Safety and efficacy of fixed versus variable-dose prothrombin complex concentrate for emergent reversal of vitamin K antagonists: A systematic review and meta-analysis.

STUDY OBJECTIVE: Four-factor prothrombin complex concentrate (4F-PCC) is standard of care for emergent vitamin K antagonist (VKA) reversal but optimal dosing is uncertain. This meta-analysis estimated the proportion of patients treated with fixed dose (FD) 4F-PCC who achieved adequate reversal and compared safety and efficacy of FD versus weight-based dose (WB) strategies. METHODS: This review was conducted according to PRISMA guidelines. Medline and Scopus were searched and included studies evaluating FD regimens and comparing FD and WB for emergent VKA reversal. Data was pooled using random effects. Subgroup analyses examined heterogeneity. Risk of bias was assessed with Newcastle-Ottawa Scale and RoB2 score. RESULTS: Twenty-three studies (n = 2055) were included with twelve (n = 1143) comparing FD versus WB. The proportion of patients achieving goal INR with FD varied depending on the INR target, being significantly higher for INR <2 (90.9%, 95% Confidence Interval (CI) 87.2, 94.06) compared to INR <1.6 (70.97%, 95%CI 65.33, 76.31). Compared to WB, FD was less likely to achieve a goal INR <1.6 (Risk Difference (RD) -13%, 95% CI -21, -4) but achieved similar reversal for a goal INR <2.0, (RD -1%, 95%CI -7, 4). There was no difference in hospital mortality (RD 4%, 95%CI -2, 9) or thrombosis (RD 0.0%, 95%CI -3, 3). CONCLUSION: FD VKA reversal was associated with significantly lower attainment of goal INR compared to WB with lower INR targets. This did not translate to differences in hospital mortality, but these results should be interpreted cautiously in light of the observational nature of the included studies.

Antibiotic Prescribing Errors in Patients Discharged From the Pediatric Emergency Department.

OBJECTIVES: The pediatric emergency department (PED) is an especially high-risk setting for medication errors. Several factors contribute to this risk including the need to provide care to complex patients who are unknown to staff, the frequent use of verbal orders, and the necessity of weight-based dosing. This investigation sought to assess one potentially error-prone event, antibiotic prescriptions written for patients being discharged from the PED, and to characterize the occurrence of medication errors to identify opportunities for improvement. METHODS: This was a retrospective study of pediatric patients seen at a large academic medical center PED. All prescriptions written for an antibiotic for patients 18 years or younger that were discharged from the PED from 2015 to 2018 were evaluated for errors in directions, indication, dose, quantity, and refills. Because antibiotic dosing can vary based on indications, only disease states with guideline-specific dosing recommendations were evaluated for dosing errors. RESULTS: A total of 11,815 antibiotic prescriptions were analyzed for patients discharged from the PED, and 1986 (16.8%) errors were identified. Of all the prescriptions reviewed, 517 (4.4%) contained an incomplete prescription error. Discharge prescriptions written by off-service physicians were more likely to contain incomplete prescription errors (5.1%) when compared with emergency medicine physicians (3.9%; P = 0.022). A dosing error rate of 18.5% (1469 prescriptions) was identified for the 7930 disease state-specific prescriptions reviewed. Underdosing errors were significantly more common (51.6%) than overdosing errors (29.3%; P < 0.0001). Among the different agents, there was noted to be a significant difference in the antibiotics most commonly involved in dosing errors (P < 0.0001). Additionally, there was also a significant difference in the incidence of dosing errors between different disease states (P < 0.0001). No significant difference was found in the incidence of dosing errors across physician specialties (P = 0.872). CONCLUSIONS: We identified 1986 (16.8%) total errors in this analysis of antibiotic prescriptions written on discharge from the PED. Among the disease states evaluated, dosing errors were identified in 18.5% of prescriptions with the most common error being underdosing. Literature evaluating pediatric prescription errors, and specifically antibiotic discharge prescriptions, is quite limited. Further investigation is necessary in this area, and strategies should be developed leveraging technology, enhancing education, and using pharmacy personnel to help reduce antibiotic prescribing errors for patients discharged from the PED.

Characterization of Emergency Department Rabies Post-Exposure Prophylaxis Procedures with an Infectious Diseases Clinic Referral Process.

Purpose: Rabies post-exposure prophylaxis (rPEP) in the emergency department (ED) is associated with high costs, complicated administration protocols, and a time-sensitive vaccination series that often requires ED follow-up visits for subsequent vaccine administration. This study sought to characterize the number of redirected vaccine administrations in those patients referred to ID Clinic, guideline compliance, and opportunities for improvement. Methods: Retrospective chart review of adult and pediatric patients presenting to the ED from 2016 to 2019 and prescribed rabies immunoglobulin. Results: Of the 89 patients included, 66.3% were referred to ID Clinic. Those referred to clinic had significantly fewer average visits to the ED for repeat vaccination (P < .001). Of the 177 vaccinations prescribed for patients referred, 105 were administered in clinic. Overall, having insurance significantly increased the odds of completing the prescribed vaccination series (Odds Ratio (OR) = 4.34, 95% Confidence Interval (CI) = 1.34 to 15.52). Among those patients referred to clinic, having insurance significantly increased the odds of receiving any follow-up doses in clinic (OR = 6.00, 95% CI = 1.48 to 25.98), receiving all of their prescribed follow-up doses in clinic (OR = 10.00, 95% CI = 1.72 to 190.80), and completing the entirety of their vaccination series (OR = 5.89, 95% CI = 1.50 to 26.21). Conclusions: The use of an ID Clinic referral process for rPEP resulted in a significant reduction in the average number of visits to the ED for repeat vaccination, hence avoiding 105 ED visits. Insurance status was a significant factor in both the utilization of the ID Clinic referral system and overall completion of the vaccination series. Future research should explore workflows inclusive of both ED care and outpatient follow-up, care plans for the uninsured, and mechanisms to limit the number of patients that fail to complete the recommended vaccination series.

Risk Factors for Antibiotic Resistant Urinary Pathogens in Patients Discharged From the Emergency Department.

Purpose: Urinary tract infections (UTIs) are one of the most common indications for antimicrobial use in the emergency department (ED). Appropriate empiric selection is crucial to ensure optimal care while limiting broad-spectrum antibiotic use. The primary objective of this study was to evaluate the relationship between patient-specific risk factors and drug resistant urinary pathogens in patients discharged from the ED and followed by Emergency Medicine Pharmacists (EMPs). Methods: This was a single-center, retrospective chart review of adult (≥18 years old) patients with positive urine cultures discharged from the ED. The association between risk factors and pathogen resistance to ≥1 classes of antibiotics was evaluated using multivariate logistic regression. Risk factors included the following: hospitalization within the previous 30 days, intravenous antibiotic use within 90 days, diabetes, clinical atherosclerotic cardiovascular disease, psychiatric disorder, dementia, current antibiotic use for any indication, previous lifetime history of UTIs, indwelling or intermittent catheterization, hemodialysis, previous lifetime history of a urologic procedure, urinary tract abnormality, immunosuppressive disease or medications, current residence in a nursing or rehabilitation facility, and history of a multidrug resistant organism (MDRO). Results: A total of 1018 patients were included. There was an increase in the odds of antibiotic resistance in patients with cystitis and ≥2 risk factors (Odds Ratio [OR] = 1.70, 95% CI = 1.24-2.32). In those with pyelonephritis, there was a non-significant increase in the odds of resistance for those with ≥2 risk factors (OR = 1.83, 95% CI = 0.98-3.42). Patients with pyelonephritis discharged on inappropriate antibiotics were more likely to return to the ED within 30 days (P = .03). Conclusions: For patients with cystitis discharged from the ED, those with ≥2 patient-specific risk factors had significantly increased odds of antibiotic resistance. Patients with pyelonephritis, but not cystitis, who were discharged on inappropriate antibiotics were more likely to return to the ED within 30 days. In conjunction with an EMP culture follow-up program, the identification of risk factors for antimicrobial resistance can be used to design more patient-specific empiric antibiotic selections.

Efficacy of bolus-dose epinephrine to manage hypotension in the prehospital setting.

PURPOSE: Hypotension in the Emergency Department (ED) and the prehospital setting has been associated with significant morbidity and mortality. Limited literature exists exploring the utilization of intravenous (IV) bolus-dose epinephrine (BDE) by Emergency Medical Services (EMS). METHODS: A retrospective review evaluated patients transported to an academic medical center who had received IV BDE by a single urban EMS system from 2016 to 2020. The primary outcome was to assess the influence IV BDE had on systolic blood pressure (SBP). Secondary objectives were to assess changes in heart rate (HR), the impact of dose variability on SBP, and the incidence of severe hypertension (SBP > 220 mmHg). RESULTS: A total of 55 patients who received 96 administrations of IV BDE were included in the analysis. The most common individual dose was 10 µg (76.0%) and 45.5% received multiple doses. The median weight-based dose of BDE was 0.14 µg/kg. A significant increase in SBP (median 14.0 mmHg) was noted among all patients following BDE administration compared with baseline (p < 0.001). No significant difference was found in HR following BDE compared with baseline (p = 0.375). Those that received a BDE dose >10 µg were noted to have a significantly greater rise in SBP than those that received 10 µg (30.0 mmHg vs. 11.0 mmHg; p = 0.022). Similarly, patients that received a dose ≥0.2 µg/kg had a significantly greater increase in SBP compared with those that received <0.2 µg/kg (30.0 mmHg vs. 10.0 mmHg; p = 0.048). There were no incidences of severe hypertension following therapy. CONCLUSION: The utilization of IV BDE in the prehospital setting for acute hypotension resulted in a significant rise in SBP. A dose-response relationship was noted both in terms of a flat-based dose and a weight-based dose, with higher doses yielding a greater change in SBP. Additional investigations are necessary to further explore the most appropriate dose of this agent in this setting and its influence, if any, on clinical outcomes.

Intravenous insulin for the management of non-emergent hyperglycemia in the emergency department.

PURPOSE: There is currently no consensus regarding the necessity of emergency department (ED) glucose reduction to manage hyperglycemia in patients presenting without a hyperglycemic emergency. Known consequences of intravenous (IV) insulin administration include hypoglycemia, hypokalemia, and increased ED length of stay. The primary objective of this study was to assess the impact of IV regular insulin on glucose reduction and ED length of stay in patients presenting to the ED with non-emergent hyperglycemia. Secondary objectives included the characterization of potential adverse events. METHODS: This was a retrospective, observational study of patients ≥18 years who received IV regular insulin and were discharged from the ED at a large academic Trauma Center. Univariate and multivariable regression analyses were utilized to determine if an association existed between IV insulin administration and blood glucose as well as ED length of stay. RESULTS: A total of 405 patients were included in the analysis. An insulin dose >5 units was associated with a greater reduction in blood glucose (difference = 37.4 mg/dL; p < .001) but no difference in ED length of stay relative to ≤5 units. Furthermore, 7.9% of patients developed hypokalemia and 0.4% developed hypoglycemia. CONCLUSION: The use of >5 units of IV regular insulin for the management of isolated hyperglycemia in the ED was associated with a modest reduction in blood glucose and no difference in ED length of stay compared with those that received ≤5 units. However, use of IV insulin for this purpose resulted in a 7.9% occurrence of hypokalemia.

Assessment of benzodiazepine dosing strategies for the management of status epilepticus in the emergency department.

PURPOSE: Although guidelines recommend specific benzodiazepine doses for the treatment of generalized convulsive status epilepticus (GCSE), underdosing appears to be common. The purpose of this investigation was to assess benzodiazepine dosing strategies for the initial management of GCSE in patients presenting to the Emergency Department (ED). METHODS: This was a retrospective review of adult patients who received benzodiazepines in the ED for treatment of GCSE. Characteristics of those achieving seizure cessation following initial benzodiazepine therapy were assessed. RESULTS: 222 patients presented to the ED and received 403 doses of benzodiazepines, of which 1.5% conformed with recommendations. First-line therapy was successful in 86.8% of patients with an average dose of 1.6 mg (0.02 mg/kg). No difference in dosing was noted between those experiencing early cessation and those that did not (p = 0.132). Patients experiencing early cessation were significantly less likely to receive further doses, be intubated, or be admitted to the intensive care unit (ICU) or hospital (p < 0.05 for all comparisons). Those that received early antiepileptic drug therapy were significantly less likely to receive additional benzodiazepine doses, be intubated, or be admitted to the ICU or hospital (p < 0.05 for all comparisons). CONCLUSIONS: According to guideline recommendations, there was consistent underdosing of benzodiazepines noted in both prehospital and ED settings. Early seizure cessation and the early receipt of an antiepileptic drug were found to be associated with multiple significant clinical outcomes. Future investigations should explore optimal dosing strategies for benzodiazepines as well as the impact of early antiepileptic drug administration.

Incidence of prescription errors in patients discharged from the emergency department.

PURPOSE: The Emergency Department (ED) is known for its high rates of medication errors secondary to many characteristics such as unfamiliar patients, lack of continuity of care, increasing patient volumes, reliance on verbal orders, and fewer safety mechanisms. The purpose of this study was to quantify and characterize the medication errors that occur in patients discharged from the ED. METHODS: Prescriptions for patients discharged from the adult ED at an academic medical center from 2015 to 2018 were reviewed. Errors in discharge medication orders were documented as well as characteristics of these errors including medication class, errors in prescription directions, quantity prescribed, and refills given inappropriately. RESULTS: A total of 115,933 prescriptions were reviewed and a total of 20,498 errors were identified within 19,126 prescriptions. Of the errors identified, 4048 (19.7%) involved prescription directions, 6537 (31.9%) were errors in quantity prescribed, and 9913 (48.4%) were prescriptions written with refills. The proportion of errors among different prescriber statuses was significantly different when comparing all prescribers (p < .001). Prescriptions written by Non-Emergency Medicine residents had significantly more errors in quantity and refills (p < .001, p < .001), and prescriptions written by Emergency Medicine residents had significantly more errors in directions (p < .001). CONCLUSIONS: This review identified a 16.5% error rate among all prescriptions provided to patients upon ED discharge that varied among different subcategories of medications. This is consistent with the limited literature that is currently available on the topic. These results could assist institutions in developing targeted mitigation strategies to limit medication misadventures in patients discharged from the ED.

Development of a Pharmacy Residency Research Certificate Program.

Background: Similar to teaching certificate programs, which have been incorporated in many pharmacy residencies to improve teaching skills, resident research certificate programs could provide residents with more exposure to biostatistics and research design. However, few research certificate programs have been described. Objective: To assess the impact of a research certificate program on residents' attitude toward, confidence in, and knowledge of research. Methods: A resident research certificate program was created for the 2018-2019 residency class at our institution, which included 33 pharmacy residents (15 postgraduate year-1 [PGY1] and 18 PGY2 residents). The program consisted of 7 sessions aimed at providing residents with research training. To earn a certificate, participants were required to attend 6 or more sessions and achieve a score greater than or equal to 70% on a postassessment. An optional questionnaire assessing attitude, confidence, and knowledge was also administered at baseline and following the certificate program. Results: Of the 33 residents participating in the research certificate program, 21 (9 PGY1 and 12 PGY2) residents completed both the baseline and follow-up questionnaire and were included in the analysis. All items assessing attitude and 3 of 6 items assessing confidence improved significantly following the certificate program when compared to baseline (P < .05 for all). Median knowledge scores were no different on the baseline versus follow-up questionnaire (P = .54). Conclusions: After completing a research certificate program, resident knowledge scores did not differ from baseline, but attitudes toward research and confidence appeared to improve. Research certificate programs could be an avenue for providing pharmacy residents with increased exposure to and comfort with biostatistics and research design.

Weight-based versus non-weight-based diltiazem dosing in the setting of atrial fibrillation with rapid ventricular response.

PURPOSE: There is conflicting evidence to support the superiority of weight-based (WB) dosing of intravenous (IV) diltiazem over non-weight-based (NWB) dosing strategies in the management of atrial fibrillation (AFib) with rapid ventricular response (RVR). METHODS: A retrospective review evaluated patients presenting to the emergency department (ED) in AFib with RVR and receiving IV diltiazem from 2015 to 2018. Those receiving a NWB dose were compared with those receiving a WB dose based on actual body weight (ABW). Secondary analyses evaluated safety profiles of the regimens and compared response in groups defined by ABW or ideal body weight (IBW). RESULTS: A total of 371 patients were included in the analysis. No significant difference was observed in achieving a therapeutic response (66.5% vs. 73.1%, p = 0.18) or adverse events between the groups. Patients receiving a WB dose were significantly more likely to have a HR < 100 bpm than those receiving a NWB dose (40.9% vs. 53.5%, p = 0.01). When groups were defined by IBW, WB dosing was associated with a significantly higher incidence of achieving a therapeutic response (62.7% vs. 74.3%, p = 0.02). CONCLUSION: In patients presenting with AF with RVR, there was no significant difference in achieving a therapeutic response between the two strategies. A WB dosing approach did result in a greater proportion of patients with a HR < 100 bpm. The utilization of IBW for WB dosing may result in an increased achievement of a therapeutic response.

Compliance and Related Outcomes of Prophylactic Antibiotics in Traumatic Open Fractures.

Purpose: Prophylactic antibiotic therapy is a standard of care for patients who present with open fractures due to the risk of infectious complications. This study was conducted to characterize the use of initial prophylactic antibiotic use in open fractures, guideline compliance, and its impact on care. Methods: Retrospective chart review of adult patients presenting with an open fracture to a Level 1 Trauma Center Emergency Department over a 12-month period was conducted. Results: Of the 202 patients meeting inclusion criteria, overall compliance with guideline recommendations for antibiotic prophylaxis was found to be 33.2%. The duration of prophylactic therapy was significantly longer in the noncompliant group and among those who received a secondary antibiotic (P < .05 for both comparisons). The duration of therapy was found to be significantly longer in those patients who developed an infection (P < .001). Those who developed an infection had a longer hospital length of stay (LOS) (P < .001) and intensive care unit LOS (P = .002). In addition, those who developed an infection had significantly more surgeries (P < .001) and received more red blood cell transfusions (P < .001). Correlation analysis confirmed a significant association between infection and duration of antibiotic prophylaxis (P = .02), number of surgeries (P < .0001), and number of transfusions (P < .0001). Conclusion: Guideline compliance was exceedingly low due to the extended duration of initial antibiotic therapy and did not appear to yield any clinical benefits. Infection was significantly associated with longer duration of initial prophylactic therapy and morbidity. Opportunities exist to elevate compliance with guidelines and to reevaluate prophylactic antimicrobial therapy in this setting.

Safety, efficacy, and cost of four-factor prothrombin complex concentrate (4F-PCC) in patients with factor Xa inhibitor-related bleeding: a retrospective study.

Oral factor Xa (fXa) inhibitor-related bleeding is a concerning drug safety problem. There is considerable controversy surrounding available reversal strategies. The recently approved reversal agent andexanet alfa has limited data, an unclear safety profile, and imparts a substantial financial burden. This has led to the off-label use of four-factor prothrombin complex concentrates (4F-PCC) for this indication. This study aimed to assess the safety and efficacy of 4F-PCC for the management of major bleeding related to oral fXa inhibitors. This observational, retrospective study included adult patients admitted from 2014 to 2018 who received 4F-PCC (Kcentra®) for fXa inhibitor-related major bleeding. Efficacy was assessed using criteria described by Sarode et al. Secondary outcomes included the incidence of thromboembolism, mortality, and a cost analysis comparing 4F-PCC to andexanet alfa for reversal of oral fXa inhibitors. Thirty-one patients received 4F-PCC for major bleeding associated with apixaban (55%) or rivaroxaban (45%). Intracranial hemorrhage (58%) and pericardial effusion (16%) accounted for the majority of bleeding events. Most patients received a single weight-based 4F-PCC dose of 25 units/kg (38.7%) or 50 units/kg (51.6%). Effective hemostasis was achieved in 80.6% of patients. Five patients (16%) died due to acute bleeding and no thromboembolic events were observed. Administration of 4F-PCC was effective for most patients requiring emergent reversal of anticoagulation with apixaban or rivaroxaban and was associated with a low risk of thromboembolic events. Considerable cost differences limit the use of andexanet alfa and may warrant further study of 4F-PCC for fXa inhibitor reversal.

Implications of Statin Use on Vasopressor Therapy in the Setting of Septic Shock.

Background: Pleiotropic anti-inflammatory and immunomodulatory effects of statins have been associated with improved outcomes in the critically ill population. Objective: To evaluate the implications of prior statin use on the duration of vasopressor therapy in the setting of septic shock. Methods: This was a retrospective, multicenter study of adult patients who were diagnosed with septic shock. Patients were included if they were treated with any vasopressor for greater than 6 hours from the time of admission. The primary outcome was to compare the duration of vasopressor therapy in patients with septic shock with and without previous statin exposure. Results: A total of 88 statin-exposed cases and 205 unexposed controls were included in the analysis. Despite 92% of statin-exposed patients being reinitiated on therapy within 24 hours, the duration of vasopressors did not differ between groups (44 hours, statin group vs 53 hours, control group, P = .51). There were also no mortality differences between the statin group and the controls (40% vs 47%, P = .27). Conclusions: Long-term statin exposure does not impact the duration of vasopressor therapy in septic shock. The lack of differences in clinical outcomes supports the concept that sepsis involves pro- and anti-inflammatory pathways as well as other nonimmunologic pathways. Results lend further credence to the recent conceptualization of sepsis, with complications leading to organ dysfunction caused not primarily due to inflammatory responses but by a dysregulated response to infection.

Effectiveness of glucagon in relieving esophageal foreign body impaction: a multicenter study.

PURPOSE: Glucagon is thought to decrease lower esophageal sphincter tone and is used as an alternative to invasive endoscopy for esophageal foreign body impaction (EFBI). The purpose of this study was to evaluate efficacy and safety of glucagon and identify characteristics associated with success. METHODS: A multicenter, retrospective study of patients receiving glucagon for EFBI at 2 academic emergency departments was conducted between 2006 and 2010. A control group of patients that did not receive glucagon was evaluated. Data collection included demographics, type of foreign body, glucagon dose, resolution of impaction, incidence of vomiting, additional medication, and endoscopy required. Descriptive and univariate analysis was performed as appropriate. RESULTS: A total of 133 doses of glucagon were administered in 127 patients. Glucagon-related resolution of EFBI occurred in 18 patients (14.2%) and vomiting in 16 patients (12.6%). No statistical differences between successful and unsuccessful groups were seen with the exception of concomitant medication administration (benzodiazepine or nitroglycerin) being associated with less glucagon success, 33.3% vs 59.6%, respectively (P = .04). Eighty-four percent of patients in the unsuccessful group underwent endoscopy. Comparing those that received glucagon (n = 127) and the control group (n = 29), there was no significant difference in resolution of EFBI, 14.2% vs 10.3%, respectively (P = .586). CONCLUSIONS: Glucagon-related resolution occurred in 14.2% of patients and was not significantly different compared with those that did not receive glucagon (10.3%). Concomitant medication administration was associated with lower success. Overall, glucagon had a low success rate, was related to adverse effects, and does not offer advantages for treatment.

Effects of etomidate on adrenal suppression: a review of intubated septic patients.

BACKGROUND: Etomidate is a commonly used sedative during rapid sequence intubation (RSI). Septic patients are at an increased risk of independently developing adrenal suppression, which has been associated with increased mortality in some studies. Since etomidate affects cortisol production, its use in septic patients is controversial. However, data are still lacking to prove that etomidate should be avoided in this patient population. OBJECTIVES: The objective was to review patients diagnosed with sepsis who received etomidate during RSI. Our hypothesis is that patients who receive etomidate will experience clinically significant hypotension within the first 24 hours of intubation. METHODS: A retrospective cohort study was conducted on patients intubated in the emergency department (ED) and medical/surgical floors at our institution from 2004 to 2010. Once patients with a diagnosis of sepsis were identified, it was determined whether the patients received etomidate or a different sedative during intubation. The primary endpoint was clinically significant hypotension: systolic blood pressure <90 mm Hg or mean arterial pressure <60 mm Hg. RESULTS: One hundred fifty-seven patients, 110 etomidate and 47 non-etomidate, were included in the final analysis. Hypotension was seen in 79 (71.8%) patients who received etomidate and in 14 (29.8%) patients who received another sedative (P ≤ .001). There were no statistically significant differences in secondary objectives. CONCLUSION: Etomidate use for induction of anesthesia during RSI was associated with clinically significant hypotension when compared to other sedatives. The hypotension was transient and did not translate into statistically significant differences in the secondary clinical endpoints.