According to French regulation, the study was approved by the Angers University Hospital ethics committee and information letters were sent to the patients. To the best of our knowledge, our cohort ...is the first specific report of late cannulation experience in this indication and our results suggest that it is feasible and may have benefit some patients (69% survival rate in patients under 60 years of age cannulated after 7 days of mechanical ventilation in our cohort). ...a late initiation of VV-ECMO for CARDS was not associated with an increased mortality in our cohort.
Abstract
Rationale
Early corticosteroid treatment is used to treat COVID-19-related acute respiratory distress syndrome (ARDS). Infection is a well-documented adverse effect of corticosteroid ...therapy.
Objectives
To determine whether early corticosteroid therapy to treat COVID-19 ARDS was associated with ventilator-associated pneumonia (VAP).
Methods
We retrospectively included adults with COVID-19-ARDS requiring invasive mechanical ventilation (MV) for ≥ 48 h at any of 15 intensive care units in 2020. We divided the patients into two groups based on whether they did or did not receive corticosteroids within 24 h. The primary outcome was VAP incidence, with death and extubation as competing events. Secondary outcomes were day 90-mortality, MV duration, other organ dysfunctions, and VAP characteristics.
Measurements and main results
Of 670 patients (mean age, 65 years), 369 did and 301 did not receive early corticosteroids. The cumulative VAP incidence was higher with early corticosteroids (adjusted hazard ratio aHR 1.29; 95% confidence interval 95% CI 1.05–1.58;
P
= 0.016). Antibiotic resistance of VAP bacteria was not different between the two groups (odds ratio 0.94, 95% CI 0.58–1.53;
P
= 0.81). 90-day mortality was 30.9% with and 24.3% without early corticosteroids, a nonsignificant difference after adjustment on age, SOFA score, and VAP occurrence (aHR 1.15; 95% CI 0.83–1.60;
P
= 0.411). VAP was associated with higher 90-day mortality (aHR 1.86; 95% CI 1.33–2.61;
P
= 0.0003).
Conclusions
Early corticosteroid treatment was associated with VAP in patients with COVID-19-ARDS. Although VAP was associated with higher 90-day mortality, early corticosteroid treatment was not. Longitudinal randomized controlled trials of early corticosteroids in COVID-19-ARDS requiring MV are warranted.
Prevalence, risk factors and medical management of persistent pain symptoms after critical care illness have not been thoroughly investigated.
We performed a prospective multicentric study in ...patients with an intensive care unit (ICU) length of stay ≥ 48 h. The primary outcome was the prevalence of significant persistent pain, defined as a numeric rating scale (NRS) ≥ 3, 3 months after admission. Secondary outcomes were the prevalence of symptoms compatible with neuropathic pain (ID-pain score > 3) and the risk factors of persistent pain.
Eight hundred fourteen patients were included over a 10-month period in 26 centers. Patients had a mean age of 57 (± 17) years with a SAPS 2 score of 32 (± 16) (mean ± SD). The median ICU length of stay was 6 4-12 days (median interquartile). At 3 months, the median intensity of pain symptoms was 2 1-5 in the entire population, and 388 (47.7%) patients had significant pain. In this group, 34 (8.7%) patients had symptoms compatible with neuropathic pain. Female (Odds Ratio 1.5 95% CI 1.1-2.1), prior use of anti-depressive agents (OR 2.2 95% CI 1.3-4), prone positioning (OR 3 95% CI 1.4-6.4) and the presence of pain symptoms on ICU discharge (NRS ≥ 3) (OR 2.4 95% CI 1.7-3.4) were risk factors of persistent pain. Compared with sepsis, patients admitted for trauma (non neuro) (OR 3.5 95% CI 2.1-6) were particularly at risk of persistent pain. Only 35 (11.3%) patients had specialist pain management by 3 months.
Persistent pain symptoms were frequent in critical illness survivors and specialized management remained infrequent. Innovative approaches must be developed in the ICU to minimize the consequences of pain.
NCT04817696. Registered March 26, 2021.
IntroductionFever treatment is commonly applied in patients with sepsis but its impact on survival remains undetermined. Patients with respiratory and haemodynamic failure are at the highest risk for ...not tolerating the metabolic cost of fever. However, fever can help to control infection. Treating fever with paracetamol has been shown to be less effective than cooling. In the SEPSISCOOL pilot study, active fever control by external cooling improved organ failure recovery and early survival. The main objective of this confirmatory trial is to assess whether fever control at normothermia can improve the evolution of organ failure and mortality at day 60 of febrile patients with septic shock. This study will compare two strategies within the first 48 hours of septic shock: treatment of fever with cooling or no treatment of fever.Methods and analysisSEPSISCOOL II is a pragmatic, investigator-initiated, adaptive, multicentre, open-label, randomised controlled, superiority trial in patients admitted to the intensive care unit with febrile septic shock. After stratification based on the acute respiratory distress syndrome status, patients will be randomised between two arms: (1) cooling and (2) no cooling. The primary endpoint is mortality at day 60 after randomisation. The secondary endpoints include the evolution of organ failure, early mortality and tolerance. The target sample size is 820 patients.Ethics and disseminationThe study is funded by the French health ministry and was approved by the ethics committee CPP Nord Ouest II (Amiens, France). The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT04494074.
IntroductionFasting is frequently imposed to patients before extubation in the intensive care unit based on scheduled surgery guidelines. This practice has never been evaluated among critically ill ...patients and may delay extubation, increase nursing workload and reduce caloric intake. We are hypothesising that continuous enteral nutrition until extubation represents a safe alternative compared with fasting prior to extubation in the intensive care unit.Methods and analysisAdult patients ventilated more than 48 hours and receiving pre-pyloric enteral nutrition for more than 24 hours are included in this open-label cluster randomised parallel group non-inferiority trial. The participating centres are randomised allocated to continued enteral nutrition until extubation or 6-hour fasting (with concomitant gastric suctioning when feasible) prior to extubation. The primary outcome is extubation failure (ie, reintubation within 7 days following extubation).Ethics and disseminationThis study has been approved by the national ethics review board (comité de protection, des personnes Sud Mediterranée III No 2017.10.02 bis) and patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals.Trial registration numberClinicalTrials.gov Registry (NCT03335345).
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.
Graphical Abstract
Patients with critical illness due to COVID-19 exhibit increased coagulability associated with a high risk of venous thrombo-embolism (VTE). Data on prophylactic anticoagulation for these patients ...are limited and conflicting. The purpose of this study was to evaluate whether intermediate-dose prophylactic anticoagulation in patients with COVID-19 requiring ICU admission was associated with better outcomes compared to standard-dose prophylactic anticoagulation.
We retrospectively included adults admitted with severe COVID-19 to any of 15 ICUs, in 2020 or 2021. We compared the groups given intermediate-dose vs. standard-dose prophylactic anticoagulation. The primary outcome was all-cause day-90 mortality. Secondary outcomes were VTE (pulmonary embolism or deep vein thrombosis), ICU stay length, and adverse effects of anticoagulation.
Of 1174 included patients (mean age, 63 years), 399 received standard-dose and 775 intermediate-dose prophylactic anticoagulation. Of the 211 patients who died within 90 days, 86 (21%) received intermediate and 125 (16%) standard doses. After adjustment on early corticosteroid therapy and critical illness severity, there were no significant between-group differences in day-90 mortality (hazard ratio HR, 0.73; 95%CI, 0.52-1.04; p = 0.09) or ICU stay length (HR, 0.93; 95%CI, 0.79-1.10; p = 0.38). Intermediate-dose anticoagulation was significantly associated with fewer VTE events (HR, 0.55; 95%CI, 0.38-0.80; p < 0.001). Bleeding events occurred in similar proportions of patients in the two groups (odds ratio, 0.86; 95%CI, 0.50-1.47; p = 0.57).
Mortality on day 90 did not differ between the groups given standard-dose and intermediate-dose prophylactic anticoagulation, despite a higher incidence of VTE in the standard-dose group.
Purpose
Data for ANCA-associated vasculitis (AAV) patients requiring intensive care are scarce.
Methods
We included 97 consecutive patients with acute AAV manifestations (new onset or relapsing ...disease), admitted to 18 intensive care units (ICUs) over a 10-year period (2002–2012). A group of 95 consecutive AAV patients with new onset or relapsing disease, admitted to two nephrology departments with acute vasculitis manifestations, constituted the control group.
Results
In the ICU group, patients predominantly showed granulomatosis with polyangiitis and proteinase-3 ANCAs. Compared with the non-ICU group, the ICU group showed comparable Birmingham vasculitis activity score and a higher frequency of heart, central nervous system and lungs involvements. Respiratory assistance, renal replacement therapy and vasopressors were required in 68.0, 56.7 and 26.8% of ICU patients, respectively. All but one patient (99%) received glucocorticoids, 85.6% received cyclophosphamide, and 49.5% had plasma exchanges as remission induction regimens. Fifteen (15.5%) patients died during the ICU stay. The following were significantly associated with ICU mortality in the univariate analysis: the need for respiratory assistance, the use of vasopressors, the occurrence of at least one infection event in ICU, cyclophosphamide treatment, sequential organ failure assessment at admission and simplified acute physiology score II. After adjustment on sequential organ failure assessment or infection, cyclophosphamide was no longer a risk factor for mortality. Despite a higher initial mortality rate of ICU patients within the first hospital stay (
p
< 0.0001), the long-term mortality of hospital survivors did not differ between ICU and non-ICU groups (18.6 and 20.4%, respectively,
p
= 0.36). Moreover, we observed no renal survival difference between groups after a 1-year follow-up (82.1 and 80.5%,
p
= 0.94).
Conclusion
This study supports the idea that experiencing an ICU challenge does not impact the long-term prognosis of AAV patients.
IMPORTANCE: The benefit of high-flow nasal cannula oxygen (high-flow oxygen) in terms of intubation and mortality in patients with respiratory failure due to COVID-19 is controversial. OBJECTIVE: To ...determine whether the use of high-flow oxygen, compared with standard oxygen, could reduce the rate of mortality at day 28 in patients with respiratory failure due to COVID-19 admitted in intensive care units (ICUs). DESIGN, SETTING, AND PARTICIPANTS: The SOHO-COVID randomized clinical trial was conducted in 34 ICUs in France and included 711 patients with respiratory failure due to COVID-19 and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen equal to or below 200 mm Hg. It was an ancillary trial of the ongoing original SOHO randomized clinical trial, which was designed to include patients with acute hypoxemic respiratory failure from all causes. Patients were enrolled from January to December 2021; final follow-up occurred on March 5, 2022. INTERVENTIONS: Patients were randomly assigned to receive high-flow oxygen (n = 357) or standard oxygen delivered through a nonrebreathing mask initially set at a 10-L/min minimum (n = 354). MAIN OUTCOMES AND MEASURES: The primary outcome was mortality at day 28. There were 13 secondary outcomes, including the proportion of patients requiring intubation, number of ventilator-free days at day 28, mortality at day 90, mortality and length of stay in the ICU, and adverse events. RESULTS: Among the 782 randomized patients, 711 patients with respiratory failure due to COVID-19 were included in the analysis (mean SD age, 61 12 years; 214 women 30%). The mortality rate at day 28 was 10% (36/357) with high-flow oxygen and 11% (40/354) with standard oxygen (absolute difference, –1.2% 95% CI, –5.8% to 3.4%; P = .60). Of 13 prespecified secondary outcomes, 12 showed no significant difference including in length of stay and mortality in the ICU and in mortality up until day 90. The intubation rate was significantly lower with high-flow oxygen than with standard oxygen (45% 160/357 vs 53% 186/354; absolute difference, –7.7% 95% CI, –14.9% to –0.4%; P = .04). The number of ventilator-free days at day 28 was not significantly different between groups (median, 28 IQR, 11-28 vs 23 IQR, 10-28 days; absolute difference, 0.5 days 95% CI, –7.7 to 9.1; P = .07). The most common adverse events were ventilator-associated pneumonia, occurring in 58% (93/160) in the high-flow oxygen group and 53% (99/186) in the standard oxygen group. CONCLUSIONS AND RELEVANCE: Among patients with respiratory failure due to COVID-19, high-flow nasal cannula oxygen, compared with standard oxygen therapy, did not significantly reduce 28-day mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04468126
Whether patients with coronavirus disease (COVID-19) may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown.
To ...estimate the effect of ECMO on 90-day mortality versus IMV only.
Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO versus no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (Pa
/Fi
< 80 or Pa
⩾ 60 mm Hg). We controlled for confounding using a multivariable Cox model on the basis of predefined variables.
A total of 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability on Day 7 from the onset of eligibility criteria (87% vs. 83%; risk difference, 4%; 95% confidence interval, 0-9%), which decreased during follow-up (survival on Day 90: 63% vs. 65%; risk difference, -2%; 95% confidence interval, -10 to 5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand and when initiated within the first 4 days of IMV and in patients who are profoundly hypoxemic.
In an emulated trial on the basis of a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and regions with ECMO capacities specifically organized to handle high demand.
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