Influenza and associated co-infections in critically ill immunosuppressed patients.

BACKGROUND: It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. METHODS: Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. RESULTS: Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P < 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90-1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. CONCLUSIONS: Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients.

Acute respiratory failure in immunocompromised patients: outcome and clinical features according to neutropenia status.

BACKGROUND: The impact of neutropenia in critically ill immunocompromised patients admitted in a context of acute respiratory failure (ARF) remains uncertain. The primary objective was to assess the prognostic impact of neutropenia on outcomes of these patients. Secondary objective was to assess etiology of ARF according to neutropenia. METHODS: We performed a post hoc analysis of a prospective multicenter multinational study from 23 ICUs belonging to the Nine-I network. Between November 2015 and July 2016, all adult immunocompromised patients with ARF admitted to the ICU were included in the study. Adjusted analyses included: (1) a hierarchical model with center as random effect; (2) propensity score (PS) matched cohort; and (3) adjusted analysis in the matched cohort. RESULTS: Overall, 1481 patients were included in this study of which 165 had neutropenia at ICU admission (11%). ARF etiologies distribution was significantly different between neutropenic and non-neutropenic patients, main etiologies being bacterial pneumonia (48% vs 27% in neutropenic and non-neutropenic patients, respectively). Initial oxygenation strategy was standard supplemental oxygen in 755 patients (51%), high-flow nasal oxygen in 165 (11%), non-invasive ventilation in 202 (14%) and invasive mechanical ventilation in 359 (24%). Before adjustment, hospital mortality was significantly higher in neutropenic patients (54% vs 42%; p = 0.006). After adjustment for confounder and center effect, neutropenia was no longer associated with outcome (OR 1.40, 95% CI 0.93-2.11). Similar results were observed after matching (52% vs 46%, respectively; p = 0.35) and after adjustment in the matched cohort (OR 1.04; 95% CI 0.63-1.72). CONCLUSION: Neutropenia at ICU admission is not associated with hospital mortality in this cohort of critically ill immunocompromised patients admitted for ARF. In neutropenic patients, main ARF etiologies are bacterial and fungal infections.

Etiologies and Outcomes of Acute Respiratory Failure in Solid Organ Transplant Recipients: Insight Into the EFRAIM Multicenter Cohort.

BACKGROUND: Respiratory complications of solid organ transplant (SOT) are a diagnostic and therapeutic challenge when requiring intensive care unit (ICU) admission. We aimed at describing this challenge in a prospective cohort of SOT recipients admitted in the ICU. METHODS: In this post hoc analysis of an international cohort of immunocompromised patients admitted in the ICU for an acute respiratory failure, we analyzed all SOT recipients and compared their severity, etiologic diagnosis, prognosis, and outcome according to the performance of an invasive diagnostic strategy (encompassing a fiber-optic bronchoscopy and bronchoalveolar lavage), the type of transplanted organ, and the need of invasive ventilation at day 1. RESULTS: Among 1611 patients included in the primary study, 142 were SOT recipients (kidney, n = 73; 51.4%; lung, n = 33; 23.2%; liver, n = 29; 20.4%; heart, n = 7; 4.9%). Lung transplant recipients were younger than other SOT recipients, and severity did not differ across type of received organ. An invasive diagnostic strategy was more frequently performed in lung transplant recipients with a trend toward a higher rate of bacterial etiology in lung than kidney transplant recipients. Overall ICU survival of SOT recipients was 75.4%. Invasive diagnostic strategy, type of transplanted organ, and need of invasive mechanical ventilation at day 1 did not affect ICU prognosis. CONCLUSIONS: ICU management of hypoxemic acute respiratory failure in SOT recipients translated into a low ICU mortality rate, whatever the transplanted organ or the acute respiratory failure cause. The post-ICU burden of acute respiratory failure SOT recipients remains to be investigated.

Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study.

BACKGROUND: In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV). METHODS: To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational prospective cohort study in 16 countries (68 centers). RESULTS: A total of 1611 patients were enrolled (hematological malignancies 51.9%, solid tumors 35.2%, systemic diseases 17.3%, and solid organ transplantation 8.8%). The main ARF etiologies were bacterial (29.5%), viral (15.4%), and fungal infections (14.7%), or undetermined (13.2%). On admission, 915 (56.8%) patients were not intubated. They received standard oxygen (N = 496, 53.9%), high-flow oxygen (HFNC, N = 187, 20.3%), noninvasive ventilation (NIV, N = 153, 17.2%), and NIV + HFNC (N = 79, 8.6%). Factors associated with IMV included age (hazard ratio = 0.92/year, 95% CI 0.86-0.99), day-1 SOFA (1.09/point, 1.06-1.13), day-1 PaO2/FiO2 (1.47, 1.05-2.07), ARF etiology (Pneumocystis jirovecii pneumonia (2.11, 1.42-3.14), invasive pulmonary aspergillosis (1.85, 1.21-2.85), and undetermined cause (1.46, 1.09-1.98). After propensity score matching, HFNC, but not NIV, had an effect on IMV rate (HR = 0.77, 95% CI 0.59-1.00, p = 0.05). ICU, hospital, and day-90 mortality rates were 32.4, 44.1, and 56.4%, respectively. Factors independently associated with hospital mortality included age (odds ratio = 1.18/year, 1.09-1.27), direct admission to the ICU (0.69, 0.54-0.87), day-1 SOFA excluding respiratory score (1.12/point, 1.08-1.16), PaO2/FiO2 < 100 (1.60, 1.03-2.48), and undetermined ARF etiology (1.43, 1.04-1.97). Initial oxygenation strategy did not affect mortality; however, IMV was associated with mortality, the odds ratio depending on IMV conditions: NIV + HFNC failure (2.31, 1.09-4.91), first-line IMV (2.55, 1.94-3.29), NIV failure (3.65, 2.05-6.53), standard oxygen failure (4.16, 2.91-5.93), and HFNC failure (5.54, 3.27-9.38). CONCLUSION: HFNC has an effect on intubation but not on mortality rates. Failure to identify ARF etiology is associated with higher rates of both intubation and mortality. This suggests that in addition to selecting the appropriate oxygenation device, clinicians should strive to identify the etiology of ARF.