Efficacy of bougie first approach for endotracheal intubation with video laryngoscopy during continuous chest compression: a randomized crossover manikin trial.

BACKGROUND: Endotracheal intubation is challenging during cardiopulmonary resuscitation, and video laryngoscopy has showed benefits for this procedure. The aim of this study was to compare the effectiveness of various intubation approaches, including the bougie first, preloaded bougie, endotracheal tube (ETT) with stylet, and ETT without stylet, on first-attempt success using video laryngoscopy during chest compression. METHODS: This was a randomized crossover trial conducted in a general tertiary teaching hospital. We included anesthesia residents in postgraduate year one to three who passed the screening test. Each resident performed intubation with video laryngoscopy using the four approaches in a randomized sequence on an adult manikin during continuous chest compression. The primary outcome was the first-attempt success defined as starting ventilation within a one minute. RESULTS: A total of 260 endotracheal intubations conducted by 65 residents were randomized and analyzed with 65 procedures in each group. First-attempt success occurred in 64 (98.5%), 57 (87.7%), 56 (86.2%), and 46 (70.8%) intubations in the bougie-first, preloaded bougie, ETT with stylet, and ETT without stylet approaches, respectively. The bougie-first approach had a significantly higher possibility of first-attempt success than the preloaded bougie approach [risk ratio (RR) 8.00, 95% confidence interval (CI) 1.03 to 62.16, P = 0.047], the ETT with stylet approach (RR 9.00, 95% CI 1.17 to 69.02, P = 0.035), and the ETT without stylet approach (RR 19.00, 95% CI 2.62 to 137.79, P = 0.004) in the generalized estimating equation logistic model accounting for clustering of intubations operated by the same resident. In addition, the bougie first approach did not result in prolonged intubation or increased self-reported difficulty among the study participants. CONCLUSIONS: The bougie first approach with video laryngoscopy had the highest possibility of first-attempt success during chest compression. These results helped inform the intubation approach during CPR. However, further studies in an actual clinical environment are warranted to validate these findings. TRIAL REGISTRATION: Clinicaltrials.gov; identifier: NCT05689125; date: January 18, 2023.

The impact of aggressive and conservative propensity for initiation of neuromuscular blockade in mechanically ventilated patients with hypoxemic respiratory failure.

INTRODUCTION: Neuromuscular blockade (NMB) in ventilated patients may cause benefit or harm. We applied "incremental interventions" to determine the impact of altering NMB initiation aggressiveness. METHODS: Retrospective cohort study of ventilated patients with PaO2/FiO2 ratio < 150 mmHg and PEEP≥ 8cmH2O from the Medical Information Mart of Intensive Care IV database (MIMIC-IV version 1.0) estimating the effect of incremental interventions on in-hospital mortality and ventilator-free days, modifying hourly propensity for NMB initiation to be aggressive or conservative relative to usual care, adjusting for confounding with inverse probability weighting. RESULTS: 5221 patients were included (13.3% initiated on NMB). Incremental interventions estimated a strong effect on NMB usage: 5-fold higher hourly odds of initiation increased usage to 36.5% (CI = [34.3%,38.7%]) and 5-fold lower odds decreased usage to 3.8% (CI = [3.3%,4.3%]). Aggressive and conservative strategies demonstrated a U-shaped mortality relationship. 5-fold higher or lower propensity increased in-hospital mortality by 2.6% (0.95 CI = [1.5%,3.7%]) or 1.3% (0.95 CI = [0.1%,2.5%]) respectively. In secondary analysis of a healthier patient cohort, results were similar, however conservative strategies also improved ventilator-free days. INTERPRETATION: Aggressive or conservative initiation of NMB may worsen mortality. In healthier populations, marginally conservative NMB initiation strategies may lead to increased ventilator free days with minimal impact on mortality.

Adjustments of Ventilator Parameters during Operating Room-to-ICU Transition and 28-Day Mortality.

Rationale: Lung-protective mechanical ventilation strategies have been proven beneficial in the operating room (OR) and the ICU. However, differential practices in ventilator management persist, often resulting in adjustments of ventilator parameters when transitioning patients from the OR to the ICU. Objectives: To characterize patterns of ventilator adjustments during the transition of mechanically ventilated surgical patients from the OR to the ICU and assess their impact on 28-day mortality. Methods: Hospital registry study including patients undergoing general anesthesia with continued, controlled mechanical ventilation in the ICU between 2008 and 2022. Ventilator parameters were assessed 1 hour before and 6 hours after the transition. Measurements and Main Results: Of 2,103 patients, 212 (10.1%) died within 28 days. Upon OR-to-ICU transition, VT and driving pressure decreased (-1.1 ml/kg predicted body weight [IQR, -2.0 to -0.2]; P < 0.001; and -4.3 cm H2O [-8.2 to -1.2]; P < 0.001). Concomitantly, respiratory rates increased (+5.0 breaths/min [2.0 to 7.5]; P < 0.001), resulting overall in slightly higher mechanical power (MP) in the ICU (+0.7 J/min [-1.9 to 3.0]; P < 0.001). In adjusted analysis, increases in MP were associated with a higher 28-day mortality rate (adjusted odds ratio, 1.10; 95% confidence interval, 1.06-1.14; P < 0.001; adjusted risk difference, 0.7%; 95% confidence interval, 0.4-1.0, both per 1 J/min). Conclusion: During transition of mechanically ventilated patients from the OR to the ICU, ventilator adjustments resulting in higher MP were associated with a greater risk of 28-day mortality.

Inflammatory subphenotypes in patients at risk of ARDS: evidence from the LIPS-A trial.

PURPOSE: Latent class analysis (LCA) has identified hyper- and non-hyper-inflammatory subphenotypes in patients with acute respiratory distress syndrome (ARDS). It is unknown how early inflammatory subphenotypes can be identified in patients at risk of ARDS. We aimed to test for inflammatory subphenotypes upon presentation to the emergency department. METHODS: LIPS-A was a trial of aspirin to prevent ARDS in at-risk patients presenting to the emergency department. In this secondary analysis, we performed LCA using clinical, blood test, and biomarker variables. RESULTS: Among 376 (96.4%) patients from the LIPS-A trial, two classes were identified upon presentation to the emergency department (day 0): 72 (19.1%) patients demonstrated characteristics of a hyper-inflammatory and 304 (80.9%) of a non-hyper-inflammatory subphenotype. 15.3% of patients in the hyper- and 8.2% in the non-hyper-inflammatory class developed ARDS (p = 0.07). Patients in the hyper-inflammatory class had fewer ventilator-free days (median [interquartile range, IQR] 28[23-28] versus 28[27-28]; p = 0.010), longer intensive care unit (3[2-6] versus 0[0-3] days; p < 0.001) and hospital (9[6-18] versus 5[3-9] days; p < 0.001) length of stay, and higher 1-year mortality (34.7% versus 20%; p = 0.008). Subphenotypes were identified on day 1 and 4 in a subgroup with available data (n = 244). 77.9% of patients remained in their baseline class throughout day 4. Patients with a hyper-inflammatory subphenotype throughout the study period (n = 22) were at higher risk of ARDS (36.4% versus 10.4%; p = 0.003). CONCLUSION: Hyper- and non-hyper-inflammatory subphenotypes may precede ARDS development, remain identifiable over time, and can be identified upon presentation to the emergency department. A hyper-inflammatory subphenotype predicts worse outcomes.

Sodium bicarbonate for the treatment of severe metabolic acidosis with moderate or severe acute kidney injury in the critically ill: protocol for a randomised clinical trial (BICARICU-2).

INTRODUCTION: When both severe metabolic acidemia (pH equal or less than 7.20; PaCO2 equal or less than 45 mm Hg and bicarbonate concentration equal or less than of 20 mmol/L) and moderate-to-severe acute kidney injury are observed, day 28 mortality is approximately 55%-60%. A multiple centre randomised clinical trial (BICARICU-1) has suggested that sodium bicarbonate infusion titrated to maintain the pH equal or more than 7.30 is associated with a higher survival rate (secondary endpoint) in a prespecified stratum of patients with both severe metabolic acidemia and acute kidney injury patients. Whether sodium bicarbonate infusion may improve survival at day 90 (primary outcome) in these severe acute kidney injury patients is currently unknown. METHODS AND ANALYSIS: The sodium bicarbonate for the treatment of severe metabolic acidosis with moderate or severe acute kidney injury in the critically ill: a randomised clinical trial (BICARICU-2) trial is an investigator-initiated, multiple centre, stratified, parallel-group, unblinded trial with a computer-generated allocation sequence and an electronic system-based randomisation. After randomisation, the intervention group will receive 4.2% sodium bicarbonate infusion to target a plasma pH equal or more than 7.30 while the control group will not receive sodium bicarbonate. The primary outcome is the day 90 mortality. Main secondary outcomes are organ support dependences. ETHICS AND DISSEMINATION: The trial has been approved by the appropriate ethics committee (CPP Nord Ouest, Rouen, France, 25 April 2019, number: 19.03.15.72446). Informed consent is required. If sodium bicarbonate improves day 90 mortality, it will become part of the routine care. TRIAL REGISTRATION NUMBER: NCT04010630.

Mechanical power and 30-day mortality in mechanically ventilated, critically ill patients with and without Coronavirus Disease-2019: a hospital registry study.

BACKGROUND: Previous studies linked a high intensity of ventilation, measured as mechanical power, to mortality in patients suffering from "classic" ARDS. By contrast, mechanically ventilated patients with a diagnosis of COVID-19 may present with intact pulmonary mechanics while undergoing mechanical ventilation for longer periods of time. We investigated whether an association between higher mechanical power and mortality is modified by a diagnosis of COVID-19. METHODS: This retrospective study included critically ill, adult patients who were mechanically ventilated for at least 24 h between March 2020 and December 2021 at a tertiary healthcare facility in Boston, Massachusetts. The primary exposure was median mechanical power during the first 24 h of mechanical ventilation, calculated using a previously validated formula. The primary outcome was 30-day mortality. As co-primary analysis, we investigated whether a diagnosis of COVID-19 modified the primary association. We further investigated the association between mechanical power and days being alive and ventilator free and effect modification of this by a diagnosis of COVID-19. Multivariable logistic regression, effect modification and negative binomial regression analyses adjusted for baseline patient characteristics, severity of disease and in-hospital factors, were applied. RESULTS: 1,737 mechanically ventilated patients were included, 411 (23.7%) suffered from COVID-19. 509 (29.3%) died within 30 days. The median mechanical power during the first 24 h of ventilation was 19.3 [14.6-24.0] J/min in patients with and 13.2 [10.2-18.0] J/min in patients without COVID-19. A higher mechanical power was associated with 30-day mortality (ORadj 1.26 per 1-SD, 7.1J/min increase; 95% CI 1.09-1.46; p = 0.002). Effect modification and interaction analysis did not support that this association was modified by a diagnosis of COVID-19 (95% CI, 0.81-1.38; p-for-interaction = 0.68). A higher mechanical power was associated with a lower number of days alive and ventilator free until day 28 (IRRadj 0.83 per 7.1 J/min increase; 95% CI 0.75-0.91; p < 0.001, adjusted risk difference - 2.7 days per 7.1J/min increase; 95% CI - 4.1 to - 1.3). CONCLUSION: A higher mechanical power is associated with elevated 30-day mortality. While patients with COVID-19 received mechanical ventilation with higher mechanical power, this association was independent of a concomitant diagnosis of COVID-19.

Effects of aggressive and conservative strategies for mechanical ventilation liberation.

BACKGROUND: The optimal approach for transitioning from strict lung protective ventilation to support modes of ventilation when patients determine their own respiratory rate and tidal volume remains unclear. While aggressive liberation from lung protective settings could expedite extubation and prevent harm from prolonged ventilation and sedation, conservative liberation could prevent lung injury from spontaneous breathing. RESEARCH QUESTION: Should physicians take a more aggressive or conservative approach to liberation? METHODS: Retrospective cohort study of mechanically ventilated patients from the Medical Information Mart for Intensive Care IV database (MIMIC-IV version 1.0) estimating effects of incremental interventions modifying the propensity for liberation to be more aggressive or conservative relative to usual care, with adjustment for confounding via inverse probability weighting. Outcomes included in-hospital mortality, ventilator free days, and ICU free days. Analysis was performed on the entire cohort as well as subgroups differentiated by PaO2/FiO2 ratio, and SOFA. RESULTS: 7433 patients were included. Strategies multiplying the odds of a first liberation relative to usual care at each hour had a large impact on time to first liberation attempt (43 h under usual care, 24 h (0.95 CI = [23,25]) with an aggressive strategy doubling liberation odds, and 74 h (0.95 CI = [69,78]) under a conservative strategy halving liberation odds). In the full cohort, we estimated aggressive liberation increased ICU-free days by 0.9 days (0.95 CI = [0.8,1.0]) and ventilator free days by 0.82 days (0.95 CI = [0.67,0.97]), but had minimal effect on mortality (only a 0.3% (0.95 CI = [-0.2%,0.8%]) difference between minimum and maximum rates). With baseline SOFA≥ 12 (n = 1355), aggressive liberation moderately increased mortality (58.5% [0.95 CI = (55.7%,61.2%)]) compared with conservative liberation (55.1% [0.95 CI = (51.6%,58.6%)]). INTERPRETATION: Aggressive liberation may improve ventilator free and ICU free days with little impact on mortality in patients with SOFA score < 12. Trials are needed.

Severe SARS-Cov2 pneumonia in vaccinated patients: a multicenter cohort study.

Vaccination reduces risk of infection, hospitalization, and death due to SARS-Cov2. Vaccinated patients may however experience severe SARS-Cov2 disease. The objective was to describe clinical features of vaccinated patients requiring intensive care unit (ICU) admission due to SARS-Cov2 infection and compare them to a published cohort of unvaccinated patients. We performed a multicenter cohort study of patients with severe SARS-Cov2 disease admitted to 15 ICUs in France between January and September 2021. 100 consecutive vaccinated patients (68 (68%) men, median age 64 [57-71]) were included. Immunosuppression was reported in 38 (38%) patients. Among available serologies at ICU admission, 64% exhibited an optimal antibody level. Median SOFA score at ICU admission was 4 [4-6.3] and median PaO2/FiO2 ratio was 84 [69-128] mmHg. A total of 79 (79%) and 18 (18%) patients received high flow nasal oxygen and non-invasive mechanical ventilation, respectively. Invasive mechanical ventilation (IMV) was initiated in 48 (48%) with a median duration of 11 [5-19] days. During a median ICU length-of-stay of 8 [4-20] days, 31 (31%) patients died. Age (OR per 5-years increment 1.38 CI95% [1.02-1.85], p = 0.035), and SOFA at ICU admission (OR 1.40 CI95% [1.14-1.72] per point, p = 0.002) were independently associated with mortality. When compared to a cohort of 1316 unvaccinated patients (72% men, median age 63 [53-71]), vaccinated patients exhibited less frequently diabetes (16 [16%] vs. 351 [27%], p = 0.029) but were more frequently immunosuppressed (38 [38%] vs. 109 (8.3%), p < 0.0001), had more frequently chronic kidney disease (24 [24%] vs. 89 (6.8%), p < 0.0001), chronic heart failure (16 [16%] vs. 58 [4.4%], p < 0.0001), and chronic liver disease (3 [3%] vs. 8 [0.6%], p = 0.037) compared to unvaccinated patients. Despite similar severity, vaccinated patients required less frequently IMV at ICU day 1 and during ICU stay (23 [23%] vs. 785 [59.7%], p < 0.0001, and 48 [48%] vs. 930 [70.7%], p < 0.0001, respectively). There was no difference concerning ICU mortality (31 [31%] vs. 379 [28.8%], p = 0.64). Severe SARS-Cov2 infection after vaccination occurs mainly in patients with immunosuppression, chronic kidney, heart or liver failure. Age and disease severity are independently associated with mortality.

Effect of non-invasive ventilation after extubation in critically ill patients with obesity in France: a multicentre, unblinded, pragmatic randomised clinical trial.

BACKGROUND: Non-invasive ventilation (NIV) and oxygen therapy (high-flow nasal oxygen [HFNO] or standard oxygen) following extubation have never been compared in critically ill patients with obesity. We aimed to compare NIV (alternating with HFNO or standard oxygen) and oxygen therapy (HFNO or standard oxygen) following extubation of critically ill patients with obesity. METHODS: In this multicentre, parallel group, pragmatic randomised controlled trial, conducted in 39 intensive care units in France, critically ill patients with obesity undergoing extubation were randomly assigned (1:1) to either the NIV group or the oxygen therapy group. Two randomisations were performed: first, randomisation to either NIV or oxygen therapy, and second, randomisation to either HFNO or standard oxygen (also 1:1), which was nested within the first randomisation. Blinding of the randomisation was not possible, but the statistician was masked to group assignment. The primary outcome was treatment failure within 3 days after extubation, a composite of reintubation for mechanical ventilation, switch to the other study treatment, or premature discontinuation of study treatment. The primary outcome was analysed by intention to treat. Effect of medical and surgical status was assessed. The reintubation within 3 days was analysed by intention to treat and after a post-hoc crossover analysis. This study is registered with ClinicalTrials.gov, number NCT04014920. FINDINGS: From Oct 2, 2019, to July 17, 2021, of the 1650 screened patients, 981 were enrolled. Treatment failure occurred in 66 (13·5%) of 490 patients in the NIV group and in 130 (26·5%) of 491 patients in the oxygen-therapy group (relative risk 0·43; 95% CI 0·31-0·60, p<0·0001). Medical or surgical status did not modify the effect of NIV group on the treatment-failure rate. Reintubation within 3 days after extubation was similar in the non-invasive ventilation group and in the oxygen therapy group in the intention-to-treat analysis (48 (10%) of 490 patients and 59 (12%) of 491 patients, p=0·26) and lower in the NIV group than in the oxygen-therapy group in the post-hoc cross-over (51 (9%) of 560 patients and 56 (13%) of 421 patients, p=0·037) analysis. No severe adverse events were reported. INTERPRETATION: Among critically ill adults with obesity undergoing extubation, the use of NIV was effective to reduce treatment-failure within 3 days. Our results are relevant to clinical practice, supporting the use of NIV after extubation of critically ill patients with obesity. However, most of the difference in the primary outcome was due to patients in the oxygen therapy group switching to NIV, and more evidence is needed to conclude that an NIV strategy leads to improved patient-centred outcomes. FUNDING: French Ministry of Health.

Prognostic value of an automated thrombin generation assay in COVID-19 patients entering hospital: A multicentric, prospective observational study.

INTRODUCTION: The prognostic significance of the thrombin generation assay (TGA) with a thrombomodulin (TM) challenge in patients entering hospital with severe COVID-19 is uncertain. METHODS: We prospectively evaluated an automated TGA (aTGA) using the ST-ThromboScreen® assay and ST-Genesia® analyser in 179 patients with severe COVID-19 during their admission to 2 university hospitals. The primary outcome was early survival at Day 28 (D28). Secondary outcomes were late survival at Day 90 (D90), later transfer to an intensive care unit (ICU), and occurrence of any thrombotic complications during hospitalisation. RESULTS: Among the 174 patients, 50 were initially admitted to ICUs. Forty-two were transferred to ICUs before D28. Fourteen patients, all in ICUs, died before D28, and 20 before D90, all but 1 in ICUs. None of the aTGA-derived results were associated with vital status either at D28 or D90. Nine patients had a thrombotic event with no association with the aTGA results. Later transfer to the ICU was associated with higher velocity index, thrombin peak height and endogenous thrombin potential (ETP) values of the aTGA performed with TM, and mainly with a lower TM-induced decrease in ETP (odds ratio 15.5 (2.15-132), p = 0.009). CONCLUSIONS: aTGA, a global assay supposed to evidence coagulopathy, could predict neither early or late survival, nor thrombotic events, in hospitalised COVID-19 patients. Its clinical justification in that setting is thus unlikely. A relative resistance of the ETP to TM was associated with later transfer to the ICU and deserves further investigation.

Sodium flux during hemodialysis and hemodiafiltration treatment of acute kidney injury: Effects of dialysate and infusate sodium concentration at 140 and 145 mmol/L.

BACKGROUND: A higher sodium (Na) dialysate concentration is recommended during renal replacement therapy (RRT) of acute kidney injury (AKI) to improve intradialytic hemodynamic tolerance, but it may lead to Na loading to the patient. We aimed to evaluate Na flux according to Na dialysate and infusate concentrations at 140 and 145 mmol/L during hemodialysis (HD) and hemodiafiltration (HDF). METHODS: Fourteen AKI patients that underwent consecutive HD or HDF sessions with Na dialysate/infusate at 140 and 145 mmol/L were included. Per-dialytic flux of Na was estimated using mean sodium logarithmic concentration including diffusive and convective influx. We compared the flux of sodium between HD140 and 145, and between HDF140 and 145. RESULTS: Nine HD140, ten HDF140, nine HD145, and 11 HDF145 sessions were analyzed. A Na gradient from the dialysate/replacement fluid to the patient was observed with dialysate/infusate Na at 145 mmol/L in both HD and HDF (p = 0.01). The comparison of HD145 to HD140 showed that higher Na dialysate induced a diffusive Na gradient to the patient (163 mmol vs. -25 mmol, p = 0.004) and that of HDF145 to -140 (211 vs. 36 mmol, p = 0.03) as well. Intradialytic hemodynamic tolerance was similar across all RRT sessions. CONCLUSIONS: During both HD and HDF, a substantial Na loading occurred with a Na dialysate and infusate at 145 mmol/L. This Na loading is smaller in HDF with Na dialysate and infusate concentration at 140 mmol/L and inversed with HD140. Clinical and intradialytic hemodynamic tolerance was fair regardless of Na dialysate and infusate.

Long-Term Outcome of Severe Metabolic Acidemia in ICU Patients, a BICAR-ICU Trial Post Hoc Analysis.

OBJECTIVES: Long-term prognosis of ICU survivors is a major issue. Severe acidemia upon ICU admission is associated with very high short-term mortality. Since the long-term prognosis of these patients is unknown, we aimed to determine the long-term health-related quality of life and survival of these patients. DESIGN: Post hoc analysis of a multicenter, randomized, controlled trial. SETTING: Twenty-six French ICUs. PATIENTS: Day 28 critically ill survivors admitted with severe acidemia and enrolled in the BICAR-ICU trial. INTERVENTION: Sodium bicarbonate versus no sodium bicarbonate infusion according to the randomization group. MEASUREMENTS AND MAIN RESULTS: The primary outcome was health-related quality of life (HRQoL) measured with the 36-item Short Form Health Survey and the EuroQol 5-D questionnaires. Secondary outcomes were mortality, end-stage renal disease treated with renal replacement therapy or renal transplantation, place of residence, professional status, and ICU readmission. HRQoL was reduced with no significant difference between the two groups. HRQoL was reduced particularly in the role-physical health domain (64/100 ± 41 in the control group and 49/100 ± 43 in the bicarbonate group, p = 0.28), but it was conserved in the emotional domains (96/100 ± 19 in the control group and 86/100 ± 34 in the bicarbonate group, p = 0.44). Forty percent of the survivors described moderate to severe problems walking, and half of the survivors described moderate to severe problems dealing with usual activities. Moderate to severe anxiety or depression symptoms were present in one third of the survivors. Compared with the French general population, HRQoL was decreased in the survivors mostly in the physical domains. The 5-year overall survival rate was 30% with no significant difference between groups. CONCLUSIONS: Long-term HRQoL was decreased in both the control and the sodium bicarbonate groups of the BICAR-ICU trial and was lower than the general population, especially in the physical domains.

Management and outcomes of pregnant women admitted to intensive care unit for severe pneumonia related to SARS-CoV-2 infection: the multicenter and international COVIDPREG study.

PURPOSE: Management and outcomes of pregnant women with coronavirus disease 2019 (COVID-19) admitted to intensive care unit (ICU) remain to be investigated. METHODS: A retrospective multicenter study conducted in 32 ICUs in France, Belgium and Switzerland. Maternal management as well as maternal and neonatal outcomes were reported. RESULTS: Among the 187 pregnant women with COVID-19 (33 ± 6 years old and 28 ± 7 weeks' gestation), 76 (41%) were obese, 12 (6%) had diabetes mellitus and 66 (35%) had pregnancy-related complications. Standard oxygenation, high-flow nasal oxygen therapy (HFNO) and non-invasive ventilation (NIV) were used as the only oxygenation technique in 41 (22%), 55 (29%) and 18 (10%) patients, respectively, and 73 (39%) were intubated. Overall, 72 (39%) patients required several oxygenation techniques and 15 (8%) required venovenous extracorporeal membrane oxygenation. Corticosteroids and tocilizumab were administered in 157 (84%) and 25 (13%) patients, respectively. Awake prone positioning or prone positioning was performed in 49 (26%) patients. In multivariate analysis, risk factors for intubation were obesity (cause-specific hazard ratio (CSH) 2.00, 95% CI (1.05-3.80), p = 0.03), term of pregnancy (CSH 1.07, 95% CI (1.02-1.10), per + 1 week gestation, p = 0.01), extent of computed tomography (CT) scan abnormalities > 50% (CSH 2.69, 95% CI (1.30-5.60), p < 0.01) and NIV use (CSH 2.06, 95% CI (1.09-3.90), p = 0.03). Delivery was required during ICU stay in 70 (37%) patients, mainly due to maternal respiratory worsening, and improved the driving pressure and oxygenation. Maternal and fetal/neonatal mortality rates were 1% and 4%, respectively. The rate of maternal and/or neonatal complications increased with the invasiveness of maternal respiratory support. CONCLUSION: In ICU, corticosteroids, tocilizumab and prone positioning were used in few pregnant women with COVID-19. Over a third of patients were intubated and delivery improved the driving pressure.

Severe but reversible impaired diaphragm function in septic mechanically ventilated patients.

BACKGROUND: Whether sepsis-associated diaphragm dysfunction may improve despite the exposure of mechanical ventilation in critically ill patients is unclear. This study aims at describing the diaphragm function time course of septic and non-septic mechanically ventilated patients. METHODS: Secondary analysis of two prospective observational studies of mechanically ventilated patients in whom diaphragm function was assessed twice: within the 24 h after intubation and when patients were switched to pressure support mode, by measuring the endotracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (Ptr,stim). Change in diaphragm function was expressed as the difference between Ptr,stim measured under pressure support mode and Ptr,stim measured within the 24 h after intubation. Sepsis was defined according to the Sepsis-3 international guidelines upon inclusion. In a sub-group of patients, the right hemidiaphragm thickness was measured by ultrasound. RESULTS: Ninety-two patients were enrolled in the study. Sepsis upon intubation was present in 51 (55%) patients. In septic patients, primary reason for ventilation was acute respiratory failure related to pneumonia (37/51; 73%). In non-septic patients, main reasons for ventilation were acute respiratory failure not related to pneumonia (16/41; 39%), coma (13/41; 32%) and cardiac arrest (6/41; 15%). Ptr,stim within 24 h after intubation was lower in septic patients as compared to non-septic patients: 6.3 (4.9-8.7) cmH2O vs. 9.8 (7.0-14.2) cmH2O (p = 0.004), respectively. The median (interquartile) duration of mechanical ventilation between first and second diaphragm evaluation was 4 (2-6) days in septic patients and 3 (2-4) days in non-septic patients (p = 0.073). Between first and second measurements, the change in Ptr,stim was + 19% (- 13-61) in septic patients and - 7% (- 40-12) in non-septic patients (p = 0.005). In the sub-group of patients with ultrasound measurements, end-expiratory diaphragm thickness decreased in both, septic and non-septic patients. The 28-day mortality was higher in patients with decrease or no change in diaphragm function. CONCLUSION: Septic patients were associated with a more severe but reversible impaired diaphragm function as compared to non-septic patients. Increase in diaphragm function was associated with a better survival.

Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients.

Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. Patients aged ⩾18 years on invasive mechanical ventilation for ⩾4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) (n = 57) or standard of care (control) (n = 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain. Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [-10 to 25]), P = 0.59. Mechanical ventilation duration (mean ± SD) was 12.7 ± 9.9 days and 14.1 ± 10.8 days, respectively, P = 0.50; maximal inspiratory pressure increased by 16.6 cm H2O and 4.8 cm H2O, respectively (difference [95% CI], 11.8 [5 to 19]), P = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and -14%, respectively, P = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain). Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction. Clinical trial registered with www.clinicaltrials.gov (NCT03096639) and the European Database on Medical Devices (CIV-17-06-020004).

Monocyte human leukocyte antigen-DR but not ß-D-glucan may help early diagnosing invasive Candida infection in critically ill patients.

BACKGROUND: Precision medicine risk stratification is desperately needed to both avoid systemic antifungals treatment delay and over prescription in the critically ill with risk factors. The aim of the present study was to explore the combination of host immunoparalysis biomarker (monocyte human leukocyte antigen-DR expression (mHLA-DR)) and Candida sp wall biomarker ß-D-glucan in risk stratifying patients for secondary invasive Candida infection (IC). METHODS: Prospective observational study. Two intensive care units (ICU). All consecutive non-immunocompromised septic shock patients. Serial blood samples (n = 286) were collected at day 0, 2 and 7 and mHLA-DR and ß-D-glucan were then retrospectively assayed after discharge. Secondary invasive Candida sp infection occurrence was then followed at clinicians' discretion. RESULTS: Fifty patients were included, 42 (84%) had a Candida score equal or greater than 3 and 10 patients developed a secondary invasive Candida sp infection. ICU admission mHLA-DR expression and ß-D-glucan (BDG) failed to predict secondary invasive Candida sp infection. Time-dependent cause-specific hazard ratio of IC was 6.56 [1.24-34.61] for mHLA-DR < 5000 Ab/c and 5.25 [0.47-58.9] for BDG > 350 pg/mL. Predictive negative value of mHLA-DR > 5000 Ab/c and BDG > 350 pg/mL combination at day 7 was 81% [95% CI 70-92]. CONCLUSIONS: This study suggests that mHLA-DR may help predicting IC in high-risk patients with septic shock. The added value of BDG and other fungal tests should be regarded according to the host immune function markers.

Shear Wave Elastography, a New Tool for Diaphragmatic Qualitative Assessment: A Translational Study.

Rationale: Prolonged mechanical ventilation is often associated with either a decrease (known atrophy) or an increase (supposed injury) in diaphragmatic thickness. Shear wave elastography is a noninvasive technique that measures shear modulus, a surrogate of tissue stiffness and mechanical properties. Objectives: To describe changes in shear modulus (SM) during the ICU stay and the relationship with alterations in muscle thickness. To perform a comprehensive ultrasound-based characterization of histological and force production changes occurring in the diaphragm. Methods: Translational study using critically ill patients and mechanically ventilated piglets. Serial ultrasound examination of the diaphragm collecting thickness and SM was performed in both patients and piglets. Transdiaphragmatic pressure and diaphragmatic biopsies were collected in piglets. Measurements and Main Results: We enrolled 102 patients, 88 of whom were invasively mechanically ventilated. At baseline, SM was 14.3 ± 4.3 kPa and diaphragm end-expiratory thickness was 2.0 ± 0.5 mm. Decrease or increase by more than 10% from baseline was reported in 86% of the patients for thickness and in 92% of the patients for SM. An increase in diaphragmatic thickness during the stay was associated with a decrease in SM (ß = -9.34 ± 4.41; P = 0.03) after multivariable analysis. In the piglet sample, a decrease in SM over 3 days of mechanical ventilation was associated with loss of force production, slow and fast fiber atrophy, and increased lipid droplets accumulation. Conclusions: Increases in diaphragm thickness during critical illness is associated with decreased tissue stiffness as demonstrated by shear wave ultrasound elastography, consistent with the development of muscle injury and weakness. Clinical trial registered with www.clinicaltrials.gov (NCT03550222).

Energetic dysfunction in sepsis: a narrative review.

BACKGROUND: Growing evidence associates organ dysfunction(s) with impaired metabolism in sepsis. Recent research has increased our understanding of the role of substrate utilization and mitochondrial dysfunction in the pathophysiology of sepsis-related organ dysfunction. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions. MAIN TEXT: Sepsis is characterized by systemic and organ-specific changes in metabolism. Alterations of oxygen consumption, increased levels of circulating substrates, impaired glucose and lipid oxidation, and mitochondrial dysfunction are all associated with organ dysfunction and poor outcomes in both animal models and patients. The pathophysiological relevance of bioenergetics and metabolism in the specific examples of sepsis-related immunodeficiency, cerebral dysfunction, cardiomyopathy, acute kidney injury and diaphragmatic failure is also described. CONCLUSIONS: Recent understandings in substrate utilization and mitochondrial dysfunction may pave the way for new diagnostic and therapeutic approaches. These findings could help physicians to identify distinct subgroups of sepsis and to develop personalized treatment strategies. Implications for their use as bioenergetic targets to identify metabolism- and mitochondria-targeted treatments need to be evaluated in future studies.

Association between increased mortality and bronchial fibroscopy in intensive care units and intermediate care units during COPD exacerbations: an analysis of the 2014 and 2015 National French Medical-based Information System Databases (PMSI).

BACKGROUND: The course of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations, most often of infectious origin, responsible for many intensive care unit (ICU) and intermediate care unit (IMCU) admissions. Our objective was to study in-hospital mortality during severe COPD exacerbations in ICU and IMCU based on the performance of bronchoscopy. METHODS: A retrospective analysis was carried out on stays in ICUs for COPD exacerbation from the French Programme for the Medicalisation of Information Systems databases for the years 2014 and 2015. Propensity score matching of stays made it possible to constitute two comparable groups on the factors of excess mortality described in the literature (age, sex, SAPS 2, type of admission and bronchial tumour). RESULTS: We identified 14,491 stays for COPD exacerbation in ICUs, 2586 of which received a bronchoscopy. Mortality was significantly higher in the fibroscopy group (31.32% versus 19.8%). After propensity score matching, we found an excess of mortality in the intervention group (OR = 1.749 [1.516-2.017]) associated with a significantly longer length of stay. The main diagnoses associated with an increased risk of death were pulmonary embolism (OR = 3.251 [1.126-9.384]), bacterial pneumonia (OR = 1.906 [1.173-3.098]) and acute respiratory failure (OR = 1.840 [1.486-2.278]). CONCLUSIONS: Performing bronchoscopy during ICU hospitalisations for severe COPD exacerbations was associated with increased mortality. This increased mortality appears to be related to a bias in patient selection with a procedure reserved for patients with the adverse course.