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Background Protective ventilation during the acute phase of ARDS and weaning from mechanical ventilation are well-established in current guidelines. However, the intermediate transition phase between these stages remains poorly characterized. Objectives To describe the transition phase in moderate-to-severe ARDS and evaluate the factors associated with neuromuscular blockade (NMBA) weaning failure and pressure support ventilation (PSV) failure. Methods This bicentric observational cohort study included patients with moderate-to-severe ARDS requiring NMBA continuous infusion within 72 h post-intubation. The transition phase was defined as the 72 h following the first NMBA weaning attempt. The main endpoints were the rates of NMBA reintroduction and PSV failure. Secondary outcomes included predictive factors for NMBA weaning failure and PSV failure and the impact of tidal volume on patient outcomes. Main results A total of 196 patients were included. NMBA weaning failure occurred in 74 (38%) patients. COVID-19 (OR 3.98 [1.95–8.41], p  < 0.001), pH (OR 0.50 [0.30–0.79], p  = 0.004), PaO 2 /FiO 2 ratio (OR 0.92 [0.87–0.97], p  = 0.007), and high or low driving pressure before first NMBA weaning attempt (< 12 or ≥ 14 cmH 2 O) (OR 2.77 [1.16–7.14], p  = 0.027) were significantly associated with NMBA reintroduction. PSV was initiated in 147 (75%) patients, with a failure rate of 57%, occurring after a median of 9 h [6–24]. Tidal volume (OR 1.28 [1.06–1.56], p  = 0.012) was significantly associated with PSV failure. During PSV, 43% of patients exhibited high tidal volumes (> 8 mL/kg PBW). NMBA weaning failure was associated with fewer ventilator-free days and increased mortality at day 28. PSV failure was associated with fewer ventilator-free days. Conclusion The transition phase represents a high-risk period in ARDS, with significant failure rates for NMBA weaning and PSV trials that may influence patient outcomes. The transition phase therefore represents a critical area for future research to optimize management during this vulnerable period.

Background The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients. Methods The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7. Results Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively ( p  = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7. Conclusion In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.

BackgroundInhaled nitric oxide (iNO) has been widely used in patients with COVID-19-related acute respiratory distress syndrome (C-ARDS), though its physiological effects and outcome are debated in this setting. The objective of this cohort study was to describe the modalities of iNO use, clinical response, and outcomes in a large cohort of C-ARDS patients.MethodsMulticentre, retrospective cohort study conducted in France.ResultsFrom end February to December 2020, 300 patients (22.3% female) were included, 84.5% were overweight and 69.0% had at least one comorbidity. At ICU admission, their median (IQR) age, SAPS II, and SOFA score were 66 (57–72) years, 37 (29–48), and 5 (3–8), respectively. Patients were all ventilated according to a protective ventilation strategy, and 68% were prone positioned before iNO initiation. At iNO initiation, 2%, 37%, and 61% of patients had mild, moderate, and severe ARDS, respectively. The median duration of iNO treatment was 2.8 (1.1–5.5) days with a median dosage of 10 (7–13) ppm at initiation. Responders (PaO2/FiO2 ratio improving by 20% or more) represented 45.7% of patients at 6 h from iNO initiation. The severity of ARDS was the only predictive factor associated with iNO response. Among all evaluable patients, the crude mortality was not significantly different between responders at 6 h and their counterparts. Of the 62 patients with refractory ARDS (who fulfilled extracorporeal membrane oxygenation criteria before iNO initiation), 32 (51.6%) no longer fulfilled these criteria after 6 h of iNO. The latter showed significantly lower mortality than the other half (who remained ECMO eligible), including after confounder adjustment (adjusted OR: 0.23, 95% CI 0.06, 0.89, p = 0.03).ConclusionsOur study reports the benefits of iNO in improving arterial oxygenation in C-ARDS patients. This improvement seems more relevant in the most severe cases. In patients with ECMO criteria, an iNO-driven improvement in gas exchange was associated with better survival. These results must be confirmed in well-designed prospective studies.

Background Alcohol related hepatitis is responsible for high morbidity and mortality, but little is known about the management of patients with hepatitis specifically in intensive care units (ICU). Methods Retrospective study including patients with alcohol related hepatitis hospitalized in 9 French ICUs (2006–2017). Alcohol related hepatitis was defined histologically or by an association of clinical and biological criteria according to current guidelines. Results 187 patients (median age: 53 [43–60]; male: 69%) were included. A liver biopsy was performed in 51% of cases. Patients were admitted for impaired consciousness (71%), sepsis (64%), shock (44%), respiratory failure (37%). At admission, median SOFA and MELD scores were 10 [7–13] and 31 [26–40] respectively. 63% of patients received invasive mechanical ventilation, 62% vasopressors, and 36% renal replacement therapy. 66% of patients received corticosteroids, and liver transplantation was performed in 16 patients (8.5%). ICU and in-hospital mortality were 37% and 53% respectively. By multivariate analysis, ICU mortality was associated with SOFA score (without total bilirubin) (SHR 1.08 [1.02–1.14] per one-point increase), arterial lactate (SHR 1.08 [1.03–1.13] per 1 mmol/L) and MELD score (SHR 1.09 [1.04–1.14] per 1 point), while employment was associated with increased survival (HR 0.49 [0.28–0.86]). After propensity score weighting, the use of corticosteroids did not affect ICU mortality in the overall population but had a beneficial effect in the subgroup of patients with histological proof. Patient prognosis was also better in responders assessed by Lille score at day 7 (OR 6.67 [2.44–20.15], p  < 0.001). Conclusion Alcohol related hepatitis is a severe condition leading to high mortality in ICU patients. Severity of organ failure at admission are mortality risk factors. Outcome was significantly better in responders to corticosteroids therapy according to Lille score. Early referral to tertiary centers to discuss liver transplantation should more widely be considered.

Background Accurate microbiological documentation seems central for managing severe pneumonia. While the FilmArray ® Pneumonia + panel (FA-PP) offers rapid pathogen identification, its effectiveness during antibiotic treatment and in predicting clinical outcomes remains unclear. Methods We conducted a prospective observational study across four ICUs from April 2022 to June 2024, including patients with ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP). Bacterial loads were monitored on days 0, 1, 3, 7 and 10 and 3 days after stopping antibiotics, using endotracheal aspirates (ETAs) analyzed by FA-PP and standard cultures. The main objective was to assess the correlation between quantitative changes in FA-PP results and clinical success. Quantitative changes over time were analyzed using mixed ordinal logistic regression. Results Of the 93 patients enrolled, 60.2% ( n  = 56) achieved clinical success, while the ICU mortality rate was 25.8% ( n  = 24). Although FA-PP and culture quantification results declined over time ( p  < 0.0001), neither method consistently correlated with clinical success (non-significant for both). At diagnosis, FA-PP showed excellent diagnostic performance compared to culture, with a sensitivity of 94% [95% CI: 87–97] and a specificity of 98% [95% CI: 97–98]. Quantitative concordance improved with higher DNA copies, from 22.9% at the culture threshold at 10⁴ DNA copies/ml in FA-PP to 100% at ≥ 10⁷ DNA copies/ml. Diagnostic performance remained stable during antibiotic treatment with 94% sensitivity and 95% specificity in follow-up ETAs. Conclusions FA-PP provides rapid and accurate diagnostics, but repeated testing did not predict clinical outcomes during treatment, however our small sample size limited the study power.

Background Ventilator associated pneumonia (VAP) due to wild-type AmpC-producing Enterobacterales (wtAE) is frequent in intensive care unit (ICU) patients. Despite a low level of evidence, definitive antimicrobial therapy (AMT) with third generation cephalosporins (3GCs) or piperacillin is discouraged. Methods Observational prospective study including consecutive wtAE VAP patients in 20 French ICUs. The primary objective was to assess the association of the choice of definitive AMT, i.e. piperacillin ± tazobactam (PTZ), 3GCs or other molecule (4GCs, carbapenems, quinolones, cotrimoxazole; control group), with treatment success at day-7. Recurrence of infection was collected as a secondary outcome, and analyzed accounting for the competing risk of death. Results From February 2021 to June 2022, 274 patients were included. Enterobacter cloacae was the most prevalent specie (31%). Seventy-eight patients (28%) had PTZ as definitive AMT while 44 (16%) had 3GCs and 152 (56%) were classified in the control group. Day-7 success rate was similar between the 3 groups (74% vs. 73% vs. 68% respectively, p  = 0.814). Recurrence probability at day-28 was 31% (95% CI 21–42), 40% (95% CI 26–55) and 21% (95% CI 15–28) for PTZ, 3GCs and control groups ( p  = 0.020). In multivariable analysis, choice of definitive AMT was not associated with clinical success, but definitive AMT with 3GCs was associated with recurrence at day-28 [csHR(95%CI) 10.9 (1.92–61.91)]. Conclusion Choice of definitive antimicrobial therapy was not associated with treatment success at day 7. However, recurrence of pneumonia at day-28 was higher in patients treated with third generation cephalosporins with no differences in mortality or mechanical ventilation duration.

Abstract Background The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients. Methods The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7. Results Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively ( p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7. Conclusion In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.

Objective: Our main objective was to evaluate the short- and long-term efficacy of Celon radiofrequency-induced thermal therapy for endovenous treatment of incompetent great saphenous vein. The secondary objectives were to report on possible short-term side effects and complications. Methods: This was a retrospective study of 112 consecutive patients included between 2013 and June 2015. These patients were treated (146 great saphenous vein, C2–C6) either at the hemodynamic room using local anesthesia or at the operating theater under general anesthesia with or without phlebectomy. All patients received radiofrequency-induced thermal therapy at 18 W power, 1 s/cm pullback rate and 5–7 pullbacks per segment of 10 cm (i.e. maximum 10 pullbacks). A clinical follow-up via ultrasound monitoring was done at 1 week, 1 month, 6 months, 1 year, 2 years and 3 years. Results: The 3-year survival occlusion rate was 96.71% and 98% for overall and radiofrequency-induced thermal therapy patients, respectively. No major side effects were observed. A case of endovenous heat-induced thrombosis was reported. Slight neurological disorders were reported (0.88%). Conclusion: Our unit’s endovenous Celon radiofrequency-induced thermal therapy of incompetent great saphenous vein was efficient, well tolerated, without major side effects. Moreover, in order to reduce possible neurological disorders, we advise multiple pullbacks at 1 s/cm and using tumescence anesthesia.