Validation of Adult Sepsis Event and Epidemiologic Analysis of Sepsis Prevalence and Mortality Using Adult Sepsis Event's Electronic Health Records-Based Sequential Organ Failure Assessment Criteria: A Single-Center Study in South Korea.

OBJECTIVES: In 2018, the Centers for Disease Control and Prevention introduced the Adult Sepsis Event (ASE) definition, using electronic health records (EHRs) data for surveillance and sepsis quality improvement. However, data regarding ASE outside the United States remain limited. We therefore aimed to validate the diagnostic accuracy of the ASE and to assess the prevalence and mortality of sepsis using ASE. DESIGN: Retrospective cohort study. SETTING: A single center in South Korea, with 2732 beds including 221 ICU beds. PATIENTS: During the validation phase, adult patients who were hospitalized or visiting the emergency department between November 5 and November 11, 2019, were included. In the subsequent phase of epidemiologic analysis, we included adult patients who were admitted from January to December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ASE had a sensitivity of 91.6%, a specificity of 98.3%, a positive predictive value (PPV) of 57.4%, and a negative predictive value of 99.8% when compared with the Sepsis-3 definition. Of 126,998 adult patient hospitalizations in 2020, 6,872 cases were diagnosed with sepsis based on the ASE (5.4% per year), and 893 patients were identified as having sepsis according to the International Classification of Diseases, 10th Edition (ICD-10) (0.7% per year). Hospital mortality rates were 16.6% (ASE) and 23.5% (ICD-10-coded sepsis). Monthly sepsis prevalence and hospital mortality exhibited less variation when diagnosed using ASE compared with ICD-10 coding (coefficient of variation [CV] for sepsis prevalence: 0.051 vs. 0.163, Miller test p < 0.001; CV for hospital mortality: 0.087 vs. 0.261, p = 0.001). CONCLUSIONS: ASE demonstrated high sensitivity and a moderate PPV compared with the Sepsis-3 criteria in a Korean population. The prevalence of sepsis, as defined by ASE, was 5.4% per year and was similar to U.S. estimates. The prevalence of sepsis by ASE was eight times higher and exhibited less monthly variability compared with that based on the ICD-10 code.

Pre-Sepsis Length of Hospital Stay and Mortality: A Nationwide Multicenter Cohort Study.

BACKGROUND: Prolonged length of hospital stay (LOS) is associated with an increased risk of hospital-acquired conditions and worse outcomes. We conducted a nationwide, multicenter, retrospective cohort study to determine whether prolonged hospitalization before developing sepsis has a negative impact on its prognosis. METHODS: We analyzed data from 19 tertiary referral or university-affiliated hospitals between September 2019 and December 2020. Adult patients with confirmed sepsis during hospitalization were included. In-hospital mortality was the primary outcome. The patients were divided into two groups according to their LOS before the diagnosis of sepsis: early- (< 5 days) and late-onset groups (≥ 5 days). Conditional multivariable logistic regression for propensity score matched-pair analysis was employed to assess the association between late-onset sepsis and the primary outcome. RESULTS: A total of 1,395 patients were included (median age, 68.0 years; women, 36.3%). The early- and late-onset sepsis groups comprised 668 (47.9%) and 727 (52.1%) patients. Propensity score-matched analysis showed an increased risk of in-hospital mortality in the late-onset group (adjusted odds ratio [aOR], 3.00; 95% confidence interval [CI], 1.69-5.34). The same trend was observed in the entire study population (aOR, 1.85; 95% CI, 1.37-2.50). When patients were divided into LOS quartile groups, an increasing trend of mortality risk was observed in the higher quartiles (P for trend < 0.001). CONCLUSION: Extended LOS before developing sepsis is associated with higher in-hospital mortality. More careful management is required when sepsis occurs in patients hospitalized for ≥ 5 days.

Polymicrobial bloodstream infections per se do not increase mortality compared to monomicrobial bloodstream infections in sepsis patients: a Korean nationwide sepsis cohort study.

BACKGROUND: There is limited information about the outcomes of polymicrobial bloodstream infections in patients with sepsis. We aimed to investigate outcomes of polymicrobial bloodstream infections compared to monomicrobial bloodstream infections. METHODS: This study used data from the Korean Sepsis Alliance Registry, a nationwide database of prospective observational sepsis cohort. Adult sepsis patients with bloodstream infections from September 2019 to December 2021 at 20 tertiary or university-affiliated hospitals in South Korea were analyzed. RESULTS: Among the 3,823 patients with bloodstream infections, 429 of them (11.2%) had polymicrobial bloodstream infections. The crude hospital mortality of patients with sepsis with polymicrobial bloodstream infection and monomicrobial bloodstream infection was 35.7% and 30.1%, respectively (p = 0.021). However, polymicrobial bloodstream infections were not associated with hospital mortality in the proportional hazard analysis (HR 1.15 [0.97-1.36], p = 0.11). The inappropriate use of antibiotics was associated with increased mortality (HR 1.37 [1.19-1.57], p < 0.001), and source control was associated with decreased mortality (HR 0.51 [0.42-0.62], p < 0.001). CONCLUSIONS: Polymicrobial bloodstream infections per se were not associated with hospital mortality in patients with sepsis as compared to monomicrobial bloodstream infections. The appropriate use of antibiotics and source control were associated with decreased mortality in bloodstream infections regardless of the number of microbial pathogens.

Prognosis of mechanically ventilated patients with COVID-19 after failure of high-flow nasal cannula: a retrospective cohort study.

BACKGROUND: There is an argument whether the delayed intubation aggravate the respiratory failure in Acute respiratory distress syndrome (ARDS) patients with coronavirus disease 2019 (COVID-19). We aimed to investigate the effect of high-flow nasal cannula (HFNC) failure before mechanical ventilation on clinical outcomes in mechanically ventilated patients with COVID-19. METHODS: This retrospective cohort study included mechanically ventilated patients who were diagnosed with COVID-19 and admitted to the intensive care unit (ICU) between February 2020 and December 2021 at Asan Medical Center. The patients were divided into HFNC failure (HFNC-F) and mechanical ventilation (MV) groups according to the use of HFNC before MV. The primary outcome of this study was to compare the worst values of ventilator parameters from day 1 to day 3 after mechanical ventilation between the two groups. RESULTS: Overall, 158 mechanically ventilated patients with COVID-19 were included in this study: 107 patients (67.7%) in the HFNC-F group and 51 (32.3%) in the MV group. The two groups had similar profiles of ventilator parameter from day 1 to day 3 after mechanical ventilation, except of dynamic compliance on day 3 (28.38 mL/cmH2O in MV vs. 30.67 mL/H2O in HFNC-F, p = 0.032). In addition, the HFNC-F group (5.6%) had a lower rate of ECMO at 28 days than the MV group (17.6%), even after adjustment (adjusted hazard ratio, 0.30; 95% confidence interval, 0.11-0.83; p = 0.045). CONCLUSIONS: Among mechanically ventilated COVID-19 patients, HFNC failure before mechanical ventilation was not associated with deterioration of respiratory failure.

Shock indices are associated with in-hospital mortality among patients with septic shock and normal left ventricular ejection fraction.

BACKGROUND: The understanding of shock indices in patients with septic shock is limited, and their values may vary depending on cardiac function. METHODS: This prospective cohort study was conducted across 20 university-affiliated hospitals (21 intensive care units [ICUs]). Adult patients (≥19 years) with septic shock admitted to the ICUs during a 29-month period were included. The shock index (SI), diastolic shock index (DSI), modified shock index (MSI), and age shock index (Age-SI) were calculated at sepsis recognition (time zero) and ICU admission. Left ventricular (LV) function was categorized as either normal LV ejection fraction (LVEF ≥ 50%) or decreased LVEF (<50%). RESULTS: Among the 1,194 patients with septic shock, 392 (32.8%) who underwent echocardiography within 24 h of time zero were included in the final analysis (normal LVEF: n = 246; decreased LVEF: n = 146). In patients with normal LVEF, only survivors demonstrated significant improvement in SI, DSI, MSI, and Age-SI values from time zero to ICU admission; however, no notable improvements were found in all patients with decreased LVEF. The completion of vasopressor or fluid bundle components was significantly associated with improved indices in patients with normal LVEF, but not in those with decreased LVEF. In multivariable analysis, each of the four indices at ICU admission was significantly associated with in-hospital mortality (P < 0.05) among patients with normal LVEF; however, discrimination power was better in the indices for patients with lower lactate levels (≤ 4.0 mmol/L), compared to those with higher lactate levels. CONCLUSIONS: The SI, DSI, MSI, and Age-SI at ICU admission were significantly associated with in-hospital mortality in patients with septic shock and normal LVEF, which was not found in those with decreased LVEF. Our study emphasizes the importance of interpreting shock indices in the context of LV function in septic shock.

Association between mechanical power and intensive care unit mortality in Korean patients under pressure-controlled ventilation.

BACKGROUND: Mechanical power (MP) has been reported to be associated with clinical outcomes. Because the original MP equation is derived from paralyzed patients under volume-controlled ventilation, its application in practice could be limited in patients receiving pressure-controlled ventilation (PCV). Recently, a simplified equation for patients under PCV was developed. We investigated the association between MP and intensive care unit (ICU) mortality. METHODS: We conducted a retrospective analysis of Korean data from the Fourth International Study of Mechanical Ventilation. We extracted data of patients under PCV on day 1 and calculated MP using the following simplified equation: MPPCV = 0.098 ∙ respiratory rate ∙ tidal volume ∙ (ΔPinsp + positive end-expiratory pressure), where ΔPinsp is the change in airway pressure during inspiration. Patients were divided into survivors and non-survivors and then compared. Multivariable logistic regression was performed to determine association between MPPCV and ICU mortality. The interaction of MPPCV and use of neuromuscular blocking agent (NMBA) was also analyzed. RESULTS: A total of 125 patients was eligible for final analysis, of whom 38 died in the ICU. MPPCV was higher in non-survivors (17.6 vs. 26.3 J/min, P<0.001). In logistic regression analysis, only MPPCV was significantly associated with ICU mortality (odds ratio, 1.090; 95% confidence interval, 1.029-1.155; P=0.003). There was no significant effect of the interaction between MPPCV and use of NMBA on ICU mortality (P=0.579). CONCLUSIONS: MPPCV is associated with ICU mortality in patients mechanically ventilated with PCV mode, regardless of NMBA use.

Age distribution and clinical results of critically ill patients above 65-year-old in an aging society: A retrospective cohort study.

Background: Increasing age has been observed among patients admitted to the intensive care unit(ICU). Age traditionally considered a risk factor for ICU mortality. We investigated how the epidemiology and clinical outcomes of older ICU patients have changed over a decade. Methods: We analyzed patients admitted to the ICU at a university hospital in Seoul, South Korea. We defined patients aged 65 and older as older patients. Changes in age groups and mortality risk factors over the study period were analyzed. Results: A total of 32,322 patients were enrolled who aged ≥ 65 years admitted to the ICUs between January 1, 2007, and December 31, 2017. Patients aged 65 years accounted for 35% and of these, the older(O: 65-74 yrs) comprised 19,630(66.5%), very older(VO: 75-84 yrs) group 8,573(29.1%), and very very older(VVO: 85 years) group 1,300(4.4 %). The mean age of ICU patients over the study period increased(71.9±5.6yrs in 2007 vs. 73.2±6.1yrs in 2017) and the proportions of the VO and VVO group both increased. Over the period, the proportion of female increased(37.9% in 2007 vs. 43.3% in 2017), and increased ICU admissions for medical reasons(39.7% in 2007 vs. 40.2% in 2017). In-hospital mortality declined across all older age groups, from 10.3% in 2007 to 7.6% in 2017. Hospital length of stay(LOS) decreased in all groups, but ICU LOS decreased only in the O and VO groups. Conclusion: The study indicates a changing demographic in ICUs with an increase in older patients, and suggests a need for customized ICU treatment strategies and resources.

Early Prediction of Mortality for Septic Patients Visiting Emergency Room Based on Explainable Machine Learning: A Real-World Multicenter Study.

BACKGROUND: Worldwide, sepsis is the leading cause of death in hospitals. If mortality rates in patients with sepsis can be predicted early, medical resources can be allocated efficiently. We constructed machine learning (ML) models to predict the mortality of patients with sepsis in a hospital emergency department. METHODS: This study prospectively collected nationwide data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Patients were enrolled from 19 hospitals between September 2019 and December 2020. For acquired data from 3,657 survivors and 1,455 deaths, six ML models (logistic regression, support vector machine, random forest, extreme gradient boosting [XGBoost], light gradient boosting machine, and categorical boosting [CatBoost]) were constructed using fivefold cross-validation to predict mortality. Through these models, 44 clinical variables measured on the day of admission were compared with six sequential organ failure assessment (SOFA) components (PaO2/FIO2 [PF], platelets (PLT), bilirubin, cardiovascular, Glasgow Coma Scale score, and creatinine). The confidence interval (CI) was obtained by performing 10,000 repeated measurements via random sampling of the test dataset. All results were explained and interpreted using Shapley's additive explanations (SHAP). RESULTS: Of the 5,112 participants, CatBoost exhibited the highest area under the curve (AUC) of 0.800 (95% CI, 0.756-0.840) using clinical variables. Using the SOFA components for the same patient, XGBoost exhibited the highest AUC of 0.678 (95% CI, 0.626-0.730). As interpreted by SHAP, albumin, lactate, blood urea nitrogen, and international normalization ratio were determined to significantly affect the results. Additionally, PF and PLTs in the SOFA component significantly influenced the prediction results. CONCLUSION: Newly established ML-based models achieved good prediction of mortality in patients with sepsis. Using several clinical variables acquired at the baseline can provide more accurate results for early predictions than using SOFA components. Additionally, the impact of each variable was identified.

Early Sepsis-Associated Acute Kidney Injury and Obesity.

Importance: The prevalence of obesity is increasing in the intensive care unit (ICU). Although obesity is a known risk factor for chronic kidney disease, its association with early sepsis-associated acute kidney injury (SA-AKI) and their combined association with patient outcomes warrant further investigation. Objective: To explore the association between obesity, early SA-AKI incidence, and clinical outcomes in patients with sepsis. Design, Setting, and Participants: This nationwide, prospective cohort study analyzed patients aged 19 years or older who had sepsis and were admitted to 20 tertiary hospital ICUs in Korea between September 1, 2019, and December 31, 2021. Patients with preexisting stage 3A to 5 chronic kidney disease and those with missing body mass index (BMI) values were excluded. Exposures: Sepsis and hospitalization in the ICU. Main Outcomes and Measures: The primary outcome was SA-AKI incidence within 48 hours of ICU admission, and secondary outcomes were mortality and clinical recovery (survival to discharge within 30 days). Patients were categorized by BMI (calculated as weight in kilograms divided by height in meters squared), and data were analyzed by logistic regression adjusted for key characteristics and clinical factors. Multivariable fractional polynomial regression models and restricted cubic spline models were used to analyze the clinical outcomes with BMI as a continuous variable. Results: Of the 4041 patients (median age, 73 years [IQR, 63-81 years]; 2349 [58.1%] male) included in the study, 1367 (33.8%) developed early SA-AKI. Obesity was associated with a higher incidence of SA-AKI compared with normal weight (adjusted odds ratio [AOR], 1.40; 95% CI, 1.15-1.70), as was every increase in BMI of 10 (OR, 1.75; 95% CI, 1.47-2.08). While obesity was associated with lower in-hospital mortality in patients without SA-AKI compared with their counterparts without obesity (ie, underweight, normal weight, overweight) (AOR, 0.72; 95% CI, 0.54-0.94), no difference in mortality was observed in those with SA-AKI (AOR, 0.85; 95% CI, 0.65-1.12). Although patients with obesity without SA-AKI had a greater likelihood of clinical recovery than their counterparts without obesity, clinical recovery was less likely among those with both obesity and SA-AKI. Conclusions and Relevance: In this cohort study of patients with sepsis, obesity was associated with a higher risk of early SA-AKI and the presence of SA-AKI modified the association of obesity with clinical outcomes.

Automatic adjustment of oxygen concentration during high-flow nasal cannula treatment using a targeted SpO2 feedback system.

AIM: To test whether targeted SpO2 feedback (TSF), an automatic control system for fraction of inspired oxygen (FiO2), achieves more time in the optimal SpO2 range and/or reduces the frequency of manual adjustments to administered FiO2 compared with conventional manual titration in patients with hypoxia on high-flow nasal cannula (HFNC) therapy. STUDY DESIGN: Twenty-two patients were recruited from two hospitals. For each, two sessions of manual mode and two sessions of TSF were applied in a random order, each session lasting 2 h. The target SpO2 on TSF was 95%. Oxygen monitoring levels were classified into four SpO2 ranges: hypoxia (≤ 89%), borderline (90%-93%), optimal (94%-96%) and hyperoxia (≥ 97%). The two modes were compared based on the proportion of time spent in each SpO2 range and the number of manual FiO2 adjustments. RESULTS: The proportion of time in the optimal SpO2 range was 20.5% under manual titration mode and 65.4% under TSF (p < .01). The proportions of time in the hypoxia range were 1.1% and 0.4%, respectively (p = .31), in the borderline range 4.7% and 3.5%, respectively (p = .54), and in the hyperoxia range 73.7% and 30.7%, respectively (p < .01). There were statistical differences only in the optimal and hyperoxia SpO2 ranges. During the 8 h, the frequency of manual FiO2 adjustment was 0.7 times for the manual mode and 0.2 times for TSF, showing no statistically significant difference (p = 0.076). CONCLUSION: Compared with manual titration, TSF achieved greater time of the optimal SpO2 and less time of hyperoxia during HFNC. The frequency of manual adjustments on TSF tended to be less than on manual titration mode. RELEVANCE TO CLINICAL PRACTICE: Automatic closed-loop algorithm FiO2 monitoring systems can achieve better oxygen treatments than conventional monitoring and may reduce nurse workloads. In the era of pandemic respiratory diseases, this system can also facilitate contactless SpO2 monitoring during HFNC therapy.

Mechanical ventilation practices in Asian intensive care units: A multicenter cross-sectional study.

PURPOSE: This study investigated current practices of mechanical ventilation in Asian intensive care units, focusing on tidal volume, plateau pressure, and positive end-expiratory pressure (PEEP). MATERIALS AND METHODS: In this multicenter cross-sectional study, data on mechanical ventilation and clinical outcomes were collected. Predictors of mortality were analyzed by univariate and multivariable logistic regression. A scoring system was generated to predict 28-day mortality. RESULTS: A total of 1408 patients were enrolled. In 138 patients with acute respiratory distress syndrome (ARDS), 65.9% were on a tidal volume ≤ 8 ml/kg predicted body weight (PBW), and 71.3% were on sufficient PEEP. In 1270 patients without ARDS, 88.8% were on a tidal volume ≤ 10 ml/kg PBW. A plateau pressure < 30 cmH2O was measured in 92.2% of patients. Mortality rates increased from 13% to 74% as the generated predictive score increased from 5 to ≥8.5. Income classification, age, SOFA score, PaO2/FiO2 ratio, plateau pressure, number of vasopressors, and steroid use were associated with mortality. CONCLUSIONS: In Asia, low tidal volume ventilation and sufficient PEEP were underused in patients with ARDS. The majority of patients without ARDS were on intermediate tidal volumes. Country income, age, and severity of illness were associated with mortality.

Clinical effects of bacteremia in sepsis patients with community-acquired pneumonia.

BACKGROUND: Data regarding the clinical effects of bacteremia on severe community-acquired pneumonia (CAP) are limited. Thus, we investigated clinical characteristics and outcomes of severe CAP patients with bacteremia compared with those of subjects without bacteremia. In addition, we evaluated clinical factors associated with bacteremia at the time of sepsis awareness. METHODS: We enrolled sepsis patients diagnosed with CAP at emergency departments (EDs) from an ongoing nationwide multicenter observational registry, the Korean Sepsis Alliance, between September 2019 and December 2020. For evaluation of clinical factors associated with bacteremia, we divided eligible patients into bacteremia and non-bacteremia groups, and logistic regression analysis was performed using the clinical characteristics at the time of sepsis awareness. RESULT: During the study period, 1,510 (47.9%) sepsis patients were caused by CAP, and bacteremia was identified in 212 (14.0%) patients. Septic shock occurred more frequently in the bacteremia group than in the non-bacteremia group (27.4% vs. 14.8%; p < 0.001). In multivariable analysis, hematologic malignancies and septic shock were associated with an increased risk of bacteremia. However, chronic lung disease was associated with a decreased risk of bacteremia. Hospital mortality was significantly higher in the bacteremia group than in the non-bacteremia group (27.3% vs. 40.6%, p < 0.001). The most prevalent pathogen in blood culture was Klebsiella pneumoniae followed by Escherichia coli in gram-negative pathogens. CONCLUSION: The incidence of bacteremia in severe CAP was low at 14.0%, but the occurrence of bacteremia was associated with increased hospital mortality. In severe CAP, hematologic malignancies and septic shock were associated with an increased risk of bacteremia.

The Association Between Tachycardia and Mortality in Septic Shock Patients According to Serum Lactate Level: A Nationwide Multicenter Cohort Study.

BACKGROUND: This study aimed to evaluate whether the effect of tachycardia varies according to the degree of tissue perfusion in septic shock. METHODS: Patients with septic shock admitted to the intensive care units were categorized into the tachycardia (heart rate > 100 beats/min) and non-tachycardia (≤ 100 beats/min) groups. The association of tachycardia with hospital mortality was evaluated in each subgroup with low and high lactate levels, which were identified through a subpopulation treatment effect pattern plot analysis. RESULTS: In overall patients, hospital mortality did not differ between the two groups (44.6% vs. 41.8%, P = 0.441), however, tachycardia was associated with reduced hospital mortality rates in patients with a lactate level ≥ 5.3 mmol/L (48.7% vs. 60.3%, P = 0.030; adjusted odds ratio [OR], 0.59, 95% confidence interval [CI], 0.35-0.99, P = 0.045), not in patients with a lactate level < 5.3 mmol/L (36.5% vs. 29.7%, P = 0.156; adjusted OR, 1.39, 95% CI, 0.82-2.35, P = 0.227). CONCLUSION: In septic shock patients, the effect of tachycardia on hospital mortality differed by serum lactate level. Tachycardia was associated with better survival in patients with significantly elevated lactate levels.

Impact of sepsis on Eastern Cooperative Oncology Group performance status among fully ambulatory patients: a prospective nationwide multicenter cohort.

Background: Investigations of the impact of sepsis on the Eastern Cooperative Oncology Group performance status (ECOG PS) of fully ambulatory patients are scarce. Methods: This is a retrospective analysis of prospectively collected nationwide data on septic patients recruited from 19 hospitals of the Korean Sepsis Alliance between August 2019 and December 2020. Adult septic patients with good ECOG PS (i.e., 0 or 1) before sepsis were enrolled in this study. The change in ECOG PS and the prevalence of disability (ECOG PS ≥2) at hospital discharge were recorded. Results: Of the 4,145 septic patients, 1,735 (41.9%) patients who had ECOG PS of 0 or 1 before sepsis and eventually survived to discharge were selected. After treatment for sepsis, the ECOG PS deteriorated in 514 (29.6%) patients; 376 (21.7%) patients had poor ECOG PS (i.e., ≥2) at hospital discharge. The proportion of patients with poor ECOG PS at hospital discharge increased with increases in the initial sequential organ failure assessment (SOFA) score and lactate level. Furthermore, poor ECOG PS at hospital discharge was found in young patients (aged <65 years, 17.4%), those with no history of cancer (18.2%) or with low comorbidities [Charlson comorbidity index (CCI) ≤2; 13.6%], and those without septic shock (19.9%). In multivariable analysis, age, solid cancer, immunocompromised condition, SOFA score, mechanical ventilation, and use of inappropriate empirical antibiotics (odds ratio: 1.786; 95% confidence interval: 1.151-2.771) were significant risk factors for poor ECOG PS. Conclusions: One in five septic patients who were fully ambulatory before sepsis were not functionally independent at hospital discharge. Incomplete functional recovery was also seen in a substantial proportion of younger patients, those with low comorbidities, and those without septic shock. However, the adequacy of empirical antibiotics may improve the functional status in such patients.

Extended Versus Intermittent Meropenem Infusion in the Treatment of Nosocomial Pneumonia: A Retrospective Single-Center Study.

The efficacy of extended meropenem infusions in patients with nosocomial pneumonia is not well defined. Therefore, we compared the clinical outcomes of extended versus intermittent meropenem infusions in the treatment of nosocomial pneumonia. We performed a retrospective analysis of extended versus intermittent meropenem infusions in adult patients who had been treated for nosocomial pneumonia at a medical ICU between 1 May 2018 and 30 April 2020. The primary outcome was mortality at 14 days. Overall, 64 patients who underwent an extended infusion and 97 with an intermittent infusion were included in this study. At 14 days, 10 (15.6%) patients in the extended group and 22 (22.7%) in the intermittent group had died (adjusted hazard ratio (HR), 0.55; 95% confidence interval (CI): 0.23-1.31; p = 0.174). In the subgroup analysis, significant differences in mortality at day 14 were observed in patients following empirical treatment with meropenem (adjusted HR, 0.17; 95% CI: 0.03-0.96; p = 0.045) and in Gram-negative pathogens identified by blood or sputum cultures (adjusted HR, 0.01; 95% CI: 0.01-0.83; p = 0.033). Extended infusion of meropenem compared with intermittent infusion as a treatment option for nosocomial pneumonia may have a potential advantage in specific populations.

Impact of a cumulative positive fluid balance during the first three ICU days in patients with sepsis: a propensity score-matched cohort study.

BACKGROUND: The optimal strategy for fluid management during the first few days of ICU in sepsis patients remains controversial. We aimed to investigate the impact of cumulative fluid balance during the first three days of ICU on the mortality of patients with sepsis. METHODS: This study analyzed prospectively collected data from the Korean Sepsis Alliance Database, which registered 11,981 sepsis patients from 20 hospitals. We selected three propensity score-matched cohorts consisting of patients with a negative or positive cumulative fluid balance during the first three ICU days: from ICU admission to the first midnight as the D1 cohort, until the second midnight as the D2 cohort, and until the third midnight as the D3 cohort. The propensity score for fluid balance was calculated using covariates including the amount of fluid output during the first three ICU days. The primary outcome was mortality at day 28 in the ICU. RESULTS: From a total of 11,981 patients, 2516 patients were included for propensity score matching. After matching in a 1:1 ratio, there were 483, 373, and 392 matched pairs of patients assigned to the D1, D2, and D3 cohorts, respectively. In the D1 cohort, there were no significant differences in mortality at day 28 (hazard ratio [HR], 1.17; 95% confidence interval [CI] 0.85-1.60; P = 0.354) between the two groups. The positive fluid groups in both the D2 (HR, 2.13; 95% CI 1.48-3.06; P < 0.001) and D3 (HR, 1.56; 95% CI 1.10-2.22; P = 0.012) cohorts had significantly higher mortality rates than the negative fluid groups. CONCLUSIONS: In patients with sepsis, a positive fluid balance on the first ICU day was not associated with mortality at day 28. In contrast, cumulative positive fluid balances on the second and third ICU days were associated with higher mortality at day 28.

A targeted metabolomics approach for sepsis-induced ARDS and its subphenotypes.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is etiologically and clinically a heterogeneous disease. Its diagnostic characteristics and subtype classification, and the application of these features to treatment, have been of considerable interest. Metabolomics is becoming important for identifying ARDS biology and distinguishing its subtypes. This study aimed to identify metabolites that could distinguish sepsis-induced ARDS patients from non-ARDS controls, using a targeted metabolomics approach, and to identify whether sepsis-induced direct and sepsis-induced indirect ARDS are metabolically distinct groups, and if so, confirm their metabolites and associated pathways. METHODS: This study retrospectively analyzed 54 samples of ARDS patients from a sepsis registry that was prospectively collected from March 2011 to February 2018, along with 30 non-ARDS controls. The cohort was divided into direct and indirect ARDS. Metabolite concentrations of five analyte classes (energy metabolism, free fatty acids, amino acids, phospholipids, sphingolipids) were measured using liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry by targeted metabolomics. RESULTS: In total, 186 metabolites were detected. Among them, 102 metabolites could differentiate sepsis-induced ARDS patients from the non-ARDS controls, while 14 metabolites could discriminate sepsis-induced ARDS subphenotypes. Using partial least-squares discriminant analysis, we showed that sepsis-induced ARDS patients were metabolically distinct from the non-ARDS controls. The main distinguishing metabolites were lysophosphatidylethanolamine (lysoPE) plasmalogen, PE plasmalogens, and phosphatidylcholines (PCs). Sepsis-induced direct and indirect ARDS were also metabolically distinct subgroups, with differences in lysoPCs. Glycerophospholipid and sphingolipid metabolism were the most significant metabolic pathways involved in sepsis-induced ARDS biology and in sepsis-induced direct/indirect ARDS, respectively. CONCLUSION: Our study demonstrated a marked difference in metabolic patterns between sepsis-induced ARDS patients and non-ARDS controls, and between sepsis-induced direct and indirect ARDS subpheonotypes. The identified metabolites and pathways can provide clues relevant to the diagnosis and treatment of individuals with ARDS.

Influence of gender on age-associated in-hospital mortality in patients with sepsis and septic shock: a prospective nationwide multicenter cohort study.

BACKGROUND: Numerous epidemiological studies investigating gender-dependent clinical outcomes in sepsis have shown conflicting evidence. This study aimed to investigate the effect of gender on in-hospital mortality due to sepsis according to age group. METHODS: This study used data from the Korean Sepsis Alliance, an ongoing nationwide prospective multicenter cohort from 19 participating hospitals in South Korea. All adult patients diagnosed with sepsis in the emergency departments of the participating hospitals between September 2019 and December 2021 were included in the analysis. Clinical characteristics and outcomes were compared between male and female. Eligible patients were stratified by age into 19-50 years, 50-80 years, and ≥ 80 years old individuals. RESULTS: During the study period, 6442 patients were included in the analysis, and 3650 (56.7%) were male. The adjusted odds ratio (OR) [95% confidence interval (CI)] for in-hospital mortality for male compared with female was 1.15 (95% CI = 1.02-1.29). Interestingly, in the age 19-50 group, the risk of in-hospital mortality for males was significantly lower than that of females [0.57 (95% CI = 0.35-0.93)]. For female, the risk of death remained relatively stable until around age 80 (P for linearity = 0.77), while in males, there was a linear increase in the risk of in-hospital death until around age 80 (P for linearity < 0.01). Respiratory infection (53.8% vs. 37.4%, p < 0.01) was more common in male, whereas urinary tract infection (14.7% vs. 29.8%, p < 0.01) was more common in female. For respiratory infection, male had significantly lower in-hospital mortality than female in the age 19-50 groups (adjusted OR = 0.29, 95% CI = 0.12-0.69). CONCLUSIONS: Gender may influence age-associated sepsis outcomes. Further studies are needed to replicate our findings and fully understand the interaction of gender and age on the outcomes of patients with sepsis.

Longitudinal trajectories of sedation level and clinical outcomes in patients who are mechanically ventilated based on a group-based trajectory model: a prospective, multicentre, longitudinal and observational study in Korea.

OBJECTIVES: Changes in sedation levels over a long time in patients who are mechanically ventilated are unknown. Therefore, we investigated the long-term sedation levels of these patients by classifying them into different longitudinal patterns. DESIGN: This was a multicentre, prospective, longitudinal, and observational study. SETTING: Twenty intensive care units (ICUs) spanning several medical institutions in Korea. PARTICIPANTS: Patients who received mechanical ventilation and sedatives in ICU within 48 hours of admission between April 2020 and July 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary objective of this study was to identify the pattern of sedation practice. Additionally, we analysed the associations of trajectory groups with clinical outcomes as the secondary outcome. RESULTS: Sedation depth was monitored using Richmond Agitation-Sedation Scale (RASS). A group-based trajectory model was used to classify 631 patients into four trajectories based on sedation depth: persistent suboptimal (13.2%, RASS ≤ -3 throughout the first 30 days), delayed lightening (13.9%, RASS ≥ -2 after the first 15 days), early lightening (38.4%, RASS ≥ -2 after the first 7 days) and persistent optimal (34.6%, RASS ≥ -2 during the first 30 days). 'Persistent suboptimal' trajectory was associated with delayed extubation (HR: 0.23, 95% CI: 0.16 to 0.32, p<0.001), longer ICU stay (HR: 0.36, 95% CI: 0.26 to 0.51, p<0.001) and hospital mortality (HR: 13.62, 95% CI: 5.99 to 30.95, p<0.001) compared with 'persistent optimal'. The 'delayed lightening' and 'early lightening' trajectories showed lower extubation probability (HR: 0.30, 95% CI: 0.23 to 0.41, p<0.001; HR: 0.72, 95% CI: 0.59 to 0.87, p<0.001, respectively) and ICU discharge (HR: 0.44, 95% CI: 0.33 to 0.59, p<0.001 and HR: 0.80, 95% CI: 0.65 to 0.97, p=0.024) compared with 'persistently optimal'. CONCLUSIONS: Among the four trajectories, 'persistent suboptimal' trajectory was associated with higher mortality.

The Profile of Early Sedation Depth and Clinical Outcomes of Mechanically Ventilated Patients in Korea.

BACKGROUND: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. METHODS: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation-Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. RESULTS: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death (P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.55-0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% CI, 0.56-0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79-1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65-2.17; P = 0.582). CONCLUSION: In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.