Anne-Sophie Moreau

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.

Outcomes of mechanically ventilated hematology patients with invasive pulmonary aspergillosis

BackgroundInvasive pulmonary aspergillosis (IPA) is a life-threatening infection documented in up to 15% of hematology patients who require intensive care for acute respiratory failure. We report outcomes in hematology patients given mechanical ventilation (MV) with IPA.MethodsRetrospective study of all hematology patients given MV with IPA between January 1998 and March 2011 at a single center. Predictors of 6-month survival or mortality were identified using multivariable analysis.ResultsWe studied 67 patients including 49 (73%) with neutropenia, 23 (34%) with long-term steroid therapy, and 14 (21%) with allogeneic bone marrow transplantation. Incidence of IPA in the ICU decreased between 1998 and 2011, and mortality in patients receiving mechanical ventilation did not change. IPA was confirmed in 6 patients by autopsy and was probable in 61 patients based on host factors, clinical and radiographic features, and either Aspergillus isolation (50 patients) or Aspergillus antigen detection alone (11 patients). Concomitant bacterial infections were documented in 24 (36%) patients. ICU and 6-month mortality rates were 67 and 82%, respectively. Mortality was stable throughout the study period. Concomitant bacterial infection was independently associated with higher mortality [HR, 2.1 (1.2–3.8)]. Mortality was lower in patients given voriconazole [OR, 0.5 (0.3–0.9)].ConclusionHospital mortality remains high in hematology patients requiring MV with IPA, particularly when concommittant infection occurred. The use of voriconazole improved survival.

Clinical assessment for identifying causes of acute respiratory failure in cancer patients

In cancer patients with acute respiratory failure (ARF), early adequate therapy is associated with better outcomes. We investigated the performance of the DIRECT approach, which uses criteria available at the bedside at admission to the intensive care unit (ICU), to identify causes of ARF in cancer patients. This cohort study included cancer patients with ARF of determined aetiology. Associations of aetiological groups with the selected criteria were evaluated using correspondence analysis. 424 cancer patients were included: 201 (47%) with bacterial pneumonia, 131 (31%) with opportunistic infections and 92 (22%) with noninfectious disorders. Mechanical ventilation (both invasive and noninvasive) was needed in 328 (77%) patients, treatment for shock in 217 (51%) patients and dialysis in 82 (19%) patients. 142 (34%) patients died in the ICU. Correspondence plots showed that bacterial pneumonia was associated with neutropenia, solid tumour, multiple myeloma, <3 days since symptom onset, shock, unilateral crackles and unilateral radiographic pattern. Opportunistic infections were associated with steroids, lymphoproliferative disorders and haematopoietic stem-cell transplantation, whereas noninfectious disorders were associated with acute leukaemia The selected criteria are strongly associated with causes of ARF in cancer patients and could be used to develop an algorithm for selecting first-line diagnostic investigations and empirical treatments.

The Clinical Picture of Severe Systemic Capillary-leak Syndrome Episodes Requiring Icu Admission

Objective: Systemic capillary-leak syndrome is a very rare cause of recurrent hypovolemic shock. Few data are available on its clinical manifestations, laboratory findings, and outcomes of those patients requiring ICU admission. This study was undertaken to describe the clinical pictures and ICU management of severe systemic capillary-leak syndrome episodes. Design, Setting, Patients: This multicenter retrospective analysis concerned patients entered in the European Clarkson’s disease (EurêClark) Registry and admitted to ICUs between May 1992 and February 2016. Measurements and Main Results: Fifty-nine attacks occurring in 37 patients (male-to-female sex ratio, 1.05; mean ± SD age, 51 ± 11.4 yr) were included. Among 34 patients (91.9%) with monoclonal immunoglobulin G gammopathy, 20 (58.8%) had kappa light chains. ICU-admission hemoglobin and proteinemia were respectively median (interquartile range) 20.2 g/dL (17.9–22 g/dL) and 50 g/L (36.5–58.5 g/L). IV immunoglobulins were infused (IV immunoglobulin) during 15 episodes (25.4%). A compartment syndrome developed during 12 episodes (20.3%). Eleven (18.6%) in-ICU deaths occurred. Bivariable analyses (the 37 patients’ last episodes) retained Sequential Organ-Failure Assessment score greater than 10 (odds ratio, 12.9 [95% CI, 1.2–140]; p = 0.04) and cumulated fluid-therapy volume greater than 10.7 L (odds ratio, 16.8 [1.6–180]; p = 0.02) as independent predictors of hospital mortality. Conclusions: We described the largest cohort of severe systemic capillary-leak syndrome flares requiring ICU admission. High-volume fluid therapy was independently associated with poorer outcomes. IV immunoglobulin use was not associated with improved survival; hence, their use should be considered prudently and needs further evaluation in future studies.

Impact of immunosuppression on incidence, aetiology and outcome of ventilator-associated lower respiratory tract infections

The aim of this planned analysis of the prospective multinational TAVeM database was to determine the incidence, aetiology and impact on outcome of ventilator-associated lower respiratory tract infections (VA-LRTI) in immunocompromised patients. All patients receiving mechanical ventilation for >48 h were included. Immunocompromised patients (n=663) were compared with non-immunocompromised patients (n=2297). The incidence of VA-LRTI was significantly lower among immunocompromised than among non-immunocompromised patients (16.6% versus 24.2%; sub-hazard ratio 0.65, 95% CI 0.53–0.80; p<0.0001). Similar results were found regarding ventilator-associated tracheobronchitis (7.3% versus 11.6%; sub-hazard ratio 0.61, 95% CI 0.45–0.84; p=0.002) and ventilator-associated pneumonia (9.3% versus 12.7%; sub-hazard ratio 0.72, 95% CI 0.54–0.95; p=0.019). Among patients with VA-LRTI, the rates of multidrug-resistant bacteria (72% versus 59%; p=0.011) and intensive care unit mortality were significantly higher among immunocompromised than among non-immunocompromised patients (54% versus 30%; OR 2.68, 95% CI 1.78–4.02; p<0.0001). In patients with ventilator-associated pneumonia, mortality rates were higher among immunocompromised than among non-immunocompromised patients (64% versus 34%; p<0.001). Incidence of VA-LRTI was significantly lower among immunocompromised patients, but it was associated with a significantly higher mortality rate. Multidrug-resistant pathogens were more frequently found in immunocompromised patients with VA-LRTI. Ventilator-associated lower respiratory tract infections are less common in immunocompromised patients http://ow.ly/p4Ew30ia2fO

Acute Respiratory Failure in Patients with Hematologic Malignancies

Acute respiratory failure occurs in up to 50% of patients treated for hematologic malignancies and is associated with a high case fatality rate. Because of residual organ dysfunction and time spent receiving respiratory care, underlying disease control is affected. Early admission to an intensive care unit for acute respiratory failure has proven benefit because it is the best place for rapid implementation of noninvasive diagnostic and therapeutic strategies. This article reviews the clinical approach and diagnostic strategies for acute respiratory failure in patients with hematologic malignancies.

Oxygenation/non-invasive ventilation strategy and risk for intubation in immunocompromised patients with hypoxemic acute respiratory failure

We investigated how the initial ventilation/oxygenation management may influence the need for intubation on the coming day in a cohort of immunocompromised patients with acute hypoxemic respiratory failure (ARF). Data from 847 immunocompromised patients with ARF were used to estimate the probability of intubation at day+1 within the first 3 days of ICU admission, according to oxygenation management. First, noninvasive ventilation (NIV) was compared to oxygen therapy whatever the administration device; then standard oxygen was compared to High Flow Nasal Cannula therapy alone (HFNC), NIV alone or NIV+HFNC. To take into account the oxygenation regimens over time and to handle confounders, propensity score weighting models were used. In the original sample, the probability of intubation at day+1 was higher in the NIV group vs oxygenation therapy (OR = 1.64, 95CI, 1.09–2.48) or vs the standard oxygen group (OR = 2.05, 95CI: 1.29–3.29); it was also increased in the HFNC group compared to standard oxygen (OR = 2.85, 95CI: 1.37–5.67). However, all these differences disappeared by handling confounding-by-indication in the weighted samples, as well as in the pooled model. Note that adjusted OR for day-28 mortality increased with the day of intubation. In this large cohort of immunocompromised patients, ventilation/oxygenation management had no impact on the probability of intubation on the coming day.

Purpuric rash and right infectious endocarditis

A 34-year-old man with a Buprenorphine-substituted toxicomania was admitted to ICU for septic shock. He suffered from Staphylococcus aureus endocarditis with massive tricuspid insufficiency and septic pulmonary emboli. The patient presented with acute kidney injury requiring renal replacement therapy. Concomitantly, he developed a purpuric rash of the four limbs associated with oedemas (Fig. 1) and polyneuropathy. Urinary assessment revealed massive proteinuria (12 g/24 h) with haematuria. Immunological results showed classical complement pathway activation and the presence of circulating immune complexes and rheumatoid factors. Skin biopsy showed leukocytoclastic vasculitis and IgA perivascular deposit using immunofuorescence (Figs. 2, 3). Cryoglobulinemia type IIb was positive (153 g/L). Viral serologies (HCV, HBV, HIV) were negative. Taken together, these findings led us to the diagnosis of cryovasculitis with glomerulonephritis triggered by endocarditis. Because of persistent symptomatology despite an adequate antiinfectious therapy, the patient underwent a tricuspid valve replacement. After cardiac surgery, nephrotic syndrome, complement pathway activation and cryoglobulinemia regressed completely. Our patient received corticosteroids for 3 months to prevent glomerular aftermath, and never needed plasma exchange or rituximab therapy.