Effect of Noninvasive Ventilation vs Oxygen Therapy on Mortality Among Immunocompromised Patients With Acute Respiratory Failure: A Randomized Clinical Trial.

IMPORTANCE: Noninvasive ventilation has been recommended to decrease mortality among immunocompromised patients with hypoxemic acute respiratory failure. However, its effectiveness for this indication remains unclear. OBJECTIVE: To determine whether early noninvasive ventilation improved survival in immunocompromised patients with nonhypercapnic acute hypoxemic respiratory failure. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized trial conducted among 374 critically ill immunocompromised patients, of whom 317 (84.7%) were receiving treatment for hematologic malignancies or solid tumors, at 28 intensive care units (ICUs) in France and Belgium between August 12, 2013, and January 2, 2015. INTERVENTIONS: Patients were randomly assigned to early noninvasive ventilation (n = 191) or oxygen therapy alone (n = 183). MAIN OUTCOMES AND MEASURES: The primary outcome was day-28 mortality. Secondary outcomes were intubation, Sequential Organ Failure Assessment score on day 3, ICU-acquired infections, duration of mechanical ventilation, and ICU length of stay. RESULTS: At randomization, median oxygen flow was 9 L/min (interquartile range, 5-15) in the noninvasive ventilation group and 9 L/min (interquartile range, 6-15) in the oxygen group. All patients in the noninvasive ventilation group received the first noninvasive ventilation session immediately after randomization. On day 28 after randomization, 46 deaths (24.1%) had occurred in the noninvasive ventilation group vs 50 (27.3%) in the oxygen group (absolute difference, -3.2 [95% CI, -12.1 to 5.6]; P = .47). Oxygenation failure occurred in 155 patients overall (41.4%), 73 (38.2%) in the noninvasive ventilation group and 82 (44.8%) in the oxygen group (absolute difference, -6.6 [95% CI, -16.6 to 3.4]; P = .20). There were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays. CONCLUSIONS AND RELEVANCE: Among immunocompromised patients admitted to the ICU with hypoxemic acute respiratory failure, early noninvasive ventilation compared with oxygen therapy alone did not reduce 28-day mortality. However, study power was limited. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01915719.

Relation between chest compression rate and depth: the ENFONCE Study.

INTRODUCTION: Chest compressions are the cornerstone of cardiopulmonary resuscitation. The recent International Liaison Committee on Resuscitation guidelines recommend increasing the rate and the depth of chest compressions, to 100-120/min and 5-6 cm, based on theoretical arguments and observational studies. We hypothesized that an increased chest compressions rate could decrease chest compressions depth. METHODS: Operators were asked to perform continuous chest compressions on a mannequin. Chest compressions rate and depth were collected. The ratio of chest compressions compliance to the guidelines, that is rate 100-120/min and depth 5-6 cm, was calculated. RESULTS: In total 951 sequences of chest compressions were studied. Median chest compressions rate: 114 (104-130)/min. Median chest compressions depth: 4.5 (3.4-5.3) cm. Correlation between rate and depth: low (R2 = 0.12). Chest compressions in compliance with the recommended rate: 434 (46%). Rate >120/min in 285 (30%) cases and <100/min in 223 (23%) cases. Chest compressions in compliance with the recommended depth: 286 (30%). Depth >6 cm in 50 (5%) cases and <5 cm in 621 (65%) cases. Finally, chest compressions were in compliance with the guidelines for both rate and depth in 141 (15%) cases. The ratio of chest compressions in compliance with the recommended depth significantly decreased with the increase of the rate: 40% for a rate <100/min, 32% for a rate in the target (100-120/min) and 18% for a rate >100/min (P < 0.0001). DISCUSSION: The ratio of chest compressions in compliance with the recommended rate and depth was as low as 15%. The rate of chest compressions in compliance with the recommended depth significantly decreased when the chest compressions rate increased. To reach both recommended rate and depth seems illusive.

Identifying early indicators of secondary peritonitis in critically ill patients with cirrhosis.

Ascitic fluid infection (AFI) is a life-threatening complication of cirrhosis. We aimed to identify early indicators of secondary peritonitis (SP), which requires emergency surgery, and to describe the outcomes of SP and spontaneous bacterial/fungal peritonitis (SBFP). Adults with cirrhosis and AFI admitted to 16 university or university-affiliated ICUs in France between 2002 and 2017 were studied retrospectively. Cases were identified by searching the hospital databases for relevant ICD-10 codes and hospital charts for AFI. Logistic multivariate regression was performed to identify factors associated with SP. Secondary outcomes were short- and long-term mortality and survivors' functional outcomes. Of 178 included patients (137 men and 41 women; mean age, 58 ± 11 years), 21 (11.8%) had SP, confirmed by surgery in 16 cases and by abdominal computed tomography in 5 cases. Time to diagnosis exceeded 24 h in 7/21 patients with SP. By multivariate analysis, factors independently associated with SP were ascitic leukocyte count > 10,000/mm3 (OR 3.70; 95%CI 1.38-9.85; P = 0.009) and absence of laboratory signs of decompensated cirrhosis (OR 4.53; 95%CI 1.30-15.68; P = 0.017). The 1-year mortality rates in patients with SBFP and SP were 81.0% and 77.5%, respectively (Log-rank test, P = 0.92). Patients with SP vs. SBFP had no differences in 1-year functional outcomes. This multicenter retrospective study identified two indicators of SP as opposed to SBFP in patients with cirrhosis. Using these indicators may help to provide early surgical treatment.

Impact and consequences of intensive chemotherapy on intestinal barrier and microbiota in acute myeloid leukemia: the role of mucosal strengthening.

Induction chemotherapy (7 + 3 regimen) remains the gold standard for patients with acute myeloid leukemia (AML) but is responsible for gut damage leading to several complications such as bloodstream infection (BSI). We aimed to investigate the impact of induction chemotherapy on the intestinal barrier of patients with AML and in wild-type mice. Next, we assessed the potential benefit of strengthening the mucosal barrier in transgenic mice releasing a recombinant protein able to reinforce the mucus layer (Tg222). In patients, we observed a decrease of plasma citrulline, which is a marker of the functional enterocyte mass, of short-chain fatty acids and of fecal bacterial load, except for Escherichia coli and Enterococcus spp., which became dominant. Both the α and ß-diversities of fecal microbiota decreased. In wild-type mice, citrulline levels decreased under chemotherapy along with an increase of E. coli and Enterococcus spp load associated with concomitant histologic impairment. By comparison with wild-type mice, Tg222 mice, 3 days after completing chemotherapy, had higher citrulline levels, a faster healing epithelium, and preserved α-diversity of their intestinal microbiota. This was associated with reduced bacterial translocations. Our results highlight the intestinal damage and the dysbiosis induced by the 7 + 3 regimen. As a proof of concept, our transgenic model suggests that strengthening the intestinal barrier is a promising approach to limit BSI and improve AML patients' outcome.

Epidemiology, clinical features, and management of severe hypercalcemia in critically ill patients.

BACKGROUND: Severe hypercalcemia (HCM) is a common reason for admission in intensive-care unit (ICU). This case series aims to describe the clinical and biological features, etiologies, treatments, and outcome associated with severe HCM. This study included all patients with a total calcemia above 12 mg/dL (3 mmol/L) admitted in two ICUs from January 2007 to February 2017. RESULTS: 131 patients with HCM were included. HCM was related to hematologic malignancy in 58 (44.3%), solid tumors in 29 (22.1%), endocrinopathies in 16 (12.2%), and other causes in 28 (21.3%) patients. 108 (82.4%) patients fulfilled acute kidney injury (AKI) criteria. Among them, 25 (19%) patients required renal replacement therapy (RRT). 51 (38.9%) patients presented with neurological symptoms, 73 (55.7%) patients had cardiovascular manifestations, and 50 (38.1%) patients had digestive manifestations. The use of bisphosphonates (HR, 0.42; 95% CI, 0.27-0.67; P < 0.001) was the only treatment significantly associated with a decrease of total calcemia below 12 mg/dL (3 mmol/L) at day 5. ICU and Hospital mortality rates were, respectively, 9.9% and 21.3%. Simplified Acute Physiologic Score (SAPS II) (OR, 1.05; 95% CI 1.01-1.1; P = 0.03) and an underlying solid tumor (OR, 13.83; 95% CI 2.24-141.25; P = 0.01) were two independent factors associated with hospital mortality in multivariate analysis. CONCLUSIONS: HCM is associated with high mortality rates, mainly due to underlying malignancies. The course of HCM may be complicated by organ failures which are most of the time reversible with early ICU management. Early ICU admission and prompt HCM management are crucial, especially in patients with an underlying solid tumor presenting with neurological symptoms.

[Consortium for detection and management of lung damage induced by bleomycin]. / Consortium de détection et prise en charge des atteintes pulmonaires induites par la bléomycine.

Bleomycin is a cytotoxic antibiotic and a component of chemotherapy regimens of germ cell tumors and lymphoma. Bleomycin lung injuries occur in 10% of patients, and lead to severe interstitial pneumonia in 3% of patients. Pulmonary toxicity is related to endothelial cells injury induce by free radicals and inflammatory cytokines. Diagnosis of bleomycin-induced lung toxicity is based on the combination of clinical and radiological features, and requires to rule out differential diagnoses including pneumocystis. "Bleomycin-induced pneumonitis" is the most frequent pattern; eosinophilic pneumonitis and organizing pneumonia are rarer. Occurrence of bleomycin lung toxicity requires an immediate and often permanent discontinuation. Treatment is based on steroid. Regular clinical and pulmonary function tests monitoring are mandatory for early detection of bleomycin-induced lung toxicity.

Methicillin-resistant Staphylococcus aureus bloodstream infections are associated with a higher energy deficit than other ICU-acquired bacteremia.

PURPOSE: Caloric insufficiency during the first week of intensive care unit (ICU) stay was reported to be associated with increased infection rates, especially ICU-acquired bloodstream infection (ICU-BSI). However, the predisposition to ICU-BSI by a given pathogen remains not well known. We aimed to determine the impact of early energy-calorie deficit on the pathogens responsible for ICU-BSI. DESIGN: Prospective, observational, cohort study in a 18-bed medical ICU of a tertiary care hospital. METHODS: Daily energy balance (energy-calorie intakes minus calculated energy-calorie expenditure) was compared according to the microbiological results of the blood cultures of 92 consecutive prolonged (at least 96 h) acute mechanically ventilated patients who developed a first episode of ICU-BSI. RESULTS: Among the 92 ICU-BSI, nine were due to methicillin-resistant Staphylococcus aureus (MRSA). The cumulated energy deficit of patients with MRSA ICU-BSI was greater than those with ICU-BSI caused by other pathogens (-1,348 ± 260 vs -1,000 ± 401 kcal/day from ICU admission to day of ICU-BSI, p = 0.008). ICU admission, risk factors for nosocomial infections, nutritional status, and conditions potentially limiting feeding did not differ significantly between the two groups. Patients with MRSA ICU-BSI had lower delivered energy and similar energy expenditure, causing higher energy deficits. More severe energy deficit and higher rate of MRSA blood cultures (p = 0.01 comparing quartiles) were observed. CONCLUSIONS: Early in-ICU energy deficit was associated with MRSA ICU-BSI in prolonged acute mechanically ventilated patients. Results suggest that limiting the early energy deficit could be a way to optimize MRSA ICU-BSI prevention.