Critical illness-associated limb and diaphragmatic weakness.

PURPOSE OF REVIEW: In the current review, we aim to highlight the evolving evidence on the diagnosis, prevention and treatment of critical illness weakness (CIW) and critical illness associated diaphragmatic weakness (CIDW). RECENT FINDINGS: In the ICU, several risk factors can lead to CIW and CIDW. Recent evidence suggests that they have different pathophysiological mechanisms and impact on outcomes, although they share common risk factors and may overlap in several patients. Their diagnosis is challenging, because CIW diagnosis is primarily clinical and, therefore, difficult to obtain in the ICU population, and CIDW diagnosis is complex and not easily performed at the bedside. All of these issues lead to underdiagnosis of CIW and CIDW, which significantly increases the risk of complications and the impact on both short and long term outcomes. Moreover, recent studies have explored promising diagnostic techniques that are may be easily implemented in daily clinical practice. In addition, this review summarizes the latest research aimed at improving how to prevent and treat CIW and CIDW. SUMMARY: This review aims to clarify some uncertain aspects and provide helpful information on developing monitoring techniques and therapeutic interventions for managing CIW and CIDW.

Increasing sweep gas flow reduces respiratory drive and dyspnea in non-intubated veno-arterial ECMO patients - a pilot study.

BACKGROUND.: Data on assessment and management of dyspnea in patients on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock are lacking. We hypothesized that increasing sweep gas flow through the VA-ECMO oxygenator may decrease dyspnea in non-intubated VA-ECMO patients exhibiting clinically significant dyspnea, with a parallel reduction in respiratory drive. METHODS.: Non-intubated, spontaneously breathing, supine patients on VA-ECMO for cardiogenic shock who presented with a visual analog dyspnea scale (dyspnea-VAS) ≥ 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 dyspnea-VAS and Multidimensional Dyspnea Profile. The respiratory drive was assessed by the electromyographic activity of the alae nasi and parasternal muscles. RESULTS.: We included 21 patients. On inclusion, median dyspnea-VAS was 50 ([interquartile range] 45-60) mm and sweep gas flow was 1.0 L/min (0.5-2.0). An increase in sweep gas flow significantly decreased dyspnea-VAS (50[45-60] at baseline vs 20[10-30] at 6L/min; p<0.001). The decrease in dyspnea was greater for the sensory component of dyspnea (-50%[43-75]) than for the affective and emotional components (-17%[0-25] and -12%[0-17], p<0.001). An increase in sweep gas flow significantly decreased electromyographic activity of the alae nasi and parasternal muscles (-23%[36-10] and -20[41-0], p<0.001). There was a significant correlation between the sweep gas flow and the dyspnea-VAS (r=-0.91 95%CI[-0.94, -0.87]), between the respiratory drive and the sensory component of dyspnea (r=0.29 95%CI[0.13, 0.44]), between the respiratory drive and the affective component of dyspnea (r=0.29 95%CI[0.02, 0.54]) and between the sweep gas flow and the alae nasi and parasternal (r=-0.31 95%CI[-0.44, -0.22] and r=-0.25 95%CI[-0.44, -0.16]). CONCLUSION.: In critically ill patients with VA-ECMO, an increase in sweep gas flow through the oxygenation membrane decreases dyspnea, possibly mediated by a decrease in respiratory drive.

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.

Kidney Increase Natriuresis but Not Glomerular Filtration Under Veno-venous ECMO, a Retrospective Study.

PURPOSE: Acute kidney injury is a frequent complication of acute respiratory distress syndrome (ARDS). We aim to study the evolution of kidney function in patients presenting severe ARDS and requiring veno-venous extracorporeal membrane oxygenation (VV ECMO). METHODS: We conducted a multicenter retrospective study, including adult patients requiring VV ECMO for ARDS. The primary outcome was the evolution of the serum creatinine level after VV ECMO initiation. Secondary outcomes were change in urine output, and urine biochemical parameters after VV ECMO initiation. RESULTS: One hundred and two patients were included. VV ECMO was initiated after a median of 6 days of mechanical ventilation, mainly for ARDS caused by COVID-19 (73%). Serum creatinine level did not significantly differ after VV ECMO initiation (P = .20). VV ECMO was associated with a significant increase in daily urine output (+6.6 mL/kg/day, [3.8;9.3] P < .001), even after adjustment for potential confounding factors; with an increase in natriuresis. The increase in urine output under VV ECMO was associated with a reduced risk of receiving kidney replacement therapy (OR 0.4 [0.2;0.8], P = .026). CONCLUSIONS: VV ECMO initiation in severe ARDS is associated with an increase in daily urine output and natriuresis, without change in glomerular filtration rate.

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.

Diaphragm Dysfunction Predicts Weaning Outcome after Bilateral Lung Transplant.

BACKGROUND: Diaphragm dysfunction and its effects on outcomes of ventilator weaning have been evaluated in mixed critical care populations using diaphragm thickening fraction (the ratio of the difference between ultrasound diaphragm thickness at end-inspiration and end-expiration to diaphragm thickness at end-expiration) or neuroventilatory efficiency (the ratio of tidal volume and peak electrical activity of the diaphragm). Such data are not available in bilateral-lung transplant recipients. The authors hypothesized that (1) diaphragm dysfunction, as defined by a diaphragm thickening fraction less than 29%, is more likely to occur in difficult weaning; (2) diaphragm thickening fraction and neuroventilatory efficiency predict weaning outcome; and (3) duration of mechanical ventilation before the first spontaneous breathing trial is associated with diaphragm dysfunction. METHODS: Adult bilateral-lung transplant patients admitted to the intensive care unit were screened at the time of the first spontaneous breathing trial (pressure-support of 5 cm H2O and 0 positive end-expiratory pressure). At the fifth minute, diaphragm thickening fraction and neuroventilatory efficiency were measured during three respiratory cycles. Weaning was classified as simple, difficult, or prolonged (successful extubation at the first spontaneous breathing trial, within three or after three spontaneous breathing trials, respectively). RESULTS: Forty-four subjects were enrolled. Diaphragm dysfunction occurred in 14 subjects (32%), all of whom had difficult weaning (78% of the subgroup of 18 patients experiencing difficult weaning). Both diaphragm thickening fraction (24 [20 to 29] vs. 39 [35 to 45]%) and neuroventilatory efficiency (34 [26 to 45] vs. 55 [43 to 62] ml/µV) were lower in difficult weaning (both P < 0.001). The areas under the receiver operator curve predicting difficult weaning were 0.88 (95% CI, 0.73 to 0.99) for diaphragm thickening fraction and 0.85 (95% CI, 0.71 to 0.95) for neuroventilatory efficiency. The duration of ventilation demonstrated a linear inverse correlation with both diaphragm thickening fraction and neuroventilatory efficiency. CONCLUSIONS: Diaphragm dysfunction is common after bilateral-lung transplantation and associated with difficult weaning. In such patients, average values for diaphragm thickening fraction and neuroventilatory efficiency were reduced compared to patients with simple weaning. Both parameters showed similar accuracy for predicting success of ventilator weaning, demonstrating an inverse relationship with duration of ventilation.

Prone Positioning During Extracorporeal Membrane Oxygenation in Patients With Severe ARDS: The PRONECMO Randomized Clinical Trial.

Importance: Prone positioning may improve outcomes in patients with severe acute respiratory distress syndrome (ARDS), but it is unknown whether prone positioning improves clinical outcomes among patients with ARDS who are undergoing venovenous extracorporeal membrane oxygenation (VV-ECMO) compared with supine positioning. Objective: To test whether prone positioning vs supine positioning decreases the time to successful ECMO weaning in patients with severe ARDS supported by VV-ECMO. Design, Setting, and Participants: Randomized clinical trial of patients with severe ARDS undergoing VV-ECMO for less than 48 hours at 14 intensive care units (ICUs) in France between March 3, 2021, and December 7, 2021. Interventions: Patients were randomized 1:1 to prone positioning (at least 4 sessions of 16 hours) (n = 86) or to supine positioning (n = 84). Main Outcomes and Measures: The primary outcome was time to successful ECMO weaning within 60 days following randomization. Secondary outcomes included ECMO and mechanical ventilation-free days, ICU and hospital length of stay, skin pressure injury, serious adverse events, and all-cause mortality at 90-day follow-up. Results: Among 170 randomized patients (median age, 51 [IQR, 43-59] years; n = 60 women [35%]), median respiratory system compliance was 15.0 (IQR, 10.7-20.6) mL/cm H2O; 159 patients (94%) had COVID-19-related ARDS; and 164 (96%) were in prone position before ECMO initiation. Within 60 days of enrollment, 38 of 86 patients (44%) had successful ECMO weaning in the prone ECMO group compared with 37 of 84 (44%) in the supine ECMO group (risk difference, 0.1% [95% CI, -14.9% to 15.2%]; subdistribution hazard ratio, 1.11 [95% CI, 0.71-1.75]; P = .64). Within 90 days, no significant difference was observed in ECMO duration (28 vs 32 days; difference, -4.9 [95% CI, -11.2 to 1.5] days; P = .13), ICU length of stay, or 90-day mortality (51% vs 48%; risk difference, 2.4% [95% CI, -13.9% to 18.6%]; P = .62). No serious adverse events were reported during the prone position procedure. Conclusions and Relevance: Among patients with severe ARDS supported by VV-ECMO, prone positioning compared with supine positioning did not significantly reduce time to successful weaning of ECMO. Trial Registration: ClinicalTrials.gov Identifier: NCT04607551.

Phrenic nerve stimulation to prevent diaphragmatic dysfunction and ventilator-induced lung injury.

Side effects of mechanical ventilation, such as ventilator-induced diaphragmatic dysfunction (VIDD) and ventilator-induced lung injury (VILI), occur frequently in critically ill patients. Phrenic nerve stimulation (PNS) has been a valuable tool for diagnosing VIDD by assessing respiratory muscle strength in response to magnetic PNS. The detection of pathophysiologically reduced respiratory muscle strength is correlated with weaning failure, longer mechanical ventilation time, and mortality. Non-invasive electromagnetic PNS designed for diagnostic use is a reference technique that allows clinicians to measure transdiaphragm pressure as a surrogate parameter for diaphragm strength and functionality. This helps to identify diaphragm-related issues that may impact weaning readiness and respiratory support requirements, although lack of lung volume measurement poses a challenge to interpretation. In recent years, therapeutic PNS has been demonstrated as feasible and safe in lung-healthy and critically ill patients. Effects on critically ill patients' VIDD or diaphragm atrophy outcomes are the subject of ongoing research. The currently investigated application forms are diverse and vary from invasive to non-invasive and from electrical to (electro)magnetic PNS, with most data available for electrical stimulation. Increased inspiratory muscle strength and improved diaphragm activity (e.g., excursion, thickening fraction, and thickness) indicate the potential of the technique for beneficial effects on clinical outcomes as it has been successfully used in spinal cord injured patients. Concerning the potential for electrophrenic respiration, the data obtained with non-invasive electromagnetic PNS suggest that the induced diaphragmatic contractions result in airway pressure swings and tidal volumes remaining within the thresholds of lung-protective mechanical ventilation. PNS holds significant promise as a therapeutic intervention in the critical care setting, with potential applications for ameliorating VIDD and the ability for diaphragm training in a safe lung-protective spectrum, thereby possibly reducing the risk of VILI indirectly. Outcomes of such diaphragm training have not been sufficiently explored to date but offer the perspective for enhanced patient care and reducing weaning failure. Future research might focus on using PNS in combination with invasive and non-invasive assisted ventilation with automatic synchronisation and the modulation of PNS with spontaneous breathing efforts. Explorative approaches may investigate the feasibility of long-term electrophrenic ventilation as an alternative to positive pressure-based ventilation.

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).

Lung aeration estimated by chest electrical impedance tomography and lung ultrasound during extubation.

BACKGROUND: This study hypothesized that patients with extubation failure exhibit a loss of lung aeration and heterogeneity in air distribution, which could be monitored by chest EIT and lung ultrasound. Patients at risk of extubation failure were included after a successful spontaneous breathing trial. Lung ultrasound [with calculation of lung ultrasound score (LUS)] and chest EIT [with calculation of the global inhomogeneity index, frontback center of ventilation (CoV), regional ventilation delay (RVD) and surface available for ventilation] were performed before extubation during pressure support ventilation (H0) and two hours after extubation during spontaneous breathing (H2). EIT was then repeated 6 h (H6) after extubation. EIT derived indices and LUS were compared between patients successfully extubated and patients with extubation failure. RESULTS: 40 patients were included, of whom 12 (30%) failed extubation. Before extubation, when compared with patients with successful extubation, patients who failed extubation had a higher LUS (19 vs 10, p = 0.003) and a smaller surface available for ventilation (352 vs 406 pixels, p = 0.042). After extubation, GI index and LUS were higher in the extubation failure group, whereas the surface available for ventilation was lower. The RVD and the CoV were not different between groups. CONCLUSION: Before extubation, a loss of lung aeration was observed in patients who developed extubation failure afterwards. After extubation, this loss of lung aeration persisted and was associated with regional lung ventilation heterogeneity. Trial registration Clinical trials, NCT04180410, Registered 27 November 2019-prospectively registered, https://clinicaltrials.gov/ct2/show/NCT04180410 .

The COVID-19 Driving Force: How It Shaped the Evidence of Non-Invasive Respiratory Support.

During the COVID-19 pandemic, the use of non-invasive respiratory support (NIRS) became crucial in treating patients with acute hypoxemic respiratory failure. Despite the fear of viral aerosolization, non-invasive respiratory support has gained attention as a way to alleviate ICU overcrowding and reduce the risks associated with intubation. The COVID-19 pandemic has led to an unprecedented increased demand for research, resulting in numerous publications on observational studies, clinical trials, reviews, and meta-analyses in the past three years. This comprehensive narrative overview describes the physiological rationale, pre-COVID-19 evidence, and results of observational studies and randomized control trials regarding the use of high-flow nasal oxygen, non-invasive mechanical ventilation, and continuous positive airway pressure in adult patients with COVID-19 and associated acute hypoxemic respiratory failure. The review also highlights the significance of guidelines and recommendations provided by international societies and the need for further well-designed research to determine the optimal use of NIRS in treating this population.

Differences in clinical characteristics and outcomes between COVID-19 and influenza in critically ill adult patients: A national database study.

OBJECTIVE: Prior to the coronavirus disease 2019 (COVID-19) pandemic, influenza was the most frequent cause of viral respiratory pneumonia requiring intensive care unit (ICU) admission. Few studies have compared the characteristics and outcomes of critically ill patients with COVID-19 and influenza. METHODS: This was a French nationwide study comparing COVID-19 (March 1, 2020-June 30, 2021) and influenza patients (January 1, 2014-December 31, 2019) admitted to an ICU during pre-vaccination era. Primary outcome was in-hospital death. Secondary outcome was need for mechanical ventilation. RESULTS: 105,979 COVID-19 patients were compared to 18,763 influenza patients. Critically ill patients with COVID-19 were more likely to be men with more comorbidities. Patients with influenza required more invasive mechanical ventilation (47 vs. 34%, p < 0·001), vasopressors (40% vs. 27, p < 0·001) and renal-replacement therapy (22 vs. 7%, p < 0·001). Hospital mortality was 25% and 21% (p < 0·001) in patients with COVID-19 and influenza, respectively. In the subgroup of patients receiving invasive mechanical ventilation, ICU length of stay was significantly longer in patients with COVID-19 (18 [10-32] vs. 15 [8-26] days, p < 0·001). Adjusting for age, gender, comorbidities, and modified SAPS II score, in-hospital death was higher in COVID-19 patients (adjusted sub-distribution hazard ratio [aSHR]=1.69; 95%CI=1.63-1.75) compared with influenza patients. COVID-19 was also associated with less invasive mechanical ventilation (aSHR=0.87; 95%CI=0.85-0.89) and a higher likelihood of death without invasive mechanical ventilation (aSHR=2.40; 95%CI=2.24-2.57). CONCLUSION: Despite younger age and lower SAPS II score, critically ill COVID-19 patients had a longer hospital stay and higher mortality than patients with influenza.

The increase in cardiac output induced by a decrease in positive end-expiratory pressure reliably detects volume responsiveness: the PEEP-test study.

BACKGROUND: In patients on mechanical ventilation, positive end-expiratory pressure (PEEP) can decrease cardiac output through a decrease in cardiac preload and/or an increase in right ventricular afterload. Increase in central blood volume by fluid administration or passive leg raising (PLR) may reverse these phenomena through an increase in cardiac preload and/or a reopening of closed lung microvessels. We hypothesized that a transient decrease in PEEP (PEEP-test) may be used as a test to detect volume responsiveness. METHODS: Mechanically ventilated patients with PEEP ≥ 10 cmH2O ("high level") and without spontaneous breathing were prospectively included. Volume responsiveness was assessed by a positive PLR-test, defined as an increase in pulse-contour-derived cardiac index (CI) during PLR ≥ 10%. The PEEP-test consisted in reducing PEEP from the high level to 5 cmH2O for one minute. Pulse-contour-derived CI (PiCCO2) was monitored during PLR and the PEEP-test. RESULTS: We enrolled 64 patients among whom 31 were volume responsive. The median increase in CI during PLR was 14% (11-16%). The median PEEP at baseline was 12 (10-15) cmH2O and the PEEP-test resulted in a median decrease in PEEP of 7 (5-10) cmH2O, without difference between volume responsive and unresponsive patients. Among volume responsive patients, the PEEP-test induced a significant increase in CI of 16% (12-20%) (from 2.4 ± 0.7 to 2.9 ± 0.9 L/min/m2, p < 0.0001) in comparison with volume unresponsive patients. In volume unresponsive patients, PLR and the PEEP-test increased CI by 2% (1-5%) and 6% (3-8%), respectively. Volume responsiveness was predicted by an increase in CI > 8.6% during the PEEP-test with a sensitivity of 96.8% (95% confidence interval (95%CI): 83.3-99.9%) and a specificity of 84.9% (95%CI 68.1-94.9%). The area under the receiver operating characteristic curve of the PEEP-test for detecting volume responsiveness was 0.94 (95%CI 0.85-0.98) (p < 0.0001 vs. 0.5). Spearman's correlation coefficient between the changes in CI induced by PLR and the PEEP-test was 0.76 (95%CI 0.63-0.85, p < 0.0001). CONCLUSIONS: A CI increase > 8.6% during a PEEP-test, which consists in reducing PEEP to 5 cmH2O, reliably detects volume responsiveness in mechanically ventilated patients with a PEEP ≥ 10 cmH2O. Trial registration ClinicalTrial.gov (NCT 04,023,786). Registered July 18, 2019. Ethics Committee approval CPP Est III (N° 2018-A01599-46).

Managing respiratory muscle weakness during weaning from invasive ventilation.

Weaning is a critical stage of an intensive care unit (ICU) stay, in which the respiratory muscles play a major role. Weakness of the respiratory muscles, which is associated with significant morbidity in the ICU, is not limited to atrophy and subsequent dysfunction of the diaphragm; the extradiaphragmatic inspiratory and expiratory muscles also play important parts. In addition to the well-established deleterious effect of mechanical ventilation on the respiratory muscles, other risk factors such as sepsis may be involved. Weakness of the respiratory muscles can be suspected visually in a patient with paradoxical movement of the abdominal compartment. Measurement of maximal inspiratory pressure is the simplest way to assess respiratory muscle function, but it does not specifically take the diaphragm into account. A cut-off value of -30 cmH2O could identify patients at risk for prolonged ventilatory weaning; however, ultrasound may be better for assessing respiratory muscle function in the ICU. Although diaphragm dysfunction has been associated with weaning failure, this diagnosis should not discourage clinicians from performing spontaneous breathing trials and considering extubation. Recent therapeutic developments aimed at preserving or restoring respiratory muscle function are promising.

Effects of Standard-Dose Prophylactic, High-Dose Prophylactic, and Therapeutic Anticoagulation in Patients With Hypoxemic COVID-19 Pneumonia: The ANTICOVID Randomized Clinical Trial.

Importance: Given the high risk of thrombosis and anticoagulation-related bleeding in patients with hypoxemic COVID-19 pneumonia, identifying the lowest effective dose of anticoagulation therapy for these patients is imperative. Objectives: To determine whether therapeutic anticoagulation (TA) or high-dose prophylactic anticoagulation (HD-PA) decreases mortality and/or disease duration compared with standard-dose prophylactic anticoagulation (SD-PA), and whether TA outperforms HD-PA; and to compare the net clinical outcomes among the 3 strategies. Design, Settings, and Participants: The ANTICOVID randomized clinical open-label trial included patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram at 23 health centers in France from April 14 to December 13, 2021. Of 339 patients randomized, 334 were included in the primary analysis-114 patients in the SD-PA group, 110 in the HD-PA, and 110 in the TA. At randomization, 90% of the patients were in the intensive care unit. Data analyses were performed from April 13, 2022, to January 3, 2023. Interventions: Patients were randomly assigned (1:1:1) to receive either SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days. Main Outcomes and Measures: A hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28. Main secondary outcome was net clinical outcome at day 28 (composite of thrombosis, major bleeding, and all-cause death). Results: Among the study population of 334 individuals (mean [SD] age, 58.3 [13.0] years; 226 [67.7%] men and 108 [32.3%] women), use of HD-PA and SD-PA had similar probabilities of favorable outcome (47.3% [95% CI, 39.9% to 54.8%] vs 52.7% [95% CI, 45.2% to 60.1%]; P = .48), as did TA compared with SD-PA (50.9% [95% CI, 43.4% to 58.3%] vs 49.1% [95% CI, 41.7% to 56.6%]; P = .82) and TA compared with HD-PA (53.5% [95% CI 45.8% to 60.9%] vs 46.5% [95% CI, 39.1% to 54.2%]; P = .37). Net clinical outcome was met in 29.8% of patients receiving SD-PA (20.2% thrombosis, 2.6% bleeding, 14.0% death), 16.4% receiving HD-PA (5.5% thrombosis, 3.6% bleeding, 11.8% death), and 20.0% receiving TA (5.5% thrombosis, 3.6% bleeding, 12.7% death). Moreover, HD-PA and TA use significantly reduced thrombosis compared with SD-PA (absolute difference, -14.7 [95% CI -6.2 to -23.2] and -14.7 [95% CI -6.2 to -23.2], respectively). Use of HD-PA significantly reduced net clinical outcome compared with SD-PA (absolute difference, -13.5; 95% CI -2.6 to -24.3). Conclusions and Relevance: This randomized clinical trial found that compared with SD-PA, neither HD-PA nor TA use improved the primary hierarchical outcome of all-cause mortality or time to clinical improvement in patients with hypoxemic COVID-19 pneumonia; however, HD-PA resulted in significantly better net clinical outcome by decreasing the risk of de novo thrombosis. Trial Registration: ClinicalTrials.gov Identifier: NCT04808882.

Diaphragm Neurostimulation Assisted Ventilation in Critically Ill Patients.

Diaphragm neurostimulation consists of placing electrodes directly on or in proximity to the phrenic nerve(s) to elicit diaphragmatic contractions. Since its initial description in the 18th century, indications have shifted from cardiopulmonary resuscitation to long-term ventilatory support. Recently, the technical development of devices for temporary diaphragm neurostimulation has opened up the possibility of a new era for the management of mechanically ventilated patients. Combining positive pressure ventilation with diaphragm neurostimulation offers a potentially promising new approach to the delivery of mechanical ventilation which may benefit multiple organ systems. Maintaining diaphragm contractions during ventilation may attenuate diaphragm atrophy and accelerate weaning from mechanical ventilation. Preventing atelectasis and preserving lung volume can reduce lung stress and strain and improve homogeneity of ventilation, potentially mitigating ventilator-induced lung injury. Furthermore, restoring the thoracoabdominal pressure gradient generated by diaphragm contractions may attenuate the drop in cardiac output induced by positive pressure ventilation. Experimental evidence suggests diaphragm neurostimulation may prevent neuroinflammation associated with mechanical ventilation. This review describes the historical development and evolving approaches to diaphragm neurostimulation during mechanical ventilation and surveys the potential mechanisms of benefit. The review proposes a research agenda and offers perspectives for the future of diaphragm neurostimulation assisted mechanical ventilation for critically ill patients.

Job Strain, Burnout, and Suicidal Ideation in Tenured University Hospital Faculty Staff in France in 2021.

Importance: The ability to attract and retain university hospital faculty staff is in jeopardy because of the high levels of mental symptoms in this professional group. Objective: To examine the prevalence and determinants of symptoms of severe burnout, job strain, and suicidal ideation in tenured associate and full professors in university hospitals. Design, Setting, and Participants: This nationwide cross-sectional study offered online surveys to 5332 tenured university hospital faculty members in France from October 25, 2021, to December 20, 2021. Exposures: Burnout and job strain. Main Outcomes and Measures: Participants completed the 22-item Maslach Burnout Inventory and a 12-item job strain assessment tool, reported suicidal ideation, and used visual analog scales to evaluate unidimensional parameters. The primary outcome was presence of severe burnout symptoms. Factors associated with mental health symptoms were identified by multivariable logistic regression. Results: Completed questionnaires were returned by 2390 of 5332 faculty members (response rate, 45%; range, 43%-46%). Tenured associate professors were a median of 40 (IQR, 37-45) years old with a sex ratio of 1:1, whereas tenured full professors were a median of 53 (IQR, 46-60) years old with a sex ratio of 1:5. Of 2390 respondents, 952 (40%) reported symptoms of severe burnout. Symptoms of job strain (296 professors [12%]) and suicidal ideation (343 professors [14%]) were also reported. Compared with full professors, significantly more associate professors reported feeling overwhelmed at work (496 [73%] vs 972 [57%]; P < .001), considering resignation (365 [54%] vs 834 [49%]; P = .004), or considering a career change (277 [41%] vs 496 [29%]; P < .001). Factors independently associated with less burnout were a longer time being a professor (adjusted odds ratio [aOR], 0.97; 95% CI, 0.96-0.98 per year of age), sleeping well (aOR, 0.88; 95% CI, 0.83-0.92), feeling valued by colleagues (aOR, 0.91; 95% CI, 0.86-0.95 per visual analog scale point) or the public (aOR, 0.92; 95% CI, 0.88-0.96 per visual analog scale point), and accepting more tasks (aOR, 0.82; 95% CI, 0.72-0.93). Factors independently associated with more burnout were having a nonclinical position (OR, 2.48; 95% CI, 1.96-3.16), reporting work encroachment on private life (OR, 1.17; 95% CI, 1.10-1.25), feeling the need to constantly put on a brave face (OR, 1.82; 95% CI, 1.32-2.52), considering a career change (OR, 1.53; 95% CI, 1.22-1.92), and having experienced harassment (OR, 1.52; 95% CI, 1.22-1.88). Conclusions and Relevance: These findings suggest that the psychological burden on tenured university hospital faculty staff in France is considerable. Hospital administrators and health care authorities should urgently develop strategies for burden prevention and alleviation and for attraction of the next generation.