Breathlessness assessment, management and impact in the intensive care unit: a rapid review and narrative synthesis.

BACKGROUND: Adults in the intensive care unit (ICU) commonly experience distressing symptoms and other concerns such as pain, delirium, and breathlessness. Breathlessness management is not supported by any ICU guidelines, unlike other symptoms. AIM: To review the literature relating to (i) prevalence, intensity, assessment, and management of breathlessness in critically ill adults in the ICU receiving invasive and non-invasive mechanical ventilation (NIV) and high-flow oxygen therapy, (HFOT), (ii) the impact of breathlessness on ICU patients with regard to engagement with rehabilitation. METHODS: A rapid review and narrative synthesis using the Cochrane Methods Group Recommendations was conducted and reported in accordance with PRISMA. All study designs investigating breathlessness in adult ICU patients receiving either invasive mechanical ventilation (IMV), NIV or HFOT were eligible. PubMed, MEDLINE, The Cochrane Library and CINAHL databased were searched from June 2013 to June 2023. Studies were quality appraised. RESULTS: 19 studies representing 2822 ICU patients were included (participants mean age 48 years to 71 years; proportion of males 43-100%). The weighted mean prevalence of breathlessness in ICU patients receiving IMV was 49% (range 34-66%). The proportion of patients receiving NIV self-reporting moderate to severe dyspnoea was 55% prior to initiation. Breathlessness assessment tools included visual analogue scale, (VAS), numerical rating scale, (NRS) and modified BORG scale, (mBORG). In patients receiving NIV the highest reported median (interquartile range [IQR]) VAS, NRS and mBORG scores were 6.2cm (0-10 cm), 5 (2-7) and 6 (2.3-7) respectively (moderate to severe breathlessness). In patients receiving either NIV or HFOT the highest reported median (IQR) VAS, NRS and mBORG scores were 3 cm (0-6 cm), 8 (5-10) and 4 (3-5) respectively. CONCLUSION: Breathlessness in adults receiving IMV, NIV or HFOT in the ICU is prevalent and clinically important with median intensity ratings indicating the presence of moderate to severe symptoms.

Organ Involvement Related to Death in Critically Ill Patients With Leptospirosis: Unsupervised Analysis in a French West Indies ICU.

OBJECTIVES: To identify distinct phenotypes of critically ill leptospirosis patients upon ICU admission and their potential associations with outcome. DESIGN: Retrospective observational study including all patients with biologically confirmed leptospirosis admitted to the ICU between January 2014 and December 2022. Subgroups of patients with similar clinical profiles were identified by unsupervised clustering (factor analysis for mixed data and hierarchical clustering on principal components). SETTING: All patients admitted to the ICU of the University Hospital of Guadeloupe on the study period. PATIENTS: One hundred thirty critically ill patients with confirmed leptospirosis were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At ICU admission, 34% of the patients had acute respiratory failure, and 26% required invasive mechanical ventilation. Shock was observed in 52% of patients, myocarditis in 41%, and neurological involvement in 20%. Unsupervised clustering identified three clusters-"Weil's Disease" (48%), "neurological leptospirosis" (20%), and "multiple organ failure" (32%)-with different ICU courses and outcomes. Myocarditis and neurological involvement were key components for cluster identification and were significantly associated with death in ICU. Other factors associated with mortality included shock, acute respiratory failure, and requiring renal replacement therapy. CONCLUSIONS AND RELEVANCE: Unsupervised analysis of critically ill patients with leptospirosis revealed three patient clusters with distinct phenotypic characteristics and clinical outcomes. These patients should be carefully screened for neurological involvement and myocarditis at ICU admission.

Low dose of morphine to relieve dyspnea in acute respiratory failure: the OpiDys double-blind randomized controlled trial.

BACKGROUND: Morphine relieves dyspnea in various clinical circumstances. Whether or not this applies to patients admitted to intensive care units (ICUs) for acute respiratory failure (ARF) is unknown. We evaluated the efficacy and safety of low-dose morphine on dyspnea in patients admitted to the ICU for ARF. METHODS: In this single-center, double-blind, phase 2, randomized, controlled trial, we assigned non-intubated adults admitted to the ICU for ARF with severe dyspnea, defined by a visual analog scale for dyspnea (dyspnea-VAS) from zero (no dyspnea) to 100 mm (worst imaginable dyspnea) ≥40 mm, to receive a low dose of Morphine Hydrochloride (intravenous titration followed by subcutaneous relay) or Placebo. All patients received standard therapy, including etiological treatment and non-invasive respiratory support. RESULTS: Twenty-two patients were randomized, 11 in each group. The average dyspnea (median [interquartile range]) over 24 hours did not significantly differ between the two groups (40 [25 - 43] mm in the Morphine group vs. 40 [36 - 49] mm in the Placebo group, p=0.411). Dyspnea-VAS was lower in the Morphine group than in the Placebo group at the end of intravenous titration (30 [11 - 30] vs. 35 [30 - 44], p=0.044) and four hours later (18 [10 - 29] vs. 50 [30 - 60], p=0.043). The cumulative probability of intubation was higher in the Morphine group than in the Placebo group (p=0.046) CONCLUSION: In this phase 2 pilot trial, morphine did not improve 24-hour average dyspnea in adult patients with ARF, even though it had a statistically significant immediate effect. Of concern, Morphine use was associated with a higher intubation rate. TRIAL REGISTRATION: The protocol was declared on the ClinicalTrial.gov database (no. NCT04358133) and was published in September 2022.

Operator independent continuous ultrasound monitoring of diaphragm excursion predicts successful weaning from mechanical ventilation: a prospective observational study.

BACKGROUND: In mechanically ventilated patients, diaphragm ultrasound can identify diaphragm weakness and predict weaning failure. We evaluated whether a novel operator-independent ultrasound-based medical device allowing continuous monitoring of the diaphragm (CUSdi) could reliably (1) measure diaphragm excursion (EXdi) and peak contraction velocity (PCVdi), (2) predict weaning outcome, and (3) approximate transdiaphragmatic pressure (Pdi). METHODS: In 49 mechanically ventilated patients, CUSdi was recorded during a 30-min spontaneous breathing trial (SBT), and EXdi and PCVdi were measured. In subgroups of patients, standard ultrasound measurement of EXdi and PCVdi was performed (n = 36), and Pdi derived parameters (peak and pressure time product, n = 30) were measured simultaneously. RESULTS: The agreement bias between standard ultrasound and CUSdi for EXdi was 0.1 cm (95% confidence interval -0.7-0.9 cm). The regression of Passing-Bablok indicated a lack of systematic difference between EXdi measured with standard ultrasound and CUSdi, which were positively correlated (Rho = 0.84, p < 0.001). Weaning failure was observed in 54% of patients. One, two and three minutes after the onset of the SBT, EXdi was higher in the weaning success group than in the failure group. Two minutes after the onset of the SBT, an EXdi < 1.1 cm predicted weaning failure with a sensitivity of 0.83, a specificity of 0.68, a positive predictive value of 0.76, and a negative predictive value of 0.24. There was a weak correlation between EXdi and both peak Pdi (r = 0.22, 95% confidence interval 0.15 - 0.28) and pressure time product (r = 0.13, 95% confidence interval 0.06 - 0.20). Similar results were observed with PCVdi. CONCLUSIONS: Operator-independent continuous diaphragm monitoring quantifies EXdi reliably and can predict weaning failure with an identified cut-off value of 1.1 cm. Trial registration clinicaltrial.gov, NCT04008875 (submitted 12 April 2019, posted 5 July 2019) and NCT03896048 (submitted 27 March 2019, posted 29 March 2019).

Bloodstream infections among patients receiving therapeutic plasma exchanges in the intensive care unit: a 10 year multicentric study.

BACKGROUND: Therapeutic plasma exchanges (TPE), which affect the humoral response, are often performed in combination with immunosuppressive drugs. For this reason, TPE may be associated with an increased susceptibility to infections. We aimed to describe blood stream infection (BSI) incidence in ICU patients treated with TPE and to identify associated risk factors. METHODS: We retrospectively included patients that had received at least one session of TPE in the ICU of one of the 4 participating centers (all in Paris, France) between January 1st 2010 and December 31th 2019. Patients presenting with a BSI during ICU stay were compared to patients without such an infection. Risk factors for BSI were identified by a multivariate logistic regression model. RESULTS: Over 10 years in the 4 ICUs, 387 patients were included, with a median of 5 [2-7] TPE sessions per patient. Most frequent indications for TPE were thrombotic microangiopathy (47%), central nervous system inflammatory disorders (11%), hyperviscosity syndrome (11%) and ANCA associated vasculitis (8.5%). Thirty-one patients (8%) presented with a BSI during their ICU stay, a median of 7 [3-11] days after start of TPE. In a multivariate logistic regression model, diabetes (OR 3.32 [1.21-8.32]) and total number of TPE sessions (OR 1.14 [1.08-1.20]) were independent risk factors for BSI. There was no difference between TPE catheter infection related BSI (n = 11 (35%)) and other sources of BSI (n = 20 (65%)) regarding catheter insertion site (p = 0.458) or rate of TPE catheter related deep vein thrombosis (p = 0.601). ICU course was severe in patients presenting with BSI when compared to patients without BSI, with higher need for mechanical ventilation (45% vs 18%, p = 0.001), renal replacement therapy (42% vs 20%, p = 0.011), vasopressors (32% vs 12%, p = 0.004) and a higher mortality (19% vs 5%, p = 0.010). CONCLUSION: Blood stream infections are frequent in patients receiving TPE in the ICU, and are associated with a severe ICU course. Vigilant monitoring is crucial particularly for patients receiving a high number of TPE sessions.

Dyspnea is severe and associated with a higher intubation rate in de novo acute hypoxemic respiratory failure.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier # NCT01320384.

Treatment of COVID-19-associated ARDS with umbilical cord-derived mesenchymal stromal cells in the STROMA-CoV-2 multicenter randomized double-blind trial: long-term safety, respiratory function, and quality of life.

BACKGROUND: The STROMA-CoV-2 study was a French phase 2b, multicenter, double-blind, randomized, placebo-controlled clinical trial that did not identify a significant efficacy of umbilical cord-derived mesenchymal stromal cells in patients with SARS-CoV-2-induced acute respiratory distress syndrome. Safety on day 28 was found to be good. The aim of our extended study was to assess the 6- and 12-month safety of UC-MSCs administration in the STROMA-CoV-2 cohort. METHODS: A detailed multi-domain assessment was conducted at 6 and 12 months following hospital discharge focusing on adverse events, lung computed tomography-scan, pulmonary and muscular functional status, and quality of life in the STROMA-CoV-2 cohort including SARS-CoV-2-related early (< 96 h) mild-to-severe acute respiratory distress syndrome. RESULTS: Between April 2020 and October 2020, 47 patients were enrolled, of whom 19 completed a 1-year follow-up. There were no significant differences in any endpoints or adverse effects between the UC-MSCs and placebo groups at the 6- and 12-month assessments. Ground-glass opacities persisted at 1 year in 5 patients (26.3%). Furthermore, diffusing capacity for carbon monoxide remained altered over 1 year, although no patient required oxygen or non-invasive ventilatory support. Quality of life revealed declines in mental, emotional and physical health throughout the follow-up period, and the six-minute walking distance remained slightly impaired at the 1-year patient assessment. CONCLUSIONS: This study suggests a favorable safety profile for the use of intravenous UC-MSCs in the context of the first French wave of SARS-CoV-2-related moderate-to-severe acute respiratory distress syndrome, with no adverse effects observed at 1 year.

One-year survival of aneurysmal subarachnoid hemorrhage after airplane transatlantic transfer - a monocenter retrospective study.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is preferentially treated by prompt endovascular coiling, which is not available in Guadeloupe. Subsequently, patients are transferred to Paris, France mainland, by commercial airplane (6751 km flight) after being managed according to guidelines. This study describes the characteristics, management and outcomes related to these patients. METHODS: Retrospective observational cohort study of 148 patients admitted in intensive care unit for a suspected aSAH and transferred by airplane over a 10-year period (2010-2019). RESULTS: The median [interquartile range] age was 53 [45-64] years and 61% were female. On admission, Glasgow coma scale was 15 [13-15], World Federation of Neurological Surgeons (WFNS) grading scale was 1 [1-3] and Fisher scale was 4 [2-4]. External ventricular drainage and mechanical ventilation were performed prior to the flight respectively in 42% and 47% of patients. One-year mortality was 16% over the study period. By COX logistic regression analysis, acute hydrocephalus (hazard ratio [HR] 2.34, 95% confidence interval [CI] 0.98-5.58) prior to airplane transfer, WFNS grading scale on admission (HR 1.53, 95% CI 1.16-2.02) and age (OR 1.03, 95% 1.00-1.07) were associated with one-year mortality. CONCLUSION: When necessary, transatlantic air transfer of patients with suspected aSAH after management according to local guidelines seems feasible and safe.

Association between arterial oxygen and mortality across critically ill patients with hematologic malignancies: results from an international collaborative network.

PURPOSE: 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. METHODS: 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. RESULTS: 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]). CONCLUSION: 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.

Increasing Sweep Gas Flow Reduces Respiratory Drive and Dyspnea in Nonintubated Venoarterial Extracorporeal Membrane Oxygenation Patients: A Pilot Study.

BACKGROUND: Data on assessment and management of dyspnea in patients on venoarterial extracorporeal membrane oxygenation (ECMO) for cardiogenic shock are lacking. The hypothesis was that increasing sweep gas flow through the venoarterial extracorporeal membrane oxygenator may decrease dyspnea in nonintubated venoarterial ECMO patients exhibiting clinically significant dyspnea, with a parallel reduction in respiratory drive. METHODS: Nonintubated, spontaneously breathing, supine patients on venoarterial ECMO for cardiogenic shock who presented with a dyspnea visual analog scale (VAS) score of greater than or equal to 40/100 mm were included. Sweep gas flow was increased up to +6 l/min by three steps of +2 l/min each. Dyspnea was assessed with the dyspnea-VAS and the Multidimensional Dyspnea Profile. The respiratory drive was assessed by the electromyographic activity of the alae nasi and parasternal muscles. RESULTS: A total of 21 patients were included in the study. Upon inclusion, median dyspnea-VAS was 50 (interquartile range, 45 to 60) mm, and sweep gas flow was 1.0 l/min (0.5 to 2.0). An increase in sweep gas flow significantly decreased dyspnea-VAS (50 [45 to 60] at baseline vs. 20 [10 to 30] at 6 l/min; P < 0.001). The decrease in dyspnea was greater for the sensory component of dyspnea (-50% [-43 to -75]) than for the affective and emotional components (-17% [-0 to -25] and -12% [-0 to -17]; P < 0.001). An increase in sweep gas flow significantly decreased electromyographic activity of the alae nasi and parasternal muscles (-23% [-36 to -10] and -20 [-41 to -0]; P < 0.001). There was a significant correlation between the sweep gas flow and the dyspnea-VAS (r = -0.91; 95% CI, -0.94 to -0.87), between the respiratory drive and the sensory component of dyspnea (r = 0.29; 95% CI, 0.13 to 0.44) between the respiratory drive and the affective component of dyspnea (r = 0.29; 95% CI, 0.02 to 0.54) and between the sweep gas flow and the alae nasi and parasternal (r = -0.31; 95% CI, -0.44 to -0.22; and r = -0.25; 95% CI, -0.44 to -0.16). CONCLUSIONS: In critically ill patients with venoarterial ECMO, an increase in sweep gas flow through the oxygenation membrane decreases dyspnea, possibly mediated by a decrease in respiratory drive.

Dyspnoea in acutely ill mechanically ventilated adult patients: an ERS/ESICM statement.

This statement outlines a review of the literature and current practice concerning the prevalence, clinical significance, diagnosis and management of dyspnoea in critically ill, mechanically ventilated adult patients. It covers the definition, pathophysiology, epidemiology, short- and middle-term impact, detection and quantification, and prevention and treatment of dyspnoea. It represents a collaboration of the European Respiratory Society and the European Society of Intensive Care Medicine. Dyspnoea ranks among the most distressing experiences that human beings can endure. Approximately 40% of patients undergoing invasive mechanical ventilation in the intensive care unit (ICU) report dyspnoea, with an average intensity of 45 mm on a visual analogue scale from 0 to 100 mm. Although it shares many similarities with pain, dyspnoea can be far worse than pain in that it summons a primal fear response. As such, it merits universal and specific consideration. Dyspnoea must be identified, prevented and relieved in every patient. In the ICU, mechanically ventilated patients are at high risk of experiencing breathing difficulties because of their physiological status and, in some instances, because of mechanical ventilation itself. At the same time, mechanically ventilated patients have barriers to signalling their distress. Addressing this major clinical challenge mandates teaching and training, and involves ICU caregivers and patients. This is even more important because, as opposed to pain which has become a universal healthcare concern, very little attention has been paid to the identification and management of respiratory suffering in mechanically ventilated ICU patients.

High Airway Occlusion Pressure Is Associated with Dyspnea and Increased Mortality in Critically Ill Mechanically Ventilated Patients.

Rationale: Airway occlusion pressure at 100 ms (P0.1) reflects central respiratory drive. Objectives: We aimed to assess factors associated with P0.1 and whether an abnormally low or high P0.1 value is associated with higher mortality and longer duration of mechanical ventilation (MV). Methods: We performed a secondary analysis of a prospective cohort study conducted in 10 ICUs in France to evaluate dyspnea in communicative MV patients. In patients intubated for more than 24 hours, P0.1 was measured with dyspnea as soon as patients could communicate and the next day. Measurements and Main Results: Among 260 patients assessed after a median time of ventilation of 4 days, P0.1 was 1.9 (1-3.5) cm H2O at enrollment, 24% had P0.1 values >3.5 cm H2O, 37% had P0.1 values between 1.5 and 3.5 cm H2O, and 39% had P0.1 values <1.5 cm H2O. In multivariable linear regression, independent factors associated with P0.1 were the presence of dyspnea (P = 0.037), respiratory rate (P < 0.001), and PaO2 (P = 0.008). Ninety-day mortality was 33% in patients with P0.1 > 3.5 cm H2O versus 19% in those with P0.1 between 1.5 and 3.5 cm H2O and 17% in those with P0.1 < 1.5 cm H2O (P = 0.046). After adjustment for the main risk factors, P0.1 was associated with 90-day mortality (hazard ratio per 1 cm H2O, 1.19 [95% confidence interval, 1.04-1.37]; P = 0.011). P0.1 was also independently associated with a longer duration of MV (hazard ratio per 1 cm H2O, 1.10 [95% confidence interval, 1.02-1.19]; P = 0.016). Conclusions: In patients receiving invasive MV, abnormally high P0.1 values may suggest dyspnea and are associated with higher mortality and prolonged duration of MV.

Dyspnoea in acutely ill mechanically ventilated adult patients: an ERS/ESICM statement.

This statement outlines a review of the literature and current practice concerning the prevalence, clinical significance, diagnosis and management of dyspnoea in critically ill, mechanically ventilated adult patients. It covers the definition, pathophysiology, epidemiology, short- and middle-term impact, detection and quantification, and prevention and treatment of dyspnoea. It represents a collaboration of the European Respiratory Society (ERS) and the European Society of Intensive Care Medicine (ESICM). Dyspnoea ranks among the most distressing experiences that human beings can endure. Approximately 40% of patients undergoing invasive mechanical ventilation in the intensive care unit (ICU) report dyspnoea, with an average intensity of 45 mm on a visual analogue scale from 0 to 100 mm. Although it shares many similarities with pain, dyspnoea can be far worse than pain in that it summons a primal fear response. As such, it merits universal and specific consideration. Dyspnoea must be identified, prevented and relieved in every patient. In the ICU, mechanically ventilated patients are at high risk of experiencing breathing difficulties because of their physiological status and, in some instances, because of mechanical ventilation itself. At the same time, mechanically ventilated patients have barriers to signalling their distress. Addressing this major clinical challenge mandates teaching and training, and involves ICU caregivers and patients. This is even more important because, as opposed to pain which has become a universal healthcare concern, very little attention has been paid to the identification and management of respiratory suffering in mechanically ventilated ICU patients.

Sensory interventions to relieve dyspnoea in critically ill mechanically ventilated patients.

BACKGROUND: In critically ill patients receiving mechanical ventilation, dyspnoea is frequent, severe and associated with an increased risk of neuropsychological sequelae. We evaluated the efficacy of sensory interventions targeting the brain rather than the respiratory system to relieve dyspnoea in mechanically ventilated patients. METHODS: Patients receiving mechanical ventilation for ≥48 h and reporting dyspnoea (unidimensional dyspnoea visual analogue scale (Dyspnoea-VAS)) first underwent increased pressure support and then, in random order, auditory stimulation (relaxing music versus pink noise) and air flux stimulation (facial versus lower limb). Treatment responses were assessed using Dyspnoea-VAS, the Multidimensional Dyspnea Profile and measures of the neural drive to breathe (airway occlusion pressure (P 0.1) and electromyography of inspiratory muscles). RESULTS: We included 46 patients (tracheotomy or intubation n=37; noninvasive ventilation n=9). Increasing pressure support decreased Dyspnoea-VAS by median 40 mm (p<0.001). Exposure to music decreased Dyspnoea-VAS compared with exposure to pink noise by median 40 mm (p<0.001). Exposure to facial air flux decreased Dyspnoea-VAS compared with limb air flux by median 30 mm (p<0.001). Increasing pressure support, but not music exposure and facial air flux, reduced P 0.1 by median 3.3 cmH2O (p<0.001). CONCLUSIONS: In mechanically ventilated patients, sensory interventions can modulate the processing of respiratory signals by the brain irrespective of the intensity of the neural drive to breathe. It should therefore be possible to alleviate dyspnoea without resorting to pharmacological interventions or having to infringe the constraints of mechanical ventilation lung protection strategies by increasing ventilatory support.

An Initial Investigation of Diaphragm Neurostimulation in Patients with Acute Respiratory Distress Syndrome.

BACKGROUND: Lung protective ventilation aims at limiting lung stress and strain. By reducing the amount of pressure transmitted by the ventilator into the lungs, diaphragm neurostimulation offers a promising approach to minimize ventilator-induced lung injury. This study investigates the physiologic effects of diaphragm neurostimulation in acute respiratory distress syndrome (ARDS) patients. The hypothesis was that diaphragm neurostimulation would improve oxygenation, would limit the distending pressures of the lungs, and would improve cardiac output. METHODS: Patients with moderate ARDS were included after 48 h of invasive mechanical ventilation and had a left subclavian catheter placed to deliver bilateral transvenous phrenic nerve stimulation. Two 60-min volume-controlled mechanical ventilation (control) sessions were interspersed by two 60-min diaphragm neurostimulation sessions delivered continually, in synchrony with the ventilator. Gas exchange, lung mechanics, chest electrical impedance tomography, and cardiac index were continuously monitored and compared across four sessions. The primary endpoint was the Pao2/fraction of inspired oxygen (Fio2) ratio at the end of each session, and the secondary endpoints were lung mechanics and hemodynamics. RESULTS: Thirteen patients were enrolled but the catheter could not be inserted in one, leaving 12 patients for analysis. All sessions were conducted without interruption and well tolerated. The Pao2/Fio2 ratio did not change during the four sessions. Median (interquartile range) plateau pressure was 23 (20 to 31) cm H2O and 21 (17 to 25) cm H2O, driving pressure was 14 (12 to 18) cm H2O and 11 (10 to 13) cm H2O, and end-inspiratory transpulmonary pressure was 9 (5 to 11) cm H2O and 7 (4 to 11) cm H2O during mechanical ventilation alone and during mechanical ventilation + neurostimulation session, respectively. The dorsal/ventral ventilation surface ratio was 0.70 (0.54 to 0.91) when on mechanical ventilation and 1.20 (0.76 to 1.33) during the mechanical ventilation + neurostimulation session. The cardiac index was 2.7 (2.3 to 3.5) l · min-1 · m-2 on mechanical ventilation and 3.0 (2.4 to 3.9) l · min-1 · m-2 on mechanical ventilation + neurostimulation. CONCLUSIONS: This proof-of-concept study showed the feasibility of short-term diaphragm neurostimulation in conjunction with mechanical ventilation in ARDS patients. Diaphragm neurostimulation was associated with positive effects on lung mechanics and on hemodynamics.

Prognosis of critically ill immunocompromised patients with virus-detected acute respiratory failure.

BACKGROUND: 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. RESULTS: 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]). CONCLUSIONS: 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.

Diaphragm function in patients with Covid-19-related acute respiratory distress syndrome on venovenous extracorporeal membrane oxygenation.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV ECMO) is frequently associated with deep sedation and neuromuscular blockades, that may lead to diaphragm dysfunction. However, the prevalence, risk factors, and evolution of diaphragm dysfunction in patients with VV ECMO are unknown. We hypothesized that the prevalence of diaphragm dysfunction is high and that diaphragm activity influences diaphragm function changes. METHODS: Patients with acute respiratory distress syndrome (ARDS) requiring VV ECMO were included in two centers. Diaphragm function was serially assessed by measuring the tracheal pressure in response to phrenic nerve stimulation (Ptr,stim) from ECMO initiation (Day 1) until ECMO weaning. Diaphragm activity was estimated from the percentage of spontaneous breathing ventilation and by measuring the diaphragm thickening fraction (TFdi) with ultrasound. RESULTS: Sixty-three patients were included after a median of 4 days (3-6) of invasive mechanical ventilation. Diaphragm dysfunction, defined by Ptr, stim ≤ 11 cmH2O, was present in 39 patients (62%) on Day 1 of ECMO. Diaphragm function did not change over the study period and was not influenced by the percentage of spontaneous breathing ventilation or the TFdi during the 1 week. Among the 63 patients enrolled in the study, 24 (38%) were still alive at the end of the study period (60 days). CONCLUSIONS: Sixty-two percent of patients undergoing ECMO for ARDS related to SARS CoV-2 infection had a diaphragm dysfunction on Day 1 of ECMO initiation. Diaphragm function remains stable over time and was not associated with the percentage of time with spontaneous breathing. CLINICALTRIALS: gov Identifier NCT04613752 (date of registration February 15, 2021).