Computer Algorithm-Based Hydroxyurea Dosing Facilitates Titration to Maximum Tolerated Dose in Sickle Cell Anemia.

Adults with sickle cell disease (SCD) experience acute and chronic complications and die prematurely. When taken at maximum tolerated dose (MTD), hydroxyurea prolongs survival; however, it has not consistently reversed organ dysfunction. Patients also frequently do not take hydroxyurea, at least in part because of physician discomfort with prescribing hydroxyurea. We sought to develop a computer program that could easily titrate hydroxyurea to MTD. This was a single-arm, open-label pilot study. Fifteen patients with homozygous SCD were enrolled in the protocol, and 10 patients were followed at baseline and then for 1 year after hydroxyurea initiation or dose titration. Fetal hemoglobin significantly increased in all 10 patients from 8.3% to 25.1% (P < .001). Nine patients were titrated to MTD in an average of 7.9 months, and the tenth patient's hydroxyurea dose was increased to 33 mg/kg/day. Computer program dosing recommendations were the same as manual dosing decisions made using the same algorithm for all patients and at all times. We also evaluated markers of cardiopulmonary, liver and renal damage. Although cardiopulmonary function did not significantly improve, direct bilirubin and alanine aminotransferase levels significantly decreased (P < .001 and P < .01, respectively). Last, although kidney function did not improve, degree of proteinuria was significantly reduced (P < .05). We have developed a computer program that reliably titrates hydroxyurea to MTD. A larger study is indicated to test the program either as a computer program or a downloadable application.

Appropriateness of peripheral parenteral nutrition use in adult patients at an academic medical center.

BACKGROUND & AIMS: Current evidence and guidelines identify patient populations who may benefit from parenteral nutrition. Peripheral parenteral nutrition (PPN) may be indicated for a subset of patients; however, PPN therapy carries a risk of associated adverse effects. The purpose of this project was to assess appropriateness of current PPN prescribing practices at an academic medical center to determine whether additional guidance and oversight may be beneficial. METHODS: Adult patients admitted from August 1, 2015 to November 30, 2015 with at least one order of PPN administered were included. PPN use was evaluated for appropriateness using definitions derived from clinical practice guidelines and standard of practice. Adverse events, including phlebitis and bacteremia, were also examined. RESULTS: Of the 159 patients included, 51 (32.1%) received appropriate PPN therapy, in which all four criteria for appropriateness were met. In regards to the criteria for appropriateness, 128 (80.5%) had an appropriate indication, 85 (53.5%) had appropriate time to PPN initiation, 157 (98.7%) had an appropriate duration of therapy, and 112 (70.4%) achieved an appropriate percentage of goal daily calories. In terms of complications associated with PPN therapy, 69 (43.4%) patients had documented phlebitis and bacteremia occurred in 5 (3.1%) of the patients. CONCLUSION: During the study period, PPN was appropriately utilized in only one-third of patients and phlebitis occurred in almost half of all patients. Restrictions on PPN prescribing may allow nutrition support clinicians to prospectively evaluate patients to optimize nutrition therapy and minimize the incidence of inappropriate PPN use.

Antimicrobial Pharmacokinetics and Pharmacodynamics.

BACKGROUND: Antimicrobial medications are beneficial when used appropriately, but adverse effects and resistance sometimes limit therapy. These effects may be more problematic with inappropriate antimicrobial use. Consideration of the pharmacokinetic and pharmacodynamic properties of these medications can help optimize drug use. METHODS: Review of the pertinent English-language literature. RESULTS: The pharmacokinetic principles of absorption, distribution, metabolism, and elimination determine whether an appropriate dose of medication reaches the intended pathogen. The pharmacodynamic properties of antimicrobial medications define the relation between the drug concentration and its observed effect on the target pathogen. Improvements in clinical outcomes have been observed when antimicrobial agents are dosed optimally according to these properties. In surgical patients, substantial changes in the volume of distribution and elimination necessitate a clear understanding of these principles. Additionally, less adverse drug effects and antimicrobial resistance may occur with optimal use of these drugs. CONCLUSION: Selecting and dosing antimicrobial medications with consideration of pharmacokinetics and pharmacodynamics may improve patient outcomes and avoid adverse effects.

Seizure prophylaxis in neurocritical care: a review of evidence-based support.

Seizures are a well-described complication of acute brain injury and neurosurgery. Antiepileptic drugs (AEDs) are frequently utilized for seizure prophylaxis in neurocritical care patients. In this review, the Neurocritical Care Society Pharmacy Section describes the evidence associated with the use of AEDs for seizure prophylaxis in patients with intracerebral tumors, traumatic brain injury, aneurysmal subarachnoid hemorrhage, craniotomy, ischemic stroke, and intracerebral hemorrhage. Clear evidence indicates that the short-term use of AEDs for seizure prophylaxis in patients with traumatic brain injury and aneurysmal subarachnoid hemorrhage may be beneficial; however, evidence to support the use of AEDs in other disease states is less clear.