to the first published guidelines focusing on severe community-acquired pneumonia. Despite the advances proposed by the present guidelines, several challenges preclude the prompt implementation of these diagnostic and therapeutic measures. The present article discusses the challenges for the broad implementation of the sCAP guidelines and proposes solutions when applicable.

Acute respiratory failure (ARF) is common in patients with hematological malignancies notably those with acute leukemia, myelodysplastic syndrome, or allogeneic stem cell transplantation. ARF is the leading reason for intensive care unit (ICU) admission, with a 35% case fatality rate. Failure to identify the ARF cause is associated with mortality. A prompt, well-designed diagnostic workup is crucial. The investigations are chosen according to pretest diagnostic probabilities, estimated by the DIRECT approach: D stands for delay, or time since diagnosis; I for pattern of immune deficiency; R and T for radiological evaluation; E refers to clinical experience, and C to the clinical picture. Thorough familiarity with rapid diagnostic tests helps to decrease the use of bronchoscopy with bronchoalveolar lavage, which can cause respiratory status deterioration in those patients with hypoxemia. A prompt etiological diagnosis shortens the time on unnecessary empirical treatments, decreasing iatrogenic harm and costs. High-quality collaboration between intensivists and hematologists and all crossdisciplinary health care workers is paramount. All oxygen delivery systems should be considered to minimize invasive mechanical ventilation. Treatment of the malignancy is started or continued in the ICU under the guidance of the hematologists. The goal is to use the ICU as a bridge to recovery, with the patient returning to the hematology ward in sufficiently good clinical condition to receive optimal anticancer treatment.

We aim to identify the clinical phenotypes of immunocompromised patients with pneumonia-related ARDS, to investigate the lung microbiota signatures and the outcomes of different phenotypes, and finally, to develop a machine learning classifier for a specified phenotype.

This prospective study included immunocompromised patients with pneumonia-related ARDS. We identified phenotypes using hierarchical clustering to analyze clinical variables and serum cytokine levels. We then compared outcomes and lung microbiota signatures between phenotypes. Based on lung microbiota markers, we developed a random forest classifier for a specified phenotype with worse outcomes.

This study included 92 patients, who were divided into three phenotypes, namely "type α" (N = 33), "type β" (N = 12), and "type γ" (N = 47). Compared to type α or type β, patients with type γ had no obvious inflammatory presentation and had significantly lower IL-6 levels and more severe oxygenation failure. Type γ was also related to higher 30-day mortality and lower ventilator free days. The microbiota signatures of type γ were characterized by lower alpha diversity and distinct compositions than those of other patients. We developed a lung microbiota-derived random forest model to differentiate patients with type γ from other phenotypes.

Immunocompromised patients with pneumonia-related ARDS can be clustered into three clinical phenotypes, namely type α, type β, and type γ. Phenotypes were distinguished from each other with different outcomes and lung microbiota signatures. Type γ, which was characterized by insufficient inflammation response and worse outcomes, can be detected with a random forest model based on lung microbiota markers.

The timing of transition from non-invasive ventilation (NIV) to invasive ventilation in the intensive care unit (ICU) is uncertain due to a lack of clinical evidence. This study aimed to identify the optimal timing of intubation in patients with respiratory failure managed with NIVs.

A single-center observational study was conducted in Tokyo, Japan. Patients in the ICU managed with NIV between 2013 and 2022 were screened. The primary outcome was 28-day invasive ventilator-free days. Statistical analyses used locally estimated scatter plot smoothing (LOESS) and generalized linear mixed models to estimate the association between the timing of transition and prolonged intubation duration.

During the study period, 139 of 589 adult ICU patients receiving NIV transitioned to invasive ventilation. The LOESS curve indicated the longest 28-day ventilator-free days around 24 h after NIV initiation, after which the primary outcome decreased linearly. Late intubation after 24 h of NIV initiation was associated with fewer 28-day ventilator-free days (adjusted mean difference: -0.22 days [95% confidence interval: -0.31, -0.13]).

We identified a non-linear association between the timing of intubation and 28-day invasive ventilator-free days. The critical 24-h time window for patients on NIV was associated with longer 28-day invasive ventilator-free days.

It is unclear how often survival benefits observed in single-center randomized controlled trials (sRCTs) involving critically ill patients are confirmed by subsequent multicenter randomized controlled trials (mRCTs). We aimed to perform a systemic literature review of sRCTs with a statistically significant mortality reduction and to evaluate whether subsequent mRCTs confirmed such reduction.

We searched PubMed for sRCTs published in the New England Journal of Medicine, JAMA, or Lancet, from inception until December 31, 2016. We selected studies reporting a statistically significant mortality decrease using any intervention (drug, technique, or strategy) in adult critically ill patients. We then searched for subsequent mRCTs addressing the same research question tested by the sRCT. We compared the concordance of results between sRCTs and mRCTs when any mRCT was available. We registered this systematic review in the PROSPERO International Prospective Register of Systematic Reviews (CRD42023455362).

We identified 19 sRCTs reporting a significant mortality reduction in adult critically ill patients. For 16 sRCTs, we identified at least one subsequent mRCT (24 trials in total), while the interventions from three sRCTs have not yet been addressed in a subsequent mRCT. Only one out of 16 sRCTs (6%) was followed by a mRCT replicating a significant mortality reduction; 14 (88%) were followed by mRCTs with no mortality difference. The positive finding of one sRCT (6%) on intensive glycemic control was contradicted by a subsequent mRCT showing a significant mortality increase. Of the 14 sRCTs referenced at least once in international guidelines, six (43%) have since been either removed or suggested against in the most recent versions of relevant guidelines.

Mortality reduction shown by sRCTs is typically not replicated by mRCTs. The findings of sRCTs should be considered hypothesis-generating and should not contribute to guidelines.

For COVID-19-related respiratory failure, noninvasive respiratory assistance via a high-flow nasal cannula (HFNC), helmet, and face-mask noninvasive ventilation is used. However, which of these options is most effective is yet to be determined. This study aimed to compare the three techniques of noninvasive respiratory support and to determine the superior technique.

A randomized control trial with permuted block randomization of nine cases per block for each parallel, open-labeled arm.

Adult patients with COVID-19 with a Pa o2 /F io2 ratio of less than 300, admitted between February 4, 2021, and August 9, 2021, to three tertiary centers in Oman, were studied.

This study included three interventions: HFNC ( n = 47), helmet continuous positive airway pressure (CPAP; n = 52), and face-mask CPAP ( n = 52).

The endotracheal intubation rate and mortality at 28 and 90 days were measured as the primary and secondary outcomes, respectively. Of the 159 randomized patients, 151 were analyzed. The median age was 52 years, and 74% were men. The endotracheal intubation rates were 44%, 45%, and 46% ( p = 0.99), and the median intubation times were 7.0, 5.5, and 4.5 days ( p = 0.11) in the HFNC, face-mask CPAP, and helmet CPAP, respectively. In comparison to face-mask CPAP, the relative risk of intubation was 0.97 (95% CI, 0.63-1.49) for HFNC and 1.0 (95% CI 0.66-1.51) for helmet CPAP. The mortality rates were 23%, 32%, and 38% at 28 days ( p = 0.24) and 43%, 38%, and 40% ( p = 0.89) at 90 days for HFNC, face-mask CPAP, and helmet CPAP, respectively. The trial was stopped prematurely because of a decline in cases.

This exploratory trial found no difference in intubation rate and mortality among the three intervention groups for the COVID-19 patients with hypoxemic respiratory failure; however, more evidence is needed to confirm these findings as the trial was aborted prematurely.

Acute respiratory failure (ARF) is the leading cause of ICU admission. Viruses are increasingly recognized as a cause of pneumonia in immunocompromised patients, but epidemiologic data are scarce. We used the Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologie's database (2003-2017, 72 intensive care units) to describe the spectrum of critically ill immunocompromised patients with virus-detected ARF and to report their outcomes. Then, patients with virus-detected ARF were matched based on clinical characteristics and severity (1:3 ratio) with patients with ARF from other origins.

Of the 4038 immunocompromised patients in the whole cohort, 370 (9.2%) had a diagnosis of virus-detected ARF and were included in the study. Influenza was the most common virus (59%), followed by respiratory syncytial virus (14%), with significant seasonal variation. An associated bacterial infection was identified in 79 patients (21%) and an invasive pulmonary aspergillosis in 23 patients (6%). The crude in-hospital mortality rate was 37.8%. Factors associated with mortality were: neutropenia (OR = 1.74, 95% confidence interval, CI [1.05-2.89]), poor performance status (OR = 1.84, CI [1.12-3.03]), and the need for invasive mechanical ventilation on the day of admission (OR = 1.97, CI [1.14-3.40]). The type of virus was not associated with mortality. After matching, patients with virus-detected ARF had lower mortality (OR = 0.77, CI [0.60-0.98]) than patients with ARF from other causes. This result was mostly driven by influenza-like viruses, namely, respiratory syncytial virus, parainfluenza virus, and human metapneumovirus (OR = 0.54, CI [0.33-0.88]).

In immunocompromised patients with virus-detected ARF, mortality is high, whatever the species, mainly influenced by clinical severity and poor general status. However, compared to non-viral ARF, in-hospital mortality was lower, especially for patients with detected viruses other than influenza.

Several recently published randomized controlled trials have evaluated various noninvasive oxygenation strategies for the treatment of acute hypoxemic respiratory failure.

Which available noninvasive oxygen strategies are effective for acute hypoxic respiratory failure?

A systematic review of Medline, Embase, Cochrane CENTRAL, CINAHL, Web of Science, MedRxiv, and Research Square was conducted from inception to October 1, 2022. A random effects frequentist network meta-analysis was performed, and the results are presented using absolute risk difference per 1,000 patients. The Grading of Recommendations, Assessment, Development and Evaluation framework was used to rate the certainty of the evidence. Mortality, invasive mechanical ventilation, duration of hospitalization and ICU stay, ventilator-free days, and level of comfort are reported.

Thirty-six trials (7,046 patients) were included. It was found that helmet CPAP probably reduces mortality compared with standard oxygen therapy (SOT) (231 fewer deaths per 1,000; 95% CI, 126-273 fewer) (moderate certainty). A high-flow nasal cannula (HFNC) probably reduces the need for invasive mechanical ventilation (103.5 fewer events per 1,000; 95% CI, 40.5-157.5 fewer) (moderate certainty). All noninvasive oxygenation strategies may reduce the duration of hospitalization as compared with SOT (low certainty). Helmet bilevel ventilation (4.84 days fewer; 95% CI, 2.33-7.36 days fewer) and helmet CPAP (1.74 days fewer; 95% CI, 4.49 fewer-1.01 more) may reduce the duration of ICU stay as compared with SOT (both low certainty). SOT may be more comfortable than face mask noninvasive ventilation and no different in comfort compared with an HFNC (both low certainty).

A helmet interface for noninvasive ventilation probably reduces mortality and the risk of mechanical ventilation, as well as the duration of hospital and ICU stay. An HFNC probably reduces the risk of invasive mechanical ventilation and may be as comfortable as SOT. Further research is necessary to understand the role of these interfaces in acute hypoxemic respiratory failure.

High-flow nasal cannula (HFNC) has several benefits in patients affected by different forms of acute respiratory failure, based on its own mechanisms. We postulated that HFNC may have some advantages over conventional oxygen therapy (COT) on the heart function in patients with acute-on-chronic respiratory failure with concomitant pulmonary hypertension (PH). We therefore designed this retrospective observational study to assess if HFNC improves the right and left ventricle functions and morphologies, arterial blood gases (ABGs), and patients' dyspnea, compared to COT. We enrolled 17 hospitalized patients receiving HFNC, matched with 17 patients receiving COT. Echocardiographic evaluation was performed at the time of admission (baseline) and 10 days after (T10). HFNC showed significant improvements in right ventricular morphology and function, and a reduction in sPAP. However, there were no significant changes in the left heart measurements with HFNC application. Conversely, COT did not lead to any modifications in echocardiographic measurements. In both groups, oxygenation significantly improved from baseline to T10 (in the HFNC group, from 155 ± 47 to 204 ± 61 mmHg while in the COT group, from 157 ± 27 to 207 ± 27 mmHg; p < 0.0001 for both comparisons). In conclusion, these data suggest an improvement of oxygenation with both treatments; however, only HFNC was able to improve the right ventricular morphology and function after 10 days from the beginning of treatment in a small cohort of patients with acute-on-chronic respiratory failure with PH.

The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.