Increased mortality in hematological malignancy patients with acute respiratory failure from undetermined etiology: a Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologique (Grrr-OH) study

Abstract

Background: Acute respiratory failure (ARF) is the most frequent complication in patients with hematological malignancies and is associated with high morbidity and mortality. ARF etiologies are numerous, and despite extensive diagnostic workflow, some patients remain with undetermined ARF etiology.

Methods: This is a post-hoc study of a prospective multicenter cohort performed on 1011 critically ill hematological patients. Relationship between ARF etiology and hospital mortality was assessed using a multivariable regression model adjusting for confounders.

Results: This study included 604 patients with ARF. All patients underwent noninvasive diagnostic tests, and a bronchoscopy and bronchoalveolar lavage (BAL) was performed in 155 (25.6%). Definite diagnoses were classified into four exclusive etiological categories: pneumonia (44.4%), non-infectious diagnoses (32.6%), opportunistic infection (10.1%) and undetermined (12.9%), with corresponding hospital mortality rates of 40, 35, 55 and 59%, respectively. Overall hospital mortality was 42%. By multivariable analysis, factors associated with hospital mortality were invasive pulmonary aspergillosis (OR 7.57 (95% CI 3.06-21.62); p < 0.005), use of invasive mechanical ventilation (OR 1.65 (95% CI 1.07-2.55); p = 0.02), a SOFA score >7 (OR 3.32 (95% CI 2.15-5.15); p < 0.005) and an undetermined ARF etiology (OR 2.92 (95% CI 1.71-5.07); p < 0.005).

Conclusions: In patients with hematological malignancies and ARF, up to 13% remain with undetermined ARF etiology despite comprehensive diagnostic workup. Undetermined ARF etiology is independently associated with hospital mortality. Studies to guide second-line diagnostic strategies are warranted. ClinicalTrials.Gov NCT01172132.

Keywords: Acute respiratory failure; Bronchoalveolar lavage; Diagnostic strategy; Etiologies; Hematological malignancies; Outcome.

Fig. 1

Patients flow diagram. Patients with respiratory symptoms were excluded if they didn’t reach any pre-defined ARF criterion. ICU Intensive care unit, ARF Acute respiratory failure

Fig. 2

Hospital mortality according to ARF etiology (univariate analysis). Undetermined ARF etiology has been used as a reference

Fig. 3

Hospital mortality according to diagnostic category. Survival curves were obtained using the Kaplan Meier estimator. Four diagnostic categories were compared: (1) Infectious: pneumonia as defined by a clinically or microbiologically documented low respiratory tract infection. (2) Noninfectious: patients with non-infectious diagnoses, mostly corresponding to cases of ARF from pulmonary infiltration by the malignancy [26], cardiac pulmonary edema and drug-related pulmonary toxicity [27]. (3) Opportunistic infection: patients with ARF from opportunistic infections (probable or proven invasive pulmonary aspergillosis according to EORTC criteria [37], pneumocystis pneumonia, other cases of invasive fungal infections, CMV infections or parasitic infections [33]. (4) Undetermined diagnosis

Fig. 4

Multivariable analysis of risk factors for hospital mortality. Box size is proportional to the accuracy of the estimate. A selection procedure was performed using a backward algorithm with a stopping criteria defined by p values below 0.05 for all variables included in the model. Goodness-of-fit test of the final model was checked using the le Cessie–van Houwelingen test statistic