Hyun DG, et al. J Korean Med Sci. 2020 Feb;35(15):e106. https://doi.org/10.3346/jkms.2020.35.e106

Continuous infusion of beta-lactam antibiotics has emerged as an alternative for the treatment of sepsis because of the favourable pharmacokinetics of continuous infusion. This study aimed to evaluate the survival benefits of continuous vs. intermittent infusion of piperacillin-tazobactam in critically ill patients with sepsis. We retrospectively conducted a single-centre study of continuous infusion vs. intermittent infusion of piperacillin-tazobactam for adult patients who met the Sepsis-3 criteria and were treated at a medical ICU within 48 h after hospitalisation between 1 May 2018 and 30 April 2020. The primary outcome was mortality at 28 days. A total of 157 patients (47 in the continuous group and 110 in the intermittent group) met the inclusion criteria for evaluation. The 28-day mortality rates were 12.8% in the continuous group and 27.3% in the intermittent group (p = 0.07). However, after adjustment for potential covariables, patients in the continuous group (12.8%) showed significantly lower mortality at 28 days than those in the intermittent group (27.3%; adjusted hazard ratio (HR), 0.31; 95% confidence interval (CI), 0.13–0.79; p = 0.013). In sepsis patients, continuous infusion of piperacillin-tazobactam may confer a benefit regarding the avoidance of mortality at 28 days compared with intermittent infusion.

In patients with epidermal growth factor receptor (EGFR)-mutant non–small-cell lung cancer (NSCLC) with brain metastases, it remains controversial whether the use of EGFR-tyrosine kinase inhibitor (TKI) alone without radiotherapy (RT) is an optimal approach. Here, we investigated the clinical outcomes according to the use of upfront RT as well as the subsequent therapy following intracranial progression. This single-centre retrospective study included a total of 173 patients who were treated with EGFR-TKI alone (TKI alone group) or with upfront whole-brain RT (WBRT) or stereotactic radiosurgery (SRS) followed by EGFR-TKI (RT plus TKI group). Clinical outcomes according to initial and subsequent therapies following intracranial progression were analysed. There was no significant difference in OS according to the use of upfront RT (TKI alone group, 24.5 months vs. WBRT group, 20.0 months vs. SRS group, 17.8 months; P = 0.186). Intracranial progression was found in 35 (32.7%) of 107 patients in the TKI alone group. Among them, 19 patients who received salvage RT had the better prognosis than others [median overall survival (OS); 28.6 vs. 11.2 months; P = 0.041]. In the RT plus TKI group, 12 (18.1%) of the 66 patients experienced intracranial progression and 3 of them received salvage RT (median OS; 37.4 vs. 20.0 months; P = 0.044). In multivariate analysis, upfront WBRT was associated with trends towards a lower probability of intracranial progression, whereas upfront SRS was found to be an independent risk factor for poor OS. In conclusion, using EGFR-TKI alone for brain metastasis in EGFR-mutant lung cancer patients showed outcomes comparable to those using upfront RT followed by EGFR-TKI. Patients who could not receive salvage RT following intracranial progression had the worst survival regardless of the type of initial treatment.

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.

Background: Sepsis‐induced cardiac dysfunction, known as septic cardiomyopathy, is a common complication associated with increased mortality. Cardiac troponins serve as markers for myocardial injury and are frequently elevated in patients with sepsis. However, the role of troponin elevation at sepsis recognition in risk stratification remains controversial. Methods and Results: This nationwide multicenter prospective cohort study analyzed 2141 adult patients with sepsis without prior cardiovascular disease from the Korean Sepsis Alliance registry. These patients were classified as having either elevated troponin levels or troponin levels in the normal range at the time of sepsis recognition, according to the reference ranges specific to each participating institution. The primary outcome was hospital mortality, and propensity score matching was used to control for confounding factors. In the propensity score‐matched cohort (523 pairs), there were no significant differences in hospital mortality (35.2% versus 32.7%, odds ratio [OR], 1.12 [95% CI, 0.86–1.44], P =0.396), hospital length of stay (13.0 versus 15.0 days, OR, 1.00 [95% CI, 0.99–1.00], P =0.128), intensive care unit mortality (24.7% versus 25.0%, OR, 0.98 [95% CI, 0.74–1.30], P =0.886), or intensive care unit length of stay between the elevated troponin and control groups. However, landmark analysis revealed that the elevated troponin group had a lower survival probability after 1 week (log‐rank P =0.033) and significantly higher kidney Sequential Organ Failure Assessment scores from intensive care unit admission to day 7 ( P =0.003). Conclusions: Troponin elevation at sepsis recognition was not significantly associated with increased hospital mortality or worse clinical outcomes in patients with sepsis.

Hyun DG, et al. J Korean Med Sci. 2023 Apr;38(19):e141. https://doi.org/10.3346/jkms.2023.38.e141