Outcomes in Critically Ill Allogeneic Hematopoietic Stem-Cell Transplantation Recipients.

Rationale: Allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) recipients are still believed to be poor candidates for ICU management. Methods: We investigated outcomes and determinants of mortality in a large multicenter retrospective cohort of Allo-HSCT patients admitted between January 1, 2015, and December 31, 2020, to 14 French ICUs. The primary endpoint was 90-day mortality. Measurements and Main Results: In total, 1,164 patients were admitted throughout the study period. At the time of ICU admission, 765 (66%) patients presented with multiple organ dysfunction, including acute respiratory failure in 40% (n = 461). The median sepsis-related organ failure assessment score was 6 (interquartile range, 4-8). Invasive mechanical ventilation, renal replacement therapy, and vasopressors were required in 438 (38%), 221 (19%), and 468 (41%) patients, respectively. ICU mortality was 26% (302 deaths). Ninety-day, 1-year, and 3-year mortality rates were 48%, 63%, and 70%, respectively. By multivariable analysis, age > 56 years (odds ratio [OR], 2.0 [95% confidence interval (CI), 1.53-2.60]; P < 0.001), time from Allo-HSCT to ICU admission between 30 and 90 days (OR, 1.68 [95% CI, 1.17-2.40]; P = 0.005), corticosteroid-refractory acute graft-versus-host disease (OR, 1.63 [95% CI, 1.38-1.93]; P < 0.001), need for vasopressors (OR, 1.9 [95% CI, 1.42-2.55]; P < 0.001), and mechanical ventilation (OR, 3.1 [95% CI, 2.29-4.18]; P < 0.001) were independently associated with 90-day mortality. In patients requiring mechanical ventilation, mortality rates ranged from 39% (no other risk factors for mortality) to 100% (four associated risk factors for mortality). Conclusions: Most critically ill Allo-HSCT recipients survive their ICU stays, including those requiring mechanical ventilation, with an overall 90-day survival rate reaching 51.8%. A careful assessment of goals of care is required in patients with two or more risk factors for mortality.

Incidence, risk factors and outcomes of nosocomial infection in adult patients supported by extracorporeal membrane oxygenation: a systematic review and meta-analysis.

BACKGROUND: An increasing number of patients requires extracorporeal membrane oxygenation (ECMO) for life support. This supportive modality is associated with nosocomial infections (NIs). This systematic review and meta-analysis aim to assess the incidence and risk factors of NIs in adult. METHODS: We searched PubMed, Scopus, Web of Science, and ProQuest databases up to 2022. The primary endpoint was incidence of NI. Secondary endpoints included time to infection, source of infection, ECMO duration, Intensive care and hospital length of stay (LOS), ECMO survival and overall survival. Incidence of NI was reported as pooled proportions and 95% confidence intervals (CIs), while dichotomous outcomes were presented as risk ratios (RR) as the effective index and 95% CIs using a random-effects model. RESULTS: Among the 4,733 adult patients who received ECMO support in the 30 included studies, 1,249 ECMO-related NIs per 1000 ECMO-days was observed. The pooled incidence of NIs across 18 studies involving 3424 patients was 26% (95% CI 14-38%).Ventilator-associated pneumonia (VAP) and bloodstream infections (BSI) were the most common NI sources. Infected patients had lower ECMO survival and overall survival rates compared to non-infected patients, with risk ratio values of 0.84 (95% CI 0.74-0.96, P = 0.01) and 0.80 (95% CI 0.71-0.90, P < 0.001), respectively. CONCLUSION: Results showed that 16% and 20% lower of ECMO survival and overall survival in patients with NI than patients without NI, respectively. However, NI increased the risk of in-hospital mortality by 37% in infected patients compared with non-infected patients. In addition, this study identified the significant positive correlation between ECMO duration and ECMO-related NI.

Septic shock in the immunocompromised cancer patient: a narrative review.

Immunosuppressed patients, particularly those with cancer, represent a momentous and increasing portion of the population, especially as cancer incidence rises with population growth and aging. These patients are at a heightened risk of developing severe infections, including sepsis and septic shock, due to multiple immunologic defects such as neutropenia, lymphopenia, and T and B-cell impairment. The diverse and complex nature of these immunologic profiles, compounded by the concomitant use of immunosuppressive therapies (e.g., corticosteroids, cytotoxic drugs, and immunotherapy), superimposed by the breakage of natural protective barriers (e.g., mucosal damage, chronic indwelling catheters, and alterations of anatomical structures), increases the risk of various infections. These and other conditions that mimic sepsis pose substantial diagnostic and therapeutic challenges. Factors that elevate the risk of progression to septic shock in these patients include advanced age, pre-existing comorbidities, frailty, type of cancer, the severity of immunosuppression, hypoalbuminemia, hypophosphatemia, Gram-negative bacteremia, and type and timing of responses to initial treatment. The management of vulnerable cancer patients with sepsis or septic shock varies due to biased clinical practices that may result in delayed access to intensive care and worse outcomes. While septic shock is typically associated with poor outcomes in patients with malignancies, survival has significantly improved over time. Therefore, understanding and addressing the unique needs of cancer patients through a new paradigm, which includes the integration of innovative technologies into our healthcare system (e.g., wireless technologies, medical informatics, precision medicine), targeted management strategies, and robust clinical practices, including early identification and diagnosis, coupled with prompt admission to high-level care facilities that promote a multidisciplinary approach, is crucial for improving their prognosis and overall survival rates.

Resilience after severe critical illness: a prospective, multicentre, observational study (RESIREA).

BACKGROUND: Critical-illness survivors may experience post-traumatic stress disorder (PTSD) and quality-of-life impairments. Resilience may protect against psychological trauma but has not been adequately studied after critical illness. We assessed resilience and its associations with PTSD and quality of life, and also identified factors associated with greater resilience. METHODS: This prospective, multicentre, study in patients recruited at 41 French ICUs was done in parallel with the NUTRIREA-3 trial in patients given mechanical ventilation and vasoactive amines for shock. Three months to one year after intensive-care-unit admission, survivors completed the Connor-Davidson Resilience Scale (CD-RISC-25), Impact of Event-Revised scale for PTSD symptoms (IES-R), SF-36 quality-of-life scale, Multidimensional Scale of Perceived Social Support (MSPSS), and Brief Illness Perception Questionnaire (B-IPQ). RESULTS: Of the 382 included patients, 203 (53.1%) had normal or high resilience (CD-RISC-25 ≥ 68). Of these resilient patients, 26 (12.8%) had moderate to severe PTSD symptoms (IES-R ≥ 24) vs. 45 (25.4%) patients with low resilience (p = 0.002). Resilient patients had higher SF-36 scores. Factors independently associated with higher CD-RISC-25 scores were higher MSPSS score indicating stronger social support (OR, 1.027; 95%CI 1.008-1.047; p = 0.005) and lower B-IPQ scores indicating a more threatening perception of the illness (OR, 0.973; 95%CI 0.950-0.996; p = 0.02). CONCLUSIONS: Resilient patients had a lower prevalence of PTSD symptoms and higher quality of life scores, compared to patients with low resilience. Higher scores for social support and illness perception were independently associated with greater resilience. Thus, our findings suggest that interventions to strengthen social support and improve illness perception may help to improve resilience. Such interventions should be evaluated in trials with PTSD mitigation and quality-of-life improvement as the target outcomes.

Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease in the ICU: An Observational Study From the OUTCOMEREA Database, 1997-2018.

OBJECTIVES: Our aim was to describe changes in the management of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) by ICUs and patient outcomes. DESIGN: We extracted data from the OutcomeRea database concerning patients admitted for AECOPD between 1997 and 2018. We analyzed trends in the use of ventilatory support, corticosteroid therapy, antibiotic therapy, and patient survival. SETTING: ICUs at 32 French sites. PATIENTS: One thousand eight hundred sixteen patients in the database had a diagnosis of AECOPD. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over time, there was a reduction in the prescription of corticosteroids and antibiotics. In a time-series analysis, these changes in practice were not linked with ICU mortality. The proportion of patients treated with invasive mechanical ventilation (IMV) also gradually declined (from 51% between 1997 and 2002 to 35% between 2013 and 2018) with an association between decrease in IMV use and reduction in ICU mortality in a time series analysis. Rates of noninvasive ventilation (NIV) failure decreased with an increase in NIV use to support weaning from IMV. There was a reduction in the median ICU length of stay (from 8 d in 1997-2002 to 4 d in 2013-2018) and in the median total duration of hospitalization (from 23 d in 1997-2002 to 14 d in 2013-2018). We observed an improvement in prognosis, with decreases in overall hospital mortality (from 24% between 1997 and 2002 to 15% between 2013 and 2018), ICU mortality (from 14% between 1997 and 2002 to 10% between 2013 and 2018), and 90-day mortality (from 41% between 1997 and 2002 to 22% between 2013 and 2018). CONCLUSIONS: The length of stay and mortality of patients with AECOPD admitted to ICUs has decreased over the last 20 years, with a wider use of NIV and a reduction in antibiotic and corticosteroid prescriptions.

Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP) in patients with acute exacerbation of COPD: From the French OUTCOMEREA cohort.

BACKGROUND: Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP), a nosocomial pneumonia that is not related to invasive mechanical ventilation (IMV), has been less studied than ventilator-associated pneumonia, and never in the context of patients in an ICU for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD), a common cause of ICU admission. This study aimed to determine the factors associated with NV-ICU-AP occurrence and assess the association between NV-ICU-AP and the outcomes of these patients. METHODS: Data were extracted from the French ICU database, OutcomeRea™. Using survival analyses with competing risk management, we sought the factors associated with the occurrence of NV-ICU-AP. Then we assessed the association between NV-ICU-AP and mortality, intubation rates, and length of stay in the ICU. RESULTS: Of the 844 COPD exacerbations managed in ICUs without immediate IMV, NV-ICU-AP occurred in 42 patients (5%) with an incidence density of 10.8 per 1,000 patient-days. In multivariate analysis, prescription of antibiotics at ICU admission (sHR, 0.45 [0.23; 0.86], p = 0.02) and no decrease in consciousness (sHR, 0.35 [0.16; 0.76]; p < 0.01) were associated with a lower risk of NV-ICU-AP. After adjusting for confounders, NV-ICU-AP was associated with increased 28-day mortality (HR = 3.03 [1.36; 6.73]; p < 0.01), an increased risk of intubation (csHR, 5.00 [2.54; 9.85]; p < 0.01) and with a 10-day increase in ICU length of stay (p < 0.01). CONCLUSION: We found that NV-ICU-AP incidence reached 10.8/1000 patient-days and was associated with increased risks of intubation, 28-day mortality, and longer stay for patients admitted with AECOPD.

Prevalence, Intensity, and Clinical Impact of Dyspnea in Critically Ill Patients Receiving Invasive Ventilation.

Rationale: Dyspnea is a traumatic experience. Only limited information is available on dyspnea in intubated critically ill patients. Objectives: Our objectives were 1) to quantify the prevalence and severity of dyspnea; and 2) to evaluate the impact of dyspnea on ICU length of stay and post-traumatic stress disorder (PTSD) 90 days after ICU discharge. Methods: This was a prospective cohort study in 10 ICUs in France. In patients intubated for more than 24 hours, dyspnea was quantified with a visual analog scale (from 0 to 10) as soon as they were able to communicate, the following day, and before spontaneous breathing trials. PTSD was defined by an Impact of Event Scale-Revised score of at least 22. Measurements and Main Results: Among the 612 patients assessed, 34% reported dyspnea, with a median dyspnea rating of 5 (interquartile range, 4-7). ICU length of stay was not significantly different between patients with versus without dyspnea (6 [3-12] and 6 [3-13] days, respectively; P = 0.781). Mortality was not different between groups. Of the 153 patients interviewed on Day 90, a higher proportion of individuals with probable PTSD was observed among patients who were dyspneic on enrollment (29% vs. 13%; P = 0.017). The density of dyspnea (number of dyspneic episodes divided by time from enrollment to extubation) was independently associated with PTSD (odds ratio, 1.07; 95% confidence interval, 1.01-1.13; P = 0.031). Conclusions: Dyspnea was frequent and intense in intubated critically ill patients. ICU length of stay was not significantly different among patients reporting dyspnea, but PTSD was more frequent at Day 90. Clinical trial registered with www.clinicaltrials.gov (NCT02336464).

Performance of Doppler-Based Resistive Index and Semiquantitative Renal Perfusion in Predicting Persistent Acute Kidney Injury According to Operator Experience: Post Hoc Analysis of a Prospective Multicenter Study.

OBJECTIVES: The Doppler-based resistive index and semiquantitative evaluation of renal perfusion using color Doppler failed to discriminate renal recovery patterns in a recent study. The influence of operator experience on resistive index and semiquantitative evaluation of renal perfusion performances is however unknown. This study aimed at evaluating the performance of resistive index and semiquantitative evaluation of renal perfusion according to the operator experience to predict short-term renal prognosis in critically ill patients. DESIGN: Preplanned ancillary analysis of a prospective multicenter cohort study. SETTING: Seven ICUs. PATIENTS: Unselected ICU patients. INTERVENTION: Renal Doppler was performed at admission to the ICU. The diagnostic performance of resistive index and semiquantitative evaluation of renal perfusion to predict persistent acute kidney injury at day 3 was evaluated. MAIN RESULTS: Overall, 371 patients were included, of whom 351 could be assessed for short-term renal recovery. Two thirds of the included patients had acute kidney injury (n = 233; 66.3%), of whom 136 had persistent acute kidney injury (58.4%). Overall performance in discriminating persistent acute kidney injury was however null with an area under the receiver operating characteristic curve less than 0.6 for both resistive index and semiquantitative evaluation of renal perfusion, and no difference across operator experience. A multivariate analysis using logistic regression with the center as a random effect adjusted on the operator experience showed no association between resistive index (odds ratio, 0.02 per international units (95% CI, 0.00-18.60 international units]) or semiquantitative evaluation of renal perfusion (odds ratio, 0.96 per international units [95% CI, 0.43-2.11 international units]) and persistent acute kidney injury. Similar results were obtained within subgroups of expert and nonexpert operators. CONCLUSIONS: Doppler-based measurements performed by an expert or a nonexpert operator did not discriminate renal recovery patterns and neither modified the risk stratification of acute kidney injury persistence.

Predictive factors for severe long-term chronic kidney disease after acute kidney injury requiring renal replacement therapy in critically ill patients: an ancillary study of the ELVIS randomized controlled trial.

BACKGROUND: Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious complication in the ICU that results in increased mortality and risk of chronic kidney disease (CKD). Some studies suggest RRT modality may have an impact on long-term renal recovery after AKI. However, other predictive factors of severe long-term CKD in ICU patients with AKI requiring RRT are unknown. METHODS: We performed an ancillary study of the multicenter ELVIS trial in the population with AKI requiring RRT. Patients alive 3 months after RRT initiation were eligible. Serum creatinine levels available at 3, 6 and 12 months and 3 and 5 years were recorded. CKD stage was determined according to the glomerular filtration rate as estimated by the CKD-EPI formula. At each timepoint, two groups of patients were compared, a no/mild CKD group with normal or mildly to moderately decreased renal function (stages 1, 2 and 3 of the international classification) and a severe CKD group (stages 4 and 5). Our objective was to identify predictive factors of severe long-term CKD. RESULTS: Of the 287 eligible patients, 183 had follow-up at 3 months, 136 (74.3%) from the no/mild CKD group and 47 (25.7%) from the severe CKD group, and 122 patients at 5 years comprising 96 (78.7%) from the no/mild CKD group and 26 (21.3%) from the severe CKD group. Multivariate analysis showed that a long RRT period was associated with severe CKD up to 12 months (ORM12 = 1.03 95% CI [1.02-1.05] per day) and that a high SOFA score at the initiation of RRT was not associated with severe CKD up to 5 years (ORM60 = 0.85 95% CI [0.77-0.93] per point). CONCLUSION: Severe long-term CKD was found in 21% of ICU survivors who underwent RRT for AKI. The duration of the RRT in AKI patients was identified as a new predictive factor for severe long-term CKD. This finding should be taken into consideration in future studies on the prognosis of ICU patients with AKI requiring RRT. Trial registration ELVIS trial was registered with ClinicalTrials.gov, number: NCT00875069 (June 16, 2014), and this ancillary study was registered with ClinicalTrials.gov, number: NCT03302624 (October 6, 2017).

Survival in Immunocompromised Patients Ultimately Requiring Invasive Mechanical Ventilation: A Pooled Individual Patient Data Analysis.

Rationale: Acute respiratory failure (ARF) is associated with high mortality in immunocompromised patients, particularly when invasive mechanical ventilation is needed. Therefore, noninvasive oxygenation/ventilation strategies have been developed to avoid intubation, with uncertain impact on mortality, especially when intubation is delayed. Objectives: We sought to report trends of survival over time in immunocompromised patients receiving invasive mechanical ventilation. The impact of delayed intubation after failure of noninvasive strategies was also assessed. Methods: Systematic review and meta-analysis using individual patient data of studies that focused on immunocompromised adult patients with ARF requiring invasive mechanical ventilation. Studies published in English were identified through PubMed, Web of Science, and Cochrane Central (2008-2018). Individual patient data were requested from corresponding authors for all identified studies. We used mixed-effect models to estimate the effect of delayed intubation on hospital mortality and described mortality rates over time. Measurements and Main Results: A total of 11,087 patients were included (24 studies, three controlled trials, and 21 cohorts), of whom 7,736 (74%) were intubated within 24 hours of ICU admission (early intubation). The crude mortality rate was 53.2%. Adjusted survivals improved over time (from 1995 to 2017, odds ratio [OR] for hospital mortality per year, 0.96 [0.95-0.97]). For each elapsed day between ICU admission and intubation, mortality was higher (OR, 1.38 [1.26-1.52]; P < 0.001). Early intubation was significantly associated with lower mortality (OR, 0.83 [0.72-0.96]), regardless of initial oxygenation strategy. These results persisted after propensity score analysis (matched OR associated with delayed intubation, 1.56 [1.44-1.70]). Conclusions: In immunocompromised intubated patients, survival has improved over time. Time between ICU admission and intubation is a strong predictor of mortality, suggesting a detrimental effect of late initial oxygenation failure.

Critically ill patients with severe infections related to Geotrichum species: A French retrospective multicentre study.

OBJECTIVES: Geotrichum spp can be responsible for severe infections in immunocompromised patients. We aim to describe Geotrichum-related infections in the ICU and to assess risk factors of mortality. METHODS: Retrospective multicentre study, conducted in 14 French ICUs between 2002 and 2018, including critically ill adult patients with proven or probable infection related to Geotrichum species. Data were obtained from the medical charts. RESULTS: Thirty-six patients, median age 60 years IQR [53; 66] were included. Most of the patients had haematological malignancies (78%). The reason for ICU admission was shock in half of the patients (n = 19, 53%) and respiratory failure in thirteen patients (36%). Median SOFA score was 8.5 IQR [7; 15]. Time between ICU admission and fungal diagnosis was 2.5 days [-1; 4]. Infection was disseminated in 27 (75%) patients with positive blood cultures in 25 patients (69%). Thirty patients (83%) received curative antifungal treatment in the ICU, in a median time of 1 day [0;1] after ICU admission. Twenty-four patients (67%) died in the ICU and hospital mortality rate was 69%. The number and extent of organ failures, as represented by SOFA score, were associated with mortality. CONCLUSIONS: This study demonstrates poor outcome in critically ill patients with Geotrichum-related infections, which encourages a high level of suspicion.

Diagnostic Performance of Hemophagocytic Lymphohistiocytosis Criteria and HScore in Critically Ill Patients With Severe Hemophagocytic Syndrome.

OBJECTIVES: To assess whether critically ill hematologic patients without diagnosis of hemophagocytic lymphohistiocytosis may have features mimicking hemophagocytic lymphohistiocytosis according to both diagnostic scores. DESIGN: A retrospective case-control study. SETTING: Hemophagocytic syndrome diagnosis was standardized and based on a consensual diagnosis by at least two experts of a university hospital which is a reference center for hemophagocytic syndrome. PATIENTS: Cases (hemophagocytic syndrome+) consisted in a group of consecutive patients (n = 150) admitted in our ICU between 2007 and 2018. Control group (hemophagocytic syndrome-) consisted in patients included in a prospective multicenter cohort of hematologic patients in whom three independent experts ruled out the diagnosis of hemophagocytic syndrome (n = 1011). MEASUREMENTS AND MAIN RESULTS: Overall, 1,161 patients were included. Hospital mortality was 45.8% in hemophagocytic syndrome- patients (n = 66) and 38.8% in control patients (n = 392; p = 0.126). Median HScore was 235 (205-262) in hemophagocytic syndrome+ and 42 (18-62) in hemophagocytic syndrome- patients (p < 0.001); number of hemophagocytic lymphohistiocytosis criteria was 4 (4-5) vs 1 (0-1), respectively (p < 0.001). Diagnostic performances of both scores were excellent with area under receiver operating characteristic curve of 0.99 (95% CI, 0.99-0.99) and 0.99 (95% CI, 0.99-0.99) for hemophagocytic lymphohistiocytosis and HScore, respectively. After propensity score matching (n = 144 × 2), the median HScore was 234 (205-262) in hemophagocytic syndrome+ patients versus 49 (18-71) in hemophagocytic syndrome- patients (p < 0.001). Median number of hemophagocytic lymphohistiocytosis criteria was 4 (4-5) in hemophagocytic syndrome+ and 1 (0-1) in hemophagocytic syndrome- patients (p < 0.001). Area under receiver operating characteristic curve was then of 0.98 (95% CI, 0.96-0.99) for hemophagocytic lymphohistiocytosis criteria and 0.99 (95% CI, 0.99-1) for HScore. CONCLUSIONS: In ICU patients, several conditions share some similarities with hemophagocytic syndrome, explaining the poor predictive value of isolated biological markers such as ferritin level. Despite these potential confounding factors, our study suggests HScore and hemophagocytic lymphohistiocytosis criteria to be highly discriminant identifying hemophagocytic syndrome in critically ill patients.

Acute Kidney Injury Recovery Patterns in Critically Ill Patients: Results of a Retrospective Cohort Study.

OBJECTIVES: Acute kidney injury, acute kidney injury severity, and acute kidney injury duration are associated with both short- and long-term outcomes. Despite recent definitions, only few studies assessed pattern of renal recovery and time-dependent competing risks are usually disregarded. Our objective was to describe pattern of acute kidney injury recovery, change of transition probability over time and their risk factors. DESIGN: Monocenter retrospective cohort study. Acute kidney injury was defined according to Kidney Disease Improving Global Outcomes definition. Renal recovery was defined as normalization of both serum creatinine and urine output criteria. Competing risk analysis, time-inhomogeneous Markov model, and group-based trajectory modeling were performed. SETTING: Monocenter study. PATIENTS: Consecutive patients admitted in ICU from July 2018 to December 2018 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three-hundred fifty patients were included. Acute kidney injury occurred in 166 patients at ICU admission, including 64 patients (38.6%) classified as acute kidney disease according to Acute Disease Quality Initiative definition and 44 patients (26.5%) who could not be classified. Cumulative incidence of recovery was 25 % at day 2 (95% CI, 18-32%) and 35% at day 7 (95% CI, 28-42%). After adjustment, need for mechanical ventilation (subdistribution hazard ratio, 0.42; 95% CI, 0.23-0.74) and severity of the acute kidney injury (stage 3 vs stage 1 subdistribution hazard ratio, 0.11; 95% CI, 0.03-0.35) were associated with lack of recovery. Group-based trajectory modeling identified three clusters of temporal changes in this setting, associated with both acute kidney injury recovery and patients' outcomes. CONCLUSIONS: In this study, we demonstrate Acute Disease Quality Initiative to allow recovery pattern classification in 75% of critically ill patients. Our study underlines the need to take into account competing risk factors when assessing recovery pattern in critically ill patients.

Pattern of Brain Injury in Patients With Thrombotic Thrombocytopenic Purpura in the Precaplacizumab Era.

OBJECTIVES: To describe short- and long-term neurologic prognosis of patients with thrombotic thrombocytopenic purpura and to identify clusters associated with evolution. DESIGN: Prospective French cohort. SETTING: ICU in a reference center. PATIENTS: All consecutive patients with newly diagnosed thrombocytopenic purpura. INTERVENTION: Comprehensive clinical, biological, and radiological evaluation at admission. Neurocognitive recovery was assessed using Glasgow Outcome Scale (range 1-5, with 1 representing death and 5 representing no or minimal neurologic deficit). MEASUREMENTS AND MAIN RESULTS: Among the 130 newly diagnosed patients with thrombocytopenic purpura, 108 (83%; age 43 [30-52]; 73% women) presented with neurologic signs, including headaches (51%), limb weakness, paresthesia, and/or aphasia (49%), pyramidal syndrome (30%), decreased consciousness (20%), seizure (19%), cognitive impairment (34%), cerebellar syndrome (18%), and visual symptoms (20%). A hierarchical cluster analysis identified three distinct groups of patients. Cluster 1 included younger patients (37 [27-48], 41 [32-52], and 48 [35-54], in clusters 1, 2 and 3, respectively; p = 0.045), with a predominance of headaches (75%, 27%, and 36%; p < 0.0001). Cluster 2 patients had ataxic gait and cerebellar syndrome (77%, 0%, and 0%; p < 0.0001) and dizziness (50%, 0%, and 0%; p < 0.0001). Cluster 3 included patients with delirium (36%, 0%, and 9%; p < 0.0001), obtundation (58%, 0%, and 24%; p < 0.0001), and seizure (36%, 0%, and 14%; p < 0.0001). Acute kidney injury was 32%, 68%, and 77%, in clusters 1, 2, and 3, respectively (p < 0.0001). The three clusters did not differ for other biological or brain imaging. After a median follow-up of 34 months (12-71 mo), 100 patients (93%) were alive with full neurocognitive recovery (i.e., Glasgow Outcome Scale score 5) in 89 patients (89%). Patients from cluster 1 more frequently exhibited full recovery (Glasgow Outcome Scale score of 5) compared with clusters 2 and 3, (44 [98%], 13 [65%], and 21 [60%] at 3 mo; p < 0.0001), (44 [100%], 15 [68%], and 23 [69%] at 6 mo; p < 0.0001), and (40 [100%], 15 [79%], and 20 [57%] at 1 yr; p < 0.0001). CONCLUSIONS: Initial clinical neurologic evaluation in thrombocytopenic purpura patients distinguishes three groups of patients with different clinical and functional outcomes.

Diagnostic strategy for trigger identification in severe reactive hemophagocytic lymphohistiocytosis: A diagnostic accuracy study.

Reactive hemophagocytic lymphohistiocytosis (rHLH) management requires early recognition, trigger identification, and adequate treatment in order to reduce mortality. We assessed the diagnostic yield of tissue biopsies to identify trigger in severe rHLH. We included all consecutive patients presenting an rHLH diagnosis (HLH-2004 criteria) admitted to the intensive care unit (ICU) of a tertiary hospital. This retrospective diagnostic accuracy study was conducted according to the Standards for Reporting Diagnostic Accuracy Statement. Among the 134 included patients (median age 47 years [IQR 47-56]), an underlying immunodeficiency was previously known in 61.2%. rHLH trigger was identified in 127 patients (94.8%) (hematological disorder 75%, infection 16%, systemic disease 4%). Diagnostic yield of tissue biopsies was as follows: lymph node 75% (95% confidence interval [CI], 61-85), skin 50% (95% CI, 27-73), bone marrow 44% (95% CI, 34-55), liver 30% (95% CI, 15-49). Splenectomy (yield 77%; 95% CI, 46-95) was reserved to cases of diagnostic deadlock. Procedural severe adverse events included two cases of reversible hemorrhagic shock. Seventy-eight percent of patients received etoposide regarding to the rHLH severity, and 68% could receive trigger-specific treatment in the ICU. A comprehensive diagnostic workup led to an rHLH trigger identification in 95% of patients, allowing prompt initiation of appropriate therapy. Prospective studies to validate a standardized diagnostic approach are warranted.

Symptoms of Anxiety, Depression, and Peritraumatic Dissociation in Critical Care Clinicians Managing Patients with COVID-19. A Cross-Sectional Study.

Rationale: Frontline healthcare providers (HCPs) during the coronavirus disease (COVID-19) pandemic are at high risk of mental morbidity.Objectives: To assess the prevalence of symptoms of anxiety, depression, and peritraumatic dissociation in HCPs.Methods: This was a cross-sectional study in 21 ICUs in France between April 20, 2020, and May 21, 2020. The Hospital Anxiety and Depression Scale and the Peritraumatic Dissociative Experience Questionnaire were used. Factors independently associated with reported symptoms of mental health disorders were identified.Measurements and Main Results: The response rate was 67%, with 1,058 respondents (median age 33 yr; 71% women; 68% nursing staff). The prevalence of symptoms of anxiety, depression, and peritraumatic dissociation was 50.4%, 30.4%, and 32%, respectively, with the highest rates in nurses. By multivariable analysis, male sex was independently associated with lower prevalence of symptoms of anxiety, depression, and peritraumatic dissociation (odds ratio of 0.58 [95% confidence interval, 0.42-0.79], 0.57 [95% confidence interval, 0.39-0.82], and 0.49 [95% confidence interval, 0.34-0.72], respectively). HCPs working in non-university-affiliated hospitals and nursing assistants were at high risk of symptoms of anxiety and peritraumatic dissociation. Importantly, we identified the following six modifiable determinants of symptoms of mental health disorders: fear of being infected, inability to rest, inability to care for family, struggling with difficult emotions, regret about the restrictions in visitation policies, and witnessing hasty end-of-life decisions.Conclusions: HCPs experience high levels of psychological burden during the COVID-19 pandemic. Hospitals, ICU directors, and ICU staff must devise strategies to overcome the modifiable determinants of adverse mental illness symptoms.

Incidence and Outcome of Subclinical Acute Kidney Injury Using penKid in Critically Ill Patients.

Rationale: Subclinical acute kidney injury (sub-AKI) refers to patients with low serum creatinine but elevated alternative biomarkers of AKI. Its incidence and outcome in critically ill patients remain, however, largely unknown. Plasma proenkephalin A 119-159 (penKid) has been proposed as a sensitive biomarker of glomerular function.Objectives: In this ancillary study of two cohorts, we explored the incidence and outcome of sub-AKI based on penKid.Methods: A prospective observational study in ICUs was conducted. FROG-ICU (French and European Outcome Registry in ICUs) enrolled 2,087 critically ill patients, and AdrenOSS-1 (Adrenomedullin and Outcome in Severe Sepsis and Septic Shock-1) enrolled 583 septic patients. The primary endpoint was 28-day mortality after ICU admission. Sub-AKI was defined by an admission penKid concentration above the normal range (i.e., >80 pmol/L) in patients not meeting the definition of AKI. A sensitivity analysis was performed among patients with estimated glomerular filtration rate above 60 ml/min/1.73 m2 at ICU admission.Measurements and Main Results: In total, 6.1% (122/2,004) and 6.7% (39/583) of patients from the FROG-ICU and AdrenOSS-1 cohorts met the definition of sub-AKI (11.6% and 17.5% of patients without AKI). In patients without AKI or with high estimated glomerular filtration rate, penKid was associated with higher mortality (adjusted standardized hazard ratio [HR], 1.4 [95% confidence interval, 1.1-1.8]; P = 0.010; and HR, 1.6 [95% confidence interval, 1.3-1.8]; P < 0.0001, respectively) after adjustment for age, sex, comorbidities, diagnosis, creatinine, diuresis, and study. Patients with sub-AKI had higher mortality compared with no AKI (HR, 2.4 [95% confidence interval, 1.5-3.7] in FROG-ICU and 2.5 [95% confidence interval, 1.1-5.9] in AdrenOSS-1).Conclusions: Sub-AKI defined using penKid occurred in 11.6-17.5% of patients without AKI and was associated with a risk of death close to patients with AKI.

Bioactive Adrenomedullin, Organ Support Therapies, and Survival in the Critically Ill: Results from the French and European Outcome Registry in ICU Study.

OBJECTIVES: Adrenomedullin has vascular properties and elevated plasma adrenomedullin levels were detected in sepsis. We assessed, in septic and nonseptic ICU patients, the relation between circulating adrenomedullin, the need for organ support and mortality, using an assay of bioactive adrenomedullin. DESIGN: Prospective multicenter observational cohort study. SETTING: Data from the French and euRopean Outcome reGistry in ICUs study. PATIENTS: Consecutive patients admitted to intensive care with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 hours following ICU admission and discharged from ICU were included. INTERVENTIONS: Clinical and biological parameters were collected at baseline, including bioactive-adrenomedullin. Status of ICU survivors was assess until 1 year after discharge. The main outcome was the need for organ support, including renal replacement therapy and/or for inotrope(s) and/or vasopressor(s). Secondary endpoints were the ICU length of stay and the 28-day all-cause mortality. MEASUREMENTS AND MAIN RESULTS: Median plasma bioactive adrenomedullin (n = 2,003) was 66.6 pg/mL (34.6-136.4 pg/mL) and the median Simplified Acute Physiology Score II score 49 (36-63). Renal replacement therapy was needed in 23% and inotropes(s) and/or vasopressor(s) in 77% of studied patients. ICU length of stay was 13 days (7-21 d) and mortality at 28 days was 22 %. Elevated bioactive adrenomedullin independently predicted 1) the need for organ support (odds ratio, 4.02; 95% CI, 3.08-5.25) in ICU patients whether admitted for septic or nonseptic causes and 2) the need for renal replacement therapy (odds ratio, 4.89; 3.83-6.28), and for inotrope(s) and/or vasopressor(s) (odds ratio, 3.64; 2.84-4.69), even in patients who were not on those supports at baseline. Elevated bioactive adrenomedullin was also associated with a prolonged length of stay (odds ratio, 1.85; 1.49-2.29) and, after adjustment for Simplified Acute Physiology Score II, with mortality (odds ratio, 2.31; 1.83-2.92). CONCLUSIONS: Early measurement of bioactive adrenomedullin is a strong predictor of the need of organ support and of short-term mortality in critically ill patients.

Oxygenation Strategy During Acute Respiratory Failure in Critically-Ill Immunocompromised Patients.

OBJECTIVES: To assess the response to initial oxygenation strategy according to clinical variables available at admission. DESIGN: Multicenter cohort study. SETTING: Thirty French and Belgium medical ICU. SUBJECTS: Immunocompromised patients with hypoxemic acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were extracted from the Groupe de Recherche en Reanimation Respiratoire du patient d'Onco-Hématologie database. Need for invasive mechanical ventilation was the primary endpoint. Secondary endpoint was day-28 mortality. Six-hundred forty-nine patients were included. First oxygenation strategies included standard oxygen (n = 245, 38%), noninvasive ventilation (n = 285; 44%), high-flow nasal cannula oxygen (n = 55; 8%), and noninvasive ventilation + high-flow nasal cannula oxygen (n = 64; 10%). Bilateral alveolar pattern (odds ratio = 1.67 [1.03-2.69]; p = 0.04), bacterial (odds ratio = 1.98 [1.07-3.65]; p = 0.03) or opportunistic infection (odds ratio = 4.75 [2.23-10.1]; p < 0.001), noninvasive ventilation use (odds ratio = 2.85 [1.73-4.70]; p < 0.001), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10-1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.96 [1.27-3.02]; p = 0.0002) were independently associated with intubation rate. Day-28 mortality was independently associated with bacterial (odds ratio = 2.34 [1.10-4.97]; p = 0.03) or opportunistic infection (odds ratio = 4.96 [2.11-11.6]; p < 0.001), noninvasive ventilation use (odds ratio = 2.35 [1.35-4.09]; p = 0.003), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10-1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.97 [1.26-3.09]; p = 0.003). High-flow nasal cannula oxygen use was neither associated with intubation nor mortality rates. CONCLUSIONS: Some clinical characteristics at ICU admission including etiology and severity of acute respiratory failure enable to identify patients at high risk for intubation.

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.