Hemostatic Efficacy and Safety of Weight-Based Versus Fixed-Dose 4F-PCC for Vitamin K Antagonist Reversal.

Background: Four-factor prothrombin complex concentrate (4F-PCC) is indicated for vitamin K antagonist (VKA) reversal but is associated with thrombotic events (TE). In 2018, the institution revised 4F-PCC dosing for VKA reversal from INR and weight-based dosing to a fixed-dose of 1500 units. Objective: The purpose of this study was to compare hemostatic efficacy and TE rate of fixed-dose 4PCC to weight-based dosing. Methods: This was a retrospective, single-center, quasi-experimental study of adult patients who received 4F-PCC for VKA reversal from January 2014 through May 2016 (INR and weight-based dosing) or April through October 2018 (fixed-dosing). The primary endpoint was hemostatic efficacy, defined by achieving an INR of ≤1.4, or an INR of ≤1.7 with evidence of hemostasis. The key secondary endpoint was TE within 14 days of 4F-PCC administration. Data were analyzed using descriptive statistics, chi-squared for nominal data and Mann-Whitney U for ordinal and continuous data. Results: The study included 163 patients who received weight-based dosing and 45 who received fixed-dose 4F-PCC. Hemostatic efficacy was 76.9% of patients in the weight-based group and 77.4% of patients in the fixed-dose group (P = .229). TE occurred in 13.5% of the weight-based vs 6.7% of the fixed-dose group (P = .181). Conclusion: This study found no difference in hemostatic efficacy with fixed-dose 4F-PCC for VKA reversal compared to INR and weight-based dosing. The occurrence of TE was reduced by 50% with the 4F-PCC fixed-dose strategy; however, this difference was not statistically significant. Further randomized studies are needed to confirm these results.

Standardizing Opioids Prescribed at Discharge in Trauma Surgery.

INTRODUCTION: Excessive opioid use after sustaining trauma has contributed to the opioid epidemic. Standardizing the quantity of opioids prescribed at discharge can improve prescribing behavior. We hypothesized that adopting new electronic medical record order sets would be associated with decreased morphine milligram equivalents (MME) prescribed at discharge for trauma patients. METHODS: This was a quasi-experimental study examining opioid prescribing practices at a Level 1 Trauma Center. All patients ages 18-89 admitted to the Trauma Service from January 2017 through March 2021 and hospitalized for at least 2 d were included. In November 2020, new trauma admission and discharge order sets were implemented with recommended discharge opioid quantity based on inpatient opioid usage the day prior to discharge multiplied by five. Postintervention prescribing practices were compared to historical controls. The primary outcome was MME at discharge. RESULTS: Baseline characteristics between preintervention and postintervention cohorts were comparable. There was a significant reduction in median MME prescribed at discharge postintervention (112.5 versus 75.0, P < 0.0001). Median inpatient MME usage also significantly reduced postintervention (184.1 versus 160.5; P < 0.0001). There were trends toward increased ideal prescribing per order set recommendation and a reduction in overprescribing. Patients receiving the recommended opioid quantity at discharge had the lowest opioid refill prescription rate (under: 29.6%, ideal: 7.3%, over: 19.7%, P < 0.0001). CONCLUSIONS: For trauma patients requiring inpatient opioid therapy, a pragmatic and individualized intervention was associated with a reduced quantity of discharge opioids without negative outcomes. Reduction in inpatient opioid use was also associated with standardizing prescribing practices of surgeons with electronic medical record order sets.

Low-dose Ketamine Does Not Improve Migraine in the Emergency Department: A Randomized Placebo-controlled Trial.

INTRODUCTION: Patients frequently present to the emergency department (ED) with migraine headaches. Although low-dose ketamine demonstrates analgesic efficacy for acute pain complaints in the ED, headaches have historically been excluded from these trials. This study evaluates the efficacy and safety of low-dose ketamine for treatment of acute migraine in the ED. METHODS: This randomized, double-blinded, placebo-controlled trial evaluated adults 18 to 65 years of age with acute migraine at a single academic ED. Subjects were randomized to receive 0.2 milligrams per kilogram of intravenous (IV) ketamine or an equivalent volume of normal saline. Numeric Rating Scale (NRS-11) pain scores, categorical pain scores, functional disability scores, side effects, and adverse events were assessed at baseline (T0) and 30 minutes post-treatment (T30). The primary outcome was between-group difference in NRS score reduction at 30 minutes. RESULTS: We enrolled 34 subjects (ketamine=16, placebo=18). Demographics were similar between treatment groups. There was no statistically significant difference in NRS score reductions between ketamine and placebo-treated groups after 30 minutes. Median NRS score reductions at 30 minutes were 1.0 (interquartile range [IQR] 0 to 2.25) for the ketamine group and 2.0 (IQR 0 to 3.75) for the placebo group. Between-group median difference at 30 minutes was -1.0 (IQR -2 to 1, p=0.5035). No significant differences between treatment groups occurred in categorical pain scores, functional disability scores, rescue medication request rate, and treatment satisfaction. Side Effect Rating Scale for Dissociative Anesthetics scores in the ketamine group were significantly greater for generalized discomfort at 30 minutes (p=0.008) and fatigue at 60 minutes (p=0.0216). No serious adverse events occurred in this study. CONCLUSION: We found that 0.2mg/kg IV ketamine did not produce a greater reduction in NRS score compared to placebo for treatment of acute migraine in the ED. Generalized discomfort at 30 minutes was significantly greater in the ketamine group. Overall, ketamine was well tolerated by migraine-suffering subjects. To optimize low-dose ketamine as an acute migraine treatment, future studies should investigate more effective dosing and routes of administration.

Ketamine as an Adjunct to Opioids for Acute Pain in the Emergency Department: A Randomized Controlled Trial.

OBJECTIVES: This study had five objectives: 1) to measure and compare total opioid use and number of opioid doses in patients treated with opioids versus ketamine in conjunction with opioids; 2) to measure pain scores up to 2 hours after presentation in the ED patient with pain, comparing standard opioid pain control to ketamine in conjunction with opioids; 3) to compare patient satisfaction with pain control using opioids alone versus ketamine in conjunction with opioids; 4) to monitor and compare side effects in patients treated with opioids versus ketamine in conjunction with opioids; and 5) to identify effect variation between different subgroups of patients, with the purpose of focusing future research. We hypothesized that low-dose ketamine, compared to placebo, as an adjunctive treatment to opioids would result in better pain control over 2 hours and greater patient satisfaction with pain control; further, this protocol will result in a lower opioid dosage over 2 hours. METHODS: This was a randomized, double-blinded, placebo-controlled trial at a single academic emergency department evaluating the use of ketamine versus placebo in conjunction with opioids for moderate to severe pain. Subjects with a continued high level of pain after an initial dose of opioid analgesia were randomized to receive either 0.1 mg/kg ketamine or placebo prior to protocol-based dosing of additional opioid analgesia, if required. Over 120 minutes, subjects were assessed for pain level (0-10), satisfaction with pain control (0-4), side effects, sedation level, and need for additional pain medication. Total opioid dose, including the initial dose, was compared between groups. RESULTS: Sixty-three subjects were randomized to the placebo group and 53 to the ketamine group. No significant differences were found in demographics between the groups. Patients receiving ketamine reported lower pain scores over 120 minutes than patients receiving placebo (p = 0.015). Total opioid dose was lower in the ketamine group (mean ± SD = 9.95 ± 4.83 mg) compared to placebo (mean ± SD = 12.81 ± 6.81 mg; p = 0.02). Satisfaction did not differ between groups. Fewer patients in the ketamine group required additional opioid doses. More patients reported light-headedness and dizziness in the ketamine group. CONCLUSIONS: Ketamine, as an adjunct to opioid therapy, was more effective at reducing pain over 120 minutes and resulted in a lower total opioid dose as well as fewer repeat doses of analgesia. More side effects were reported in the ketamine group (51% vs. 19%), but the side effect profile appears tolerable.