Incidence of Hypertriglyceridemia in Patients on Propofol, Clevidipine, or Both.

BACKGROUND: Propofol and clevidipine (PC) are commonly used in the treatment of critically ill patients. While both medications are lipid emulsions, there is limited evidence concerning the incidence of hypertriglyceridemia (HTG) when these agents are used individually or concurrently. OBJECTIVE: The objective of this study is to determine the effects of propofol, clevidipine, or concurrent PC on triglycerides (TGs) and related outcomes in critically ill adults. METHODS: This was a retrospective cohort study conducted at an academic medical center. Patients were included if they received ≥24 hours of continuous propofol and/or clevidipine. Excluded were those without TG levels after ≥24 hours of infusion, baseline HTG, acute pancreatitis at admission, or receiving total parenteral nutrition with lipids. The primary outcome was incidence of HTG (defined as a TG level >400 mg/dL). Secondary outcomes included median and peak TG levels, hospital length of stay, intensive care unit length of stay, total lipid infused, time to peak TG level, peak lipase level, and development of pancreatitis. RESULTS: In total, 190 patients were studied: 109 in the propofol group, 50 in the clevidipine group, and 31 in the PC group. Incidence of HTG was similar (19 [17.4%] vs 6 [12%] vs 4 [12.9%] patients, P = 0.6246). Peak and median TG levels were similar for propofol, clevidipine, and PC groups (216 mg/dL vs 189.5 mg/dL vs 205 mg/dL, P = 0.7069; 177 mg/dL vs 185.5 mg/dL vs 177 mg/dL, P = 0.6791). CONCLUSIONS AND RELEVANCE: There was a similar incidence of HTG in all groups. The results of this study suggest that the concurrent use of PC should not modify the frequency of TG level monitoring.

Outcomes Associated With Levetiracetam Use After Spontaneous Intracerebral Hemorrhage.

Background and Purpose: The purpose of this study was to assess the incidence of seizures in patients with spontaneous intracerebral hemorrhage (ICH) who received prophylactic levetiracetam. Methods: This was a retrospective cohort study evaluating the use of levetiracetam in patients without a history of seizures who experienced a spontaneous intracerebral hemorrhage. Patients were excluded if they were younger than 18 years of age, had a documented history of a seizure disorder, or had an antiseizure drug documented on their home medication list. Patients were based on their exposure to levetiracetam. The primary outcome was incidence of seizure during hospital admission. Secondary outcomes included occurrence of adverse events, intensive care unit (ICU) length of stay (LOS), and hospital LOS. Results: Of the 229 patients included in the final analysis, 21 were in the levetiracetam group (LEV) and 208 were in the no levetiracetam group (no LEV). No statistical difference in seizure incidence was observed when comparing the LEV and no LEV groups (1 [4.8%] LEV vs 3 [1.4%] no LEV; P = .32). There was also no statistical difference in the median ICU LOS (2 days [1 day, 5 days] LEV vs 2 days [1 day, 3 days] no LEV; P = .27), median hospital LOS (6 days [2 days, 8 days] LEV vs 6 days [3 days, 9 days] no LEV; P = .27), or adverse events. Conclusions: This study does not support the use of levetiracetam prophylaxis in patients who have experienced an ICH.

Predictive value of methicillin-resistant staphylococcus aureus nasal swab in patients with COVID-19 pneumonia and secondary bacterial pneumonia.

OBJECTIVE: To determine the performance measures of admission methicillin-resistant Staphylococcus aureus (MRSA) nasal swabs for MRSA bacterial pneumonia in patients co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The study included patients admitted with SARS-CoV-2-positive nasopharyngeal specimens, MRSA nasal screens, and bacterial cultures to assess secondary MRSA pneumonia. RESULTS: 293 patients and 662 microbiological cultures evaluated. Overall, the specificity (91.8% [95% CI 88.6% to 95%]) and negative predictive value (NPV 97.4% [95% CI 95.4% - 99.3%]) of MRSA nasal swabs was high. However, the sensitivity (46.2%; 95% CI 19.1% to 73.3%) and positive predictive value (PPV 20.7%; 95% CI 59.5 - 35.4%) were low. Those patients in the MRSA nasal swab negative group had a shorter median duration of linezolid therapy. CONCLUSIONS: SARS-CoV-2 infection doesn't reduce the specificity or negative predictive value of MRSA nasal swabs for secondary MRSA pneumonia.

Activated Prothrombin Complex Concentrates for the Treatment of Factor Xa Inhibitor-Associated Spontaneous Intracerebral Hemorrhage.

Background: Anticoagulant-associated intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality. Despite approval of a specific reversal agent for factor Xa inhibitors, there is still much interest in nonspecific reversal agents, such as activated prothrombin complex concentrates (aPCCs). Objective: The objective of this study was to describe ICH expansion in a cohort of patients with factor Xa inhibitor-associated ICH who were treated with aPCC. Methods: This was a retrospective cohort study conducted at an academic medical center designated as a comprehensive stroke center. Consecutive patients admitted for ICH who reported use of apixaban or rivaroxaban prior to admission were considered for inclusion in the study. Patients were treated with 25 to 50 units/kg of aPCC. Intracerebral hemorrhage volume was measured before administration of aPCC and then again within 36 hours of aPCC administration. Results: A total of 40 patients were included in the final analysis. Overall, the cohort was predominantly male (24 [60%]), white (27 [67.5%]), and the mean age was 75.3 ± 10.5 years. Most patients reported taking apixaban prior to admission (31 [77.5%]) and a large proportion were also taking aspirin (13 [32.5%]). The mean change in ICH volume was 1.12 ± 6.03 mL (P = 0.2475). Conclusions and Relevance: There was a nonsignificant change in mean ICH volume and no reported cases of thromboembolism. Due to the relatively high proportion of patients with significant hematoma expansion, more studies are needed on which patient population would best benefit from treatment with aPCC.

Comparison of nimodipine formulations and administration techniques via enteral feeding tubes in patients with aneurysmal subarachnoid hemorrhage: A multicenter retrospective cohort study.

BACKGROUND: Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent. The goal of the study was to determine if different nimodipine formulations and administration techniques were associated with the safety and effectiveness of nimodipine in aSAH. METHODS: This was a retrospective multicenter observational cohort study conducted in 21 hospitals across North America. Patients admitted with aSAH and received nimodipine by FT for ≥3 days were included. Patient demographics, disease severity, nimodipine administration, and study outcomes were collected. Safety end points included the prevalence of diarrhea and nimodipine dose reduction or discontinuation secondary to blood pressure reduction. Predictors of the study outcomes were analyzed using regression modeling. RESULTS: A total of 727 patients were included. Administration of nimodipine liquid product was independently associated with higher prevalence of diarrhea compared to other administration techniques/formulations (Odds ratio [OR] 2.28, 95% confidence interval [CI] 1.41-3.67, p-value = 0.001, OR 2.76, 95% CI 1.37-5.55, p-value = 0.005, for old and new commercially available formulations, respectively). Bedside withdrawal of liquid from nimodipine capsules prior to administration was significantly associated with higher prevalence of nimodipine dose reduction or discontinuation secondary to hypotension (OR 2.82, 95% CI 1.57-5.06, p-value = 0.001). Tablet crushing and bedside withdrawal of liquid from capsules prior to administration were associated with increased odds of delayed cerebral ischemia (OR 6.66, 95% CI 3.48-12.74, p-value <0.0001 and OR 3.92, 95% CI 2.05-7.52, p-value <0.0001, respectively). CONCLUSIONS: Our findings suggest that enteral nimodipine formulations and administration techniques might not be equivalent. This could be attributed to excipient differences, inconsistency and inaccuracy in medication administration, and altered nimodipine bioavailability. Further studies are needed.

Patient-Specific Risk Factors Associated With the Development of Hyperchloremia in a Neurocritical Care Intensive Care Unit.

BACKGROUND: Hypertonic sodium chloride (HTS) is used in intensive care unit (ICU) settings to manage cerebral edema, intracranial hypertension, and for the treatment of severe hyponatremia. It has been associated with an increased incidence of hyperchloremia; however, there is limited literature focusing on hyperchloremic risk in neurologically injured patients. Objective: The primary objective of this study was to determine risk factors associated with development of hyperchloremia in a neurocritical care (NCC) ICU population. METHODS: This was a retrospective case-control study performed in an adult NCC ICU and included patients receiving HTS. The primary outcome was to evaluate patient characteristics and treatments associated with hyperchloremia. Secondary outcomes included acute kidney injury and mortality. RESULTS: Overall, 133 patients were identified; patients who were hyperchloremic were considered cases (n = 100) and patients without hyperchloremia were considered controls (n = 33). Characteristics and treatments were evaluated with univariate analysis and a logistic regression model. In the multivariate model, APACHE II Score, initial serum osmolality, total 3% saline volume, and total 23.4% saline volume were significant predictors for hyperchloremia. In addition, patients with a serum chloride greater than 113.5 mEq/L were found to have a higher risk of acute kidney injury (AKI) (adjusted OR 3.15; 95% CI 1.10-9.04). CONCLUSIONS: This study demonstrated APACHE II Score, initial serum osmolality, and total 3% and 23.4% saline volumes were associated with developing hyperchloremia in the NCC ICU. In addition, hyperchloremia is associated with an increased risk of AKI.

Theophylline for Spinal Cord Injury Associated Bradycardia.

Background: Spinal cord injury (SCI) related bradycardia occurs frequently in patients with high cervical spine injuries. In patients with SCI-related symptomatic bradycardia, a variety of agents have been used to improve heart rate and reduce the need for vasopressor therapy. The literature concerning the use of theophylline in this disease state is sparse. Objective: The primary objective of this study was to evaluate and describe the use of theophylline for SCI-related symptomatic bradycardia. Methods: This was a retrospective case series of patients with SCI-related symptomatic bradycardia who were treated with theophylline. Patients were evaluated based on clinical response to theophylline. Patients were classified as a responder if vasopressors were discontinued or the number of bradycardia episodes decreased following the initiation of theophylline. Results: A total of twenty-six patients were included in the study. 17 (65.4%) patients were classified as responders, 5 (19.2%) patients were classified as non-responders, and 4 (15.4%) of patients were classified as undetermined. 11 patients (43.31%) were discharged on theophylline with 7 of these patients (41.2%) classified as responders. There were no significant differences between those classified as responders and those who were not. Conclusion and Relevance: This case series suggest that theophylline could be used as adjunctive therapy in patients with bradycardia secondary to acute SCI who achieve an adequate response to theophylline.

Major Bleeding Postadministration of Tenecteplase Versus Alteplase in Acute Ischemic Stroke.

BACKGROUND: Tenecteplase is a genetically engineered fibrinolytic with growing interest in the treatment of acute ischemic stroke. Compared to alteplase, tenecteplase is effective for neurologic improvement following ischemic stroke in patients with large vessel occlusions who are eligible for thrombectomy and for mild ischemic strokes with National Institutes of Health Stroke Scale of 0 to 5. OBJECTIVE: The purpose of this study is to determine if safety outcomes are different in patients receiving tenecteplase and alteplase for acute ischemic stroke. METHODS: This retrospective cohort reviewed all patients who received alteplase or tenecteplase from January 2019 to December 2020. Patients admitted before April 28, 2020, received alteplase intravenous bolus over 1 minute followed by an infusion over 1 hour, for a total of 0.9 mg/kg. Patients admitted after this date received tenecteplase 0.25 mg/kg as an intravenous bolus over 5 to 10 seconds. Any patient transferring from an outside facility was excluded. The primary outcome was major bleeding. RESULTS: There was no significant difference in major bleeding between alteplase and tenecteplase (40 [18%] vs 21 [18.1%], P = 0.985). There was no significant difference in all-cause inpatient mortality for alteplase versus tenecteplase (10 [5%] vs 5 [4%], P = 0.934) or in adverse events between the groups (22 [9%] vs 14 [12%], P = 0.541) for alteplase and tenecteplase, respectively. CONCLUSIONS AND RELEVANCE: Tenecteplase had similar rates of major bleeding versus alteplase and may be a reasonable alternative in the treatment of acute ischemic stroke.

Efficacy of Cefazolin versus Ceftriaxone for Extremity Open Fracture Management at a Level 1 Trauma Center.

Background: Antibiotic agents have been shown to improve outcomes in open extremity fractures. The first-generation cephalosporins, which are used most often, are often under-dosed based on weight and recommended frequency. Ceftriaxone offers a broader coverage and a decreased frequency of administration. Our institution began utilizing ceftriaxone for open fracture management in 2017 to address those concerns. Objective: To examine the efficacy of cefazolin versus ceftriaxone for open fracture management of extremity trauma. Patients and Methods: Retrospective study from 2015-2019 of patients who sustained open extremity fractures. Patients were stratified by antibiotic administered and Gustilo-Anderson grade. Outcomes included non-union/malunion, superficial surgical site infection (SSI), deep SSI, osteomyelitis, re-operation after index hospital visit, re-admission due to prior injury, limb loss, and death. Subgroup analysis stratified each antibiotic group by Gustilo-Anderson grade 1 or 2 and grade 3. Results: Data was collected from 2015 to 2019. Of the 1,149 patients, 619 patients met inclusion criteria. Three hundred fifty-five patients received cefazolin and 264 patients received ceftriaxone. There were no statistically significant differences between groups on specified outcomes. No statistically significant differences existed during subgroup analysis for the specified outcomes. Multivariable analysis demonstrated increased Gustilo-Anderson grade increased risk of infectious outcome. Conclusions: Ceftriaxone is a safe and effective alternative for open fracture extremity management that offers the advantage of 24-hour dosing and single antibiotic coverage for grade 3 open fractures. It does not increase infectious complications and offers benefits of resource efficiency.

Impact of Factor Xa Inhibitor Reversal with Prothrombin Complex Concentrate in Patients with Traumatic Brain Injuries.

BACKGROUND: Anticoagulant use prior to trauma has been associated with increased incidence of traumatic brain injury (TBI), intracranial hemorrhage (ICH) progression, and mortality. Prothrombin complex concentrates (PCCs) are commonly used as off-label treatments for factor Xa inhibitor-associated life-threatening hemorrhage. At this time, there is no consensus regarding appropriate indication, target dose, or outcomes of PCC administration in patients presenting with traumatic ICH. This study seeks to evaluate the impact of reversal with PCC on hemorrhage progression and outcomes in patients with TBI on preinjury factor Xa inhibitors. METHODS: This single-center retrospective cohort study included patients ≥ 18 years presenting with an acute TBI of any severity on apixaban or rivaroxaban from September 1, 2016, to September 1, 2019. Patients were grouped on the basis of receipt of PCCs for reversal (i.e., reversal or no reversal). Exclusion criteria included spontaneous ICH or known coagulopathy. Propensity score matching was conducted with the following variables: age, Abbreviated Injury Scale (head) score, and Charlson Comorbidity Index score. The primary outcome was hemorrhage stability within 48 h. Secondary outcomes included degree of hemorrhage progression, in-hospital mortality, discharge disposition, and incidence of thromboembolic events. RESULTS: Of the 115 patients meeting inclusion criteria, 84 were included in the propensity score matched data set. Baseline characteristics, comorbidities, and TBI severity were similar. The majority of patients in the reversal group (35 [83.3%]) and the no reversal (NR) group (40 [95.2%]) experienced a mild TBI (admission Glasgow Coma Scale score of 14 to 15). In the reversal group, patients received 34.3 units/kg activated PCC, 30.5 units/kg four-factor PCC, or 54.9 units/kg four-factor PCC and activated PCC on average. There was no difference observed in the incidence of hemorrhage progression (10.8% NR vs. 15.0% reversal; p = 0.739) or in median change in ICH volume (0 mL NR vs. 1 mL reversal; p = 0.2199) between groups. Additionally, reversal did not affect in-hospital mortality (3 [7.1%] NR vs. 4 [9.5%] reversal; p > 0.999). One patient in the reversal group developed a deep vein thrombosis (DVT) during the hospitalization; however, this did not result in a statistically significant difference in the occurrence of DVT (p > 0.999). CONCLUSIONS: This study demonstrated that PCC used for the treatment of factor Xa inhibitor-associated ICH related to mild TBI did not significantly impact the incidence or degree of hemorrhage progression, and PCC treatment did not result in increased thromboembolic events.

A Study of the MTHFR Gene Prevalence in a Rural Tennessee Opioid Use Disorder Treatment Center Population.

Background: Opioid Use Disorder (OUD) has been linked to dopamine and the neurological reward centers. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in the production of many neurotransmitters such as dopamine. As such, MTHFR variants that lead to decreased production of neurotransmitters may play a role in OUD. However, lacunae exist for characterizing the prevalence of the MTHFR mutations in an OUD population. The objective of this study was to determine prevalence of the MTHFR gene mutations in a rural Tennessean population with OUD. Methods: This study was a retrospective cohort of individuals with OUD that evaluated the prevalence of MTHFR variants. Patients were categorized as normal, homozygous C677T, heterozygous C677T, homozygous A1298C, or heterozygous A1298C. The primary outcome was a qualitative comparison of the prevalence of each of the MTHFR variants in our cohort to the publicly reported MTHR polymorphism prevalence. Secondary outcomes include race and ethnicity differences as well as stimulant use differences for each of the variants. Results: A total of 232 patients undergoing care for opioid use disorder were included in the study. Of those included, 30 patients had a normal MTHFR allele and 202 had a variant MTHFR allele. Overall, the prevalence of any MTHFR variant was 87.1% (95% CI 82.6-91.4%). When comparing those with a normal MTHFR allele to those with any MTHFR variant, there was no difference in age, sex, race and ethnicity, or stimulant use. Conclusion: The overall prevalence of MTHFR variants in patients with opioid use disorders is high.

Antibiotic Prophylaxis and Incidence of Infection with External Ventricular Drains and Intra-Cranial Pressure Monitors.

Objectives: Guidelines do not recommend extended antibiotic prophylaxis for external ventricular drains (EVD) or intra-cranial pressure (ICP) monitors. The study objective was to determine if infection rates are different for patients receiving antibiotic prophylaxis for EVD or ICP monitors. Patients and Methods: This single-center retrospective cohort reviewed intensive care unit patients who had an EVD or ICP monitor placed. Patients receiving antibiotic prophylaxis were compared with those who did not receive prophylaxis. The primary end point was incidence of central nervous system (CNS) infection. Results: Overall, 228 patients were included, 120 of whom received prophylaxis and 108 who did not receive prophylaxis. The primary end point of CNS infection was not different between groups (18 [17%] vs. 23 [19%]; p = 0.6236). Conclusions: Antibiotic prophylaxis was not associated with a decreased incidence of CNS infection in patients with EVD or ICP monitors. Evaluation of antibiotic use in this patient population is warranted to prevent resistance and adverse drug effects.

Incidence of thrombotic complications related to weight-based dosing of activated prothrombin complex concentrate (aPCC) for reversal of apixaban and rivaroxaban in obese patients.

Factor eight inhibitor bypassing activity (aPCC) is recommended as a non-specific reversal agent for direct oral anticoagulants (DOACs) according to the 2017 American College of Cardiology (ACC) guidelines for reversal of anticoagulation. Factor eight inhibitor bypassing activity carries a black box warning for thrombotic events such as stroke, pulmonary embolism, deep vein thrombosis, and myocardial infarction, particularly at high doses. This was a retrospective, single-center, cohort investigation that included patients who received a weight-based dose of aPCC for reversal of apixaban and rivaroxaban between January 1, 2015, and December 31, 2020. Patients were grouped by BMI as obese (BMI ≥ 30 kg/m2) or non-obese (BMI < 30 kg/m2) for analysis. The primary outcome of this investigation was the occurrence of thrombotic complications [venous thromboembolism (VTE), myocardial infarction, stroke] documented in the medical record at any point during hospitalization after administration of aPCC. Secondary outcomes included bleeding complications, in-hospital mortality, ICU and hospital length of stay. Patients in the obese group were younger [76.4 years (SD +/- 11.3 years) vs. 69.6 years (SD +/- 12.4 years); p < 0.0001] and a higher proportion had a diagnosis of diabetes mellitus prior to admission [37 (19.2%) vs. 35 (36.8%); p = 0.0011]. There was no difference in the primary outcome of thrombotic events between non-obese and obese patients [12 (6.2%) vs. 5 (5.3%); p = 0.75], or for any of the secondary outcomes of bleeding, in-hospital mortality or length of stay. This investigation did not reveal a difference in rates of thrombosis or bleeding events between obese and non-obese patients who received aPCC for reversal of apixaban and rivaroxaban.

Incorporation of a mock pharmacy and therapeutics committee as an entrustable professional activity supporting task.

INTRODUCTION: Entrustable professional activities (EPAs) denote activities and tasks students should be able to perform by graduation irrespective of their practice setting. Formulary decision-making includes several core EPA related skills, such as utilization of drug information, written, and verbal skills. The objective of this study was to describe an EPA supporting task aimed at improving utilization of evidence-based medicine skills and its impact on student self-perceived confidence, rating of skills needed, and competence. METHODS: Teams comprised of six to seven students were assigned a drug and instructed to complete the following activities: (1) background literature search, (2) drug monograph, (3) five-min presentation to simulate a live pharmacy and therapeutics (P&T) committee meeting, and (4) vote on a formulary drug in each drug class. Students completed a pre/post five-point Likert scale self-efficacy survey and a perceived importance survey. A scoring rubric assessed monograph and presentation elements (max points 30). Survey items were analyzed using Wilcoxon signed-rank test. Descriptive statistics were used for assignment grades. RESULTS: One hundred ninety students completed the pre/post self-efficacy and perceived importance survey. Confidence showed statistically significant improvement (P < .001) in nine target skill areas. In ranking importance, all 12 assessed skills exhibited a statistically significant increase following the activity. CONCLUSIONS: A mock P&T activity represents an innovative way to evaluate an EPA supporting task that allows students to improve their evidence-based analysis, written, and verbal communication skills.

INR Response to Low-Dose Vitamin K in Warfarin Patients.

BACKGROUND: Literature suggests that 2 mg of vitamin K intravenously (IV) provides a similar effect as 10 mg to reverse warfarin. Doses <5 mg haven't been studied in depth. OBJECTIVE: The objective was to determine the international normalized ratio (INR) reduction effect of ultra low-dose (ULD) IV vitamin K. METHODS: This retrospective, observational cohort study compared IV vitamin K doses of 0.25-0.5 mg (ULD) versus 1-2 mg (standard low dose [SLD]). The primary outcome assessed ΔINR at 36 hours; secondary outcomes assessed ΔINR at 12 hours and 30-day venous thromboembolism (VTE) and mortality rates. RESULTS: Of 88 patients identified (median baseline INR [IQR], 5.1 [3.1, 7.3] vs 4.5 [2.8, 8.2], ULD vs SLD, respectively), 59 had an INR at 12 hours. The ULD had fewer 12-hour INR values <2, with no statistical difference in the ΔINR at 12 hours between the ULD and SLD cohorts (median ΔINR, 2.2 [1.1, 3.4] vs 2.2 [1.1, 6.3]; P = 0.54; median INR, 2.3 vs 1.8). A total of 41 patients had both a 12- and 36-hour INR. No significant difference in the ΔINR between the 12- and 36-hour values occurred (median ΔINR, 0.52 [0.2, 0.91] vs ΔINR, 0.46 [0.18, 0.55]; P = 0.61), suggesting no rebound or excessive reversal and no difference in 30-day rates of VTE (P > 0.99) or death (P = 0.38). CONCLUSION AND RELEVANCE: ULD IV vitamin K reversed INR similarly to doses of 1-2 mg without rebound. A ULD strategy may be considered in patients requiring more cautious reversal.

Impact of Obesity on Warfarin Reversal With Fixed-Dose Factor VIII Inhibitor Bypassing Activity (aPCC).

BACKGROUND: Data are limited addressing anticoagulant reversal in obese patients using activated prothrombin complex concentrate (aPCC). OBJECTIVE: Assess the impact of obesity on INR reversal with fixed aPCC dosing. METHODS: Institutional review board-approved, retrospective cohort conducted in a large academic medical center. Patients 18 years or older who received fixed-dose aPCC for warfarin-associated hemorrhage were included. Patients who received aPCC for any other indications or who had no follow-up INR after aPCC administration were excluded. Patients with an INR of 5 or greater received 1000 units aPCC, whereas those with INR less than 5 received 500 units aPCC, per institutional protocol. Patients were stratified into obese and nonobese based on body mass index. Primary end point was INR reversal, defined as repeat INR of 1.4 or less within 4 hours following aPCC treatment, without a repeated dose. Secondary end points included percentage change in INR, proportion of patients requiring an additional dose of aPCC, bleeding complications, thrombotic complications, hospital length of stay, and in-hospital mortality. RESULTS: 259 patients were included, of whom 83 were obese (32%). A significantly higher proportion of nonobese patients achieved an INR of 1.4 or less within 4 hours of treatment (169 [96.02%] vs 69 [83.13%]; P = 0.0004). There were no differences in any secondary end points. CONCLUSION AND RELEVANCE: When fixed-dose aPCC is used for warfarin reversal, obesity is associated with a significantly lower rate of INR reversal, without increased bleeding. This study adds to the limited amount of literature on aPCC dosing in obesity.

23.4% Sodium Chloride Versus Mannitol for the Reduction of Intracranial Pressure in Patients With Traumatic Brain Injury: A Single-Center Retrospective Cohort Study.

BACKGROUND: Intermittent doses of mannitol or hypertonic saline are recommended to treat elevated intracranial pressure (ICP). However, it is unclear if one agent is more effective than the other. Previous studies have compared mannitol and hypertonic saline in reduction of ICP, with conflicting results. However, no study thus far has compared 23.4% sodium chloride with mannitol. OBJECTIVE: The objective of this study was to determine the difference in absolute reduction of ICP 60 minutes after infusion of 23.4% sodium chloride versus mannitol. METHODS: This was a single-center retrospective cohort study that included patients at least 16 years old admitted to the trauma/surgical intensive care unit between August 8, 2016, and August 30, 2018, who received either 23.4% sodium chloride 30 mL and/or mannitol 0.5 g/kg and had an ICP monitor or external ventricular drain in place. The primary outcome was absolute reduction in ICP 60 minutes after infusion of hyperosmolar therapy. RESULTS: In all, 31 patients and 162 doses of hyperosmolar therapy were included in the analysis. There was no statistically significant difference in the primary end point of absolute reduction of ICP 60 minutes after infusion of hyperosmolar therapy comparing 23.4% sodium chloride 30 mL with 0.5 g/kg mannitol (P = 0.2929). There was no statistically significant difference found for any secondary end points. CONCLUSION AND RELEVANCE: No difference was found for absolute reduction of ICP at 30, 60, and 120 minutes, respectively, after infusion of hyperosmolar agent or time to next elevated ICP. Patient-specific parameters should be used to guide the choice of hyperosmolar agent to be administered.

Applying safety lessons from aviation to pre-licensure health professions education: A narrative critical review.

BACKGROUND: Significant numbers of patients continue to be harmed annually by healthcare systems in the United States (US) and around the world. Through a lens of safety, the fields of aviation and healthcare share many similarities in the non-technical skills required by team members, including situational awareness, communication, problem-solving, and leadership. Despite these links and evidence of effective interventions in the clinical setting, there is a lack of a guidance on how to incorporate non-technical skills training into pre-licensure health professions curricula. METHODS: Following guidance for a narrative critical review, a comprehensive literature search was conducted looking for studies incorporating non-technical skills training including crew resource management (CRM) and human factors and ergonomics (HFE) into pre-licensure health professions curricula. RESULTS: Eleven example articles were organized into three broad themes: (1) changing the teaching paradigm around errors, (2) targeted curricular interventions, and (3) interprofessional team training. Several useful tools for evaluating training effectiveness were highlighted, but consistent measures of efficacy for CRM/HFE training are lacking. Interprofessional team training may have the most tangible and broadly applicable link to pre-licensure curricula. IMPLICATIONS: Additional research is needed to identify best practices for consistent incorporation of non-technical skills into pre-licensure curricula. A cultural shift to focus on error management (vs. solely error avoidance) is also needed early in training with development of a common language to discuss patient safety issues and opportunities for improvement across various healthcare settings.

Analysis of anticoagulation reversal survey (ARES).

OBJECTIVES: Despite the availability of FDA-labeled anticoagulant reversal agents, there is considerable variability in clinical practice as to the regimen and agent used for reversal. The objective of this study was to characterize the current practices of pharmacists surrounding the reversal of anticoagulant-associated life-threatening hemorrhage. Methods: A cross-sectional analysis of critical care and emergency medicine pharmacists. Current practice was compared for the type of hospital, country region, and type of ordering physician. In addition, pharmacists were asked to rank their involvement with activities involved with the reversal of anticoagulants. Respondents ranked their involvement with these activities as either never involved, rarely involved, occasionally involved, frequently involved, or always involved. Results:281 respondents were included. The majority used 4-factor PCC for warfarin reversal (92.9%) and factor Xa inhibitor reversal (79.7%). However, only 58.7% used the labeled dose of 4-PCC for warfarin reversal. Of the 30.6% that utilized a fixed-dose regimen, the most common regimen was 1500 units once. A higher proportion of respondents practicing in a teaching hospital reported that they used activated prothrombin complex concentrates for reversal of factor Xa inhibitor (22 [12.2%] vs. 5 [5%]; p < 0.05) or coagulation factor Xa (recombinant)-inactivated-zhzo (31 [17.2%] vs. 5 [5%]; p < 0.05). In addition, the majority of respondents utilized idarucizumab for dabigatran reversal. The only involvement activity in which <50% of respondents said they were frequently involved or always involved was 'administration of reversal agent.' Conclusions: There is considerable variability in which agents were utilized for anticoagulant-associated bleeding reversal.

Identification of Risk Factors for Refractory Status Epilepticus.

Objective: The objective of this study is to identify risk factors for the development of refractory status epilepticus (RSE). Methods: This was an IRB-approved, retrospective case control study that included patients admitted with status epilepticus between August 1, 2014, and July 31, 2017. Cases were defined as those with RSE, and controls were those who did not develop RSE. A bivariate analysis was conducted comparing those with RSE and those without RSE. A stepwise logistic regression model was constructed predicting for progression to RSE. Risk factors for progression to RSE were extrapolated from this model. Results: A total of 184 patients met inclusion criteria for the study (99 controls and 49 cases). After adjusting for covariates in the logistic regression, patients with convulsive seizures had a lower odds of developing RSE (odds ratio [OR] = 0.375; 95% CI = 0.148 to 0.951; P = 0.0388). Treatment with benzodiazepines plus levetiracetam had a higher odds of developing RSE (OR = 3.804; 95% CI = 1.523 to 9.499; P = 0.0042). Conclusion and Relevance: This study found that patients with convulsive seizures had a lower odds of developing RSE. In addition, patients treated with benzodiazepines and levetiracetam had a higher odds of developing RSE. This information can be used to potentially identify patients at higher risk of developing RSE, so that treatment can be modified to reduce morbidity and mortality. These results may warrant further investigation into the effectiveness of levetiracetam as a first-line agent for the treatment of SE.