Immediate vs. culture-initiated antibiotic therapy in suspected non-severe ventilator-associated pneumonia: a before-after study (DELAVAP).

BACKGROUND: Ventilator-associated pneumonia (VAP) is the leading nosocomial infection in critical care and is associated with adverse outcomes. When VAP is suspected, starting antibiotic therapy (AT) immediately after pulmonary sampling may expose uninfected patients to unnecessary treatment, whereas waiting for bacteriological confirmation may delay AT in infected patients. As no robust data exist to choose between these strategies, the decision must balance the pre-test diagnostic probability, clinical severity, and risk of antimicrobial resistance. The objective of this study in patients with suspected non-severe VAP was to compare immediate AT started after sampling to conservative AT upon receipt of positive microbiological results. The outcomes were antibiotic sparing, AT suitability, and patient outcomes. METHODS: This single-center, before-after study included consecutive patients who underwent distal respiratory sampling for a first suspected non-severe VAP episode (no shock requiring vasopressor therapy or severe acute respiratory distress syndrome). AT was started immediately after sampling in 2019 and upon culture positivity in 2022 (conservative strategy). The primary outcome was the number of days alive without AT by day 28. The secondary outcomes were mechanical ventilation duration, day-28 mortality, and AT suitability (active necessary AT or spared AT). RESULTS: The immediate and conservative strategies were applied in 44 and 43 patients, respectively. Conservative and immediate AT were associated with similar days alive without AT (median [interquartile range], 18.0 [0-21.0] vs. 16.0 [0-20.0], p = 0.50) and without broad-spectrum AT (p = 0.53) by day 28. AT was more often suitable in the conservative group (88.4% vs. 63.6%, p = 0.01), in which 27.9% of patients received no AT at all. No significant differences were found for mechanical ventilation duration (median [95%CI], 9.0 [6-19] vs. 9.0 [6-24] days, p = 0.65) or day-28 mortality (hazard ratio [95%CI], 0.85 [0.4-2.0], p = 0.71). CONCLUSION: In patients with suspected non-severe VAP, waiting for microbiological confirmation was not associated with antibiotic sparing, compared to immediate AT. This result may be ascribable to low statistical power. AT suitability was better with the conservative strategy. None of the safety outcomes differed between groups. These findings would seem to allow a large, randomized trial comparing immediate and conservative AT strategies.

Features and outcomes of patients admitted to the ICU for chimeric antigen receptor T cell-related toxicity: a French multicentre cohort.

BACKGROUND: Chimeric antigen receptor T-cell (CAR-T) therapy is increasingly used in patients with refractory haematological malignancies but can induce severe adverse events. We aimed to describe the clinical features and outcomes of patients admitted to the intensive care unit (ICU) after CAR-T therapy. METHODS: This retrospective observational cohort study included consecutive adults admitted to either of two French ICUs in 2018-2022 within 3 months after CAR-T therapy. RESULTS: Among 238 patients given CAR-T therapy, 84 (35.3%) required ICU admission and were included in the study, a median of 5 [0-7] days after CAR-T infusion. Median SOFA and SAPSII scores were 3 [2-6] and 39 [30-48], respectively. Criteria for cytokine release syndrome were met in 80/84 (95.2%) patients, including 18/80 (22.5%) with grade 3-4 toxicity. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 46/84 (54.8%) patients, including 29/46 (63%) with grade 3-4 toxicity. Haemophagocytic lymphohistiocytosis was diagnosed in 15/84 (17.9%) patients. Tocilizumab was used in 73/84 (86.9%) patients, with a median of 2 [1-4] doses. Steroids were given to 55/84 (65.5%) patients, including 21/55 (38.2%) given high-dose pulse therapy. Overall, 23/84 (27.4%) patients had bacterial infections, 3/84 (3.6%) had fungal infections (1 invasive pulmonary aspergillosis and 2 Mucorales), and 2 (2.4%) had cytomegalovirus infection. Vasopressors were required in 23/84 (27.4%), invasive mechanical ventilation in 12/84 (14.3%), and dialysis in 4/84 (4.8%) patients. Four patients died in the ICU (including 2 after ICU readmission, i.e., overall mortality was 4.8% of patients). One year after CAR-T therapy, 41/84 (48.9%) patients were alive and in complete remission, 14/84 (16.7%) were alive and in relapse, and 29/84 (34.5%) had died. These outcomes were similar to those of patients never admitted to the ICU. CONCLUSION: ICU admission is common after CAR-T therapy and is usually performed to manage specific toxicities. Our experience is encouraging, with low ICU mortality despite a high rate of grade 3-4 toxicities, and half of patients being alive and in complete remission at one year.

Clinical features and outcomes of patients admitted to the ICU for Cyclophosphamide-associated cardiac toxicity: a retrospective cohort.

PURPOSE: To describe the management and outcome of critically-ill patients with Cyclophosphamide (CY)-associated cardiac toxicity. METHODS: All patients admitted to the intensive care units (ICUs) of the Nantes and Rennes University Hospitals for a CY-associated cardiac toxicity between January 2015 and December 2020 were included. RESULTS: Of the thirty-four patients included in the study, twenty-four (70%) underwent allogeneic hematopoietic stem cell transplantation (HSCT), four (12%) autologous HSCT, and six (18%) chemotherapy for hematological malignancies. Acute pulmonary edema (65%), cardiac arrest (9%), and cardiac arrhythmia (6%) were the most common reasons for ICU admission. Patients were admitted to the ICU 6.5 (4-12) days after the intravenous administration of a median dose of CY of 100 [60-101] mg/Kg. Echocardiographic findings showed moderate to severe left ventricular systolic dysfunction (69%) and pericardial effusion (52%). Eighteen (53%) patients ultimately developed cardiogenic shock and required vasopressors (47%) and/or inotropes (18%). Invasive mechanical ventilation and renal replacement therapy were required in twenty (59%) and five (14%) patients, respectively. Sixteen (47%) patients died of whom 12 (35.3%) died from refractory cardiogenic shock. The left ventricular ejection fraction improved over time in most survivors with a median time until full recovery of 33 (12-62) days. Two (11%) patients had a persistent left ventricular dysfunction at 6 months. CONCLUSION: Refractory cardiogenic shock is the primary cause of death of patients with severe CY-related cardiotoxicity. Nonetheless, the cardiac function of most survivors recovered within a month.

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.

Outcomes of patients admitted to the ICU for acute stroke: a retrospective cohort.

BACKGROUND: Although acute stroke is a leading cause of morbidity and mortality worldwide, data on outcomes of stroke patients requiring ICU admission are limited. We aimed to identify factors associated with a good neurological outcome (defined as a modified Rankin Scale score [mRS] of 0-2) 6 months after ICU admission. METHODS: We retrospectively studied consecutive patients who were admitted to the ICU of a French university-affiliated hospital between January 2014 and December 2018 and whose ICD-10 code indicated acute stroke. Patients with isolated subarachnoid hemorrhage or posttraumatic stroke were excluded. RESULTS: The 323 identified patients had a median age of 67 [54.5-77] years; 173 (53.6%) were male. The main reasons for ICU admission were neurological failure (87%), hemodynamic instability (28.2%), acute respiratory failure (26%), and cardiac arrest (5.3%). At ICU admission, the Glasgow Coma Scale score was 6 [4-10] and the SAPSII was 54 [35-64]. The stroke was hemorrhagic in 248 (76.8%) patients and ischemic in 75 (23.2%). Mechanical ventilation was required in 257 patients (79.6%). Six months after ICU admission, 61 (19.5%) patients had a good neurological outcome (mRS, 0-2), 50 (16%) had significant disability (mRS, 3-5), and 202 (64.5%) had died; 10 were lost to follow-up. By multivariable analysis, factors independently associated with not having an mRS of 0-2 at 6 months were older age (odds ratio, 0.93/year; 95% confidence interval, 0.89-0.96; P < 0.01) and lower Glasgow Coma Scale score at ICU admission (odds ratio, 1.23/point; 95% confidence interval, 1.07-1.40; P < 0.01). CONCLUSIONS: Acute stroke requiring ICU admission carried a poor prognosis, with less than a fifth of patients having a good neurological outcome at 6 months. Age and depth of coma independently predicted the outcome.

Extensive myelitis with eosinophilic meningitis after Chimeric antigen receptor T cells therapy.

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent adverse event after Chimeric antigen receptor T cells (CAR-T cells). A patient treated with anti-CD19 CAR-T cells for a refractory mantle cell lymphoma presented at Day 8 post-infusion with extensive myelitis. Unusual eosinophilia was disclosed in the patient's cerebrospinal fluid. After treatment with methylprednisolone and siltuximab, a decrease in clinical symptoms and magnetic resonance imaging lesions were obtained. This unprecedented presentation of eosinophilic meningitis after CAR-T cells therapy highlights the need for a better understanding of the physiopathology of ICANS, especially to identify potentially targetable pathways.

When targeted therapy for cancer leads to ICU admission. RETRO-TARGETICU multicentric study.

PURPOSE: To study prevalence of targeted therapy (TT)-related adverse events requiring ICU admission in solid tumor patients. METHODS: Retrospective multicenter study from the Nine-i research group. Adult patients who received TT for solid tumor within 3 months prior to ICU admission were included. Patients admitted for TT-related adverse event were compared to those admitted for other reasons. RESULTS: In total, 140 patients, median age of 63 (52-69) years were included. Primary cancer site was mostly digestive (n=27, 19%), kidney (n=27, 19%), breast (n=24, 17%), and lung (n=20, 14%). Targeted therapy was anti-VEGF/VEGFR for 27% (n=38) patients, anti-EGFR for 22% (n=31) patients, anti-HER2 for 14% (n=20) patients and anti-BRAF for 9% (n=5) patients. ICU admission was related to TT adverse events for 30 (21%) patients. The most frequent complications were interstitial pneumonia (n=7), cardiac failure (n=5), anaphylaxis (n=4) and bleeding (n=4). At ICU admission, no significant difference was found between patients admitted for a TT-related adverse event and the other patients. One-month survival rate was higher in patients admitted for TT adverse event (OR=5.733 [2.031-16.182] P<0.001). CONCLUSIONS: Adverse events related to targeted therapy accounted for 20% of ICU admission in our population and carried a 16% one-month mortality. Outcome was associated with admission for TT related to adverse event, breast cancer and good performance status.

Dramatic Recovery after Etoposide Phosphate Infusion for Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome following Treatment with Tisagenlecleucel in a Young Patient with Relapsed Acute Lymphoblastic Leukemia: A Case Report.

The occurrence of a secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) after CAR T-cell infusion is very rare and mostly fatal. Treatment recommendations for such a complication are not yet established. Here, we report the dramatic recovery of HLH/MAS following tisagenlecleucel infusion in a young patient with relapsed acute lymphoblastic leukemia using etoposide phosphate (EP). We propose that monitoring for the occurrence of HLH/MAS should be part of surveillance after CAR T-cell infusion and that EP treatment appears to be useful to control this severe and rare complication.

Alcohol withdrawal syndrome in ICU patients: Clinical features, management, and outcome predictors.

BACKGROUND: Alcohol withdrawal syndrome (AWS) is a common condition in hospitalized patients, yet its epidemiology in the ICU remains poorly characterized. METHODS: Retrospective cohort of patients admitted to the Nantes University Hospital ICU between January 1, 2017, and December 31, 2019, and coded for AWS using ICD-10 criteria. The objective of the study was to identify factors associated with complicated hospital stay defined as ICU length of stay ≥7 days or hospital mortality. RESULTS: Among 5,641 patients admitted to the ICU during the study period, 246 (4.4%) were coded as having AWS. Among them, 42 had exclusion criteria and 204 were included in the study. The three main reasons for ICU admission were sepsis (29.9%), altered consciousness (29.4%), and seizures (24%). At ICU admission, median Cushman's score was 6 [4-9] and median SOFA score was 3 [2-6]. Delirium tremens occurred in half the patients, seizures in one fifth and pneumonia in one third. Overall, 48% of patients developed complicated hospital stay, of whom 92.8% stayed in the ICU for ≥7 days, 36.7% received MV for ≥7 days, and 16.3% died during hospital stay. By multivariable analysis, two factors were associated with complicated hospital stay: a higher number of organ dysfunctions at ICU admission was associated with a higher risk of complicated hospital stay (OR, 1.18; 95CI, 1.05-1.32, P = 0.005), whereas ICU admission for seizures was associated with a lower risk of complicated hospital stay (OR, 0.14; 95%CI, 0.026-0.80; P = 0.026). CONCLUSIONS: AWS in ICU patients chiefly affects young adults and is often associated with additional factors such as sepsis, trauma, or surgery. Half the patients experienced an extended ICU stay or death during the hospital stay. The likelihood of developing complicated hospital stay relied on the reason for ICU admission and the number of organ dysfunctions at ICU admission.

Deleterious neurological impact of diagnostic delay in immune-mediated thrombotic thrombocytopenic purpura.

BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare life-threatening thrombotic microangiopathy requiring urgent therapeutic plasma exchange (TPE). However, the exact impact of a slight delay in TPE initiation on the subsequent patients' outcome is still controversial. AIM: We aimed to study the frequency, short-term neurological consequences, and determinants of diagnostic delay in iTTP. METHODS: We conducted a retrospective monocentric study including patients with a first acute episode of iTTP (2005-2020) classified into 2 groups: delayed (>24h from first hospital visit, group 1) and immediate diagnosis (≤24h, group 2). RESULTS: Among 42 evaluated patients, 38 were included. Eighteen cases (47%) had a delayed diagnosis (median: 5 days). The main misdiagnosis was immune thrombocytopenia (67%). The mortality rate was 5% (1 death in each group). Neurological events (stroke/TIA, seizure, altered mental status) occurred in 67% vs 30% patients in group 1 and 2, respectively (p = 0.04). Two patients in group 1 exhibited neurological sequelae. The hospital length of stay was longer in group 1 (p = 0.02). At the first hospital evaluation, potential alternative causes of thrombocytopenia were more prevalent in group 1 (33% vs 5%, p = 0.04). Anemia was less frequent in group 1 (67% vs 95%, p = 0.04). All patients had undetectable haptoglobin levels. By contrast, 26% of schistocytes counts were <1%, mostly in group 1 (62% vs 11%, p = 0.01). CONCLUSION: Diagnostic delay is highly prevalent in iTTP, with a significant impact on short-term neurological outcome. In patients with profound thrombocytopenia, the thorough search for signs of incipient organ dysfunction, systematic hemolysis workup, and proper interpretation of schistocytes count are the key elements of early diagnosis of TTP.

Oxygen reserve index for non-invasive early hypoxemia detection during endotracheal intubation in intensive care: the prospective observational NESOI study.

BACKGROUND: To evaluate the ability of the oxygen reserve index (ORI) to predict the occurrence of mild hypoxemia (defined as SpO2 < 97%) during endotracheal intubation (ETI) of patients in the intensive care unit (ICU). METHODS: This observational single-centre study included patients without hypoxemia (defined as SpO2/FiO2 > 214) who required ETI in the ICU. Patients were followed during preoxygenation and ETI then until hospital discharge and/or day 28. We recorded cases of mild hypoxemia, moderate (SpO2 < 90%) and severe (SpO2 < 80%) hypoxemia, moderate arterial hypotension (systolic arterial pressure < 90 mmHg), oesophageal intubation, aspiration, cardiac arrest, and death. RESULTS: Between January 2019 and July 2020, 56 patients were included prospectively and 51 patients were analysed. Twenty patients had mild hypoxemia between the end of preoxygenation and the end of intubation; in 10 of these patients, the decrease in SpO2 below 97% was preceded by an ORI < 0.4, the median time difference being 81 s [interquartile range, 34-146]. By multivariable analysis, a higher ORI (by 0.1 increase) value during preoxygenation was associated with absence of hypoxemia (odds ratio, 0.76; 95% confidence interval, 0.61;0.95; P = 0.0141). CONCLUSION: In non-hypoxemic patients, the 81-s [34-146] median time between the ORI decrease below 0.4 and the SpO2 decrease below 97% during apnoea may allow preventive action. A higher ORI value during preoxygenation was independently protective against hypoxemia. Whether these findings also apply to hypoxemic patients, and the clinical impact of a preoxygenation strategy based on ORI monitoring, remain to be evaluated prospectively. Trial Registration ClinicalTrial.gov, #NCT03600181.

Shiga Toxin-Associated Hemolytic Uremic Syndrome in Adults, France, 2009-2017.

We conducted a retrospective study on hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC) in 96 adults enrolled in the cohort of the National Reference Center for Thrombotic Microangiopathies network in France during 2009-2017. Most infections were caused by STEC strains not belonging to the O157 or O104 serogroups. Thirty (31.3%) patients had multiple risk factors for thrombotic microangiopathy. In total, 61 (63.5%) patients required dialysis, 50 (52.1%) had a serious neurologic complication, 34 (35.4%) required mechanical ventilation, and 19 (19.8%) died during hospitalization. We used multivariate analysis to determine that the greatest risk factors for death were underlying immunodeficiency (hazard ratio 3.54) and severe neurologic events (hazard ratio 3.40). According to multivariate analysis and propensity score-matching, eculizumab treatment was not associated with survival. We found that underlying conditions, especially immunodeficiency, are strongly associated with decreased survival in adults who have hemolytic uremic syndrome caused by STEC.

Outcomes in patients treated with chimeric antigen receptor T-cell therapy who were admitted to intensive care (CARTTAS): an international, multicentre, observational cohort study.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy can induce side-effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS), which often require intensive care unit admission. The aim of this study was to describe management of critically ill CAR T-cell recipients in intensive care. METHODS: This international, multicentre, observational cohort study was done in 21 intensive care units in France, Spain, the USA, the UK, Russia, Canada, Germany, and Austria. Eligible patients were aged 18 years or older; had received CAR T-cell therapy in the past 30 days; and had been admitted to intensive care for any reason. Investigators retrospectively included patients admitted between Feb 1, 2018, and Feb 1, 2019, and prospectively included patients admitted between March 1, 2019, and Feb 1, 2020. Demographic, clinical, laboratory, treatment, and outcome data were extracted from medical records. The primary endpoint was 90-day mortality. Factors associated with mortality were identified using a Cox proportional hazard model. FINDINGS: 942 patients received CAR T-cell therapy, of whom 258 (27%) required admission to intensive care and 241 (26%) were included in the analysis. Admission to intensive care was needed within median 4·5 days (IQR 2·0-7·0) of CAR T-cell infusion. 90-day mortality was 22·4% (95% CI 17·1-27·7; 54 deaths). At initial evaluation on admission, isolated cytokine release syndrome was identified in 101 patients (42%), cytokine release syndrome and ICANS in 93 (39%), and isolated ICANS in seven (3%) patients. Grade 3-4 cytokine release syndrome within 1 day of admission to intensive care was found in 50 (25%) of 200 patients and grade 3-4 ICANS in 38 (35%) of 108 patients. Bacterial infection developed in 30 (12%) patients. Life-saving treatments were used in 75 (31%) patients within 24 h of admission to intensive care, primarily vasoactive drugs in 65 (27%) patients. Factors independently associated with 90-day mortality by multivariable analysis were frailty (hazard ratio 2·51 [95% CI 1·37-4·57]), bacterial infection (2·12 [1·11-4·08]), and lifesaving therapy within 24 h of admission (1·80 [1·05-3·10]). INTERPRETATION: Critical care management is an integral part of CAR T-cell therapy and should be standardised. Studies to improve infection prevention and treatment in these high-risk patients are warranted. FUNDING: Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique.

Performance of the ROX index to predict intubation in immunocompromised patients receiving high-flow nasal cannula for acute respiratory failure.

BACKGROUND: Delayed intubation is associated with high mortality. There is a lack of objective criteria to decide the time of intubation. We assessed a recently described combined oxygenation index (ROX index) to predict intubation in immunocompromised patients. The study is a secondary analysis of randomized trials in immunocompromised patients, including all patients who received high-flow nasal cannula (HFNC). The first objective was to evaluate the accuracy of the ROX index to predict intubation for patients with acute respiratory failure. RESULTS: In the study, 302 patients received HFNC. Acute respiratory failure was mostly related to pneumonia (n = 150, 49.7%). Within 2 (1-3) days, 115 (38.1%) patients were intubated. The ICU mortality rate was 27.4% (n = 83). At 6 h, the ROX index was lower for patients who needed intubation compared with those who did not [4.79 (3.69-7.01) vs. 6.10 (4.48-8.68), p < 0.001]. The accuracy of the ROX index to predict intubation was poor [AUC = 0.623 (0.557-0.689)], with low performance using the threshold previously found (4.88). In multivariate analysis, a higher ROX index was still independently associated with a lower intubation rate (OR = 0.89 [0.82-0.96], p = 0.04). CONCLUSION: A ROX index greater than 4.88 appears to have a poor ability to predict intubation in immunocompromised patients with acute respiratory failure, although it remains highly associated with the risk of intubation and may be useful to stratify such risk in future studies.

A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP.

The anti-von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.

Assessing physicians' and nurses' experience of dying and death in the ICU: development of the CAESAR-P and the CAESAR-N instruments.

BACKGROUND: As an increasing number of deaths occur in the intensive care unit (ICU), studies have sought to describe, understand, and improve end-of-life care in this setting. Most of these studies are centered on the patient's and/or the relatives' experience. Our study aimed to develop an instrument designed to assess the experience of physicians and nurses of patients who died in the ICU, using a mixed methodology and validated in a prospective multicenter study. METHODS: Physicians and nurses of patients who died in 41 ICUs completed the job strain and the CAESAR questionnaire within 24 h after the death. The psychometric validation was conducted using two datasets: a learning and a reliability cohort. RESULTS: Among the 475 patients included in the main cohort, 398 nurse and 417 physician scores were analyzed. The global score was high for both nurses [62/75 (59; 66)] and physicians [64/75 (61; 68)]. Factors associated with higher CAESAR-Nurse scores were absence of conflict with physicians, pain control handled with physicians, death disclosed to the family at the bedside, and invasive care not performed. As assessed by the job strain instrument, low decision control was associated with lower CAESAR score (61 (58; 65) versus 63 (60; 67), p = 0.002). Factors associated with higher CAESAR-Physician scores were room dedicated to family information, information delivered together by nurse and physician, families systematically informed of the EOL decision, involvement of the nurse during implementation of the EOL decision, and open visitation. They were also higher when a decision to withdraw or withhold treatment was made, no cardiopulmonary resuscitation was performed, and the death was disclosed to the family at the bedside. CONCLUSION: We described and validated a new instrument for assessing the experience of physicians and nurses involved in EOL in the ICU. This study shows important areas for improving practices.

Aminoglycosides in Immunocompromised Critically Ill Patients With Bacterial Pneumonia and Septic Shock: A Post-Hoc Analysis of a Prospective Multicenter Multinational Cohort.

BACKGROUND: The routine use of empiric combination therapy with aminoglycosides during critical illness is associated with uncertain benefit and increased risk of acute kidney injury. This study aimed to assess the benefits of aminoglycosides in immunocompromised patients with suspected bacterial pneumonia and sepsis. METHODS: Secondary analysis of a prospective multicenter study. Adult immunocompromised patients with suspected bacterial pneumonia and sepsis or septic shock were included. Primary outcome was hospital mortality. Secondary outcomes were needed for renal replacement therapy (RRT). Mortality was also assessed in neutropenic patients and in those with confirmed bacterial pneumonia. Results were further analyzed in a cohort matched on risk of receiving aminoglycosides combination. RESULTS: Five hundred thirty-five patients were included in this analysis, of whom 187 (35%) received aminoglycosides in addition to another antibiotic effective against gram-negative bacteria. Overall hospital mortality was 59.6% (58.3% vs. 60.3% in patients receiving and not receiving combination therapy; P = 0.71). Lack of association between mortality and aminoglycosides was confirmed after adjustment for confounders and center effect (adjusted OR 1.14 [0.69-1.89]) and in a propensity matched cohort (adjusted OR = 0.89 [0.49-1.61]). No association was found between aminoglycosides and need for RRT (adjusted OR = 0.83 [0.49-1.39], P = 0.477), nor between aminoglycoside use and outcome in neutropenic patients or in patients with confirmed bacterial pneumonia (adjusted OR 0.66 [0.23-1.85] and 1.25 [0.61-2.57], respectively). CONCLUSION: Aminoglycoside combination therapy was not associated with hospital mortality or need for renal replacement therapy in immunocompromised patients with pulmonary sepsis.