Interpretation of results of PCR and B-D-glucan for the diagnosis of Pneumocystis Jirovecii Pneumonia in immunocompromised adults with acute respiratory failure.

BACKGROUND: The accuracy of a diagnostic test depends on its intrinsic characteristics and the disease incidence. This study aims to depict post-test probability of Pneumocystis pneumonia (PJP), according to results of PCR and Beta-D-Glucan (BDG) tests in patients with acute respiratory failure (ARF). MATERIALS AND METHODS: Diagnostic performance of PCR and BDG was extracted from literature. Incidence of Pneumocystis pneumonia was assessed in a dataset of 2243 non-HIV immunocompromised patients with ARF. Incidence of Pneumocystis pneumonia was simulated assuming a normal distribution in 5000 random incidence samples. Post-test probability was assessed using Bayes theorem. RESULTS: Incidence of PJP in non-HIV ARF patients was 4.1% (95%CI 3.3-5). Supervised classification identified 4 subgroups of interest with incidence ranging from 2.0% (No ground glass opacities; 95%CI 1.4-2.8) to 20.2% (hematopoietic cell transplantation, ground glass opacities and no PJP prophylaxis; 95%CI 14.1-27.7). In the overall population, positive post-test probability was 32.9% (95%CI 31.1-34.8) and 22.8% (95%CI 21.5-24.3) for PCR and BDG, respectively. Negative post-test probability of being infected was 0.10% (95%CI 0.09-0.11) and 0.23% (95%CI 0.21-0.25) for PCR and BDG, respectively. In the highest risk subgroup, positive predictive value was 74.5% (95%CI 72.0-76.7) and 63.8% (95%CI 60.8-65.8) for PCR and BDG, respectively. CONCLUSION: Although both tests yield a high intrinsic performance, the low incidence of PJP in this cohort resulted in a low positive post-test probability. We propose a method to illustrate pre and post-test probability relationship that may improve clinician perception of diagnostic test performance according to disease incidence in predefined clinical settings.

Acute pulmonary embolism in cancer patients admitted to intensive care unit: Impact of anticoagulant treatment on 90-day mortality and risk factors, results of a multicentre retrospective study.

BACKGROUND: Acute pulmonary embolism (PE) is a life-threatening situation in cancer patients. In this situation, anticoagulant therapy is complex to administer due to the risk of bleeding. Only few studies have been conducted when these patients are admitted to the intensive care unit (ICU). The aim of this study was to assess the association between anticoagulation strategies as well as other factors with 90-day mortality in patients with cancer and PE admitted to ICU. Major bleeding was also evaluated according to the type of anticoagulation. METHODS: Retrospective study carried out in 4 ICUs in France over a 12-year period (2009-2021). All patients with cancer and PE were included. An overlap propensity score weighting analysis was performed in the subgroup of patients treated with either unfractionated heparins (UFH) alone or low-molecular-weight heparins (LMWH) alone on 90-day mortality and major bleeding. RESULTS: A total of 218 consecutive cancer patients admitted to ICU and presenting PE were included. The 90-day mortality rate was 42 % for the global cohort. After propensity score analysis in the subgroup of patients treated with either "UFH alone" (n = 80) or "LMWH alone" (n = 71), the 90-day mortality was similar in patients treated with UFH alone (42.6 %) vs LMWH alone (39.9 %): OR = 1.124, CI 95 % [0.571-2.214], p = 0.750. There was a significant increased toward major bleeding rates in the "UFH alone" group (25.5 %) as compared to "LMWH alone" group (11.5 %), p = 0.04. CONCLUSION: In 218 patients admitted to ICU and presenting PE, the 90-day mortality rate was 42 %. Treatment with UFH alone was associated with a mortality comparable to treatment with LMWH alone but it appeared to be more prone to major bleeding.

Association between arterial oxygen and mortality across critically ill patients with hematologic malignancies: results from an international collaborative network.

PURPOSE: Patients with hematological malignancies are at high risk for life-threatening complications. To date, little attention has been paid to the impact of hyperoxemia and excess oxygen use on mortality. The aim of this study was to investigate the association between partial pressure of arterial oxygen (PaO2) and 28-day mortality in critically ill patients with hematologic malignancies. METHODS: Data from three international cohorts (Europe, Canada, Oceania) of patients who received respiratory support (noninvasive ventilation, high-flow nasal cannula, invasive mechanical ventilation) were obtained. We used mixed-effect Cox models to investigate the association between day one PaO2 or excess oxygen use (inspired fraction of oxygen ≥ 0.6 with PaO2 > 100 mmHg) on day-28 mortality. RESULTS: 11,249 patients were included. On day one, 5716 patients (50.8%) had normoxemia (60 ≤ PaO2 ≤ 100 mmHg), 1454 (12.9%) hypoxemia (PaO2 < 60 mmHg), and 4079 patients (36.3%) hyperoxemia (PaO2 > 100 mmHg). Excess oxygen was used in 2201 patients (20%). Crude day-28 mortality rate was 40.6%. There was a significant association between PaO2 and day-28 mortality with a U-shaped relationship (p < 0.001). Higher PaO2 levels (> 100 mmHg) were associated with day-28 mortality with a dose-effect relationship. Subgroup analyses showed an association between hyperoxemia and mortality in patients admitted with neurological disorders; however, the opposite relationship was seen across those admitted with sepsis and neutropenia. Excess oxygen use was also associated with subsequent day-28 mortality (adjusted hazard ratio (aHR) [95% confidence interval (CI)]: 1.11[1.04-1.19]). This result persisted after propensity score analysis (matched HR associated with excess oxygen:1.31 [1.20-1.1.44]). CONCLUSION: In critically-ill patients with hematological malignancies, exposure to hyperoxemia and excess oxygen use were associated with increased mortality, with variable magnitude across subgroups. This might be a modifiable factor to improve mortality.

Severe infections requiring intensive care unit admission in patients receiving ibrutinib for hematological malignancies: a groupe de recherche respiratoire en réanimation onco-hématologique (GRRR-OH) study.

BACKGROUND: In the last decade, Ibrutinib has become the standard of care in the treatment of several lymphoproliferative diseases such as chronic lymphocytic leukemia (CLL) and several non-Hodgkin lymphoma. Beyond Bruton tyrosine kinase inhibition, Ibrutinib shows broad immunomodulatory effects that may promote the occurrence of infectious complications, including opportunistic infections. The infectious burden has been shown to vary by disease status, neutropenia, and prior therapy but data focusing on severe infections requiring intensive care unit (ICU) admission remain scarce. We sought to investigate features and outcomes of severe infections in a multicenter cohort of 69 patients receiving ibrutinib admitted to 10 French intensive care units (ICU) from 1 January 2015 to 31 December 2020. RESULTS: Median time from ibrutinib initiation was 6.6 [3-18] months. Invasive fungal infections (IFI) accounted for 19% (n = 13/69) of severe infections, including 9 (69%; n = 9/13) invasive aspergillosis, 3 (23%; n = 3/13) Pneumocystis pneumonia, and 1 (8%; n = 1/13) cryptococcosis. Most common organ injury was acute respiratory failure (ARF) (71%; n = 49/69) and 41% (n = 28/69) of patients required mechanical ventilation. Twenty (29%; n = 20/69) patients died in the ICU while day-90 mortality reached 55% (n = 35/64). In comparison with survivors, decedents displayed more severe organ dysfunctions (SOFA 7 [5-11] vs. 4 [3-7], p = 0.004) and were more likely to undergo mechanical ventilation (68% vs. 31%, p = 0.010). Sixty-three ibrutinib-treated patients were matched based on age and underlying malignancy with 63 controls receiving conventional chemotherapy from an historic cohort. Despite a higher median number of prior chemotherapy lines (2 [1-2] vs. 0 [0-2]; p < 0.001) and higher rates of fungal [21% vs. 8%, p = 0.001] and viral [17% vs. 5%, p = 0.027] infections in patients receiving ibrutinib, ICU (27% vs. 38%, p = 0.254) and day-90 mortality (52% vs. 48%, p = 0.785) were similar between the two groups. CONCLUSION: In ibrutinib-treated patients, severe infections requiring ICU admission were associated with a dismal prognosis, mostly impacted by initial organ failures. Opportunistic agents should be systematically screened by ICU clinicians in this immunocompromised population.

Characteristics and outcomes of patients with acute myeloid leukemia admitted to intensive care unit with acute respiratory failure: a post-hoc analysis of a prospective multicenter study.

BACKGROUND: Acute respiratory failure (ARF) is the leading cause of intensive care unit (ICU) admission in patients with Acute Myeloid Leukemia (AML) and data on prognostic factors affecting short-term outcome are needed. METHODS: This is a post-hoc analysis of a multicenter, international prospective cohort study on immunocompromised patients with ARF admitted to ICU. We evaluated hospital mortality and associated risk factors in patients with AML and ARF; secondly, we aimed to define specific subgroups within our study population through a cluster analysis. RESULTS: Overall, 201 of 1611 immunocompromised patients with ARF had AML and were included in the analysis. Hospital mortality was 46.8%. Variables independently associated with mortality were ECOG performance status ≥ 2 (OR = 2.79, p = 0.04), cough (OR = 2.94, p = 0.034), use of vasopressors (OR = 2.79, p = 0.044), leukemia-specific pulmonary involvement [namely leukostasis, pulmonary infiltration by blasts or acute lysis pneumopathy (OR = 4.76, p = 0.011)] and liver SOFA score (OR = 1.85, p = 0.014). Focal alveolar chest X-ray pattern was associated with survival (OR = 0.13, p = 0.001). We identified 3 clusters, that we named on the basis of the most frequently clinical, biological and radiological features found in each cluster: a "leukemic cluster", with high-risk AML patients with isolated, milder ARF; a "pulmonary cluster", consisting of symptomatic, highly oxygen-requiring, severe ARF with diffuse radiological findings in heavily immunocompromised patients; a clinical "inflammatory cluster", including patients with multi-organ failures in addition to ARF. When included in the multivariate analysis, cluster 2 and 3 were independently associated with hospital mortality. CONCLUSIONS: Among AML patients with ARF, factors associated with a worse outcome are related to patient's background (performance status, leukemic pulmonary involvement), symptoms, radiological findings, the need for vasopressors and the liver SOFA score. We identified three specific ARF syndromes in AML patients, which showed a prognostic significance and could guide clinicians to optimize management strategies.

Multiplex Polymerase Chain Reaction Assay to Detect Nasopharyngeal Viruses in Immunocompromised Patients With Acute Respiratory Failure.

BACKGROUND: In immunocompromised patients with acute respiratory failure (ARF), the clinical significance of respiratory virus detection in the nasopharynx remains uncertain. RESEARCH QUESTION: Is viral detection in nasopharyngeal swabs associated with causes and outcomes of ARF in immunocompromised patients? STUDY DESIGN AND METHODS: This preplanned post hoc analysis of a randomized controlled trial enrolled immunocompromised patients admitted to 32 ICUs for ARF between May 2016 and December 2017. Nasopharyngeal swabs sampled at inclusion were assessed for 23 respiratory pathogens using multiplex polymerase chain reaction (PCR) assay. Causes of ARF were established by managing physicians and were reviewed by three expert investigators masked to the multiplex PCR assay results. Associations between virus detection in nasopharyngeal swabs, causes of ARF, and composite outcome of day 28 mortality, invasive mechanical ventilation (IMV), or both were assessed. RESULTS: Among the 510 sampled patients, the multiplex PCR assay results were positive in 103 patients (20.2%), and a virus was detected in 102 samples: rhinoviruses or enteroviruses in 35.5%, coronaviruses in 10.9%, and flu-like viruses (influenza virus, parainfluenza virus, respiratory syncytial virus, human metapneumovirus) in 52.7%. The cause of ARF varied significantly according to the results of the multiplex PCR assay, especially the proportion of viral pneumonia: 50.0% with flu-like viruses, 14.0% with other viruses, and 3.6% when no virus was detected (P < .001). No difference was found in the composite outcome of day 28 mortality, IMV, or both according to positive assay findings (54.9% vs 54.7%; P = .965). In a pre-established subgroup analysis, flu-like virus detection was associated with a higher rate of day 28 mortality, IMV, or both among recipients of allogeneic hematopoietic stem cell transplantation compared with those without detected virus. INTERPRETATION: In immunocompromised patients with ARF, the results of nasopharyngeal multiplex PCR assays are not associated with IMV or mortality. A final diagnosis of viral pneumonia is retained in one-third of patients with positive assay results and in one-half of the patients with a flu-like virus.

Etiologies and Outcome of Patients with Solid Tumors Admitted to ICU with Acute Respiratory Failure: A Secondary Analysis of the EFRAIM Study.

BACKGROUND: Acute respiratory failure (ARF) remains the most frequent reason for ICU admission in patients who are immunocompromised. This study reports etiologies and outcomes of ARF in subjects with solid tumors. METHODS: This study was a post hoc analysis of the EFRAIM study, a prospective multinational cohort study that included 1611 subjects who were immunocompromised and with ARF admitted to the ICU. Subjects with solid tumors admitted to the ICU with ARF were included in the analysis. RESULTS: Among the subjects from the EFRAIM cohort, 529 subjects with solid tumors (32.8%) were included in the analysis. At ICU admission, the median (interquartile range) Sequential Organ Failure Assessment score was 5 (3-9). The types of solid tumor were mostly lung cancer (n = 111, 21%), breast cancer (n = 52, 9.8%), and digestive cancer (n = 47, 8.9%). A majority, 379 subjects (71.6%) were full code at ICU admission. The ARF was caused by bacterial or viral infection (n = 220, 41.6%), extrapulmonary sepsis (n = 62, 11.7%), or related to cancer or treatment toxicity (n = 83, 15.7%), or fungal infection (n = 23, 4.3%). For 63 subjects (11.9%), the ARF etiology remained unknown after an extensive diagnostic workup. The hospital mortality rate was 45.7% (n = 232/508). Hospital mortality was independently associated with chronic cardiac failure (odds ratio 1.78, 95% CI 1.09-2.92; P = .02), lung cancer (odds ratio 2.50, 95% CI 1.51-4.19; P < .001), day 1 Sequential Organ Failure Assessment score (odds ratio 1.97, 95% CI 1.32-2.96; P < .001). ARF etiologies other than infectious, related to cancer, or treatment toxicity were associated with better outcomes (odds ratio 0.32, 95% CI 0.16-0.61; P < .001). CONCLUSIONS: Infectious diseases remained the most frequent cause of ARF in subjects with solid tumors admitted to the ICU. Hospital mortality was related to severity at ICU admission, previous comorbidities, and ARF etiologies related to non-malignant causes or pulmonary embolism. Lung tumor was also independently associated with higher mortality.

ICU admission for solid cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICI) have revolutionized the management of cancer. They can induce immune-related adverse events (irAE) leading to intensive care unit (ICU) admission. We aimed to describe irAEs for ICU admissions in solid cancer patients treated with ICIs. METHODS: This prospective multicenter study was conducted in France and Belgium. Adult patients with solid tumor and treated with systemic ICIs within the last 6 months, requiring non-programmed ICU admission were included. Patients admitted for microbiologically documented sepsis were excluded. Imputability of irAEs in ICU admissions was described according to the WHO-UMC classification system at ICU admission and at ICU discharge. The use of immunosuppressant treatment was reported. RESULTS: 115 patients were eligible. Solid tumor was mainly lung cancer (n = 76, 66%) and melanoma (n = 18, 16%). They were mainly treated with an anti-PD-(L)1 alone (n = 110, 96%). Main ICU admission reasons were acute respiratory failure (n = 66, 57%), colitis (n = 14, 13%), and cardiovascular disease (n = 13, 11%). ICU admission was considered "likely" associated with irAE for 48% (n = 55) of patients. Factors independently associated with irAE were a good ECOG performance status (PS) (ECOG-PS of 0 or 1 vs. ECOG-PS of 2-3, odds ratio [OR] = 6.34, 95% confidence interval [95% CI] 2.13-18.90, and OR = 3.66, 95% CI 1.33-10.03, respectively), and a history of irAE (OR = 3.28, 95% CI 1.19-9.01). Steroids were prescribed for 41/55 (75%) patients with ICU admission "likely" related to irAE. Three patients were subsequently treated with immunosuppressants. CONCLUSION: IrAEs accounted for half of ICU admissions in cancer patients receiving ICIs. They could be treated with steroids. Identifying the imputability of irAEs in ICU admissions remains a challenge.

Outcome of patients with newly diagnosed AML admitted to the ICU, including preemptive admission - a multi-center study.

Acute myeloid leukemia (AML) can lead to life-threatening complications that may require intensive care unit (ICU) management. It has been advocated that early preemptive (ePE) ICU admission, before the onset of organ failure, could benefit some high-risk patients such as those with hyperleukocytosis. The aim of this study was to retrospectively analyze the outcome of newly diagnosed AML patients who required ICU admission in five academic centers with a special focus on patients with an ePE admission strategy, i.e., those transferred to the ICU without any organ failure (modified SOFA score ≤ 2 [omitting thrombocytopenia] and no life-sustaining intervention in the first 24 h following ICU admission) before the start of induction therapy. Between January 2017 and December 2019, 428 patients were included among which 101 were admitted to the ICU. Among patients requiring life-sustaining interventions (n = 83), 18 (22%) died while in the ICU but ICU survivors had the same survival as those not admitted to the ICU. Patients with an ePE admission (n = 18) had more comorbidities and high-risk disease features such as hyperleukocytosis but required no life-sustaining interventions while in the ICU. In a subgroup analysis of patients with hyperleukocytosis ≥ 50 G/l at diagnosis (n = 85), patients not admitted to the ICU and those admitted with an ePE strategy had similar outcomes. This study provides encouraging results about ICU outcome in AML patients during induction therapy but the potential benefit of an ePE strategy must be confirmed prospectively.

Impact of a strategy based on unique blood culture sampling on contamination rate and detection of bloodstream infections in critically ill patients.

BACKGROUND: Unique blood culture (UBC) has been proposed to limit the number of venipuncture and to decrease the risk of BC contaminations (BCC) without affecting their yield. We hypothesized that a multi-faceted program based on UBC in the ICU may reduce the rate of contaminants with a similar performance for bloodstream infections (BSI) identification. METHODS: In a before and after design, we compared the proportion of BSI and BCC. A first 3-year period with multi-sampling (MS) strategy followed by a 4-month washout period, where staff received education and training for using UBC, and a 32-month period, where UBC was routinely used, while education and feedback were maintained. During the UBC period, a large volume of blood (40 mL) was sampled through a unique venipuncture with additional BC collections discouraged for 48 h. RESULTS: Of the 4,491 patients included (35% female patients, mean age 62 years) 17,466 BC were collected. The mean volume of blood per bottle collected increased from 2.8 ± 1.8 mL to 8.2 ± 3.9 mL between the MS and UBC periods, P < 0.01. A 59.6% reduction (95% CI 56.7-62.3; P < 0.001) of BC bottles collected per week was observed between the MS and UBC periods. The rate of BCC per patient decreased between the two periods from 11.2% to 3.8% (73.4% reduction; P < 0.001) for the MS and UBC periods, P < 0.001. Meanwhile, the rate of BSI per patient remained stable at 13.2% and 13.2% for the MS and UBC periods, P = 0.98. CONCLUSIONS: In ICU patients, a strategy based on UBC reduces the contamination rate of cultures without affecting their yield.

Sepsis-associated coagulopathy in onco-hematology patients presenting with thrombocytopenia: a multicentric observational study.

Coagulation disorders increase mortality rate during septic shock, but the impact of concomitant hematological malignancies remains unknown. The study assessed coagulation disorders in onco-hematological patients with thrombocytopenia (<100 G/L) admitted to ICU for septic shock. Among 146 included patients, 50 patients had lymphoma and 49 patients had acute leukemia. ICU mortality rate was 43.8% (n = 64). Median increase in prothrombin time (PT) at day(d) 1 was 4.7 s (IQR 3.2-7.9) in ICU survivors vs. 6.4 s (IQR 4.5-13.7; p < 0.01) in non-survivors. Fibrinogen kinetics (increase in fibrinogen levels between d1 and d2) was +0.55 (-0.22-1.55) vs. +0.10 g/L (-0.40-0.50; p = 0.03) in surviving and non-surviving patients, respectively. PT increase ≥6 s at d1 (OR 5.5; 95% CI 1.1-6.0; p = 0.03) and mechanical ventilation (OR 7.4; 95% CI 3.3-17.7; p < 0.001) were independently associated with ICU mortality. This study provides information and new ways to identify hematological patients with high-risk mortality.

End of life decisions in immunocompromised patients with acute respiratory failure.

PURPOSE: To identify patient, disease and organizational factors associated with decisions to forgo life-sustaining therapies (DFLSTs) in critically ill immunocompromised patients admitted to the intensive care unit (ICU) for acute respiratory failure. MATERIAL AND METHODS: We performed a secondary analysis of the international EFRAIM prospective study, which enrolled 1611 immunocompromised patients with acute respiratory failure admitted to 68 ICUs in 16 countries between October 2015 and June 2016. Multivariate logistic analysis was performed to identify independent predictors of DFLSTs. RESULTS: The main causes of immunosuppression were hematological malignancies (50%) and solid tumor (38%). Patients had a median age of 63 yo (54-71). A pulmonologist was involved in the patient management in 38% of cases. DFLSTs had been implemented in 28% of the patients. The following variables were independently associated with DFLSTs: 1) patient-related: older age (OR 1.02 per one year increase, 95% confidence interval(CI) 1.01-1.03,P < 0.001), poor performance status (OR 2.79, 95% CI 1.98-3.93, P < 0.001); 2) disease-related: shock (OR 2.00, 95% CI 1.45-2.75, P < 0.001), liver failure (OR 1.59, 95% CI 1.14-2.21, P = 0.006), invasive mechanical ventilation (OR 1.79, 95% CI 1.31-2.46, P < 0.001); 3) organizational: having a pulmonologist involved in patient management (OR 1.85, 95% CI 1.36-2.52, P < 0.001), and the presence of a critical care outreach services (OR 1.63, 95% CI 1.11-2.38, P = 0.012). CONCLUSIONS: A DFLST is made in one in four immunocompromised patient admitted to the ICU for acute respiratory failure. Involving a pulmonologist in patient's management is associated with less non beneficial care.

Serum phosphate level and its kinetic as an early marker of acute kidney injury in tumor lysis syndrome.

INTRODUCTION: Acute kidney injury (AKI) is a major cause of mortality in tumor lysis syndrome. The biochemical parameters and kinetics of tumor lysis syndrome remain poorly described. Particularly, whether blood serum phosphate variations may help in the identification and management of patients who will eventually develop AKI remains to be studied. METHODS: In this retrospective study, we included patients with tumor lysis syndrome episodes without AKI at diagnosis, and analyzed serum phosphate kinetic, clinical and tumor lysis syndrome biochemical variables to identify factors associated with AKI onset, and determine threshold values of phosphatemia associated with AKI development. RESULTS: One hundred thirty tumor lysis syndrome episodes occurred in 120 patients during an 11-year period at the University Hospital of Angers. AKI developed in 56 tumor lysis syndrome episodes. In multivariable analysis, among the analyzed factors, only an increase in serum phosphate levels (before AKI diagnosis), exposure to platinum salts and an increase in LDH levels were associated with AKI development. Before AKI onset, a serum phosphate cut-off of 2.1 mmol/L was not effective in predicting AKI development (sensitivity 48%, specificity 84%, area under the receiver operating characteristic curve (AUC) 0.63 [0.52-0.74]). No other biochemical parameters were effective to better predict AKI occurrence. CONCLUSION: This work suggests that increases in serum phosphate and LDH appear to be early and reliable biomarkers of AKI in tumor lysis syndrome. No valuable threshold value of serum phosphate was found to effectively predict AKI. This work is the basis for further prospective controlled studies on phosphate monitoring and phosphate lowering therapies to prevent AKI during tumor lysis syndrome.

Bacteremia in critically ill immunocompromised patients with acute hypoxic respiratory failure: A post-hoc analysis of a prospective multicenter multinational cohort.

PURPOSE: The characteristics and impact of bacteremia have not been widely investigated in immunocompromised patients with acute respiratory failure (ARF). METHODS: We performed a secondary analysis of a prospective cohort of immunocompromised patients with ARF (EFRAIM study). After exclusion of blood cultures positive for coagulase negative Staphylococci, we compared patients with (n = 236) and without (n = 1127) bacteremia. RESULTS: The incidence of bacteremia was 17%. Bacterial pneumonia and extra-pulmonary ARDS were the main causes of ARF in bacteremic patients. Bacteremia involved gram negative rods (48%), gram positive cocci (40%) or were polymicrobial (10%). Bacteremic patients had more hematological malignancy, higher SOFA scores and increased organ support within 7 days. Bacteremia was associated with higher crude ICU mortality (40% versus 32%, p = 0.02), but neither hospital (49% versus 44%, p = 0.17) nor 90-day mortality (60% versus 56%, p = 0.25) were different from non-bacteremic patients. After propensity score matching based on baseline characteristics, the difference in ICU mortality lost statistical significance (p = 0.06), including in a sensitivity analysis restricted to patients with pneumonia. CONCLUSIONS: We analyzed a large population of immunocompromised patients with ARF and an incidence of bacteremia of 17%. We could not demonstrate an impact of bacteremia on mortality after adjusting for baseline characteristics.

Sinusoidal Obstruction Syndrome in Critically Ill Patients in the Era of Defibrotide: A Retrospective Multicenter Study.

Sinusoidal obstruction syndrome (SOS) is a life-threatening liver complication of high- dose chemotherapy. Defibrotide is the only available therapeutic option approved for SOS. The prognosis of SOS in patients requiring intensive care unit (ICU) admission remains unknown. The primary objective of this study was to assess the outcome of SOS patients in ICU. This retrospective study was conducted between 2007 and 2019 in 13 French ICUs. Seventy-one critically ill adult patients with SOS defined according to European Society for Blood and Marrow Transplantation criteria and treated with defibrotide were included. The main reasons for ICU admission were respiratory failure and acute kidney injury. Mechanical ventilation, vasopressors, and renal replacement therapy were required in 59%, 52%, and 49% of patients, respectively. Twenty-three percent of patients experienced a bleeding event during defibrotide treatment. Hospital mortality was 54%, mainly related to multiorgan failure. Older age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00 to 1.04), mechanical ventilation (HR, 1.99; 95% CI, 1.00 to 3.99), renal replacement therapy (HR, 2.55; 95% CI, 1.32 to 4.91) were independent predictors of hospital mortality. Defibrotide prophylaxis (HR, 0.35; 95% CI, 0.13 to 0.92) was associated with better outcomes. Critically ill patients with SOS have a high mortality rate in the ICU, especially if organ support is required. Additional studies assessing the impact of defibrotide prophylaxis are warranted.

Hepatic dysfunction impairs prognosis in critically ill patients with hematological malignancies: A post-hoc analysis of a prospective multicenter multinational dataset.

PURPOSE: Hyperbilirubinemia is frequent in patients with hematological malignancies admitted to the intensive care unit (ICU). Literature about hepatic dysfunction (HD) in this context is scarce. METHODS: We investigated the prognostic impact of HD analyzing a prospective multicenter cohort of 893 critically ill hematology patients. Two groups were defined: patients with HD (total bilirubin ≥33 µmol/L at ICU admission) and patients without HD. RESULTS: Twenty one percent of patients were found to have HD at ICU admission. Cyclosporine, antimicrobials before ICU admission, abdominal symptoms, ascites, history of liver disease, neutropenia, increased serum creatinine and myeloma were independently associated with HD. Etiology remained undetermined in 73% of patients. Hospital mortality was 56.3% and 36.3% respectively in patients with and without HD (p < 0.0001). Prognostic factors independently associated with hospital mortality in HD group were, performance status >1 (OR = 2.07, 95% CI = 1.49-2.87, p < 0.0001), invasive mechanical ventilation (OR = 3.92, 95% CI = 2.69-5.71, p < 0.0001), renal replacement therapy (OR = 1.74, 95% CI = 1.22-2.47, p = 0.002), vasoactive drug (OR = 1.81, 95% CI = 1.21-2.71, p = 0.004) and SOFA score without bilirubin level at ICU admission (OR = 1.09, 95% CI = 1.04-1.14, p < 0.0001). CONCLUSIONS: HD is common, underestimated, infrequently investigated, and is associated with impaired outcome in critically ill hematology patients. HD should be considered upon ICU admission and managed as other organ dysfunctions.

Impact of early ICU admission for critically ill cancer patients: Post-hoc analysis of a prospective multicenter multinational dataset.

OBJECTIVES: Early intensive care unit (ICU) admission, in Critically Ill Cancer Patients (CICP), is believed to have contributed to the prognostic improvement of critically ill cancer patients. The primary objective of this study was to assess the association between early ICU admission and hospital mortality in CICP. DESIGN: Retrospective analysis of a prospective multicenter dataset. Early admission was defined as admission in the ICU < 24 h of hospital admission. We assessed the association between early ICU admission and hospital mortality in CICP via survival analysis and propensity score matching. RESULTS: Of the 1011patients in our cohort, 1005 had data available regarding ICU admission timing and were included. Overall, early ICU admission occurred in 455 patients (45.3%). Crude hospital mortality in patients with early and delayed ICU admission was 33.6% (n = 153) vs. 43.1% (n = 237), respectively (P = 0.02). After adjustment for confounders, early compared to late ICU admission was not associated with hospital mortality (HR 0.92; 95%CI 0.76-1.11). After propensity score matching, hospital mortality did not differ between patients with early (35.2%) and late (40.6%) ICU admission (P = 0.13). In the matched cohort, early ICU admission was not associated with mortality after adjustment on SOFA score (HR 0.89; 95%CI 0.71-1.12). Similar results were obtained after adjustment for center effect. CONCLUSION: In this cohort, early ICU admission was not associated with a better outcome after adjustment for confounder and center effect. The uncertainty with regard to the beneficial effect of early ICU on hospital mortality suggests the need for an interventional study.

Sepsis and Septic Shock in Patients With Malignancies: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique Study.

OBJECTIVES: Cancer affects up to 20% of critically ill patients, and sepsis is one of the leading reasons for ICU admission in this setting. Early signals suggested that survival might be increasing in this population. However, confirmation studies have been lacking. The goal of this study was to assess trends in survival rates over time in cancer patients admitted to the ICU for sepsis or septic shock over the last 2 decades. DATA SOURCE: Seven European ICUs. STUDY SELECTION: A hierarchical model taking into account the year of admission and the source dataset as random variables was used to identify risk factors for day 30 mortality. DATA EXTRACTION: Data from cancer patients admitted to ICUs for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique database (1994-2015). DATA SYNTHESIS: Overall, 2,062 patients (62% men, median [interquartile range] age 59 yr [48-67 yr]) were included in the study. Underlying malignancies were solid tumors (n = 362; 17.6%) or hematologic malignancies (n = 1,700; 82.4%), including acute leukemia (n = 591; 28.7%), non-Hodgkin lymphoma (n = 461; 22.3%), and myeloma (n = 244; 11.8%). Two-hundred fifty patients (12%) underwent allogeneic hematopoietic stem cell transplantation and 640 (31.0%) were neutropenic at ICU admission. Day 30 mortality was 39.9% (823 deaths). The year of ICU admission was associated with significant decrease in day 30 mortality over time (odds ratio, 0.96; 95% CI, 0.93-0.98; p = 0.001). Mechanical ventilation (odds ratio, 3.25; 95% CI, 2.52-4.19; p < 0.01) and vasopressors use (odds ratio, 1.42; 95% CI, 1.10-1.83; p < 0.01) were independently associated with day 30 mortality, whereas underlying malignancy, allogeneic hematopoietic stem cell transplantation, and neutropenia were not. CONCLUSIONS: Survival in critically ill oncology and hematology patients with sepsis improved significantly over time. As outcomes improve, clinicians should consider updating admission policies and goals of care in this population.

Pasteurella bacteraemia: Impact of comorbidities on outcome, based on a case series and literature review.

OBJECTIVES: Pasteurella bacteraemia is rare, but has been associated with a high mortality rate. The aim of this study was to estimate the impact of comorbidities on patients with Pasteurella bacteraemia. METHODS: All cases of Pasteurella bacteraemia in adults treated in our centre between January 2008 and December 2017 were included retrospectively and compared with cases identified in a systematic review of the literature via MEDLINE covering the years 1951-2017. The epidemiological, bacteriological, and clinical data were collected, as well as the instances of death after 30 days. RESULTS: Twenty cases of Pasteurella bacteraemia identified in our centre and 99 cases from the literature review were included. A major comorbidity was found in 80/119 (67.2%) patients. The death rate at 30 days was 31.1%. The most common comorbidities were cirrhosis, immunosuppressive therapy, and malignant diseases. Age was not associated with mortality. On multivariate analysis, the only factor associated with mortality was a major comorbidity (odds ratio 2.78, 95% confidence interval 1.01-7.70; p = 0.04). CONCLUSIONS: This study confirms the high mortality rate and highlights the importance of the host background, independent of age, in Pasteurella bacteraemia. Clinicians should be aware of the comorbidities in cases of Pasteurella infection, due to the poor prognosis of bacteraemia.