Efficacy of therapeutic drug monitoring-based antibiotic regimen in critically ill patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of therapeutic drug monitoring (TDM)-based antimicrobial dosing optimization strategies on pharmacokinetics/pharmacodynamics and specific drug properties for critically ill patients is unclear. Here, we conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effectiveness of TDM-based regimen in these patients. METHODS: Articles from three databases were systematically retrieved to identify relevant randomized control studies. Version two of the Cochrane tool for assessing risk of bias in randomized trials was used to assess the risk of bias in studies included in the analysis, and quality assessment of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation approach. Primary outcome was the 28-day mortality and secondary outcome were in-hospital mortality, clinical cure, length of stay in the intensive care unit (ICU) and target attainment at day 1 and 3. RESULTS: In total, 5 studies involving 1011 patients were included for meta-analysis of the primary outcome, of which no significant difference was observed between TDM-based regimen and control groups (risk ratio [RR] 0.94, 95% confidence interval [CI]: 0.77-1.14; I2 = 0%). In-hospital mortality (RR 0.96, 95% CI: 0.76-1.20), clinical cure (RR 1.23, 95% CI: 0.91-1.67), length of stay in the ICU (mean difference 0, 95% CI: - 2.18-2.19), and target attainment at day 1 (RR 1.14, 95% CI: 0.88-1.48) and day 3 (RR 1.35, 95% CI: 0.90-2.03) were not significantly different between the two groups, and all evidence for the secondary outcomes had a low or very low level of certainty because the included studies had serious risk of bias, variation of definition for outcomes, and small sample sizes. CONCLUSION: TDM-based regimens had no significant efficacy for clinical or pharmacological outcomes. Further studies with other achievable targets and well-defined outcomes are required. TRIAL REGISTRATION: Clinical trial registration; PROSPERO ( https://www.crd.york.ac.uk/prospero/ ), registry number: CRD 42022371959. Registered 24 November 2022.

Absence of calvarial fracture could predict the need for tracheostomy in traumatic brain injury.

AIM: Tracheostomy is a common procedure for intubated patients with traumatic brain injury (TBI) in the intensive care unit (ICU) but optimal timing and the predictors of tracheostomy are still unclear. The aim of our study was to explore whether the traumatic variables of head injury predict the need for tracheostomy in intubated TBI patients. METHODS: A single-center, retrospective observational study including a series of TBI patients admitted to Fukui Prefectural Hospital from April 1, 2004 to March 31, 2020 was carried out. Our primary outcome was tracheostomy. Patients with TBI who were intubated and admitted into the ICU within 24 h after injury were enrolled. Exclusion criteria were age less than 18 years, pregnancy, mortality within 24 h, post-cardiac arrest syndrome, and patients for whom life-sustaining interventions were withheld. Radiologic images were also reviewed and the morphology of the head injury was categorized. RESULTS: Seventy-six patients were included. Forty-six patients (60.5%) underwent tracheostomy and 30 patients (39.5%) were successfully extubated. Calvarial fracture (odds ratio [OR] 0.34; 95% confidence interval [CI], 0.13-0.88; P = 0.03), Injury Severity Score (OR 1.07; 95% CI, 1.00-1.15; P = 0.04), and Glasgow Comas Scale score (OR 0.84; 95% CI, 0.73-0.96) were statistically significant in the univariable analysis. Multivariate logistic regression identified calvarial fracture as an independent predictor for tracheostomy. The model involving calvarial fracture, Injury Severity Score ≥16, and Glasgow Coma Scale score ≤8 showed the area under the receiver operating characteristic curve for the model was 0.737 (95% CI, 0.629-0.846). CONCLUSIONS: The absence of calvarial fracture could predict the necessity for tracheostomy in intubated TBI patients when combined with other factors. Further prospective randomized trials are necessary to confirm the findings.

Point-of-care procalcitonin may predict the need for surgical treatment in patients with small bowel obstruction.

BACKGROUND: The early identification of patients with small bowel obstruction who require surgical treatment could potentially lead to improved patient outcomes. We evaluated the efficacy of point-of-care procalcitonin for predicting surgical treatment among patients with small bowel obstruction. METHODS: This was a prospective observational study. We measured serum procalcitonin levels in patients who presented to the emergency department and were diagnosed with small bowel obstruction from April 1, 2018 through March 31, 2019. Patients were grouped into two groups: the elevated procalcitonin and normal procalcitonin groups. Our primary outcome was surgical treatment. RESULTS: A total of 53 patients with small bowel obstruction were included in the study, and 11 patients (20.8%) were treated operatively. Baseline characteristics were similar, except for age, between the elevated procalcitonin (≥0.12 ng/ml) and normal procalcitonin groups. The elevated procalcitonin level was significantly correlated with surgical treatment and hospital length of stay (p < 0.05). The sensitivity, specificity, and positive likelihood of procalcitonin for the former were 45.5%, 85.7%, and 5.0 respectively. CONCLUSION: The patients with small bowel obstruction who had elevated procalcitonin levels on presentation showed significantly higher rate of surgical treatment than those who had normal procalcitonin levels. Point-of-care procalcitonin might predict the need for surgical treatment in patients with small bowel obstruction and could be used as an additional diagnostic test. Further studies with more patients are needed to investigate the predictive value of point-of-care procalcitonin for surgical treatment.

A comprehensive validation of very early rule-out strategies for non-ST-segment elevation myocardial infarction in emergency departments: protocol for a multicentre prospective cohort study.

INTRODUCTION: Recent advances in troponin sensitivity enabled early and accurate judgement of ruling-out myocardial infarction, especially non-ST elevation myocardial infarction (NSTEMI) in emergency departments (EDs) with development of various prediction-rules and high-sensitive-troponin-based strategies (hs-troponin). Reliance on clinical impression, however, is still common, and it remains unknown which of these strategies is superior. Therefore, our objective in this prospective cohort study is to comprehensively validate the diagnostic accuracy of clinical impression-based strategies, prediction-rules and hs-troponin-based strategies for ruling-out NSTEMIs. METHODS AND ANALYSIS: In total, 1500 consecutive adult patients with symptoms suggestive of acute coronary syndrome will be prospectively recruited from five EDs in two tertiary-level, two secondary-level community hospitals and one university hospital in Japan. The study has begun in July 2018, and recruitment period will be about 1 year. A board-certified emergency physician will complete standardised case report forms, and independently perform a clinical impression-based risk estimation of NSTEMI. Index strategies to be compared will include the clinical impression-based strategy; prediction rules and hs-troponin-based strategies for the following types of troponin (Roche Elecsys hs-troponin T; Abbott ARCHITECT hs-troponin I; Siemens ADVIA Centaur hs-troponin I; Siemens ADVIA Centaur sensitive-troponin I). The reference standard will be the composite of type 1 MI and cardiac death within 30 days after admission to the ED. Outcome measures will be negative predictive value, sensitivity and effectiveness, defined as the proportion of patients categorised as low risk for NSTEMI. We will also evaluate inter-rater reliability of the clinical impression-based risk estimation. ETHICS AND DISSEMINATION: The study is approved by the Ethics Committees of the Kyoto University Graduate School and Faculty of Medicine and of the five hospitals where we will recruit patients. We will disseminate the study results through conference presentations and peer-reviewed journals.

Implementation of an empirical antimicrobial protocol in a critical care setting: A single-center retrospective observational cohort study in bacteremic patients.

In the treatment of severe infections in critical care settings, the selection of initial empirical antimicrobials affects patient outcomes and antimicrobial overuse. The application of a comprehensive treatment guidance might facilitate appropriate antimicrobial selection. Therefore, we developed such an antimicrobial guidance for use in emergency and critical care center and verified its efficacy. We retrospectively analyzed the data of 195 patients (96 patients before guidance introduction [control group] and 99 after guidance introduction [intervention group]) who were ultimately diagnosed with bacteremia to assess the effects of the guidance (the intervention). The appropriateness of the empirical therapy was greater in the intervention than in the control group (96% vs. 90%, respectively; P = 0.10). Moreover, the rate of carbapenem use was significantly lower in the intervention than in the control group (6% vs. 20%, respectively; P < 0.01). The control and intervention groups had similar 28-day survival rates of 81% and 85%, respectively; P = 0.50). These findings imply that introducing an empirical antimicrobial guidance in emergency outpatient and emergency intensive care settings could improve antimicrobial stewardship without affecting patient mortality. The data of this study can be used as a reference for establishing the study design of a large-scale prospective trial, aimed at verifying guidance efficacy.

Displaced anterior pelvic fracture on initial pelvic radiography predicts massive hemorrhage.

INTRODUCTION: Massive hemorrhage is often associated with unstable pelvic fractures with posterior ring injury. Initial pelvic radiography alone may not detect these posterior lesions. We examined whether the presence of an anterior pelvic fracture on initial pelvic radiography alone may identify patients who are at a high risk of major hemorrhage. MATERIALS AND METHODS: A total of 288 patients with pelvic fractures were admitted to the Fukui Prefectural Hospital during an 11-year period. After excluding 33 patients who were in cardiopulmonary arrest on arrival and nine with concomitant abdominal organ injuries requiring emergency laparotomy, 246 eligible patients were retrospectively reviewed. Anterior pelvic fractures were defined as displacement of the obturator ring, obturator ring with laterality, or displacement of the pubic symphysis on pelvic radiography. RESULTS: Massive hemorrhage was identified in 106 of 246 patients. Patients with massive hemorrhage had a higher frequency of anterior pelvic fractures on pelvic radiography and higher frequency of posterior pelvic fractures on computed tomography than those without massive hemorrhage. Logistic regression analysis identified displacement of the obturator ring by ≥5mm, obturator ring with laterality of ≥5mm, and displacement of the pubic symphysis by ≥4mm on pelvic radiography as predictors of massive pelvic hemorrhage. CONCLUSION: The results of the present study suggested that the presence of displaced anterior lesions of the pelvic ring on pelvic radiography alone, without the use of computed tomography during the initial treatment stage, may promptly identify patients at high risk of massive pelvic hemorrhage who require intervention for hemorrhage control.

Small tube thoracostomy (20-22 Fr) in emergent management of chest trauma.

BACKGROUND: The optimal tube size for an emergent thoracostomy for traumatic pneumothorax or hemothorax is unknown. Both small catheter tube thoracostomy and large-bore chest tube thoracostomy have been shown to work for the nonemergent management of patients with traumatic pneumothorax or hemothorax. This study was conducted to compare the efficacy of a small chest tube with that of a large tube in emergent thoracostomy due to chest trauma. Our hypothesis was that there would be no difference in clinical outcomes including tube-related complications, the need for additional tube placement, and thoracotomy, with the replacement of large tubes with small tubes. METHODS: A retrospective review of all patients with chest trauma requiring tube thoracostomy within the first 2h from arrival at our emergency department over a 7-year period was conducted. Charts were reviewed for demographic data and outcomes including complications and initial drainage output. Small chest tubes (20-22 Fr) were compared with a large tube (28 Fr). Our primary outcome was tube-related complications. Secondary outcomes included additional invasive procedures, such as additional tube insertion and thoracotomy. RESULTS: There were 124 tube thoracostomies (small: 68, large: 56) performed in 116 patients. There were no significant differences between the small- and large-tube groups with regard to age, gender, injury mechanism, systolic blood pressure, heart rate, and injury severity score. Both groups were similar in the posterior direction of tube insertion, initial drainage output, and the duration of tube insertion. There was no significant difference in the primary outcomes of tube-related complications, including empyema (small: 1/68 vs. large: 1/56; p=1.000) or retained hemothorax (small: 2/68 vs. large: 2/56; p=1.000). Secondary outcomes, including the need for additional tube placement (small: 2/68 vs. large: 4/56; p=0.408) or thoracotomy (small: 2/68 vs. large: 1/56; p=1.000), were also similar. CONCLUSION: For patients with chest trauma, emergent insertion of 20-22 Fr chest tubes has no difference in the efficacy of drainage, rate of complications, and need for additional invasive procedures compared with a large tube (28 Fr).