The association between levosimendan and mortality in patients with sepsis or septic shock: a systematic review and meta-analysis.

BACKGROUND: Levosimendan is increasingly being used in patients with sepsis or septic shock because of its potential to improve organ function and reduce mortality. We aimed to determine if levosimendan can reduce mortality in patients with sepsis or septic shock via meta-analysis. EVIDENCE SOURCES AND STUDY SELECTION: We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane Library databases from inception through 1 October 2022. Literature evaluating the efficacy of levosimendan in patients with sepsis or septic shock was included. DATA EXTRACTION AND OUTCOME MEASUREMENTS: Two reviewers extracted data and assessed study quality. A meta-analysis was performed to calculate an odds ratio (OR), 95% confidence intervals (CI), and P -values for 28-day mortality (primary outcome). Secondary outcomes included changes in indexes reflecting cardiac function before and after treatment, changes in serum lactate levels in the first 24 h of treatment, and the mean SOFA score during the study period. Safety outcomes included rates of tachyarrhythmias and total adverse reactions encountered with levosimendan. RESULTS: Eleven randomized controlled trials were identified, encompassing a total of 1044 patients. After using levosimendan, there was no statistical difference between groups for 28-day mortality (34.9% and 36.2%; OR: 0.93; 95% CI [0.72-1.2]; P  = 0.57; I 2  = 0%; trial sequential analysis-adjusted CI [0.6-1.42]) and sequential organ failure assessment (SOFA) score, and more adverse reactions seemed to occur in the levosimendan group, although the septic shock patient's heart function and serum lactate level improved. CONCLUSION: There was no association between the use of levosimendan and 28-day mortality and SOFA scores in patients with septic shock, though there was statistically significant improvement in cardiac function and serum lactate.

Establishment and evaluation of animal models of sepsis-associated encephalopathy.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is a critical disease caused by sepsis. In addition to high mortality, SAE can also adversely affect life quality and lead to significant socioeconomic costs. This review aims to explore the development of evaluation animal models of SAE, giving insight into the direction of future research in terms of its pathophysiology and therapy. METHODS: We performed a literature search from January 1, 2000, to December 31, 2022, in MEDLINE, PubMed, EMBASE, and Web of Science using related keywords. Two independent researchers screened all the accessible articles based on the inclusion and exclusion criteria and collected the relevant data of the studies. RESULTS: The animal models for sepsis are commonly induced through cecal ligation and puncture (CLP) or lipopolysaccharide (LPS) injection. SAE can be evaluated using nervous reflex scores and sepsis evaluation during the acute phase, or through Morris water maze (MWM), open-field test, fear condition (FC) test, inhibitory avoidance, and other tests during the late phase. CONCLUSION: CLP and LPS injection are the most common methods for establishing SAE animal models. Nervous reflexs cores, MWM, FC test, and inhibitory avoidance are widely used in SAE model analysis. Future research should focus on establishing a standardized system for SAE development and analysis.

CLINICAL PHENOTYPES OF SEPSIS-ASSOCIATED ENCEPHALOPATHY: A RETROSPECTIVE COHORT STUDY.

ABSTRACT: Background: Sepsis-associated encephalopathy (SAE) is a dysfunction of the central nervous system experienced during sepsis with variable clinical and pathophysiologic features. We sought to identify distinct SAE phenotypes in relation to clinical outcomes. Methods: The Medical Information Mart for Intensive Care IV (MIMIC-IV) database and the eICU database were used to conduct a retrospective cohort study. Adult sepsis patients were included and SAE was defined as having a Glasgow Coma Scale (GCS) score ˂15 or delirium. The following our clinical phenotypes were defined as: ischemic-hypoxic, metabolic, mixed (ischemic-hypoxic and metabolic), and unclassified. The primary outcome was in-hospital mortality. Results: The study enrolled 4,120 sepsis patients, 2,239 from MIMIC-IV (including 1,489 patients with SAE, 67%), and 1,881 from eICU (1,291, 69%). For the SAE cohort, 2,780 patients in total were enrolled (median age, 67 years; interquartile range, 56-76.8; 1,589 (57%) were male; median GCS score was 12 [8-14]; median Sequential Organ Failure Assessment score was 6 [4-9]). The SAE phenotype distributions between the MIMIC-IV and eICU cohorts were as follows (39% vs. 35% ischemic-hypoxic, P = 0.043; 38% vs. 40% metabolic, P = 0.239; 15% vs. 15% mixed, P = 0.972; 38% vs. 40% unclassified, P = 0.471). For the overall cohort, the in-hospital mortality for patients with ischemic-hypoxic, metabolic, mixed, or unclassified phenotypes was 33.9% (95% confidence interval, 0.3-0.37), 28.4% (0.26-0.31), 41.5% (0.37-0.46), and 14.2% (0.12-0.16), respectively. In the multivariable logistic analysis, the mixed phenotype was associated with the highest risk of in-hospital mortality after adjusting for age, sex, GCS, and modified Sequential Organ Failure Assessment score (adjusted odds ratio, 2.11; 95% confidence interval, 1.67-2.67; P < 0.001). Conclusions: Four SAE phenotypes had different clinical outcomes. The mixed phenotype had the worst outcomes. Further understanding of these phenotypes in sepsis may improve trial design and targeted SAE management.

Is rosuvastatin protective against sepsis-associated encephalopathy? A secondary analysis of the SAILS trial.

BACKGROUND: Sepsis is a common cause of death in emergency departments and sepsis-associated encephalopathy (SAE) is a major complication. Rosuvastatin may play a neuroprotective role due to its protective effects on the vascular endothelium and its anti-inflammatory functions. Our study aimed to explore the potential protective function of rosuvastatin against SAE. METHODS: Sepsis patients without any neurological dysfunction on admission were prospectively enrolled in the "Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome" study (SAILS trial, ClinicalTrials.gov number: NCT00979121). Patients were divided into rosuvastatin and placebo groups. This is a secondary analysis of the SAILS dataset. Baseline characteristics, therapy outcomes, and adverse drug events were compared between groups. RESULTS: A total of 86 patients were eligible for our study. Of these patients, 51 were treated with rosuvastatin. There were significantly fewer cases of SAE in the rosuvastatin group than in the placebo group (32.1% vs. 57.1%, P=0.028). However, creatine kinase levels were significantly higher in the rosuvastatin group than in the placebo group (233 [22-689] U/L vs. 79 [12-206] U/L, P=0.034). CONCLUSION: Rosuvastatin appears to have a protective role against SAE but may result in a higher incidence of adverse events.

Norepinephrine use in cardiogenic shock patients is associated with increased 30 day mortality.

AIMS: Norepinephrine is recommended as a first-line vasopressor agent in the haemodynamic stabilization of cardiogenic shock. The survival benefit of norepinephrine therapy has not been demonstrated in clinical practice, however. This study aimed to explore the relationship between norepinephrine use and outcomes in cardiogenic shock patients in real-world conditions. METHODS AND RESULTS: We conducted a retrospective cohort study based on the Medical Information Mart for Intensive Care III (MIMIC-III) database. Cardiogenic shock patients were enrolled and categorized into a norepinephrine group or a non-norepinephrine group. Propensity score matching (PSM) was used to control for confounders. Cox proportional-hazards models and multivariable logistic regression were used to investigate the relationship between norepinephrine treatment and mortality. A total of 927 eligible patients were included: 552 patients in the norepinephrine group and 375 patients in the non-norepinephrine group. After PSM, 222 cases from each group were matched using a 1:1 matching algorithm. Thirty day mortality for patients treated with norepinephrine was significantly higher than for those in the non-norepinephrine group (41% vs. 30%, OR 1.61, 95% CI 1.09-2.39, P = 0.017; HR 1.50, 95% CI 1.09-2.06, P = 0.013). In the multivariable analysis, there was no significant difference between norepinephrine therapy and long-term (90 day, 180 day, or 1 year) mortality (90 day (OR 1.19, 95% CI 0.82-1.74, P = 0.363), 180 day (OR 1.17, 95% CI 0.80-1.70, P = 0.418), 1 year (OR 1.14, 95% CI 0.79-1.66, P = 0.477). Patients in the norepinephrine group required more mechanical ventilation (84% vs. 67%, OR 2.67, 95% CI 1.70-4.25, P < 0.001) and experienced longer ICU stays (median 7 vs. 4 days, OR 7.92, 95% CI 1.40-44.83, P = 0.020) than non-norepinephrine group. CONCLUSIONS: Cardiogenic shock patients treated with norepinephrine were associated with significantly increased short-term mortality, while no significant difference was found on long-term survival rates. Future trials are needed to validate and explore this association.

Development of an intensive simulating training program in emergency medicine for medical students in China.

BACKGROUND: A national standardized emergency medicine (EM) curriculum for medical students, including specific competencies in procedural skills, are absent in many countries. The development of an intensive simulating training program in EM, based on a tight schedule, is anticipated to enhance the competency of medical students. METHODS: A 3-day intensive EM training program, consisting of four procedural skills and 8-hour case-based learning (CBL), was developed by experienced physicians from the EM department in Peking Union Medical College Hospital (PUMCH). Medical students from Peking Union Medical College (PUMC) and Tsinghua University (THU) participated in the training. Three written tests were cautiously designed to examine the short-term (immediately after the program) and long-term (6 months after the program) efficacy of the training. After completion of the training program, an online personal appraisal questionnaire was distributed to the students on WeChat (a mobile messaging App commonly used in China) to achieve anonymous self-evaluation. RESULTS: Ninety-seven out of 101 students completed the intensive training and took all required tests. There was a significant increase in the average score after the intensive simulating training program (pre-training 13.84 vs. 15.57 post-training, P<0.001). Compared with the pre-training test, 63 (64.9%) students made progress. There was no significant difference in scores between the tests taken immediately after the program and 6 months later (15.57±2.22 vs. 15.38±2.37, P=0.157). Students rated a higher score in all diseases and procedural skills, and felt that their learning was fruitful. CONCLUSIONS: The introduction of a standardized intensive training program in EM focusing on key competencies can improve clinical confidence, knowledge, and skills of medical students toward the specialty. In addition, having such a program can also enhance student's interest in EM as a career choice which may enhance recruitment into the specialty and workplace planning.

Family intervention for delirium for patients in the intensive care unit: A systematic meta-analysis.

Delirium is one of the common manifestations of acute brain dysfunction in critically ill patients. We aimed to evaluate the effect of family intervention on reducing the delirium incidence in patients hospitalized in the intensive care unit (ICU). We searched electronic databases for randomized clinical trials, cohort, and before-and-after studies up to September 2021 using the MeSH terms ("family" OR "family caregiver") AND ("delirium"). A total of 6 studies including 4199 patients were analyzed. Compared to the control group, the risk of delirium was 24% lower in the family intervention group (OR 0·76 [0·67-0·86], P = 0.20, I2 = 31%). Pooled data from two trials showed that family intervention was associated with fewer delirium days (SMD: -1.13, 95% CI: -1.91 to -0.34; P = 0.08; I2 = 67%;). However, there were no significant differences between the two groups in the length of ICU stay, mechanical ventilation duration, and mortality (ICU stay days: MD: -0.62 days; 95% CI: -1.49 to 0.24; P = 0.14; I2 = 72%; mechanical ventilation days: MD: -0.48 days; 95% CI: -2.10 to 1.13; P = 0.56; I2 = 0%; mortality: OR: 0.68, 95% CI: 0.22 to 2.09; P = 0.08; I2 = 67%). Current evidence supports the use of family intervention in reducing the delirium risk and delirium days in hospitalized ICU patients. However, its effects on reducing ICU stay length, ventilation duration, and mortality require further study. Future research should consider identifying the specific family intervention strategies and their duration.