Preexisting Diabetes Mellitus and All-Cause Mortality in Adult Patients With Sepsis: A Population-Based Cohort Study.

OBJECTIVES: We assessed the association of preexisting diabetes mellitus with all-cause mortality and organ support receipt in adult patients with sepsis. DESIGN: Population-based cohort study. SETTING: Ontario, Canada (2008-2019). POPULATION: Adult patients (18 yr old or older) with a first sepsis-related hospitalization episode. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main exposure of interest was preexisting diabetes (either type 1 or 2). The primary outcome was all-cause mortality by 90 days; secondary outcomes included receipt of invasive mechanical ventilation and new renal replacement therapy. We report adjusted (for baseline characteristics using standardization) risk ratios (RRs) alongside 95% CIs. A main secondary analysis evaluated the potential mediation by prior metformin use of the association between preexisting diabetes and all-cause mortality following sepsis. Overall, 503,455 adults with a first sepsis-related hospitalization episode were included; 36% had preexisting diabetes. Mean age was 73 years, and 54% of the cohort were females. Preexisting diabetes was associated with a lower adjusted risk of all-cause mortality at 90 days (RR, 0.81; 95% CI, 0.80-0.82). Preexisting diabetes was associated with an increased risk of new renal replacement therapy (RR, 1.53; 95% CI, 1.46-1.60) but not invasive mechanical ventilation (RR, 1.03; 95% CI, 1.00-1.05). Overall, 21% (95% CI, 19-28) of the association between preexisting diabetes and reduced risk of all-cause mortality was mediated by prior metformin use. CONCLUSIONS: Preexisting diabetes is associated with a lower risk of all-cause mortality and higher risk of new renal replacement therapy among adult patients with sepsis. Future studies should evaluate the underlying mechanisms of these associations.

Real-time machine learning-assisted sepsis alert enhances the timeliness of antibiotic administration and diagnostic accuracy in emergency department patients with sepsis: a cluster-randomized trial.

Machine learning (ML) has been applied in sepsis recognition across different healthcare settings with outstanding diagnostic accuracy. However, the advantage of ML-assisted sepsis alert in expediting clinical decisions leading to enhanced quality for emergency department (ED) patients remains unclear. A cluster-randomized trial was conducted in a tertiary-care hospital. Adult patient data were subjected to an ML model for sepsis alert. Patient visits were assigned into one of two groups. In the intervention cluster, staff received alerts on a display screen if patients met the ML threshold for sepsis diagnosis, while patients in the control cluster followed the regular alert process. The study compared triage-to-antibiotic (TTA) time, length of stay, and mortality rate between the two groups. Additionally, the diagnostic performance of the ML model was assessed. A total of 256 (intervention) and 318 (control) sepsis patients were analyzed. The proportions of patients who received antibiotics within 1 and 3 h were higher in the intervention group than in the control group (in 1 h; 68.4 vs. 60.1%, respectively; P = 0.04, in 3 h; 94.5 vs. 89.0%, respectively; P = 0.02). The median TTA times were marginally shorter in the intervention group (46 vs. 50 min). The area under the receiver operating characteristic curve (AUROC) of ML in early sepsis identification was significantly higher than qSOFA, SIRS, and MEWS. The ML-assisted sepsis alert system may help sepsis ED patients receive antibiotics more rapidly than with the conventional, human-dedicated alert process. The diagnostic performance of ML in prompt sepsis detection was superior to that of the rule-based system.Trial registration Thai Clinical Trials Registry TCTR20230120001. Registered 16 January 2023-Retrospectively registered, https://www.thaiclinicaltrials.org/show/TCTR20230120001 .

Machine learning algorithms for early sepsis detection in the emergency department: A retrospective study.

BACKGROUND: Early recognition and treatment of sepsis are crucial for improving patient outcomes. However, the diagnosis of sepsis remains challenging because of vague clinical presentations. OBJECTIVES: We aim to developed novel sepsis screening tools with machine learning models and compared their performance with traditional methods. METHODS: We used machine learning algorithms to develop models for early risk prediction of sepsis based on retrospective single-center electronic health record data from adult patients who presented to the emergency department (ED) from June 2018 through May 2020. Available triage data including vital signs, baseline characteristics, and chief complaints served as predictors. In our study, 80% and 20% of the data were randomly split into training and testing sets, respectively. Derived from the training set, we built the models based on four machine learning algorithms: logistic regression, gradient boosting, random forest, and neural network. Our primary outcome was the model performance that predicted the final diagnosis of sepsis determined by the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and predictive performance compared with those of the reference models (quick sequential organ failure assessment [qSOFA], modified early warning score [MEWS], and systemic inflammatory response syndrome [SIRS]) using the testing dataset. RESULTS: In total, 133,707 ED visits were analyzed. All machine learning models outperformed the reference models by achieving a higher AUROC (e.g., AUROC 0.931 [95% CI 0.921-0.944] in our best model (random forest algorithm) vs 0.635 [95% CI 0.613-0.660] in qSOFA, 0.688 [95% CI 0.662-0.715] in MEWS, and 0.814 [95% CI 0.794-0.833] in SIRS). CONCLUSION: The machine learning models demonstrated superior performance in prediction of sepsis diagnosis among emergency patients compared with that using the traditional screening tools. Further studies are needed to determine whether the models will enhance physicians' judgments and improve patient outcomes.

Randomized Controlled Trial of Ultrasound-guided Fluid Resuscitation of Sepsis-Induced Hypoperfusion and Septic Shock.

INTRODUCTION: The ultrasound measurement of inferior vena cava (IVC) diameter change during respiratory phase to guide fluid resuscitation in shock patients is widely performed, but the benefit on reducing the mortality of sepsis patients is questionable. The study objective was to evaluate the 30-day mortality rate of patients with sepsis-induced tissue hypoperfusion (SITH) and septic shock (SS) treated with ultrasound-guided fluid management (UGFM) using ultrasonographic change of the IVC diameter during respiration compared with those treated with the usual-care strategy. METHODS: This was a randomized controlled trial conducted in an urban, university-affiliated tertiary-care hospital. Adult patients with SITH/SS were randomized to receive treatment with UGFM using respiratory change of the IVC (UGFM strategy) or with the usual-care strategy during the first six hours after emergency department (ED) arrival. We compared the 30-day mortality rate and other clinical outcomes between the two groups. RESULTS: A total of 202 patients were enrolled, 101 in each group (UGFM vs usual-care strategy) for intention-to-treat analysis. There was no significant difference in 30-day overall mortality between the two groups (18.8% and 19.8% in the usual-care and UGFM strategy, respectively; p > 0.05 by log rank test). Neither was there a difference in six-hour lactate clearance, a change in the sequential organ failure assessment score, or length of hospital stay. However, the cumulative fluid amount given in 24 hours was significantly lower in the UGFM arm. CONCLUSION: In our ED setting, the use of respiratory change of IVC diameter determined by point-of-care ultrasound to guide initial fluid resuscitation in SITH/SS ED patients did not improve the 30-day survival probability or other clinical parameters compared to the usual-care strategy. However, the IVC ultrasound-guided resuscitation was associated with less amount of fluid used.

Difficult airway predictors were associated with decreased use of neuromuscular blocking agents in emergency airway management: a retrospective cohort study in Thailand.

BACKGROUND: It is recommended that difficult airway predictors be evaluated before emergency airway management. However, little is known about how patients with difficult airway predictors are managed in emergency departments. We aimed to explore the incidence, management and outcomes of patients with difficult airway predictors in an emergency department. METHODS: We conducted a retrospective study using intubation data collected by a prospective registry in an academic emergency department from November 2017 to October 2018. Records with complete assessment of difficult airway predictors were included. Two categories of predictors were analyzed: predicted difficult intubation by direct laryngoscopy and predicted difficult bag-mask ventilation. The former was evaluated based on difficult external appearance, mouth opening and thyromental distance, Mallampati score, obstruction, and limited neck mobility as in the mnemonic "LEMON". The latter was evaluated based on difficult mask sealing, obstruction or obesity, absence of teeth, advanced age and reduced pulmonary compliance as in the mnemonic "MOANS". The incidence, management and outcomes of patients with these difficult airway predictors were explored. RESULTS: During the study period, 220 records met the inclusion criteria. At least 1 difficult airway predictor was present in 183 (83.2%) patients; 57 (25.9%) patients had at least one LEMON feature, and 178 (80.9%) had at least one MOANS feature. Among patients with at least one difficult airway predictor, both sedation and neuromuscular blocking agents were used in 105 (57.4%) encounters, only sedation was used in 65 (35.5%) encounters, and no medication was administered in 13 (7.1%) encounters. First-pass success was accomplished in 136 (74.3%) of the patients. Compared with patients without predictors, patients with positive LEMON criteria were less likely to receive neuromuscular blocking agents (OR 0.46 (95% CI 0.24-0.87), p = 0.02) after adjusting for operator experience and device used. There were no significant differences between the two groups regarding glottic view, first-pass success, or complications. The LEMON criteria poorly predicted unsuccessful first pass and glottic view. CONCLUSIONS: In emergency airway management, difficult airway predictors were associated with decreased use of neuromuscular blocking agents but were not associated with glottic view, first-pass success, or complications.

The effects of a limited infusion rate of fluid in the early resuscitation of sepsis on glycocalyx shedding measured by plasma syndecan-1: a randomized controlled trial.

BACKGROUND: Aggressive fluid administration is recommended in the resuscitation of septic patients. However, the delivery of a rapid fluid bolus might cause harm by inducing degradation of the endothelial glycocalyx. This research aimed to examine the effects of the limited infusion rate of fluid on glycocalyx shedding as measured by syndecan-1 in patients with sepsis-induced hypoperfusion. METHODS: A prospective, randomized, controlled, open-label trial was conducted between November 2018 and February 2020 in an urban academic emergency department. Patients with sepsis-induced hypoperfusion, defined as hypotension or hyperlactatemia, were randomized to receive either the standard rate (30 ml/kg/h) or limited rate (10 ml/kg/h) of fluid for the first 30 ml/kg fluid resuscitation. Subsequently, the fluid rate was adjusted according to the physician's discretion but not more than that of the designated fluid rate for the total of 6 h. The primary outcome was differences in change of syndecan-1 levels at 6 h compared to baseline between standard and limited rate groups. Secondary outcomes included adverse events, organ failure, and 90-day mortality. RESULTS: We included 96 patients in the intention-to-treat analysis, with 48 assigned to the standard-rate strategy and 48 to the limited-rate strategy. The median fluid volume in 6 h in the limited-rate group was 39 ml/kg (interquartile range [IQR] 35-52 ml/kg) vs. 53 ml/kg (IQR 46-64 ml/kg) in the standard-rate group (p < 0.001). Patients in the limited-rate group were less likely to received vasopressors (17% vs 42%; p = 0.007) and mechanical ventilation (20% vs 41%; p = 0.049) during the first 6 h. There were no significantly different changes in syndecan-1 levels at 6 h between the two groups (geometric mean ratio [GMR] in the limited-rate group, 0.82; 95% confidence interval [CI], 0.66-1.02; p = 0.07). There were no significant differences in adverse events, organ failure outcomes, or mortality between the two groups. CONCLUSIONS: In sepsis resuscitation, the limited rate of fluid resuscitation compared to the standard rate did not significantly reduce changes in syndecan-1 at 6 h. TRIAL REGISTRATION: Thai Clinical Trials Registry number: TCTR20181010001. Registered 8 October 2018, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=4064.

Plasma syndecan-1 is associated with fluid requirements and clinical outcomes in emergency department patients with sepsis.

BACKGROUND: Degradation of the endothelial glycocalyx is recognized as a major part of the pathophysiology of sepsis. Previous clinical studies, mostly conducted in intensive care settings, showed associations between glycocalyx shedding and clinical outcomes. We aimed to explore the association of plasma syndecan-1, a marker of glycocalyx degradation, with the subsequent fluid requirements and clinical outcomes of emergency department patients with sepsis. METHODS: This was a post hoc analysis of a randomized trial of fluid resuscitation in the emergency department. The study was conducted in the emergency department of an urban 1500-bed tertiary care center. The data of 95 adults who were diagnosed with sepsis-induced hypoperfusion and had undergone baseline syndecan-1 measurement were included. The syndecan-1 levels at baseline (T0) and hour 6 (T6) were studied to characterize their association with clinical outcomes, including subsequent fluid administration, organ failure outcomes and mortality. RESULTS: The median syndecan-1 levels at T0 and T6 were 207 (IQR 135-438) and 207 (IQR 128-490) ng/ml, respectively. Syndecan-1 levels at T0 were correlated with baseline sequential organ failure assessment (SOFA) score (ρ = 0.35, p < 0.001). Syndecan-1 levels at both T0 and T6 were correlated with subsequent fluid administration over 24 and 72 h and associated with the diagnosis of septic shock, the maximum dose of vasopressors and the need for renal replacement therapy (p < 0.05). Higher syndecan-1 levels at T6 were associated with higher 90-day mortality (p = 0.03). CONCLUSIONS: In the emergency department, syndecan-1 levels were associated with fluid requirements, sepsis severity, organ dysfunction, and mortality.

Intensive fever control using a therapeutic normothermia protocol in patients with febrile early septic shock: A randomized feasibility trial and exploration of the immunomodulatory effects.

OBJECTIVES: Fever control has been shown to reduce short-term mortality in patients with septic shock. This study aimed to explore the feasibility of early intensive fever control in patients with septic shock and to assess the immunomodulatory effects of this intervention. METHODS: In this single-center, randomized, open-label trial, febrile patients with septic shock presenting to the emergency department were assigned to either a standard fever control or therapeutic normothermia group. Therapeutic normothermia involved intensive fever control in maintaining normothermia below 37°C. The primary outcome was the feasibility of fever control for 24 h. Secondary outcomes included changes in immunomodulatory biomarkers and adverse events. RESULTS: Fifteen patients were enrolled and analyzed. Fever control was comparable in both groups, but significantly more patients in the therapeutic normothermia group experienced shivering (p = 0.007). Both groups demonstrated increased C-reactive protein and unchanged neutrophil chemotaxis and CD11b expression. The therapeutic normothermia group revealed significant decreased IL-6 and IL-10. The standard fever control group significantly expressed increased monocytic human leukocyte antigen. There were no significant differences between the groups in terms of immunomodulation. CONCLUSIONS: Therapeutic normothermia was feasible in patients with febrile septic shock but was not superior to standard fever control in terms of average body temperature and host defense function. Shivering was more frequent in the therapeutic normothermia group. TRIAL REGISTRATION: Thai Clinical Trials Registry number: TCTR20160321001.

Pulmonary vein thrombosis associated with a large hiatal hernia.

BACKGROUND: Pulmonary vein thrombosis is a rare and potentially life-threatening condition. Reported cases of pulmonary vein thrombosis commonly occur as a complication of pulmonary surgery. There is a paucity of literature describing its clinical manifestations and non-operative causes. OBJECTIVE: We report the unique case of pulmonary vein thrombosis associated with a large hiatal hernia in a patient initially presenting with renal infarction. CASE REPORT: A 68-year-old man initially presented with increasing intensity of left lower quadrant pain. Contrast-enhanced computed tomography of the abdomen revealed left renal infarctions. Searching for an embolic source, further investigation revealed left inferior pulmonary vein thrombosis in the setting of venous compression in the lung tissue adjacent to a large hiatal hernia. CONCLUSION: Large hiatal hernias may be a nidus for pulmonary vein thrombosis, a potential source of left-sided emboli.