Brown, Caitlin S.

ABSTRACT Introduction Patients often receive propofol for sedation and clevidipine for hypertension in the intensive care unit. Both agents are formulated as a lipid emulsion, which may increase the risk of hypertriglyceridemia and acute pancreatitis with their coadministration. We aimed to determine the incidence of hypertriglyceridemia and acute pancreatitis with concurrent administration of propofol and clevidipine and identify patient risk factors for hypertriglyceridemia. Methods This was a multicenter retrospective study of adult patients (≥ 18 years old) receiving concurrent propofol and clevidipine infusions for ≥ 6 h. The primary outcome was the frequency of triglyceride levels greater than 400 mg/dL and acute pancreatitis. The secondary outcome was risk factors associated with hypertriglyceridemia during concurrent propofol and clevidipine infusions until both infusions had been discontinued. Univariable and multivariable logistic regression analyses were used to assess risk factors of hypertriglyceridemia in patients receiving concurrent propofol and clevidipine infusions. Results Across 1,226 patients, the median duration of infusion overlap was 12.4 [interquartile range (IQR) 8.3, 22.7] hours. The mean age of the cohort was 59.6 [standard deviation (SD) 14.9] years, and 59.4% were male. Assuming those without a triglyceride level drawn did not have hypertriglyceridemia, hypertriglyceridemia after initiation of propofol and clevidipine infusion was found in 7.7% [95% confidence interval (CI) 6.3% to 9.3%] of the entire cohort. Twenty‐six patients (2.1%) had a diagnosis of pancreatitis after initiation of lipid infusions, of which 12 cases were possibly infusion‐related, and one case was likely infusion‐related. After calculating the Naranjo Scale, all 13 cases of pancreatitis were possibly related to propofol or clevidipine infusions. Based on a multivariable logistic regression of those with a triglyceride level available, risk factors for hypertriglyceridemia included pancreatitis within the past 5 years [adjusted odds ratio (aOR) 2.77, 95% CI, 1.23 to 6.23] and statin use (aOR 1.94, 95% CI, 1.13 to 3.34). Conclusions In our cohort of patients receiving concurrent propofol and clevidipine, the frequency of hypertriglyceridemia and acute pancreatitis was low. Further comparative studies are warranted to assess the risk of pancreatitis with the addition of clevidipine to propofol.

ABSTRACT Clinical pharmacists are increasingly recognized as vital contributors to acute stroke care, yet their role remains inconsistently defined and underutilized across health care systems. This consensus statement explores the expanding presence of clinical pharmacists within interdisciplinary stroke teams, particularly in the management of both acute ischemic stroke ( AIS ) and hemorrhagic stroke. This consensus statement panel was composed of clinical pharmacists, emergency medicine physicians, and a vascular neurologist. The Grading of Recommendations, Assessment, Development, and Evaluation ( GRADE ) approach was used to assess the level of certainty and strength of recommendations. We focused on two questions regarding the clinical pharmacist's role in caring for adult patients presenting to the emergency department ( ED ) with AIS or hemorrhagic stroke. Despite the very low level of evidence, a consensus was reached for the following recommendations: (1) clinical pharmacist involvement in AIS care for adult patients presenting to the ED and (2) clinical pharmacist involvement in hemorrhagic stroke care for adult patients presenting to the ED . Based on the available literature, we believe optimizing the clinical pharmacist role is a critical factor in improving time‐sensitive treatment and equity in care delivery.

Objectives: Elevated intracranial pressure (ICP) remains a challenge and immediate danger in patients with acute brain injury. Current literature supports the use of a single hyperosmolar agent to reduce ICP. However, the efficacy and safety of overlapping hyperosmolar agents have not been evaluated. The objectives of this study are to analyze the ICP lowering effects and evaluate the safety profile of overlapping hyperosmolar therapy. Materials and Methods: This single-center, retrospective study included adults (≥18 y) admitted to the Neurosciences Intensive Care Unit between May 2018 and September 2024 with acute brain injury leading to intracranial hypertension refractory to a single hyperosmolar agent and an ICP monitor. They received overlapping doses of mannitol and hypertonic sodium approximately every 3 hours. We evaluated the impact of overlapping hyperosmolar therapy on ICP. Safety outcomes included acute kidney injury incidence, electrolyte disturbances, and volume status changes. Results: Forty-six patients were included in this study with a median (IQR) age of 46.5 (35.9, 62.4) years. Median (IQR) dose of mannitol was 40.1 (34.6, 50.0) g, while median (IQR) dose of hypertonic sodium was 120 (90, 125) mEq. About 86% of patients experienced a decrease in ICP after initiation of overlapping hyperosmolar therapy. Six acute kidney injuries occurred, and 7 patients experienced pulmonary edema. Median (IQR) peak sodium, chloride, and osmolar gap values were 149 (144, 155) mEq/L, 115 (111, 119) mEq/L, and 5.7 (0.7, 9.0) mOsm/kg. Conclusions: Overlapping hyperosmolar therapy may provide a transient ICP reduction without excessive adverse effects in patients with refractory ICP to a single hyperosmolar agent.

ABSTRACT Background Older adults experience age‐related physiological changes that alter the pharmacokinetics and pharmacodynamics of certain medications, which may necessitate reduced dosing. Our objective was to assess emergency department (ED) and hospital outcomes of older patients administered opioids by emergency medical services (EMS) clinicians. Methods Retrospective cohort study of adults ≥ 65 years who received an opioid between 2019 and 2024 within a health system‐affiliated EMS agency. We excluded patients with an advanced airway and those with no documented weight. Maximum single and cumulative weight‐based opioid dosages were classified as low, therapeutic, or high. Outcomes were measured in the ED/hospital and compared using Poisson regression with Huber/White standard errors, adjusted for age, sex, vitals, Glascow Coma Scale, emergency severity index, and chief concern. Results were reported as adjusted risk ratios (aRRs). Results A total of 6406 patients, including 747 (11.7%, 95% CI: 10.9–12.5) with a high opioid dose, 3663 (57.2%, 95% CI: 56.0–58.4) with a therapeutic dose, and 1996 (31.2%, 95% CI: 30.0–32.3) with a low dose, were included. Receipt of a high maximum single opioid dose versus a low/therapeutic dose (excluding patients receiving a concomitant sedative) was associated with increased risk of altered responsiveness (aRR = 1.28, 95% CI: 1.03–1.58) and delirium (aRR = 2.43, 95% CI: 1.08–5.45) in the ED/hospital setting. When 311 (4.9%) patients who received a concomitant sedative were included, patients who received a high opioid dose similarly had an increased risk of altered responsiveness (aRR = 1.28, 95% CI: 1.06–1.56) and delirium (RR = 2.65, 95% CI: 1.25–5.59), compared to a low/therapeutic dose. There was no difference in outcomes of hypoxia, death within 30 days, or ED length of stay between dose groups. Conclusion Prehospital administration of high opioid doses to older patients was associated with increased rates of altered responsiveness and delirium. These findings highlight how out‐of‐hospital care can impact a patient's ED and hospital course.

Background: Enteral phosphate replacement offers multiple advantages over intravenous phosphate replacement, but optimal dosing and administration are unclear. Objective: This study aimed to compare 2 different dosing strategies (PRE vs POST) of enteral phosphate replacement for mild hypophosphatemia (serum phosphorus = 2.1-2.5 mg/dL) and to evaluate our dosing strategy for moderate hypophosphatemia (serum phosphorus = 1.5-2 mg/dL) in critically ill patients. Methods: This single-center quasiexperimental, institutional review board–approved study was conducted in adult patients admitted to an intensive care unit (ICU) who received enteral phosphate replacement with a follow-up serum phosphorus level obtained within 24 hours of replacement. Patients were excluded if they had diabetic ketoacidosis, acute kidney injury, or received total parenteral nutrition or targeted temperature management. The mild PRE and POST groups received 48 and 72 mmol of enteral phosphate, respectively. The moderate group received 72 mmol of enteral phosphate. Effectiveness outcomes included normalization of serum phosphorus, defined as 2.6 to 4.5 mg/dL, and median change in phosphorus concentration. Safety outcomes included the incidence of new onset diarrhea and hyperphosphatemia (serum phosphorus >4.5 mg/dL) within 24 hours after phosphate replacement. Results: Of the 138 patients included, the median age was 59 (44-70) years and 69.6% were admitted to the surgical trauma ICU. Normalization of serum phosphorus occurred in 55 (58.2%) patients in mild PRE and 44 (72.7%) patients in mild POST ( P = 0.13). Change in serum phosphorus was 0.4 (0.1-0.9) mg/dL in mild PRE vs 0.7 (0.3-1.2) mg/dL in mild POST ( P = 0.06). Normalization occurred in 39 (66.7%) patients in the moderate group with a change in serum phosphorus of 1.0 (0.6-1.6) mg/dL. Rates of new onset diarrhea and hyperphosphatemia were not significantly different between groups. Conclusion and Relevance: Enteral phosphate replacement appears safe and effective in critically ill patients with mild-to-moderate hypophosphatemia and may serve as an alternative to intravenous phosphate.

ABSTRACT Background The optimal timing for basal insulin initiation in diabetic ketoacidosis (DKA) remains unclear. British guidelines endorse early basal insulin (EBI), while the American Diabetes Association emphasises overlap duration with intravenous insulin, without mention of timing. This meta‐analysis evaluates whether EBI administration of basal insulin improves clinical outcomes in adults with DKA. Methods A systematic review and meta‐analysis were performed according to the PRISMA guidelines. Databases searched included MEDLINE, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials through December 11, 2024. Inclusion criteria included articles in the English‐language randomised controlled trials (RCTs) or observational studies evaluating EBI in adult DKA patients. Non‐human studies, conference abstracts, and case reports were excluded. The primary outcome for this study was hospital length of stay (LOS). Additional outcomes included intensive care unit (ICU) LOS, time to DKA resolution, hypoglycemia, and rebound hyperglycemia between EBI and usual care. Risk of bias was assessed using the Cochrane and Newcastle‐Ottawa tools. Grading of Recommendations Assessment, Development, and Evaluation was performed to evaluate the quality of evidence. Results From 1214 identified studies, eight (4 RCTs, 4 observational) met inclusion criteria for a total of 247 patients in the EBI group and 552 patients in the control group. No significant difference in hospital LOS was found (mean difference −11.17 h; 95% CI: −29.91 to 7.56). ICU LOS, time to DKA resolution, incidence of hypoglycemia, and rebound hyperglycemia also did not demonstrate any significant differences between groups. Significant heterogeneity existed across studies for most outcomes. All studies had a high risk of bias, and the quality of evidence was very low. Conclusion EBI did not result in significant differences in hospital LOS, ICU LOS, or time to DKA resolution; however, there were no increased adverse events with EBI. Current studies of early EBI have significant limitations. Future research should focus on developing high‐quality RCTs.

Importance The choice of induction agent during rapid sequence intubation (RSI) of critically ill adults may affect clinical outcomes. Although ketamine and etomidate are frequently used for RSI, their comparative effectiveness remains controversial. Objective To compare the safety of etomidate vs ketamine for emergency RSI in critically ill adults. Design, Setting, and Participants This cohort study used a target trial emulation with observational data collected between March 1, 2022, and April 30, 2024, from 18 emergency departments across Brazil, with data from the Brazilian Airway Registry Cooperation. Adults who underwent RSI and received either etomidate or ketamine as a sole hypnotic agent were included; those with preintubation cardiac arrest or immediate postintubation transfer were excluded. Exposure Administration of etomidate or ketamine as the induction agent for RSI. Main Outcomes and Measures The primary outcome was 28-day in-hospital mortality. Secondary outcomes included 7-day in-hospital mortality, first-attempt intubation success, and major adverse events (new hemodynamic instability, severe hypoxemia, and cardiac arrest) within 30 minutes after intubation. Inverse probability of treatment weighting was used to adjust for confounding. Risk ratios (RRs) and risk differences (RDs) with 95% CIs were used to compare outcomes between groups. Results Among 1810 patients (median age, 64 years [IQR, 50-74 years]; 1048 men [57.9%]), 514 received ketamine and 1296 received etomidate. The median shock index was higher in the ketamine group than the etomidate group (0.81 [IQR, 0.65-1.01] vs 0.76 [IQR, 0.59-0.99]), and preintubation vasopressor use was more common in the ketamine group than the etomidate group (191 of 514 [37.2%] vs 391 of 1296 [30.2%]). Weighted 28-day mortality was higher with etomidate than ketamine (60.5% [95% CI, 57.2%-63.8%] vs 54.4% [95% CI, 45.0%-63.9%]; RR, 1.14 [95% CI, 1.03-1.27]; RD, 7.6% [95% CI, 2.0%-13.3%]). Seven-day mortality was also higher with etomidate than ketamine (35.2% [95% CI, 32.0%-38.3%] vs 30.1% [95% CI, 23.5%-36.7%]; RR, 1.19 [95% CI, 1.04-1.35]). New hemodynamic instability within 30 minutes after intubation was more frequent with ketamine (24.2% [95% CI, 20.4%-28.0%] vs 18.9% [95% CI, 16.7%-21.0%]; RR, 0.78 [0.64-0.95]). There were no statistically significant differences in the other secondary outcomes. Conclusions and Relevance In this cohort study of critically ill adults undergoing RSI, etomidate use was associated with higher in-hospital mortality at 7 and 28 days compared with ketamine. These findings highlight the need for definitive randomized clinical trials to compare both agents.

ABSTRACT Background Intracranial and extracranial hemorrhages are significant causes of morbidity and mortality. Emergency medicine pharmacists (EMPs) can play a crucial role in anticoagulation reversal by identifying patients on anticoagulation, selecting the optimal anticoagulation reversal agent, and ensuring adequate dosing and prompt administration. The goal of this systematic review and meta‐analysis was to determine the impact EMPs have on time to anticoagulation reversal and patient outcomes in anticoagulation‐associated hemorrhages. Methods A medical librarian performed a literature search in EBSCO CINAHL, Ovid Cochrane Central Register of Controlled Trials, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection from inception to January 2025 for all types of oral anticoagulants and for life‐threatening bleeding that required emergent reversal. Newcastle‐Ottawa was used to assess the risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the level of certainty of the evidence. Random effects models estimating mean differences and 95% confidence intervals are reported. Results There were 2445 titles and abstracts screened, with 44 undergoing full‐text evaluation. Six observational studies including 219 patients who received an anticoagulation reversal agent with the presence of an EMP and 198 patients who received a reversal agent without an EMP were included. Time from emergency department (ED) presentation to anticoagulation reversal agent administration (75.60 min, 95% confidence interval [CI]: −101.7 to −49.5) and time from medication order to administration were faster with an EMP (−18.7 min, 95% CI: −23.5 to −14.0). There was no difference in short‐term mortality. The included studies had a high risk of bias and were deemed very low quality of evidence. Conclusion EMP involvement in patient care during anticoagulation reversal of acute hemorrhages improved time to anticoagulation reversal agent administration. Larger scale, higher‐quality studies are necessary to assess the value of EMPs in improving patient‐centered outcomes.

ABSTRACT Background Critically ill patients may be overexposed to valproate because altered protein binding leads to a disproportionate free valproate fraction. The Fraser equation was derived and internally validated to estimate critically ill patients' free valproate concentrations, but it requires external validation. Methods Adult intensive care unit (ICU) patients at two academic centers with concurrently measured free and total valproate concentrations were included. Free valproate concentrations were estimated using the Fraser equation which includes total valproate, albumin and BUN concentration, and whether the patient received propofol or aspirin. The primary outcome was Fraser equation performance, assessed using Bland–Altman methods. Comparative performance against estimates from the Doré equation (an alternative predictive equation), therapeutic concordance using a target free valproate range of 5–15 mg/L, and equation improvements were explored. Results Overall, 315 patients and 556 free‐total valproate concentration pairs were included. The mean (±SD) age was 58 (±17) years and 90 (29%) patients were on valproate prior to hospital admission. The Fraser equation estimated free valproate concentrations were correlated with measured concentrations ( r = 0.728) with a negative bias (mean bias −2.77 mg/L, 95% LOA –18.9, 13.4). The Fraser equation increasingly underestimated measured concentrations as measured concentrations increased. 71% of Fraser equation estimates were therapeutically concordant (e.g., estimate and measured both within reference range) compared to 61.9% of Doré estimates ( p = 0.001). Fraser equation modifications led to minor performance improvements but did not overcome worsening underestimation with higher measured free valproate concentrations. Conclusion The Fraser equation was moderately accurate and corresponded with an appropriate interpretation for 71% of free valproate concentrations. Worse underestimation with higher measured free valproate concentrations suggests direct measurement of free valproate concentrations is warranted. While the Fraser equation could complement therapeutic decision making at centers where direct free valproate measurements are unavailable or slow to return, its accuracy is currently insufficient to replace direct measurement.

ABSTRACT Transgender and gender diverse (TGD) individuals face minority stress and often avoid the emergency department (ED) due to previous negative experiences. The goal of this review is to prepare the emergency medicine pharmacist to care for TGD patients, with the ultimate goal of improving the care TGD patients receive. This review summarizes interactions with TGD patients, trauma‐informed considerations, physical exam and organ inventory sensitivities, and gender‐affirming hormone therapy and complications that may arise and be seen in the ED. Additionally, this review discusses common complaints and considerations that may commonly arise when caring for TGD patients.