Clinical description and outcome of overall varicella-zoster virus-related organ dysfunctions admitted in intensive care units: the VAZOREA cohort study.

BACKGROUND: Due to aging population and increasing part of immunocompromised patients, a raise in life-threatening organ damage related to VZV can be expected. Two retrospective studies were already conducted on VZV in ICU but focused on specific organ injury. Patients with high-risk of VZV disease still must be identified. The objective of this study was to report the clinical features and outcome of all life-threatening VZV manifestations requiring intensive care unit (ICU) admission. This retrospective cohort study was conducted in 26 French ICUs and included all adult patients with any life-threatening VZV-related event requiring ICU admission or occurring in ICU between 2010 and 2019. RESULTS: One-hundred nineteen patients were included with a median SOFA score of 6. One hundred eight patients (90.8%) were admitted in ICU for VZV disease, leaving 11 (9.2%) with VZV disease occurring in ICU. Sixty-one patients (51.3%) were immunocompromised. Encephalitis was the most prominent organ involvement (55.5%), followed by pneumonia (44.5%) and hepatitis (9.2%). Fifty-four patients (45.4%) received norepinephrine, 72 (60.5% of the total cohort) needed invasive mechanical ventilation, and 31 (26.3%) received renal-replacement therapy. In-hospital mortality was 36.1% and was significantly associated with three independent risk factors by multivariable logistic regression: immunosuppression, VZV disease occurring in ICU and alcohol abuse. Hierarchical clustering on principal components revealed five phenotypically distinct clusters of patients: VZV-related pneumonia, mild encephalitis, severe encephalitis in solid organ transplant recipients, encephalitis in other immunocompromised hosts and VZV disease occurring in ICU. In-hospital mortality was highly different across phenotypes, ranging from zero to 75% (p < 0.001). CONCLUSION: Overall, severe VZV manifestations are associated with high mortality in the ICU, which appears to be driven by immunosuppression status rather than any specific organ involvement. Deciphering the clinical phenotypes may help clinicians identify high-risk patients and assess prognosis.

Prevalence and risk factors of significant persistent pain symptoms after critical care illness: a prospective multicentric study.

BACKGROUND: Prevalence, risk factors and medical management of persistent pain symptoms after critical care illness have not been thoroughly investigated. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: NCT04817696. Registered March 26, 2021.

Continued enteral nutrition until extubation compared with fasting before extubation in patients in the intensive care unit: an open-label, cluster-randomised, parallel-group, non-inferiority trial.

BACKGROUND: Fasting is frequently imposed before extubation in patients in intensive care units, with the aim to reduce risk of aspiration. This unevaluated practice might delay extubation, increase workload, and reduce caloric intake. We aimed to compare continued enteral nutrition until extubation with fasting before extubation in patients in the intensive care unit. METHODS: We conducted an open-label, cluster-randomised, parallel-group, non-inferiority trial in 22 intensive care units in France. Patients aged 18 years or older were eligible for enrolment if they had received invasive mechanical ventilation for at least 48 h in the intensive care unit and received prepyloric enteral nutrition for at least 24 h at the time of extubation decision. Centres were randomly assigned (1:1) to continued enteral nutrition until extubation or 6-h fasting with concomitant gastric suctioning before extubation, to be applied for all patients within the unit. Masking was not possible because of the nature of the trial. The primary outcome was extubation failure (composite criteria of reintubation or death) within 7 days after extubation, assessed in both the intention-to-treat and per-protocol populations. The non-inferiority margin was set at 10%. Pneumonia within 14 days of extubation was a key secondary endpoint. This trial is now complete and is registered with ClinicalTrials.gov, NCT03335345. FINDINGS: Between April 1, 2018, and Oct 31, 2019, 7056 patients receiving enteral nutrition and mechanical ventilation were admitted to the intensive care units and 4198 were assessed for eligibility. 1130 patients were enrolled and included in the intention-to-treat population and 1008 were included in the per-protocol population. In the intention-to-treat population, extubation failure occurred in 106 (17·2%) of 617 patients assigned to receive continued enteral nutrition until extubation versus 90 (17·5%) of 513 assigned to fasting, meeting the a priori defined non-inferiority criterion (absolute difference -0·4%, 95% CI -5·2 to 4·5). In the per-protocol population, extubation failure occurred in 101 (17·0%) of 595 patients assigned to receive continued enteral nutrition versus 74 (17·9%) of 413 assigned to fasting (absolute difference -0·9%, 95% CI -5·6 to 3·7). Pneumonia within 14 days of extubation occurred in ten (1·6%) patients assigned to receive continued enteral nutrition and 13 (2·5%) assigned to fasting (rate ratio 0·77, 95% CI 0·22 to 2·69). INTERPRETATION: Continued enteral nutrition until extubation in critically ill patients in the intensive care unit was non-inferior to a 6-h fasting maximum gastric vacuity strategy comprising continuous gastric tube suctioning, in terms of extubation failure within 7 days (a patient-centred outcome), and thus represents a potential alternative in this population. FUNDING: French Ministry of Health. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Outcomes of Patients With Active Cancer and COVID-19 in the Intensive-Care Unit: A Multicenter Ambispective Study.

Background: Several studies report an increased susceptibility to SARS-CoV-2 infection in cancer patients. However, data in the intensive care unit (ICU) are scarce. Research Question: We aimed to investigate the association between active cancer and mortality among patients requiring organ support in the ICU. Study Design and Methods: In this ambispective study encompassing 17 hospitals in France, we included all adult active cancer patients with SARS-CoV-2 infection requiring organ support and admitted in ICU. For each cancer patient, we included 3 non cancer patients as controls. Patients were matched at the same ratio using the inverse probability weighting approach based on a propensity score assessing the probability of cancer at admission. Mortality at day 60 after ICU admission was compared between cancer patients and non-cancer patients using primary logistic regression analysis and secondary multivariable analyses. Results: Between March 12, 2020 and March 8, 2021, 2608 patients were admitted with SARS-CoV-2 infection in our study, accounting for 2.8% of the total population of patients with SARS-CoV-2 admitted in all French ICUs within the same period. Among them, 105 (n=4%) presented with cancer (51 patients had hematological malignancy and 54 patients had solid tumors). 409 of 420 patients were included in the propensity score matching process, of whom 307 patients in the non-cancer group and 102 patients in the cancer group. 145 patients (35%) died in the ICU at day 60, 59 (56%) with cancer and 86 (27%) without cancer. In the primary logistic regression analysis, the odds ratio for death associated to cancer was 2.3 (95%CI 1.24 - 4.28, p=0.0082) higher for cancer patients than for a non-cancer patient at ICU admission. Exploratory multivariable analyses showed that solid tumor (OR: 2.344 (0.87-6.31), p=0.062) and hematological malignancies (OR: 4.144 (1.24-13.83), p=0.062) were independently associated with mortality. Interpretation: Patients with cancer and requiring ICU admission for SARS-CoV-2 infection had an increased mortality, hematological malignancy harboring the higher risk in comparison to solid tumors.

Clinical spectrum and risk factors for mortality among seawater and freshwater critically ill drowning patients: a French multicenter study.

BACKGROUND: Drowning is a global threat and one of the leading causes of injury around the world. The impact of drowning conditions including water salinity on patients' prognosis remains poorly explored in Intensive Care Units (ICUs) patients. METHODS: We conducted a retrospective multicenter study on patients admitted to 14 ICUs in the west of France from January 2013 to January 2020. We first compared demographic and clinical characteristics at admission as well as clinical courses of these patients according to the salinity of drowning water. Then, we aimed to identify variables associated with 28-day survival using a Cox proportional hazard model. RESULTS: Of the 270 consecutive included patients, drowning occurred in seawater in 199 patients (73.7%) and in freshwater in 71 patients (26.3%). Day-28 mortality was observed in 55 patients (20.4%). Freshwater was independently associated with 28-day mortality (Adjusted Hazard Ratio (aHR) 1.84 [95% Confidence Interval (CI) 1.03-3.29], p = 0.04). A higher proportion of freshwater patients presented psychiatric comorbidities (47.9 vs. 19.1%; p < 0.0001) and the etiology of drowning appeared more frequently to be a suicide attempt in this population (25.7 vs. 4.2%; p < 0.0001). The other factors independently associated with 28-day mortality were the occurrence of a drowning-related cardiac arrest (aHR 11.5 [95% CI 2.51-52.43], p = 0.0017), duration of cardiopulmonary resuscitation (aHR 1.05 [95% CI 1.03-1.07], p < 0.0001) and SOFA score at day 1 (aHR 1.2 [95% CI 1.11-1.3], p < 0.0001). CONCLUSIONS: In this large multicenter cohort, freshwater drowning patients had a poorer prognosis than saltwater drowning patients. Reasons for such discrepancies include differences in underlying psychiatric comorbidity, drowning circumstances and severities. Patients with initial cardiac arrest secondary to drowning remain with a very poor prognosis.

Effect of High-Dose Baclofen on Agitation-Related Events Among Patients With Unhealthy Alcohol Use Receiving Mechanical Ventilation: A Randomized Clinical Trial.

Importance: Unhealthy alcohol use can lead to agitation in the intensive care unit (ICU). Objective: To assess whether high-dose baclofen reduces agitation-related events compared with placebo in patients with unhealthy alcohol use receiving mechanical ventilation. Design, Settings, and Participants: This phase 3, double-blind, placebo-controlled, randomized clinical trial conducted in 18 ICUs in France recruited adults receiving mechanical ventilation who met criteria for unhealthy alcohol use. Patients were enrolled from June 2016 to February 2018; the last follow-up was in May 2019. Interventions: Baclofen (n = 159), adjusted from 50 to 150 mg per day based on estimated glomerular filtration rate, or placebo (n = 155) during mechanical ventilation up to a maximum of 15 days before gradual dose reduction over 3 to 6 days. Main Outcomes and Measures: The primary end point was the percentage of patients with at least 1 agitation-related event over the treatment period. Secondary outcomes included duration of mechanical ventilation, length of ICU stay, and 28-day mortality. Results: Among 314 patients who were randomized (mean age, 57 years; 60 [17.2%] women), 313 (99.7%) completed the trial. There was a statistically significant decrease in the percentage of patients who experienced at least 1 agitation-related event in the baclofen group vs the placebo group (31 [19.7%] vs 46 [29.7%]; difference, -9.93% [95% CI, -19.45% to -0.42%]; adjusted odds ratio, 0.59 [95% CI, 0.35-0.99]). Of 18 prespecified secondary end points, 14 were not significantly different. Compared with the placebo group, the baclofen group had a significantly longer median length of mechanical ventilation (9 vs 8 days; difference, 2.00 [95% CI, 0.00-3.00]; hazard ratio [HR] for extubation, 0.76 [95% CI, 0.60-0.97]) and stay in the ICU (14 vs 11 days; difference, 2.00 [95% CI, 0.00-4.00]; HR for discharge, 0.70 [95% CI, 0.54-0.90]). At 28 days, there was no significant difference in mortality in the baclofen vs placebo group (25.3% vs 21.6%; adjusted odds ratio, 1.24 [95% CI, 0.72-2.13]). Delayed awakening (no eye opening at 72 hours after cessation of sedatives and analgesics) occurred in 14 patients (8.9%) in the baclofen group vs 3 (1.9%) in the placebo group. Conclusions and Relevance: Among patients with unhealthy alcohol use receiving mechanical ventilation, treatment with high-dose baclofen, compared with placebo, resulted in a statistically significant reduction in agitation-related events. However, considering the modest effect and the totality of findings for the secondary end points and adverse events, further research is needed to determine the possible role of baclofen in this setting and to potentially optimize dosing. Trial Registration: ClinicalTrials.gov Identifier: NCT02723383.

Severe leptospirosis in non-tropical areas: a nationwide, multicentre, retrospective study in French ICUs.

PURPOSE: To report the incidence, risk factors, clinical presentation, and outcome predictors of severe leptospirosis requiring intensive care unit (ICU) admission in a temperate zone. METHODS: LEPTOREA was a retrospective multicentre study conducted in 79 ICUs in metropolitan France. Consecutive adults admitted to the ICU for proven severe leptospirosis from January 2012 to September 2016 were included. Multiple correspondence analysis (MCA) and hierarchical classification on principal components (HCPC) were performed to distinguish different clinical phenotypes. RESULTS: The 160 included patients (0.04% of all ICU admissions) had median values of 54 years [38-65] for age, 40 [28-58] for the SAPSII, and 11 [8-14] for the SOFA score. Hospital mortality was 9% and was associated with older age; worse SOFA score and early need for endotracheal ventilation and/or renal replacement therapy; chronic alcohol abuse and worse hepatic dysfunction; confusion; and higher leucocyte count. Four phenotypes were identified: moderately severe leptospirosis (n = 34, 21%) with less organ failure and better outcomes; hepato-renal leptospirosis (n = 101, 63%) with prominent liver and kidney dysfunction; neurological leptospirosis (n = 8, 5%) with the most severe organ failures and highest mortality; and respiratory leptospirosis (n = 17, 11%) with pulmonary haemorrhage. The main risk factors for leptospirosis contamination were contact with animals, contact with river or lake water, and specific occupations. CONCLUSIONS: Severe leptospirosis was an uncommon reason for ICU admission in metropolitan France and carried a lower mortality rate than expected based on the high severity and organ-failure scores. The identification in our population of several clinical presentations may help clinicians establish an appropriate index of suspicion for severe leptospirosis.

Epidemiology of Weaning Outcome according to a New Definition. The WIND Study.

RATIONALE: The weaning process concerns all patients receiving mechanical ventilation. A previous classification into simple, prolonged, and difficult weaning ignored weaning failure and presupposed the use of spontaneous breathing trials. OBJECTIVES: To describe the weaning process, defined as starting with any attempt at separation from mechanical ventilation and its prognosis, according to a new operational classification working for all patients under ventilation. METHODS: This was a multinational prospective multicenter observational study over 3 months of all patients receiving mechanical ventilation in 36 intensive care units, with daily collection of ventilation and weaning modalities. Pragmatic definitions of separation attempt and weaning success allowed us to allocate patients in four groups. MEASUREMENTS AND MAIN RESULTS: A total of 2,729 patients were enrolled. Although half of them could not be classified using the previous definition, 99% entered the groups on the basis of our new definition as follows: 24% never started a weaning process, 57% had a weaning process of less than 24 hours (group 1), 10% had a difficult weaning of more than 1 day and less than 1 week (group 2), and 9% had a prolonged weaning duration of 1 week or more (group 3). Duration of ventilation, intensive care unit stay, and mortality (6, 17, and 29% for the three groups, respectively) all significantly increased from one group to the next. The unadjusted risk of dying was 19% after the first separation attempt and increased to 37% after 10 days. CONCLUSIONS: A new classification allows us to categorize all weaning situations. Every additional day without a weaning success after the first separation attempt increases the risk of dying.

Case report: benefits of quantitative polymerase chain reaction in the clinical management of herpes simplex virus 1 infection with prominent hepatitis and unusual secondary progression.

Herpes simplex virus (HSV) infection is rarely considered in the differential diagnosis of severe acute hepatitis and disseminated infection in immunocompetent adults. A case of disseminated HSV-1 infection in an 82-year-old woman initially presenting with neurological problems, signs of meningitis and prominent hepatitis was investigated. Initial diagnosis, monitoring, and follow-up were based on the application of molecular methods to cerebrospinal fluid, serum, and liver tissue samples from this patient. Following an initial full recovery, the patient presented delayed intracerebral haemorrhage and diffuse arthralgia. This atypical case, with delayed secondary progression, highlights the wide range of clinical features of HSV infection and the benefits of monitoring viral load by quantitative real-time polymerase chain reaction (PCR) during patient management.