Efficacy of Losartan in Hospitalized Patients With COVID-19-Induced Lung Injury: A Randomized Clinical Trial.

Importance: SARS-CoV-2 viral entry may disrupt angiotensin II (AII) homeostasis, contributing to COVID-19 induced lung injury. AII type 1 receptor blockade mitigates lung injury in preclinical models, although data in humans with COVID-19 remain mixed. Objective: To test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19. Design, Setting, and Participants: This blinded, placebo-controlled randomized clinical trial was conducted in 13 hospitals in the United States from April 2020 to February 2021. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already using a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible for participation. Data were analyzed from April 19 to August 24, 2021. Interventions: Losartan 50 mg orally twice daily vs equivalent placebo for 10 days or until hospital discharge. Main Outcomes and Measures: The primary outcome was the imputed arterial partial pressure of oxygen to fraction of inspired oxygen (Pao2:Fio2) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity; days without supplemental o2, ventilation, or vasopressors; and mortality. Losartan pharmacokinetics and RAAS components (AII, angiotensin-[1-7] and angiotensin-converting enzymes 1 and 2)] were measured in a subgroup of participants. Results: A total of 205 participants (mean [SD] age, 55.2 [15.7] years; 123 [60.0%] men) were randomized, with 101 participants assigned to losartan and 104 participants assigned to placebo. Compared with placebo, losartan did not significantly affect Pao2:Fio2 ratio at 7 days (difference, -24.8 [95%, -55.6 to 6.1]; P = .12). Compared with placebo, losartan did not improve any secondary clinical outcomes and led to fewer vasopressor-free days than placebo (median [IQR], 9.4 [9.1-9.8] vasopressor-free days vs 8.7 [8.2-9.3] vasopressor-free days). Conclusions and Relevance: This randomized clinical trial found that initiation of orally administered losartan to hospitalized patients with COVID-19 and acute lung injury did not improve Pao2:Fio2 ratio at 7 days. These data may have implications for ongoing clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04312009.

Clinical Decision Support Intervention for Rib Fracture Treatment.

BACKGROUND: Rib fractures are associated with significant morbidity and mortality. Despite the publication of management guidelines and national outcomes benchmarking, there is significant variation in evidence-based (EB) adherence and outcomes. Systems for clinical decision support intervention (CDSI) allow rapid ordering of bundled disease-specific EB treatments. We developed an EB rib fracture protocol and CDSI at our institution. The purpose of the current study was to evaluate implementation and clinical outcomes using this CDSI. STUDY DESIGN: A rib fracture care CDSI was developed, disseminated, and implemented in July 2018. Implementation outcomes were evaluated using the Proctor framework. Adherence was tracked monthly via run charts and acceptance was evaluated on a 7-point Likert scale using the Unified Theory of Acceptance and Use of Technology questionnaire. Propensity score matching was used to compare in-hospital morbidity and mortality in pre-implementation (January 1, 2016 through December 31, 2016) vs post-implementation (September 1, 2018 through April 30, 2019) cohorts. RESULTS: A total of 197 patients were eligible for the intervention. Provider CDSI adherence was 83% at 1 month and reached 100% after 7 months. Acceptance of CDSI using the Unified Theory of Acceptance and Use of Technology had a mean Likert score higher than 6 (range 6.1 to 6.8, SD 0.5 to 1.5), indicating high acceptance. A significant reduction in hospital length of stay was found post implementation (incident rate ratio 0.80; 95% CI, 0.66 to 0.98; p = 0.03) comparing propensity-matched subjects. CONCLUSIONS: The development and use of a CDSI resulted in improved provider delivery of EB practice and was associated with reduced hospital length of stay.

Ketamine as an Analgesic Adjuvant in Adult Trauma Intensive Care Unit Patients With Rib Fracture.

BACKGROUND: Rib fracture associated pain is difficult to control. There are no published studies that use ketamine as a therapeutic modality to reduce the amount of opioid to control rib fracture pain. OBJECTIVE: To examine the analgesic effects of adjuvant ketamine on pain scale scores in trauma intensive care unit (ICU) rib fracture. METHODS: This retrospective, case-control cohort chart review evaluated ICU adult patients with a diagnosis of ≥1 rib fracture and an Injury Severity Score >15 during 2016. Patients received standard-of-care pain management with the physician's choice analgesics with or without ketamine as a continuous, fixed, intravenous infusion at 0.1 mg/kg/h. RESULTS: A total of 15 ketamine treatment patients were matched with 15 control standard-of-care patients. Efficacy was measured via Numeric Pain Scale (NPS)/Behavioral Pain Scale (BPS) scores, opioid use, and ICU and hospital length of stay. Safety of ketamine was measured by changes in vital signs, adverse effects, and mortality. Average NPS/BPS, severest NPS/BPS, and opioid use were lower in the ketamine group than in controls (NPS: 4.1 vs 5.8, P < 0.001; severest NPS: 7.0 vs 8.9, P = 0.004; opioid use: 2.5 vs 3.5 mg morphine equivalents/h/d, P = 0.015). No difference was found between the cohort's length of stay or mortality. Average diastolic blood pressure was higher in the treatment group versus the control group (75.3 vs 64.6 mm Hg, P = 0.014). CONCLUSION: Low-dose ketamine appears to be a safe and effective adjuvant option to reduce pain and decrease opioid use in rib fracture.

Riding into the golden years: injury patterns and outcomes of advanced-age motorcycle trauma.

BACKGROUND: Our objectives were to characterize injury, complications, and outcomes for older riders after motorcycle accidents due to the rising trend in advanced-age motorcyclists. METHODS: From 2008 to 2013, injured motorcyclists were compared by age group: younger (0 to 54 years) vs older (≥55 years) in a retrospective review of the trauma databank at North Memorial Medical Center, a Level-1 trauma center. RESULTS: Of 432 patients, the older group (n = 100) had more fractures (60% vs 42%), injuries per patient (2 vs 1), intensive care unit admissions (48% vs 32%), ventilator days (8 vs 5), in-hospital complications (16% vs 8%), and hospital days (5.5 vs 3) than the younger group (n = 332), P < .01. The older group was also more likely to be discharged to a destination other than home, 35% vs 18%, P < .01. CONCLUSIONS: Older riders are at risk for more severe injury, longer and more complex hospitalizations, and higher care demands after discharge. Both age-specific treatment and care systems will need to evolve to accommodate the needs of the aging trauma population.

Are the frail destined to fail? Frailty index as predictor of surgical morbidity and mortality in the elderly.

BACKGROUND: America's aging population has led to an increase in the number of elderly patients necessitating emergency general surgery. Previous studies have demonstrated that increased frailty is a predictor of outcomes in medicine and surgical patients. We hypothesized that use of a modification of the Canadian Study of Health and Aging Frailty Index would be a predictor of morbidity and mortality in patients older than 60 years undergoing emergency general surgery. METHODS: Data were obtained from the National Surgical Quality Improvement Program Participant Use Files database in compliance with the National Surgical Quality Improvement Program Data Use Agreement. We selected all emergency cases in patients older than 60 years performed by general surgeons from 2005 to 2009. The effect of increasing frailty on multiple outcomes including wound infection, wound occurrence, any infection, any occurrence, and mortality was then evaluated. RESULTS: Total sample size was 35,334 patients. As the modified frailty index increased, associated increases occurred in wound infection, wound occurrence, any infection, any occurrence, and mortality. Logistic regression of multiple variables demonstrated that the frailty index was associated with increased mortality with an odds ratio of 11.70 (p < 0.001). CONCLUSION: Frailty index is an important predictive variable in emergency general surgery patients older than 60 years. The modified frailty index can be used to evaluate risk of both morbidity and mortality in these patients. Frailty index will be a valuable preoperative risk assessment tool for the acute care surgeon. LEVEL OF EVIDENCE: Prognostic study, level II.