Vitamin K to reverse excessive anticoagulation: a review of the literature.

We conducted an extensive literature review to evaluate the appropriate use, route, and dose of vitamin K to reverse excessive anticoagulation. Issues such as sample size, study design, different patient populations, and various study end points confounded results. Of 18 studies published, 8 enrolled 229 patients to evaluate parenteral vitamin K administration. Nine studies with 288 patients evaluated oral administration, and only 2 retrospective studies (280 patients) compared routes of administration. Reductions in international normalized ratios at 24 hours ranged from 21-42%, 47-86%, 25-67%, and 40-75% for temporary warfarin discontinuation alone, and intravenous, subcutaneous, and oral routes of vitamin K administration, respectively. Methodologically weak studies and indeterminate results plague interpretation of the literature on vitamin K. In general, results of this review support current guidelines for reversing excessive warfarin anticoagulation. However, it is important to realize that the quality of literature on which these recommendations are based is poor and that optimal dose and route of vitamin K administration remain unclear. Large, well-designed, randomized, controlled trials are necessary to define optimum management strategies for excessively anticoagulated patients.

A cost analysis of enterally administered lorazepam in the pediatric intensive care unit.

OBJECTIVE: To determine the cost savings of replacing intravenous midazolam with enterally administered lorazepam in mechanically ventilated children who require long-term continuous sedation. DESIGN: Retrospective review of patients treated according to a preestablished pediatric intensive care unit (ICU) sedation protocol. SETTING: Twenty-six-bed pediatric ICU in a tertiary care children's hospital. PATIENTS: The records of 30 mechanically ventilated children were analyzed. The median age was 1.5 yrs and the median weight was 8.0 kg. Patients required continuous sedation for a total of 16 days (median). INTERVENTIONS: According to our pediatric ICU sedation protocol, midazolam infusion was continued until the hourly midazolam requirement was stable for at least 24 hrs. Thereafter, patients with a nasojejunal tube who were likely to require a minimum of three additional days of continuous sedation were transitioned from intravenous midazolam to enterally administered lorazepam. The goal in transitioning therapy was to titrate the lorazepam dose and reduce midazolam administration while maintaining an unchanged level of sedation. MEASUREMENTS AND MAIN RESULTS: The rate of midazolam administration was significantly (p<.05) reduced beginning on day 1 of lorazepam treatment. Midazolam was successfully discontinued in 24 (80%) patients in 3 days (median), and adequate and appropriate sedation was maintained with lorazepam monotherapy. Six patients in whom midazolam could not be discontinued experienced a 52% reduction in the rate of midazolam administration as a result of adding lorazepam. Total projected midazolam utilization was defined as the sum of midazolam administration before initiating lorazepam and the projected midazolam requirement after initiating lorazepam. Projected midazolam cost was calculated as the product of total projected midazolam utilization and midazolam acquisition cost. Actual expenditures for both midazolam and lorazepam were subtracted from the projected midazolam cost to calculate the estimated cost savings. Overall, midazolam utilization (in milligrams) was reduced by 46.7+/-27.6% (median 52). Total projected midazolam cost for the 30 patients was $90,771. The actual cost of midazolam and lorazepam combined was $47,867, resulting in a cost savings of $42,904. CONCLUSIONS: Transitioning from intravenous midazolam to enterally administered lorazepam in critically ill children who require long-term sedation results in significant cost savings. The oral formulation of lorazepam was convenient to use, inexpensive, and effective in maintaining a continuous and appropriate level of sedation once midazolam was discontinued.