François Vincent

Outcomes of Critically Ill Patients With Hematologic Malignancies: Prospective Multicenter Data From France and Belgium—A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique Study

PURPOSE Patients with hematologic malignancies are increasingly admitted to the intensive care unit (ICU) when life-threatening events occur. We sought to report outcomes and prognostic factors in these patients. PATIENTS AND METHODS Ours was a prospective, multicenter cohort study of critically ill patients with hematologic malignancies. Health-related quality of life (HRQOL) and disease status were collected after 3 to 6 months. Results Of the 1,011 patients, 38.2% had newly diagnosed malignancies, 23.1% were in remission, and 24.9% had received hematopoietic stem-cell transplantations (HSCT, including 145 allogeneic). ICU admission was mostly required for acute respiratory failure (62.5%) and/or shock (42.3%). On day1, 733 patients (72.5%) received life-supporting interventions. Hospital, day-90, and 1-year survival rates were 60.7%, 52.5%, and 43.3%, respectively. By multivariate analysis, cancer remission and time to ICU admission less than 24 hours were associated with better hospital survival. Poor performance status, Charlson comorbidity index, allogeneic HSCT, organ dysfunction score, cardiac arrest, acute respiratory failure, malignant organ infiltration, and invasive aspergillosis were associated with higher hospital mortality. Mechanical ventilation (47.9% of patients), vasoactive drugs (51.2%), and dialysis (25.9%) were associated with mortality rates of 60.5%, 57.5%, and 59.2%, respectively. On day 90, 80% of survivors had no HRQOL alterations (physical and mental health similar to that of the overall cancer population). After 6 months, 80% of survivors had no change in treatment intensity compared with similar patients not admitted to the ICU, and 80% were in remission. CONCLUSION Critically ill patients with hematologic malignancies have good survival, disease control, and post-ICU HRQOL. Earlier ICU admission is associated with better survival.

Diagnostic Strategy for Hematology and Oncology Patients with Acute Respiratory Failure Randomized Controlled Trial

RATIONALE Respiratory events are common in hematology and oncology patients and manifest as hypoxemic acute respiratory failure (ARF) in up to half the cases. Identifying the cause of ARF is crucial. Fiberoptic bronchoscopy with bronchoalveolar lavage (FO-BAL) is an invasive test that may cause respiratory deterioration. Recent noninvasive diagnostic tests may have modified the risk/benefit ratio of FO-BAL. OBJECTIVES To determine whether FO-BAL in cancer patients with ARF increased the need for intubation and whether noninvasive testing alone was not inferior to noninvasive testing plus FO-BAL. METHODS We performed a multicenter randomized controlled trial with sample size calculations for both end points. Patients with cancer and ARF of unknown cause who were not receiving ventilatory support at intensive care unit admission were randomized to early FO-BAL plus noninvasive tests (n = 113) or noninvasive tests only (n = 106). The primary end point was the number of patients needing intubation and mechanical ventilation. The major secondary end point was the number of patients with no identified cause of ARF. MEASUREMENTS AND MAIN RESULTS The need for mechanical ventilation was not significantly greater in the FO-BAL group than in the noninvasive group (35.4 vs. 38.7%; P = 0.62). The proportion of patients with no diagnosis was not smaller in the noninvasive group (21.7 vs. 20.4%; difference, -1.3% [-10.4 to 7.7]). CONCLUSIONS FO-BAL performed in the intensive care unit did not significantly increase intubation requirements in critically ill cancer patients with ARF. Noninvasive testing alone was not inferior to noninvasive testing plus FO-BAL for identifying the cause of ARF. Clinical trial registered with www.clinicaltrials.gov (NCT00248443).

Impact of unplanned extubation and reintubation after weaning on nosocomial pneumonia risk in the intensive care unit: A prospective multicenter study

Background The authors prospectively evaluated the occurrence and outcomes of unplanned extubations (self-extubation and accidental extubation) and reintubation after weaning, and examined the hypothesis that these events may differ regarding their influence on the risk of nosocomial pneumonia. Methods Data were taken from a prospective, 2-yr database including 750 mechanically ventilated patients from six intensive care units. Results One hundred five patients (14%) experienced at least one episode of these 3 events; 51 self-extubations occurred in 38 patients, 24 accidental extubations in 22 patients, and 56 reintubations after weaning in 45 patients. The incidence density of these 3 events was 16.4 per 1,000 mechanical ventilation days. Reintubation within 48 h was needed consistently after accidental extubation but was unnecessary in 37% of self-extubated patients. Unplanned extubation and reintubation after weaning were associated with longer total mechanical ventilation (17 vs. 6 days;P < 0.0001), intensive care unit stay (22 vs. 9 days;P < 0.0001), and hospital stay (34 vs. 18 days;P < 0.0001) than in control group, but did not influence intensive care unit or hospital mortality. The incidence of nosocomial pneumonia was significantly higher in patients with unplanned extubation or reintubation after weaning (27.6%vs. 13.8%;P = 0.002). In a Cox model adjusting on severity at admission, unplanned extubation and reintubation after weaning increased the risk of nosocomial pneumonia (relative risk, 1.80; 95% confidence interval, 1.15–2.80;P = 0.009). This risk increase was entirely ascribable to accidental extubation (relative risk, 5.3; 95% confidence interval, 2.8–9.9;P < 0.001). Conclusion Accidental extubation but not self-extubation or reintubation after weaning increased the risk of nosocomial pneumonia. These 3 events may deserve evaluation as an indicator for quality-of-care studies.

Diagnostic bronchoscopy in hematology and oncology patients with acute respiratory failure: prospective multicenter data.

Objective:To describe the diagnostic yields of test strategies with and without fiberoptic bronchoscopy and bronchoalveolar lavage (FO-BAL), as well as outcomes, in cancer patients with acute respiratory failure (ARF). Design:Prospective observational study. Setting:Fifteen intensive care units in France. Patients:In all, 148 cancer patients, including 45 bone marrow transplant recipients (27 allogeneic, 18 autologous) with hypoxemic ARF. Intervention:None. Results:Overall, 146 causes of ARF were identified in 128 patients (97 [66.4%] pulmonary infections). The cause of ARF was identified in 50.5% of the 101 patients who underwent FO-BAL and in 66.7% of the other patients. FO-BAL was the only conclusive test in 34 (33.7%) of the 101 investigated patients. Respiratory status deterioration after FO-BAL occurred in 22 of 45 (48.9%) nonintubated patients, including 16 (35.5%) patients who required ventilatory support. Hospital mortality was 55.4% (82 deaths) overall and was not significantly different in the groups with and without FO-BAL. By multivariate analysis, mortality was affected by characteristics of the malignancy (remission, allogeneic bone marrow transplantation), cause of ARF (ARF during neutropenia recovery, cause not identified), and need for life-sustaining treatments (mechanical ventilation and vasopressors). Conclusion:In critically ill cancer patients with ARF, a diagnostic strategy that does not include FO-BAL may be as effective as FO-BAL without exposing the patients to respiratory status deterioration.

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.

Tracheostomy does not improve the outcome of patients requiring prolonged mechanical ventilation: a propensity analysis.

Objective: To examine the association between the performance of a tracheostomy and intensive care unit and postintensive care unit mortality, controlling for treatment selection bias and confounding variables. Design: Prospective, observational, cohort study. Setting: Twelve French medical or surgical intensive care units. Patients: Unselected patients requiring mechanical ventilation for ≥48 hrs enrolled between 1997 and 2004. Interventions: None. Measurements and Main Results: Two models of propensity scores for tracheostomy were built using multivariate logistic regression. After matching on these propensity scores, the association of tracheostomy with outcomes was assessed using multivariate conditional logistic regression. Results obtained with the two models were compared. Of the 2,186 patients included, 177 (8.1%) received a tracheostomy. Both models led to similar results. Tracheostomy did not improve intensive care unit survival (model 1: odds ratio, 0.94; 95% confidence interval, 0.63–1.39; p = .74; model 2: odds ratio, 1.12; 95% confidence interval, 0.75–1.67; p = .59). There was no difference whether tracheostomy was performed early (within 7 days of ventilation) or late (after 7 days of ventilation). In patients discharged free from mechanical ventilation, tracheostomy was associated with increased postintensive care unit mortality when the tracheostomy tube was left in place (model 1: odds ratio, 3.73; 95% confidence interval, 1.41–9.83; p = .008; model 2: odds ratio, 4.63; 95% confidence interval, 1.68–12.72, p = .003). Conclusions: Tracheostomy does not seem to reduce intensive care unit mortality when performed in unselected patients but may represent a burden after intensive care unit discharge.

Delayed intensive care unit admission is associated with increased mortality in patients with cancer with acute respiratory failure

Abstract Acute respiratory failure (ARF) is the leading reason for intensive care unit (ICU) admission in patients with cancer. The aim of this study was to identify early predictors of death in patients with cancer admitted to the ICU for ARF who were not intubated at admission. We conducted analysis of a prospective randomized controlled trial including 219 patients with cancer with ARF in which day-28 mortality was a secondary endpoint. Mortality at day 28 was 31.1%. By multivariate analysis, independent predictors of day-28 mortality were: age (odds ratio [OR] 1.30/10 years, 95% confidence interval [CI] [1.01–1.68], p = 0.04), more than one line of chemotherapy (OR 2.14, 95% CI [1.08–4.21], p = 0.03), time between respiratory symptoms onset and ICU admission > 2 days (OR 2.50, 95% CI [1.25–5.02], p = 0.01), oxygen flow at admission (OR 1.07/L, 95% CI [1.00–1.14], p = 0.04) and extra-respiratory symptoms (OR 2.84, 95%CI [1.30–6.21], p = 0.01). After adjustment for the logistic organ dysfunction (LOD) score at admission, only time between respiratory symptoms onset and ICU admission > 2 days and LOD score were independently associated with day-28 mortality. Determinants of death include both factors non-amenable to change, and delay in ARF management. These results suggest that early intensive care management of patients with cancer with ARF may translate to better survival.

Acute Exacerbation of Idiopathic Pulmonary Fibrosis: Outcome and Prognostic Factors

Background: Acute exacerbation is a substantial cause of death in patients with idiopathic pulmonary fibrosis with poorly described prognostic factors. Objectives: To review the features associated with acute exacerbation of idiopathic pulmonary fibrosis and assess its prognostic factors. Methods: Thirty-seven occurrences of acute exacerbation of idiopathic pulmonary fibrosis were retrospectively reviewed in the medical records of 27 patients. Clinical presentation, radiographic studies, pulmonary function tests, laboratory data, treatment, and outcome were analyzed. Results: Acute exacerbation of idiopathic pulmonary fibrosis occurred more frequently between December and May (75.7%) than between June and November (24.3%) (p = 0.01). In-hospital mortality was 27% and median survival was 4.2 months (range 0.2–36.6). Significant differences between nonsurvivors and survivors included the time elapsed between their admission and the initiation of treatment for acute exacerbation (6 vs. 3.1 days, p = 0.04), lactate dehydrogenase levels at admission (801 vs. 544.6 IU/l, p = 0.002), impairment of the prior forced vital capacity (51.2 vs. 65%, p = 0.01) and diffusing capacity for carbon monoxide (21.7 vs. 34%, p = 0.01). Furthermore, the evolution of gas exchange in the first 10 days after the initiation of treatment was associated with in-hospital and long-term mortality. Conclusions: Acute exacerbations of idiopathic pulmonary fibrosis are more frequent during winter and spring. The time between admission and initiation of treatment is a new reported prognostic factor that should be investigated further. This finding highlights the need for a fast diagnostic approach that should probably be standardized. Early gas exchange modifications reflect the response to treatment and predict the prognosis.

Managing critically Ill hematology patients: Time to think differently.

The number of patients living with hematological malignancies (HMs) has increased steadily over time. This is the result of intensive and effective treatments that also increase the probability of infiltrative, infectious or toxic life threatening event. Over the last two decades, the number of patients with HMs admitted to the ICU increased and their mortality has dropped sharply. ICU patients with HMs require an extensive diagnostic workup and the optimal use of ICU treatments to identify the reason for ICU admission and the nature of the complication that explains organ dysfunctions. Mortality of ARDS or septic shock is up to 50%, respectively. In this review, the authors share their experience with managing critically ill patients with HMs. They discuss the main aspects of the diagnostic and therapeutic management of critically ill patients with HMs and argue that outcomes have improved over time and that many classic determinants of mortality have become irrelevant.

Endovascular Versus External Targeted Temperature Management for Patients With Out-of-Hospital Cardiac Arrest A Randomized, Controlled Study

Background— Targeted temperature management is recommended after out-of-hospital cardiac arrest. Whether advanced internal cooling is superior to basic external cooling remains unknown. The aim of this multicenter, controlled trial was to evaluate the benefit of endovascular versus basic surface cooling. Methods and Results— Inclusion criteria were the following: age of 18 to 79 years, out-of-hospital cardiac arrest related to a presumed cardiac cause, time to return of spontaneous circulation <60 minutes, delay between return of spontaneous circulation and inclusion <240 minutes, and unconscious patient after return of spontaneous circulation and before the start of cooling. Exclusion criteria were terminal disease, pregnancy, known coagulopathy, uncontrolled bleeding, temperature on admission <30°C, in-hospital cardiac arrest, immediate need for extracorporeal life support or hemodialysis. Patients were randomized between 2 cooling strategies: endovascular femoral devices (Icy catheter, Coolgard, Zoll, formerly Alsius; n=203) or basic external cooling using fans, a homemade tent, and ice packs (n=197). The primary end point, that is, favorable outcome evaluated by survival without major neurological damage (Cerebral Performance Categories 1–2) at day 28, was not significantly different between groups (odds ratio, 1.41; 95% confidence interval, 0.93–2.16; P=0.107). Improvement in favorable outcome at day 90 in favor of the endovascular group did not reach significance (odds ratio, 1.51; 95% confidence interval, 0.96–2.35; P=0.07). Time to target temperature (33°C) was significantly shorter and target hypothermia was more strictly maintained in the endovascular than in the surface group (P<0.001). Minor side effects directly related to the cooling method were observed more frequently in the endovascular group (P=0.009). Conclusion— Despite better hypothermia induction and maintenance, endovascular cooling was not significantly superior to basic external cooling in terms of favorable outcome. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00392639.