Center effect in intubation risk in critically ill immunocompromised patients with acute hypoxemic respiratory failure.

BACKGROUND: Acute respiratory failure is the leading reason for intensive care unit (ICU) admission in immunocompromised patients, and the need for invasive mechanical ventilation has become a major clinical endpoint in randomized controlled trials (RCTs). However, data are lacking on whether intubation is an objective criteria that is used unbiasedly across centers. This study explores how this outcome varies across ICUs. METHODS: Hierarchical models and permutation procedures for testing multiple random effects were applied on both data from an observational cohort (the TRIAL-OH study: 703 patients, 17 ICUs) and a randomized controlled trial (the HIGH trial: 776 patients, 31 ICUs) to characterize ICU variation in intubation risk across centers. RESULTS: The crude intubation rate varied across ICUs from 29 to 80% in the observational cohort and from 0 to 86% in the RCT. This center effect on the mean ICU intubation rate was statistically significant, even after adjustment on individual patient characteristics (observational cohort: p value = 0.013, median OR 1.48 [1.30-1.72]; RCT: p value 0.004, median OR 1.51 [1.36-1.68]). Two ICU-level characteristics were associated with intubation risk (the annual rate of intubation procedure per center and the time from respiratory symptoms to ICU admission) and could partly explain this center effect. In the RCT that controlled for the use of high-flow oxygen therapy, we did not find significant variation in the effect of oxygenation strategy on intubation risk across centers, despite a significant variation in the need for invasive mechanical ventilation. CONCLUSION: Intubation rates varied considerably among ICUs, even after adjustment on individual characteristics.

High-flow nasal oxygen vs. standard oxygen therapy in immunocompromised patients with acute respiratory failure: study protocol for a randomized controlled trial.

BACKGROUND: Acute respiratory failure (ARF) is the leading reason for intensive care unit (ICU) admission in immunocompromised patients. High-flow nasal oxygen (HFNO) therapy is an alternative to standard oxygen. By providing warmed and humidified gas, HFNO allows the delivery of higher flow rates via nasal cannula devices, with FiO2 values of nearly 100%. Benefits include alleviation of dyspnea and discomfort, decreased respiratory distress and decreased mortality in unselected patients with acute hypoxemic respiratory failure. However, in preliminary reports, HFNO benefits are controversial in immunocompromised patients in whom it has never been properly evaluated. METHODS/DESIGN: This is a multicenter, open-label, randomized controlled superiority trial in 30 intensive care units, part of the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique (GRRR-OH). Inclusion criteria will be: (1) adults, (2) known immunosuppression, (3) ARF, (4) oxygen therapy ≥ 6 L/min, (5) written informed consent from patient or proxy. Exclusion criteria will be: (1) imminent death (moribund patient), (2) no informed consent, (3) hypercapnia (PaCO2 ≥ 50 mmHg), (4) isolated cardiogenic pulmonary edema, (5) pregnancy or breastfeeding, (6) anatomical factors precluding insertion of a nasal cannula, (7) no coverage by the French statutory healthcare insurance system, and (8) post-surgical setting from day 1 to day 6 (patients with ARF occurring after day 6 of surgery can be included). The primary outcome measure is day-28 mortality. Secondary outcomes are intubation rate, comfort, dyspnea, respiratory rate, oxygenation, ICU length of stay, and ICU-acquired infections. Based on an expected 30% mortality rate in the standard oxygen group, and 20% in the HFNO group, error rate set at 5%, and a statistical power at 90%, 389 patients are required in each treatment group (778 patients overall). Recruitment period is estimated at 30 months, with 28 days of additional follow-up for the last included patient. DISCUSSION: The HIGH study will be the largest multicenter, randomized controlled trial seeking to demonstrate that survival benefits from HFNO reported in unselected patients also apply to a large immunocompromised population. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02739451 . Registered on 15 April 2016.

Coronary Spasm after an Injection of Vincristine.

Cardiotoxicity, including heart failure, thromboembolic events, and myocardial ischemia, is a concern for cardiologists and oncologists. The most frequently involved drugs are anthracyclines. We report an episode of coronary spasm due to vincristine, a vinca alkaloid, in a 49-year-old man treated for a diffuse undifferentiated carcinoma. The patient suffered recurrent episodes of typical chest pain with ST-elevation in the inferior area. Coronary spasm was confirmed by an angiogram, which showed normal coronary arteries. No recurrence occurred with the medical management. Coronary spasm induced by vincristine is a newly described facet of chemotherapy-related cardiotoxicity.

[Wounded in action: the platinum ten minutes and the golden hour]. / Blessés au combat, dix minutes en platine, une heure en or.

In the battlefield, the majority of casualties die within ten minutes of the trauma. Most injuries result from an explosion and haemorrhage plays a central role. To improve survival rates, the French Army Health Service has developed a chain of survival from the battlefield to France based on prehospital combat casualty care, forward medical support during the first hour and damage control surgery.

The prognostic value of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency in septic shock patients involves interleukin-6 and is not dependent on disseminated intravascular coagulation.

INTRODUCTION: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency has been reported in patients with sepsis but its clinical relevance and pathophysiology remain unclear. Our objectives were to assess the clinical significance, prognostic value and pathophysiology of ADAMTS13 deficiency in patients with septic shock with and without disseminated intravascular coagulation (DIC). METHODS: This was a prospective monocenter cohort study of patients with septic shock. Von Willebrand Factor, ADAMTS13-related parameters and plasma IL-6 concentration were measured at inclusion to the study. Patients were categorized into three groups according to the presence of ADAMT13 deficiency (<30%) or DIC. RESULTS: This study included 72 patients with a median age of 59 years (interquartile range (IQR) 50 to 71). Each of the included patients received vasopressors; 55 (76%) were under mechanical ventilation and 22 (33%) underwent renal replacement therapy. Overall, 19 patients (26%) had DIC, and 36 patients had ADMTS13 deficiency (50%). Patients with DIC, ADAMTS13 deficiency or both were more severe at ICU admission. Mortality was higher in septic shock patients from group one. By multivariate analysis, Simplified Acute Physiology Score 2 (SAPS2) score (odds ratio (OR) 1.11/point; 95% CI 1.01 to 1.24) and ADAMTS13 activity <30% (OR 11.86; 95% CI 1.36 to 103.52) were independently associated with hospital mortality. There was no correlation between ADAMTS13 activity and the International Society for Thrombosis and Haemostasis (ISTH) score (rs = -0.97, P = 0.41) suggesting that ADAMTS13 functional deficiency and DIC were independent parameters. IL-6 level was higher in patients with ADAMTS13 activity <30% [895 (IQR 330 to 1843) pg/mL versus 83 (IQR 43 to 118), P = 0.0003). CONCLUSIONS: Septic shock was associated with a functional deficiency of ADAMTS13, independently of DIC. ADAMTS13 functional deficiency is then a prognostic factor for mortality in septic shock patients, independently of DIC.

Causes and risk factors of death in patients with thrombotic microangiopathies.

PURPOSE: Although plasma therapy of thrombotic micro-angiopathies (TMAs) has dramatically improved survival, the outcome remains fatal in up to 15 % of patients. We investigated the causes and risk factors of death in patients with TMA. METHODS: Retrospective matched case-control national-registry study of 57 patients who died within 180 days of TMA diagnosis and 48 survivors matched on age, gender, and baseline platelet count and creatinine level. The study period was 1995-2007. Factors associated with mortality were identified using a conditional logistic regression model. RESULTS: Median time from TMA symptom onset to death was 7 (5-14) days. The leading causes of death were nosocomial infections, myocardial infarction, stroke, and pulmonary embolism. Cases and controls did not differ significantly regarding haemolysis parameters, ADAMTS13 activity, or neurological or gastrointestinal involvement. TMA was more frequently related to HIV or cancer in patients who died. Compared to survivors, non-survivors more often had cardiac involvement at diagnosis (38 vs. 6 %, p = 0.03) and less often received plasma exchange therapy (60 vs. 92 %, p = 0.004). Only two factors were independently associated with mortality by multivariate analysis: cardiac involvement at diagnosis (odds ratio, 5.96; 95 % confidence interval, 1.06-33.4) and plasma exchange therapy (odds ratio, 0.25; 95 % confidence interval, 0.06-0.99). CONCLUSION: Our data emphasise the adverse prognostic significance of cardiac abnormalities and support routine plasma exchange in patients with TMA. Given the high risk of cardiac and neurological complications, adequate monitoring should be proposed to these patients in appropriate hospital settings.

Survival in neutropenic patients with severe sepsis or septic shock.

OBJECTIVE: To determine whether the survival gains achieved in critically ill cancer patients in recent years exist in the subset with neutropenia and severe sepsis or septic shock. DESIGN: Retrospective 11-yr study (1998-2008). SETTING: Medical intensive care unit in a teaching hospital. PATIENTS: Four hundred twenty-eight intensive care unit patients with cancer, neutropenia, and severe sepsis or septic shock. The primary outcome was hospital mortality. RESULTS: The main underlying diseases were acute leukemia (35.7%), lymphoma (31.7%), and solid tumors (16.5%). Two hundred thirty-seven (55.5%) patients had microbiologically documented infections, 141 (32.9%) clinically documented infections, and 50 (11.9%) fever of unknown origin. Acute noninfectious conditions were diagnosed in 175 of 428 (41%) patients, including 26 of 50 (52%) patients with fever of unknown origin, 66 of 141 (47%) patients with clinically documented infections, and 83 of 237 (35%) patients with microbiologically documented infections. Early indwelling catheter removal was performed routinely in the 107 (25%) patients without clinical evidence of a septic focus at intensive care unit admission. Early beta-lactam plus aminoglycoside therapy was used in 391 (91.3%) patients. Hospital mortality was 49.8%. Hospital mortality decreased from 58.7% (108 of 184) in 1998-2003 to 43% in 2004-2008 (105 of 244, p = .006). Multivariate analysis identified nine independent predictors of hospital mortality, of which six were associated with higher mortality (older age; need for vasopressors; neurologic, respiratory, or hepatic dysfunction; and acute noninfectious condition) and three with lower mortality (intensive care unit admission after 2003, combination antibiotic therapy including an aminoglycoside, and early indwelling catheter removal). CONCLUSION: In neutropenic patients with severe sepsis or septic shock, survival improved over time. Aminoglycoside use and early catheter removal in patients with undocumented sepsis may improve survival. Acute noninfectious conditions are associated with increased mortality, underlining the need for thorough and repeated clinical assessments.

Continued survival gains in recent years among critically ill myeloma patients.

OBJECTIVE: Therapeutic advances have improved survival in patients with myeloma (MM) over the past decade. We investigated whether survival has also improved in critically ill myeloma patients. DESIGN: Retrospective study. SETTING: Intensive care unit. PATIENT: Consecutive myeloma patients admitted to a teaching hospital ICU between 1990 and 2006. We compared three year-of-admission groups (1990-1995, 1996-2001, and 2002-2006) that matched changes in myeloma treatment (chemotherapy only, stem cell transplantation, and new molecules, respectively). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We included 196 patients. Reasons for ICU admission and patient characteristics were similar across groups; however, less use of conventional chemotherapy and radiotherapy and greater use of steroids were noted in the more recent periods. Over time, vasopressors and invasive mechanical ventilation were used decreasingly, and noninvasive ventilation increasingly, to treat acute respiratory failure. Hospital mortality decreased from 75% in 1990-1995 to 49% in 1996-2001 and 40% in 2002-2006 (P = 0.0007). Mortality was associated with poor performance status [OR 2.27, 95% CI (1.04-4.99)], need for mechanical ventilation [OR 4.33, 95% CI (1.86-10.10)], need for vasopressors [OR 2.57, 95% CI (1.12-5.86)], and admission for an event related to myeloma progression [OR 2.77, 95% CI (1.13-6.79)]. ICU admission within 48 h after hospital admission was associated with lower mortality [OR 0.28, 95% CI (0.19-0.89)]. CONCLUSION: Hospital mortality decreased significantly over the last 15 years in myeloma patients admitted to the ICU. Risk factors for death were organ failure and poor chronic health status. Early ICU admission was associated with lower mortality, suggesting opportunities for further improving survival.