Effect of vitamin K administration on rate of warfarin reversal.

BACKGROUND: Vitamin K is reported to begin reversing warfarin within 6 to 12 hours, but this may occur sooner. We sought to determine the rate of international normalized ratio (INR) reversal following vitamin K and relationships with dose, route, and baseline INR. METHODS: We evaluated adult patients receiving vitamin K monotherapy for warfarin reversal. Post-vitamin K INRs through 48 hours were collected. Relationships between vitamin K dose and route and baseline INR on rate of reversal and complete reversal (INR < 1.5) were evaluated. Assessment was performed graphically using scatter plots with a line of best fit and a counting process model to determine variables associated with achieving complete reversal. RESULTS: A total of 469 post-vitamin K INRs from 235 patients were included. Time to first INR follow-up after vitamin K administration averaged 10.5 ± 4.2 hours. A significant decrease was detected in INR values in comparison to the baseline INR (3.0 ± 1.9 vs. 4.7 ± 2.2; p < 0.01). Rapid and steady INR change began immediately after vitamin K administration (0-4 hr). A high vitamin K dose and intravenous route were associated with rapid INR change and complete reversal (Vitamin K 10 mg [hazard ratio, 2.4; 95% confidence interval, 1.4-4.2] and IV route [hazard ratio, 1.8; 95% confidence interval, 1.3-2.6]); however, overall complete reversal at 24 and 48 hours was low (14.5% and 41.7%, respectively). Higher baseline INR was associated with rapid INR change and lower baseline INR with complete reversal. CONCLUSION: Vitamin K alone starts to reverse warfarin immediately. High vitamin K doses and intravenous route are associated with faster INR reversal. Baseline INR also influences rate of correction and frequency of achieving complete reversal.

Pharmacologic Interventions for Intractable and Persistent Hiccups: A Systematic Review.

BACKGROUND: Chlorpromazine is the only drug approved by the US Food and Drug Administration for the treatment of hiccups; however, many other pharmacologic treatments have been proposed for intractable and persistent hiccups. Currently, there is little evidence to support the use of one agent over another. OBJECTIVE: This review aims to identify literature concerning the use of pharmacologic treatments for intractable and persistent hiccups with the goal of evaluating therapies in terms of their level of evidence, mechanism of action, efficacy, dosing, onset of action, and adverse effects. METHODS: A systematic literature search of PubMed, Embase, the Cochrane Library, and the New York Academy of Medicine was performed to find articles where a pharmacologic agent was used to treat intractable or persistent hiccups between the years 1966 and 2016. The GRADE method was used to assess the level of evidence for the studies included in this review. RESULTS: This review identified 26 articles involving 10 pharmacologic treatment options that met our inclusion criteria. Amitriptyline, baclofen, gabapentin, haloperidol, metoclopramide, midazolam, nifedipine, nimodipine, orphenadrine, and valproic acid were found in the literature to be successful in treating hiccups. CONCLUSION: Baclofen, gabapentin, and metoclopramide were the only agents that were studied in a prospective manner, while only baclofen and metoclopramide were studied in randomized controlled trials. No specific recommendations can be made for treating intractable and persistent hiccups with the evidence currently available in the literature. Therapy selection should be specific to individual patients, their underlying comorbidities, etiology of hiccups, and take into account the individual properties of the drugs.