Vollmer, Nicholas J

Objectives: In practice, midodrine has been used to reduce IV vasopressor requirements and decrease ICU length of stay. However, recent publications have failed to show clinical success when midodrine was administered every 8 hours. One possible reason for the lack of clinical efficacy at this dosing interval may be the pharmacokinetic properties of midodrine that support a more frequent dosing interval. Here, we report our institutional experience with midodrine at a dosing frequency of every 6 hours. Design: Single, quaternary academic medical center, retrospective, descriptive study. Setting: Floor and ICU patients admitted to Mayo Clinic, Rochester, from May 7, 2018, to September 30, 2020. Patients: Adult patients with an order for midodrine with a dosing frequency of “every 6 hours” or “four times daily” were eligible for inclusion. Interventions: No intervention performed. All data were abstracted retrospectively from the electronic medical record. Measurements and Main Results: Forty-four unique patients were identified that met inclusion criteria. Patients were an average of 65 years and 63.6% were male. The individual doses of midodrine ranged from 5 to 20 mg. Twenty-three patients (52.3%) were receiving IV vasopressors at the time midodrine was ordered every 6 hours. Vasopressor requirements decreased from an average of 0.10 norepinephrine equivalents 24 hours prior to the every 6-hour order to 0.05 norepinephrine equivalents 24 hours after an order for midodrine every 6 hour was placed. Conclusions: Increasing the dosing frequency of midodrine to every 6 hours may optimize its pharmacokinetic profile without compromising safety. This midodrine dosing frequency should be prospectively evaluated as a primary strategy for accelerated IV vasopressor wean.

Abstract Background Fluoroquinolones (FQs) are known to be accompanied by significant risks. However, the incidence of adverse events (ADEs) resulting in unplanned drug discontinuation when used for periprosthetic joint infections (PJIs) is currently unknown. Methods This study included 156 patients over the age of 18 treated for staphylococcal PJI with debridement, antibiotics, and implant retention between 1 January 2007 and 21 November 2019. Of the 156 patients, 64 had total hip arthroplasty (THA) and 92 had total knee arthroplasty (TKA) infections. The primary outcome was rate of unplanned drug discontinuation. Secondary outcomes included incidence of severe ADEs, unplanned rifamycin discontinuation, mean time to unplanned regimen discontinuation, and all-cause mortality. Results Overall, unplanned drug discontinuation occurred in 35.6% of patients in the FQ group and 3% of patients in the non-FQ group. The rate of unplanned discontinuation of FQ regimens as compared with non-FQ regimens was 27.5% vs 4.2% (P = .021) in THA infections and 42% vs 2.4% (P < .001) in TKA infections. There was no significant difference in severe ADEs between FQ and non-FQ regimens in both THA and TKA infections. The overall rate of nonsevere ADEs in FQ compared with non-FQ regimens was 43.3% vs 6.1% (P < .001). FQs were associated with tendinopathy, myalgia, arthralgia, and nausea. Conclusions A significantly higher rate of unplanned drug discontinuation was associated with FQ as compared with non-FQ regimens. This provides a real-world view of the implications of FQ-related ADEs on unplanned discontinuation when used in prolonged durations for the management of staphylococcal PJIs.