The effect of routine preoperative interruption of dabigatran therapy on coagulation parameters and dabigatran plasma levels in a mixed surgical population.

Dabigatran is an oral anticoagulant used for atrial fibrillation and venous thromboembolism. While an effective antibody reversal agent is available, its cost precludes routine use and the mainstay of preoperative management is timely dabigatran interruption. Unlike warfarin, there are no universally accepted protocols for interruption of dabigatran in the preoperative period and there is uncertainty around the interpretation of standard coagulation tests in the presence of dabigatran. We performed a prospective, observational pilot study in patients presenting for elective surgery to examine: 1) the preoperative plasma dabigatran concentrations on day of surgery associated with the local dabigatran interruption protocol, 2) the potential utility of dabigatran concentrations on day of surgery, and 3) the utility of standard coagulation tests in determining whether dabigatran concentrations were below a 'safe' threshold for surgery. We recruited patients presenting to pre-admission clinics for elective surgery. Dabigatran concentrations below 30 µg/L were considered adequate for proceeding with surgery. Data were obtained and analysed from 21 patients with a median (range) age of 70 (20-86) years. Median (range) dabigatran concentrations on the day of surgery were 5 (0-59) µg/L. Two patients had day of surgery concentrations exceeding 30 µg/L. Of the standard coagulation tests examined, only the thrombin clotting time (TCT) was abnormal for these two patients. Our interruption protocol was associated with safe dabigatran concentrations in most patients on the day of surgery. A minority of patients had dabigatran concentrations above the safe threshold, which were detectable by abnormal TCT results.

Metronidazole stewardship initiative at Christchurch hospitals-achievable with immediate benefits.

AIMS: To evaluate an antimicrobial stewardship (AMS) initiative to change hospital prescribing practice for metronidazole. METHODS: In October 2015, the Canterbury District Health Board (CDHB) AMS committee changed advice for metronidazole to promote two times daily dosing for most indications, prioritisation of the oral route and avoidance of double anaerobic cover. Adoption of the initiative was facilitated via change in prescribing guidelines, education and ongoing pharmacy support. Usage and expenditure on metronidazole for adult inpatients were compared for the five years pre- and two years post-change. Other district health boards (DHBs) were surveyed to determine their dosing recommendation for metronidazole IV. RESULTS: Mean annual metronidazole IV use, as defined daily doses per 1,000 occupied bed days, decreased by 43% post-initiative. Use of non-IV (oral or rectal) formulations increased by 104%. Total savings associated with the initiative were approximately $33,400 in drug costs plus $78,200 per annum in IV giving sets and post-dose flushes. Twelve of 20 (60%) DHBs (including CDHB) endorse twice daily IV dosing. CONCLUSIONS: In addition to financial savings, reduction in IV doses has potential benefits, including avoidance of IV catheter-associated complications such as bloodstream infections. Approaches to metronidazole dosing vary across DHBs and could benefit from national coordination.

Quantification of total and unbound concentrations of lorazepam, oxazepam and temazepam in human plasma by ultrafiltration and LC-MS/MS.

BACKGROUND: A fast and sensitive assay for quantifying total and unbound concentrations of lorazepam (Lzp), oxazepam (Ozp) and temazepam (Tzp) in human plasma was needed for a plasma protein binding study. RESULTS: Plasma samples were precipitated with acetonitrile for determination of total concentrations or subjected to ultrafiltration for determination of unbound concentrations. An LC-MS/MS assay was developed with an Allure® PFP propyl column and a mobile phase of 35% acetonitrile/0.1% formic acid over 4.5 min and ESI+-MS/MS detection. Matrix effects were negligible in plasma and approximately 70% in ultrafiltrate but were accounted for by the internal standards Lzp-d4, Ozp-d5 and Tzp-d5. The assay was validated for total concentrations of 10-100 ng/ml Lzp, 200-2000 ng/ml Ozp and 100-1000 ng/ml Tzp, and for unbound concentrations of 1-10 ng/ml Lzp, 20-200 ng/ml Ozp and 10-100 ng/ml Tzp. Precision was <14% CV and accuracy was 96-110% throughout the calibration range. The mean precision of triplicate analysis of 60 study samples was <4% CV for total and <8% CV for unbound concentrations. CONCLUSION: A fast and sensitive assay was developed and validated. It has been applied successfully to a protein binding study.