Daily Sepsis Research Analysis

BACKGROUND: Early and accurate diagnosis of sepsis and the ensuing organ dysfunction remain a challenge in the postoperative setting. Susceptibility to infections, as well as the subsequent immunological response, are driven to some extent by the genetic predisposition of the patient. The purpose of this study was to identify novel genetic variants associated with postoperative sepsis (POS) and surgical site infections (SSIs). METHODS: We conducted genome-wide association studies for POS and SSIs in the Electronic Medical Records and Genomics Network database. All patients with surgical and genomic information in Electronic Medical Records and Genomics were identified. Patients with a new diagnosis of sepsis/SSIs after surgery were classified as cases, and those without as controls. Analyses were performed using PLINK 2.0's logistic regression function. A p value of <5 × 10 -8 was considered statistically significant. RESULTS: A total of 59,755 participants were included in the analysis. Genetic regions on chromosomes 9 and 14 reached statistical significance for POS ( p < 5 × 10 -8 ). The most significant single-nucleotide polymorphisms (SNPs) were rs9413988 ( p = 5.59 × 10 -12 ) on chromosome 9 and rs35407594 ( p = 1.43 × 10 -10 ) on chromosome 14. The rs9413988 region is downstream to the phosphoglucomutase 5 pseudogene ( PGM5P2 ) and Zn-regulated GTPase metalloprotein activator 1F ( ZNGF1 ) and likely plays a role in transcription regulation, while rs35407594 corresponds to the olfactory receptor gene family, OR11 . Similar SNPs were also associated with SSIs. CONCLUSION: We have identified two genetic regions containing SNPs associated with POS and SSIs. These findings provide new avenues for investigation, which may help identify and guide point-of-care management for at-risk patients. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

BACKGROUND: Droplet digital PCR (ddPCR) is a highly sensitive tool for detecting bacterial DNA in bacterial bloodstream infections (BSI). This study aimed to examine the sensitivity and specificity of ddPCR and the association between bacterial DNA load in whole blood and the time-to-positivity (TTP) of blood culture (BC) in patients with Escherichia coli BSI. METHODS: This prospective study enrolled patients with E. coli BSI confirmed via BC at the Hiroshima University Hospital from June 2023 to August 2024. The E. coli DNA load in whole blood, which was simultaneously obtained from two BC sets, was measured using ddPCR with E. coli specific primer and probe. Whole blood samples from 50 patients with BC positive for pathogens other than E. coli (n = 25) and BC negative (n = 25) were also evaluated using ddPCR. RESULTS: A total of 131 patient samples were analyzed in this study. Of the 81 patients with E. coli BSI, ddPCR detected E. coli DNA in 67 (82.7%). The results of ddPCR for E. coli had a sensitivity of 82.7% (95% CI: 73.1-89.4%), specificity 100% (95% CI: 93.0-100%). Patients with positive ddPCR results had significantly shorter TTP than those with negative results (median, 8.8 h vs. 10.7 h, p < 0.001). The positivity rate for both BC sets was significantly higher in patients with positive ddPCR results than in those with negative results (89.6% vs. 35.1%, p < 0.001). Among ddPCR-positive patients, septic shock was significantly associated with intestinal perforation, higher E. coli DNA load, higher 28-d mortality, shorter TTP, and higher positivity rate for four bottles of BC than those without septic shock. The E. coli DNA load in whole blood negatively correlated with TTP (p < 0.001, R CONCLUSION: The E. coli DNA load in whole blood is inversely correlated with TTP. Notably, a higher E. coli DNA load is associated with septic shock.

OBJECTIVES: Heart rate control using beta-blockers in sepsis has traditionally been avoided because of concerns with worsening cardiac index and organ perfusion. Recent studies has explored the possible beneficial effects of targeted heart rate control in patients with septic shock who have tachycardia despite initial resuscitation. We performed a systematic review and meta-analysis to explore the effects of heart rate control in septic shock patients. METHODS: A systematic review and meta-analysis was conducted searching for studies from PubMed, Cochrane Central, and Embase registers for randomized controlled trials (RCTs) that compared the mortality of patients with sepsis and septic shock treated with targeted rate control. The literature search was done to include studies from January 2013 to December 2023. Two independent researchers independently assessed the studies and included RCTS in which adult patients (>18 years of age) with septic shock were treated with targeted heart rate control vs placebo after initial resuscitation due to persistent tachycardia. The study data was extracted by two independent researchers. A random effects model was used to present the results. A trial sequential analysis (TSA) was performed for the primary outcome of 28-day mortality. RESULTS: A total of 9 studies with a pooled sample size of 807 participants were included in the analysis.Eight of the included studies with a pooled sample size of 766 reported 28-day mortality. Targeted heart rate control was associated with a trend toward lower 28-day mortality [risk ratio (RR): 0.78; 95% CI: 0.62-0.99; CONCLUSION: Targeted heart rate control in patients with septic shock may be tolerated from a hemodynamic standpoint. However, the beneficial effect on mortality is less certain than was reported in the initial studies. HOW TO CITE THIS ARTICLE: Datta PK, Sathe P, Roy A, Baronia T, Bhattacharjee A, Kundu R. The Clinical Utility of Targeted Heart Rate Control in Septic Shock: A Systematic Review and Meta-analysis of Randomized Controlled Trials with Trial Sequential Analysis. Indian J Crit Care Med 2024;28(12):1170-1179.