Impact of intensive prone position therapy on outcomes in intubated patients with ARDS related to COVID-19.

BACKGROUND: Previous retrospective research has shown that maintaining prone positioning (PP) for an average of 40 h is associated with an increase of survival rates in intubated patients with COVID-19-related acute respiratory distress syndrome (ARDS). This study aims to determine whether a cumulative PP duration of more than 32 h during the first 2 days of intensive care unit (ICU) admission is associated with increased survival compared to a cumulative PP duration of 32 h or less. METHODS: This study is an ancillary analysis from a previous large international observational study involving intubated patients placed in PP in the first 48 h of ICU admission in 149 ICUs across France, Belgium and Switzerland. Given that PP is recommended for a 16-h daily duration, intensive PP was defined as a cumulated duration of more than 32 h during the first 48 h, whereas standard PP was defined as a duration equal to or less than 32 h. Patients were followed-up for 90 days. The primary outcome was mortality at day 60. An Inverse Probability Censoring Weighting (IPCW) Cox model including a target emulation trial method was used to analyze the data. RESULTS: Out of 2137 intubated patients, 753 were placed in PP during the first 48 h of ICU admission. The intensive PP group (n = 79) had a median PP duration of 36 h, while standard PP group (n = 674) had a median of 16 h during the first 48 h. Sixty-day mortality rate in the intensive PP group was 39.2% compared to 38.7% in the standard PP group (p = 0.93). Twenty-eight-day and 90-day mortality as well as the ventilator-free days until day 28 were similar in both groups. After IPCW, there was no significant difference in mortality at day 60 between the two-study groups (HR 0.95 [0.52-1.74], p = 0.87 and HR 1.1 [0.77-1.57], p = 0.61 in complete case analysis or in multiple imputation analysis, respectively). CONCLUSIONS: This secondary analysis of a large multicenter European cohort of intubated patients with ARDS due to COVID-19 found that intensive PP during the first 48 h did not provide a survival benefit compared to standard PP.

Immediate vs. culture-initiated antibiotic therapy in suspected non-severe ventilator-associated pneumonia: a before-after study (DELAVAP).

BACKGROUND: Ventilator-associated pneumonia (VAP) is the leading nosocomial infection in critical care and is associated with adverse outcomes. When VAP is suspected, starting antibiotic therapy (AT) immediately after pulmonary sampling may expose uninfected patients to unnecessary treatment, whereas waiting for bacteriological confirmation may delay AT in infected patients. As no robust data exist to choose between these strategies, the decision must balance the pre-test diagnostic probability, clinical severity, and risk of antimicrobial resistance. The objective of this study in patients with suspected non-severe VAP was to compare immediate AT started after sampling to conservative AT upon receipt of positive microbiological results. The outcomes were antibiotic sparing, AT suitability, and patient outcomes. METHODS: This single-center, before-after study included consecutive patients who underwent distal respiratory sampling for a first suspected non-severe VAP episode (no shock requiring vasopressor therapy or severe acute respiratory distress syndrome). AT was started immediately after sampling in 2019 and upon culture positivity in 2022 (conservative strategy). The primary outcome was the number of days alive without AT by day 28. The secondary outcomes were mechanical ventilation duration, day-28 mortality, and AT suitability (active necessary AT or spared AT). RESULTS: The immediate and conservative strategies were applied in 44 and 43 patients, respectively. Conservative and immediate AT were associated with similar days alive without AT (median [interquartile range], 18.0 [0-21.0] vs. 16.0 [0-20.0], p = 0.50) and without broad-spectrum AT (p = 0.53) by day 28. AT was more often suitable in the conservative group (88.4% vs. 63.6%, p = 0.01), in which 27.9% of patients received no AT at all. No significant differences were found for mechanical ventilation duration (median [95%CI], 9.0 [6-19] vs. 9.0 [6-24] days, p = 0.65) or day-28 mortality (hazard ratio [95%CI], 0.85 [0.4-2.0], p = 0.71). CONCLUSION: In patients with suspected non-severe VAP, waiting for microbiological confirmation was not associated with antibiotic sparing, compared to immediate AT. This result may be ascribable to low statistical power. AT suitability was better with the conservative strategy. None of the safety outcomes differed between groups. These findings would seem to allow a large, randomized trial comparing immediate and conservative AT strategies.

Covid-19-associated pulmonary aspergillosis in mechanically ventilated patients: incidence and outcome in a French multicenter observational cohort (APICOVID).

BACKGROUND: Recent studies identified coronavirus disease 2019 (COVID-19) as a risk factor for invasive pulmonary aspergillosis (IPA) but produced conflicting data on IPA incidence and impact on patient outcomes. We aimed to determine the incidence and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) in mechanically ventilated patients. METHODS: We performed a multicenter retrospective observational cohort study in consecutive adults admitted to 15 French intensive care units (ICUs) in 2020 for COVID-19 requiring mechanical ventilation. CAPA was diagnosed and graded according to 2020 ECMM/ISHAM consensus criteria. The primary objective was to determine the incidence of proven/probable CAPA, and the secondary objectives were to identify risk factors for proven/probable CAPA and to assess associations between proven/probable CAPA and patient outcomes. RESULTS: The 708 included patients (522 [73.7%] men) had a mean age of 65.2 ± 10.8 years, a median mechanical ventilation duration of 15.0 [8.0-27.0] days, and a day-90 mortality rate of 28.5%. Underlying immunosuppression was present in 113 (16.0%) patients. Corticosteroids were used in 348 (63.1%) patients. Criteria for probable CAPA were met by 18 (2.5%) patients; no patient had histologically proven CAPA. Older age was the only factor significantly associated with probable CAPA (hazard ratio [HR], 1.04; 95% CI 1.00-1.09; P = 0.04). Probable CAPA was associated with significantly higher day-90 mortality (HR, 2.07; 95% CI 1.32-3.25; P = 0.001) but not with longer mechanical ventilation or ICU length of stay. CONCLUSION: Probable CAPA is a rare but serious complication of severe COVID-19 requiring mechanical ventilation and is associated with higher day-90 mortality.

Early prone positioning in acute respiratory distress syndrome related to COVID-19: a propensity score analysis from the multicentric cohort COVID-ICU network-the ProneCOVID study.

BACKGROUND: Delaying time to prone positioning (PP) may be associated with higher mortality in acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). We evaluated the use and the impact of early PP on clinical outcomes in intubated patients hospitalized in intensive care units (ICUs) for COVID-19. METHODS: All intubated patients with ARDS due to COVID-19 were involved in a secondary analysis from a prospective multicenter cohort study of COVID-ICU network including 149 ICUs across France, Belgium and Switzerland. Patients were followed-up until Day-90. The primary outcome was survival at Day-60. Analysis used a Cox proportional hazard model including a propensity score. RESULTS: Among 2137 intubated patients, 1504 (70.4%) were placed in PP during their ICU stay and 491 (23%) during the first 24 h following ICU admission. One hundred and eighty-one patients (36.9%) of the early PP group had a PaO2/FiO2 ratio > 150 mmHg when prone positioning was initiated. Among non-early PP group patients, 1013 (47.4%) patients had finally been placed in PP within a median delay of 3 days after ICU admission. Day-60 mortality in non-early PP group was 34.2% versus 39.3% in the early PP group (p = 0.038). Day-28 and Day-90 mortality as well as the need for adjunctive therapies was more important in patients with early PP. After propensity score adjustment, no significant difference in survival at Day-60 was found between the two study groups (HR 1.34 [0.96-1.68], p = 0.09 and HR 1.19 [0.998-1.412], p = 0.053 in complete case analysis or in multiple imputation analysis, respectively). CONCLUSIONS: In a large multicentric international cohort of intubated ICU patients with ARDS due to COVID-19, PP has been used frequently as a main treatment. In this study, our data failed to show a survival benefit associated with early PP started within 24 h after ICU admission compared to PP after day-1 for all COVID-19 patients requiring invasive mechanical ventilation regardless of their severity.

Clinical features and outcome of influenza pneumonia in critically-ill immunocompromised patients.

Immunocompromised subjects are at risk of severe viral infections which may require intensive care unit (ICU) admission. Data on the outcome of influenza pneumonia in critically-ill immunocompromised subjects are limited. We conducted a single-center observational study. All subjects admitted to the ICU for influenza pneumonia between 2016 and 2020 were included. The main objective was to compare the clinical features and outcome of critically-ill subjects with flu according to their immune status. 137 subjects (age 60 years-old, 58.4% male) were included, of whom 58 (42.34%) were intubated during the ICU stay. Forty-three (31.4%) subjects were immunocompromised. Immunocompromised subjects had a higher Charlson comorbidity index. In contrast, severity scores and hypoxemia at ICU admission, and ventilatory support during ICU stay were similar between the 2 groups. There was no difference in the rate of co-infections and ventilator-associated pneumonia between the 2 groups. Among intubated subjects, 10 (23.26%) immunocompromised subjects developed severe acute respiratory distress syndrome compared to 13 (13.83%) non-immunocompromised (P = .218). ICU mortality was 13.97%, with mortality being 3-times higher in immunocompromised subjects (25.58% vs 8.6%, P = .015). On multivariable analysis, immunocompromised status, higher age and lower arterial oxygen partial pressure/fraction of inspired oxygen were associated with an increased ICU mortality. Immunocompromised subjects with severe influenza pneumonia were more likely to develop severe acute respiratory distress syndrome and had a 3-fold increase in ICU mortality compared to non-immunocompromised subjects. Such difference was not explained by an increased rate of co-infections or nosocomial pneumonia, suggesting that influenza virus was by itself responsible of a more severe form of pulmonary disease in immunocompromised subjects.

Feasibility and impact of the implementation of a clinical scale-based sedation-analgesia protocol in severe burn patients undergoing mechanical ventilation. A before-after bi-center study.

BACKGROUND: Severe burn patients undergo prolonged administration of sedatives and analgesics for burn care. There are currently no guidelines for the dose adaptation of sedation-analgesia in severe burn patients. METHODS: We performed a before-after 2-center study to demonstrate the feasibility and efficacy of a sedation-analgesia scale-based protocol in severely burned patients receiving ≥24h of invasive mechanical ventilation. Before the intervention, continuous infusion of hypnotic and morphine derivatives was continued. During the Intervention phase, general anesthesia was relayed from day 1 by RASS/BPS-titrated continuous infusion of hypnotic and morphine derivatives and with short half-life drugs adminstered for daily burn dressings. The primary outcome was the duration of invasive mechanical ventilation in the ICU. RESULTS: Eighty-seven (46.2%) patients were included in the Control phase and 101 (53.7%) in the Intervention phase. The median burned cutaneous surface was 20% [11%-38%] and median ABSI was 7 [5-9]. The durations of hypnotic and opioid infusions were not statistically different between the 2 phases (8 days [2-24] vs. 6 days [2-17] (P=0.3) and 17 days [4-32] vs. 8 days [3-23] (P=0.06), respectively). The duration of mechanical ventilation was 14 days [3-29] in the Control phase and 7 days [2-24] in the Intervention phase (P=0.7). When taking into account the competition between mortality and weaning from mechanical ventilation, we found no significant difference between the 2 phases (Gray test, P=0.4). The time-series analysis showed no difference for the duration of mechanical ventilation in the Intervention phase (P=0.6). Eighteen (20.7%) patients died in the Control phase, and 18 (18%) in the Intervention phase (P=0.6). CONCLUSION: Scale-based lightening of continuous sedation-analgesia with repeated short general anesthesia for dressing is feasible in severe burn patients but failed to demonstrate a decrease in the duration of invasive mechanical ventilation.