Activated Factor 7 Versus 4-Factor Prothrombin Complex Concentrate for Critical Bleeding Post-Cardiac Surgery.

BACKGROUND: Recombinant and plasma-derived factor products, such as activated factor seven (rFVIIa) and four-factor prothrombin complex concentrate (4-factor PCC), have been used off-label for bleeding after cardiac surgery, but little evidence has been published regarding their efficacy and safety. OBJECTIVE: To determine whether there is a difference in chest tube output in patients who have received 4-factor PCC or rFVIIa for critical postoperative bleeding associated with cardiovascular surgery. METHODS: A retrospective chart review was conducted utilizing the electronic medical record system at a 657-bed community, tertiary care hospital in Nashville, Tennessee. Nonpregnant patients ≥18 years of age experiencing significant bleeding during cardiac surgery who received either PCC or rFVIIa perioperatively or postoperatively between April 2015 through December 2016 were eligible for inclusion. Patients were excluded if they received 4-factor PCC or rFVIIa for any indication other than bleeding during cardiac surgery or if they received both agents. RESULTS: Data conclude that there is no significant difference in chest tube output 24 hours postoperatively between patients treated with 4-factor PCC or rFVIIa. There was no difference in bleeding, thromboembolic events, or re-exploration between the rFVIIa and 4-factor PCC groups, but there was a difference in units of fresh frozen plasma administered and hospital length of stay. CONCLUSION: 4-Factor PCC may be an equally efficacious alternative to rFVIIa for patients experiencing significant bleeding during cardiac surgery. There is no difference in chest tube output; therefore, there is no difference in bleeding-either at 24 hours postoperatively or total.

Treatment Considerations and the Role of the Clinical Pharmacist Throughout Transitions of Care for Patients With Acute Heart Failure.

Heart failure is associated with increased risk of morbidity and mortality, resulting in substantial health-care costs. Clinical pharmacists have an opportunity to reduce health-care costs and improve disease management as patients transition from inpatient to outpatient care by leading interventions to develop patient care plans, educate patients and clinicians, prevent adverse drug reactions, reconcile medications, monitor drug levels, and improve medication access and adherence. Through these methods, clinical pharmacists are able to reduce rates of hospitalization, readmission, and mortality. In addition, care by clinical pharmacists can improve dosing levels and adherence to guideline-directed therapies. A greater benefit in patient management occurs when clinical pharmacists collaborate with other members of the health-care team, emphasizing the importance of heart failure treatment by a multidisciplinary health-care team. Education is a key area in which clinical pharmacists can improve care of patients with heart failure and should not be limited to patients. Clinical pharmacists should provide education to all members of the health-care team and introduce them to new therapies that may further improve the management of heart failure. The objective of this review is to detail the numerous opportunities that clinical pharmacists have to improve the management of heart failure and reduce health-care costs as part of a multidisciplinary health-care team.

Acute decompensated heart failure: evolving literature and implications for future practice.

Acute decompensated heart failure (ADHF) is associated with substantial morbidity and mortality, and represents a considerable financial burden to society. Historically, few prospective, randomized, double-blinded trials have investigated the optimal management of ADHF, and most guideline recommendations are based primarily on expert opinion. However, in the last decade, a considerable amount of research has added to the understanding of the management of ADHF in both patients with fluid overload and low cardiac output. In addition, as mechanical circulatory support devices and heart transplantation continue to evolve, significant advances have also been made with regard to the proper selection of patients for advanced surgical options. Finally, several novel pharmacologic agents have shown promise in early trials and may represent the next steps in ADHF management. Although advances have been made over the past decade, many questions remain.

Review of Tolvaptan's Pharmacokinetic and Pharmacodynamic Properties and Drug Interactions.

Tolvaptan is an arginine vasopressin (AVP) antagonist that acts to increase excretion of free water (aquaresis) in patients without introducing electrolyte abnormalities or worsening renal function. It works via blockade of vasopressin-2 receptors at the renal collecting duct. Since the approval of tolvaptan for the treatment of hypervolemic and euvolemic hyponatremia in 2009, new studies have been reported to better characterize its pharmacokinetic and pharmacodynamic profile of tolvaptan. This paper is a review of both these clinical studies, as well as previous literature, in order to help guide appropriate clinical use of tolvaptan in patients. With appropriate monitoring of serum sodium, tolvaptan may be safely dose escalated from 15 mg once daily to a maximum effective dose of 60 mg once daily for multiple days, to achieve optimal aqauretic effects. In terms of drug interactions, co-administration of moderate to potent CYP3A4 inhibitors and inducers should be avoided. Tolvaptan should also be co-administered with caution and proper monitoring in the presence of P-glycoprotein substrate and strong inhibitors. Co-administration of tolvaptan with diuretic therapy did not appear to alter the aquaretic effect of tolvaptan; and was shown to be safe and well tolerated.

Relative bioavailability of tolvaptan administered via nasogastric tube and tolvaptan tablets swallowed intact.

PURPOSE: The bioavailability of a crushed tolvaptan tablet suspended in water and administered by nasogastric (NG) tube was compared to the bioavailability from the tablet administered whole. METHODS: In a randomized crossover study, 28 healthy adults received a single 15-mg dose of tolvaptan on two occasions (one dose given as an intact tablet swallowed whole and the other as a crushed tablet in suspension given by NG tube), with a washout interval of ≥7 days. During each administration period, blood samples were collected at 15 time points over 36 hours. A validated liquid chromatography-tandem mass spectrometry assay was used to obtain plasma tolvaptan concentrations. Plasma tolvaptan time-concentration data were analyzed using noncompartmental methods, and pharmacokinetic data including maximum concentration (Cmax), time to Cmax (tmax), area under the concentration-time curve (AUC) from time zero to the time of the last measurable concentration (AUCt), and AUC extrapolated to infinity (AUC∞) resulting from oral and NG tube tolvaptan delivery were compared via repeated-measures, mixed-effects analysis of variance. Due to differences in total drug exposure seen, an in vitro experiment was conducted on three dose levels to quantify drug sequestration. RESULTS: The ratios of geometric mean Cmax, AUCt, and AUC∞ values (expressed as a percentage) with NG tube versus oral tolvaptan administration were 88.9%, 74.3%, and 74.2%, respectively; the latter two values were not within the specified bioequivalence tolerance limits (80-125%). In vitro analysis showed that approximately 11% of all tolvaptan doses evaluated was sequestered by the NG tube. CONCLUSION: In healthy adults, a single 15-mg dose of tolvaptan administered as a crushed tablet suspended in water by NG tube resulted in AUCt and AUC∞ values that were approximately 25% lower than those observed after oral administration of a 15-mg tolvaptan tablet swallowed intact.

Assessment of eptifibatide clearance by hemodialysis using an in vitro system.

BACKGROUND/AIMS: Eptifibatide is a parenteral glycoprotein IIb-IIIa inhibitor that prevents platelet aggregation. Although contraindicated in dialysis patients due to limited safety and dialysis data, eptifibatide is prescribed in this population and is associated with bleeding complications. This study was done to determine dialysis clearance (CL(D)) of eptifibatide using an in vitro system. METHODS: Three common dialyzers were tested. In vitro dialysis was performed at a dialysate flow rate of 500 ml/min, 'blood' flow rate (Q(B)) of 200 and 400 ml/min, and the minimal ultrafiltration rate. Eptifibatide CL(D) and fraction removed were calculated for each condition. RESULTS: CL(D) ranged from 122 to 225 ml/min and was not significantly different among the dialyzers tested. CL(D) was flow dependent with higher clearances observed at higher Q(B). The estimated fraction of eptifibatide removed was 73-83%. CONCLUSIONS: These data suggest that hemodialysis is an effective method to decrease the effects of eptifibatide in patients with impaired kidney function.