Purpose
Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes.
Methods
We conducted a retrospective analysis of a prospective multicenter ...database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) <15 or when features of delirium were noted. Potentially modifiable risk factors for SAE at ICU admission and its impact on mortality were investigated using multivariate logistic regression analysis and Cox proportional hazard modeling, respectively.
Results
We included 2513 patients with sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19–1.67, hypoglycemia <3 mmol/l (aOR = 2.66, 95% CI 1.27–5.59), hyperglycemia >10 mmol/l (aOR = 1.37, 95% CI 1.09–1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53–2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48–3.57), and
S. aureus
(aOR = 1.54, 95% CI 1.05–2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13–14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09–1.76).
Conclusions
Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.
Thrombotic thrombocytopenic purpura (TTP) is a diagnostic and therapeutic emergency. Therapeutic plasma exchange (TPE) combined with immunosuppression has been the cornerstone of the initial ...management. To produce optimal benefits, emerging treatments must be used against a background of best standard of care. Clarifying current uncertainties is therefore crucial.
The objective of this study was to analyze a large high-quality database (Marketscan) of TTP patients managed between 2005 and 2014, in the pre-caplacizumab era, in order to assess the impact of time to first TPE and use of first-line rituximab on mortality, and whether mortality declines over time.
Among the 1096 included patients (median age 46 IQR 35-55, 70% female), 28.8% received TPE before day 2 in the ICU. Hospital mortality was 7.6% (83 deaths). Mortality was independently associated with older age (hazard ratio HR, 1.024/year; 95% confidence interval 95%CI, 1.009-1.040), diagnosis of sepsis (HR, 2.360; 95%CI 1.552-3.588), and the need for mechanical ventilation (HR, 4.103; 95%CI, 2.749-6.126). Factors independently associated with lower mortality were TPE at ICU admission (HR, 0.284; 95%CI, 0.112-0.717), TPE within one day after ICU admission (HR, 0.449; 95%CI, 0.275-0.907), and early rituximab therapy (HR, 0.229; 95% CI, 0.111-0.471). Delayed TPE was associated with significantly higher costs.
Immediate TPE and early rituximab are associated with improved survival in TTP patients. Improved treatments have led to a decline in mortality over time, and alternate outcome variables such as the use of hospital resources or longer term outcomes therefore need to be considered.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hemophagocytic syndrome (HS) is a rare life-threatening condition that can lead to multi organ failure and shock. Acute circulatory failure in these patients has been poorly studied.
Objectives of ...this study were to describe characteristics of HS patients with shock, prognostic factors and impact of etoposide infusion on hemodynamic parameters.
This is a monocenter, retrospective, observational cohort study in a French tertiary intensive care unit (ICU). All adult critically ill patients with HS managed in the ICU between 2007 and 2017, requiring vasopressors (norepinephrine) and etoposide infusion.
Thirty-four patients were included. Two-third (n = 25) were of male gender and median age was 48 years IQR 34–62. Shock (n = 14, 41%) and acute respiratory failure (n = 8, 23.5%) were the main initial reasons for ICU admission. The most common HS trigger was underlying hematological malignancy (n = 26; 76%), followed by infectious diseases in 3 patients (9%) and auto immune diseases in 2 (6%) patients. Median SOFA score at ICU admission was 14 10–17. A majority of patients required mechanical ventilation (n = 29, 85%) and initial median lactate level was 3.7 mmol/L 2.9–6.9. Hospital mortality rate was 53% (n = 18) and was associated with SOFA score and renal replacement therapy in univariate analysis. All patients received broad spectrum antibiotics under suspicion of septic shock. In 17 patients, 21 nosocomial infections were documented, mainly from bacterial origin. Etoposide infusion was followed by decreased norepinephrine doses despite an increase in lactate level, while no degradation in mean arterial pressure, heart rate or renal function were identified.
Hospital mortality remains high in critically ill HS patients with shock, but a significant improvement of hemodynamic parameters is observed following etoposide infusion, suggesting that an aggressive initial supportive care is crucial in these patients.
•Hemophagocytic syndrome (HS) is a rare life-threatening condition that can lead to multi organ failure and shock.•Acute circulatory failure in these patients has been poorly studied.•Etoposide infusion was followed by decreased norepinephrine doses.•Our results suggests that an aggressive initial supportive care is crucial in these patients
Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy related to a severe deficiency of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13; ...activity <10%). We aimed to investigate the association between mechanisms for ADAMTS13 deficiency and the epidemiology and pathophysiology of thrombotic thrombocytopenic purpura at initial presentation.
Between Jan 1, 1999, and Dec 31, 2013, we did a cross-sectional analysis of the French national registry for thrombotic microangiopathy to identify all patients with adult-onset thrombotic microangiopathy (first episode after age 18 years) who had severe ADAMTS13 deficiency at presentation. ADAMTS13 activity, anti-ADAMTS13 IgG, and ADAMTS13 gene mutations were investigated by a central laboratory. We collected patients' clinical data for correlation with their ADAMTS13 phenotype and genotype. We used logistic regression analysis to identify variables significantly associated with idiopathic thrombotic thrombocytopenic purpura, as measured by estimated odds ratios (ORs) and 95% CIs. This study is registered with ClinicalTrials.gov, number NCT00426686.
We enrolled 939 patients with adult-onset thrombotic thrombocytopenic purpura, of whom 772 (82%) patients had available data and samples at presentation and comprised the cohort of interest. The prevalence of thrombotic thrombocytopenic purpura in France was 13 cases per million people. At presentation, 378 (49%) patients had idiopathic thrombotic thrombocytopenic purpura, whereas 394 (51%) patients had disease associated with miscellaneous clinical situations (infections, autoimmunity, pregnancy, cancer, organ transplantation, and drugs). Pathophysiologically, three distinct forms of thrombotic thrombocytopenic purpura were observed: 585 (75%) patients had autoimmune disease with anti-ADAMTS13 IgG, 166 (22%) patients had acquired disease of unknown cause and 21 (3%) patients had inherited disease (Upshaw-Schulman syndrome) with mutations of the ADAMTS13 gene. Idiopathic thrombotic thrombocytopenic purpura were mainly autoimmune (345 91% cases), whereas non-idiopathic diseases were heterogeneous, including a high rate of unexplained mechanisms for ADAMTS13 deficiency (133 34% cases). Obstetrical thrombotic thrombocytopenic purpura cases (n=62) were specifically remarkable because of the high rate of patients with Upshaw-Schulman syndrome (21 34% patients).
Our study shows that thrombotic thrombocytopenic purpura is a heterogeneous syndrome, and that features of the disease at presentation are strongly associated with the mechanisms of ADAMTS13 deficiency. In addition to mechanistic insight, our findings could have implications for the initial therapeutic management of patients with this disorder.
Assistance Publique-Hôpitaux de Paris.
We retrospectively reviewed all medical charts from patients admitted to Saint-Louis Hospital between January, 1.sup.st 1997 and December, 31st 2018 with newly diagnosed AML and white blood cell ...(WBC) count above 50x10.sup.9 /L. Outcome measures were cumulative incidence of relapse (CIR), treatment-related mortality (TRM) defined as relapse-free death, and overall survival. Univariate and multivariate analyses were performed using Cox proportional hazards models. A total of 184 patients with HL AML in complete remission (CR) were included in this study. At 2 years after CR. 62.5% of patients were alive, at 5 years, cumulated incidence of relapse was 55.8%. We found that every therapeutic measure, including life-sustaining therapies carried out in the initial phase of the disease, did not increase the relapse risk. The use of hydroxyurea for more than 4 days was associated with a higher risk of relapse. At the end of the study, 94 patients (51.1%) were still alive including 23 patients out of 44 aged less than 60 yo that were able to return to work. We show that the use of emergency measures including life sustaining therapies does not come at the expense of a higher risk of relapse or mortality, except in the case of prolonged use of hydroxyurea. Patients with HL AML should be able to benefit from all available techniques, regardless of their initial severity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The Warburg effect, characterized by elevated lactate levels without tissue hypoxia or shock, has been described in patients with aggressive lymphoproliferative malignancies. However, the ...clinical characteristics and long-term outcomes in this population remain poorly understood.
Methods
We retrospectively analyzed 135 patients with aggressive lymphoproliferative malignancies admitted to the ICU between January 2017 and December 2022. Patients were classified into three groups: Clinical Warburg Effect (CWE), No Warburg with High Lactate level (NW-HL), and No Warburg with Normal Lactate level (NW-NL). Clinical characteristics and outcomes were compared between the groups and factors associated with 1-year mortality and CWE were identified using multivariable analyses.
Results
Of the 135 patients, 46 (34%) had a CWE. This group had a higher proportion of Burkitt and T cell lymphomas, greater tumor burden, and more frequent bone and cerebral involvement than the other groups. At 1 year, 72 patients (53%) died, with significantly higher mortality in the CWE and NW-HL groups (70% each) than in the NW-NL group (38%). Factors independently associated with 1-year mortality were age HR = 1.02 CI 95% (1.00–1.04), total SOFA score at admission HR = 1.19 CI 95% (1.12–1.25), and CWE HR = 3.87 CI 95% (2.13–7.02). The main factors associated with the CWE were tumor lysis syndrome OR = 2.84 CI 95% (1.14–7.42), bone involvement of the underlying malignancy OR = 3.58 CI 95% (1.02–12.91), the total SOFA score at admission OR = 0.81 CI 95% (0.69–0.91) and hypoglycemia at admission OR = 14.90 CI 95% (5.42–47.18).
Conclusion
CWE is associated with a higher tumor burden and increased 1-year mortality compared to patients without this condition. Our findings underscore the importance of recognizing patients with CWE as a high-risk cohort, as their outcomes closely resemble those of individuals with lymphoma and shock, despite not requiring advanced organ support. Clinicians should recognize the urgency of managing these patients and consider early intervention to improve their prognosis.
Background Coagulation disorders are common in patients with hemophagocytic lymphohistiocytosis (HLH), associated with an increased risk of bleeding and death. We aim to investigate coagulation ...disorders and their outcome implications in critically ill patients with HLH. Methods We prospectively evaluated 47 critically ill patients with HLH (median age of 54 years 42-67) between April 2015 and December 2018. Coagulation assessments were performed at day 1. Abnormal standard coagulation was defined as prothrombin time (PT) <50% and/or fibrinogen <2g/L. HLH aetiology was mostly ascribed to haematological malignancies (74% of patients). Results Coagulation disorders and severe bleeding events were frequent, occurring in 30 (64%) and 11 (23%) patients respectively. At day 1, median fibrinogen level was 2â65g/L 1.61-5.66. Fibrinolytic activity was high as suggested by increased median levels of D-dimers, fibrin monomers, PAI-1 (plasminogen activator inhibitor) and tPA (tissue plasminogen activator). Forty-one (91%) patients had a decreased ADAMTS13 activity (A Disintegrin-like And Metalloproteinase with ThromboSpondin type 1 repeats, member 13). By multivariable analysis, the occurrence of a severe bleeding (OR 3.215 1.194-8.653, p = 0â021) and SOFA score (Sepsis-Related Organ Failure Assessment) at day 1 (OR 1.305 per point 1.146-1.485, p<0â001) were independently associated with hospital mortality. No early biological marker was associated with severe bleeding. Conclusions Hyperfibrinolysis may be the primary mechanism responsible for hypofibrinogenemia and may also participate in ADAMTS13 degradation. Targeting the plasmin system appears as a promising approach in severe HLH-related coagulation disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diffuse alveolar hemorrhage (DAH) occurs during the course of autoimmune disease and may be life threatening. The objective was to assess characteristics and prognosis factors of DAH who required ...intensive care unit (ICU) admission in patients with autoimmune diseases.
French multicenter retrospective study including patients presenting DAH related to autoimmune diseases requiring ICU admission from 2000 to 2016.
One hundred four patients (54% of men) with median age of 56 32-68 years were included with 79 (76%) systemic vasculitis and 25 (24%) connective tissue disorders. All patients received steroids, and 72 (69%), 12 (11.5%), and 57 (55%) patients had cyclophosphamide, rituximab, and plasma exchanges, respectively. During ICU stay, 52 (50%), 36 (35%), and 55 (53%) patients required mechanical ventilation, vasopressor use, and renal replacement therapy, respectively. Factors associated with mechanical ventilation weaning were age (HR 95%CI 0.97 0.96-0.99 per 10 years, p < 0.0001), vasculitis-related DAH (0.52 0.27-0.98, p = 0.04), and time from dyspnea onset to ICU admission (0.99 0.99-1 per day, p = 0.03). ICU mortality was 15%. Factors associated with alive status at ICU discharge were chronic cardiac failure (HR 95%CI 0.37 0.15-0.94, p = 0.04), antiphospholipid syndrome-related DAH (3.17 1.89-5.32, p < 0.0001), SAPS II (0.98 0.97-0.99, p = 0.007), and oxygen flow at ICU admission (0.95 0.91-0.99 per liter/min, p = 0.04).
DAH in autoimmune diseases is a life-threatening complication which requires mechanical ventilation in half of the cases admitted to ICU.
Background
High-dose methotrexate (HD-MTX) is commonly used in the treatment of solid tumors and hematological malignancies. Severe toxicities are frequent, leading to organ dysfunction and death. ...Risk–benefit ratio of using HD-MTX in critically ill patients is unknown. This study aims to describe MTX-induced toxicities and to assess outcome in ICU patients. We conducted a retrospective single-center study conducted in a university hospital ICU between January 2002 and December 2018. Consecutive patients treated by HD-MTX were included.
Results
33 patients (24 men and 9 women) aged 48 years 34–63, were included. B cell lymphoma had been diagnosed in 31 patients (Burkitt,
n
= 14; diffuse large B-cell lymphoma with CNS (central nervous system) involvement,
n
= 9; primary CNS lymphoma,
n
= 5) and T-cell lymphoma in two patients. Patients were mainly admitted for coma (
n
= 14; 42%) or acute kidney injury (
n
= 8; 24%). MTX was administered at a median dose of 6.1 g 5–14. Fourteen patients had concomitant medication interacting with MTX. Median MTX clearance was 4 days 4–5. Frequent MTX-related complication were mucositis (
n
= 21, 64%), diarrhea (
n
= 14, 44%) or hepatic failure (
n
= 15, 45%). During ICU stay, 11 patients experienced acute kidney injury (KDIGO stage 3 2–3). Two patients received carboxypeptidase and three underwent dialysis. Overall, 19 patients (57%) required mechanical ventilation, 10 (30%) vasopressors. Hospital mortality was 30% (
n
= 10). Cox model identified MTX concentration 24 h after administration higher than 4.6 µmol/L as associated with hospital mortality (HR 6.7; 95% CI 1.6–27.3).
Conclusions
To our knowledge, this is the first study assessing characteristics and outcome of critically ill patients receiving HD-MTX. MTX concentration at H24 was associated with hospital mortality. Despite underlying malignancy, ICU support of these patients was associated with a meaningful survival.
Background
Etoposide remains the cornerstone of symptomatic management of critically ill patients with secondary hemophagocytic syndrome (sHS). Risk of healthcare-associated infections (HAIs) in this ...setting with etoposide has never been assessed. We sought to evaluate the association between etoposide administration, HAIs occurrence and survival in critically ill adult patients with sHS. In this retrospective single-center study conducted in a university hospital ICU between January 2007 and March 2020, all consecutive patients with sHS were included. HAIs were defined as any microbiologically documented infection throughout ICU stay. Competing risk survival analysis was performed to determine factors associated with HAIs. Propensity score-based overlap weighting was performed to adjust for factors associated with etoposide use.
Results
168 patients with a median age of 49 38, 59 were included. Forty-three (25.6%) patients presented with at least 1 microbiologically documented HAI throughout ICU stay. After adjustment, cumulative incidence of HAI was higher in patients receiving etoposide (
p
= 0.007), while survival was unaffected by etoposide status (
p
= 0.824). By multivariable analysis, etoposide treatment was associated with a higher incidence of HAIs (sHR 3.75 1.05, 6.67), whereas no association with survival (sHR 0.53 0.20, 1.98) was found. Other factors associated with increased mortality after adjustment included age, immunodepression, male sex, SOFA score > 13, and occurrence of HAI.
Conclusions
In patients with sHS, etoposide treatment is independently associated with increased occurrence of HAIs, whereas no association with survival was found. Intensivists should be aware of increased infectious risk, to promptly detect and treat infections in this specific setting. Studies to assess benefits from prophylactic anti-infectious agents in this setting are warranted and the lack of benefit of etoposide on survival needs to be interpreted cautiously.
PDF
