Comparison of 3-Factor Versus 4-Factor Prothrombin Complex Concentrate With Regard to Warfarin Reversal, Blood Product Use, and Costs.

BACKGROUND: Prothrombin complex concentrates (PCCs) are drug products containing varying amounts of vitamin K-dependent coagulation factors II, VII, IX, and X. The evidence comparing 3-factor PCC (3-PCC) versus 4-factor PCC (4-PCC) for warfarin reversal is conflicting. It has been hypothesized that 3-PCC may be less effective than 4-PCC because of relatively lower factor VII content. STUDY QUESTION: The primary objective of this study was to compare international normalized ratio (INR) reversal between 3-PCC and 4-factor PCC (4-PCC) in warfarin-treated patients. The secondary objectives include comparing blood product use, total reversal costs, and cost-effectiveness between the groups. STUDY DESIGN: This was a retrospective cohort study conducted in 2 affiliated, academic institutions in the United States. Consecutive adult patients who received 3-PCC or 4-PCC for warfarin reversal were included. MEASURES AND OUTCOMES: The primary outcome was adequate INR reversal defined as a final INR ≤1.5. Secondary outcomes were the utilization of plasma, red blood cells and platelets, reversal costs, and the cost-effectiveness ratio. RESULTS: There were 89 patients who were included in the overall cohort (3-PCC = 57, 4-PCC = 32). Adequate INR reversal occurred less commonly with 3-PCC (45.6%) compared with 4-PCC (87.5%) (P < 0.001). There was no significant difference in the proportion of patients who received plasma (32% vs. 28%, P = 0.813), red blood cells (37% vs. 47%, P = 0.377), or platelets (16% vs. 28%, P = 0.180) between the 3-PCC and 4-PCC groups, respectively. The median reversal cost of 3-PCC ($3663) was lower than 4-PCC ($5105) (P = 0.001). The cost-effective ratio favored 4-PCC ($5105/87.5% = $5834) compared with 3-PCC ($3663/45.6% = $8033). CONCLUSIONS: Four-PCC was more effective than 3-PCC with regard to INR reversal in patients taking warfarin, but blood product use was similar. Although 4-PCC is associated with increased reversal costs, it may be cost-effective in terms of INR reversal.

Effect of Intravenous Acetaminophen on Post-Anesthesia Care Unit Length of Stay, Opioid Consumption, Pain, and Analgesic Drug Costs After Ambulatory Surgery.

OBJECTIVES: The primary objective was to assess whether the use of intravenous acetaminophen (APAP) in the ambulatory surgery setting is associated with a decreased length of stay in the post-anesthesia care unit (PACU). The secondary outcomes evaluated were pain scores, opioid consumption, and total cost of analgesics used in the PACU. METHODS: This was a retrospective cohort study conducted in adult patients (18 years of age or older) who received an eye, ear, nose, or throat (EENT) procedure at an outpatient surgery center between January 2014 and January 2015. Patients were consecutively included until the desired sample was reached during two six-month time periods: 1) intravenous APAP available on the formulary (APAP group) and 2) intravenous APAP not available on the formulary (non-APAP group). RESULTS: The cohort included 174 patients who received an EENT procedure (87 patients in the APAP group and 87 patients in the non-APAP group). The median PACU length of stay was 66 minutes (interquartile range [IQR], 48-92) in the APAP group and 71 minutes (IQR, 52-89) in the non-APAP group (P = 0.269). Mean pain score categories in the APAP versus non-APAP group were mild (85% versus 53%, respectively; P < 0.001), moderate (13% versus 33%, respectively; P = 0.002), and severe (2% versus 14%, respectively; P = 0.005). The median opioid consumption in morphine equivalents was 9 mg (IQR, 5-13) in the APAP group and 8 mg (IQR, 5-12) in the non-APAP group (P = 0.081). The total cost of analgesics used in the PACU was significantly greater in the APAP group ($15 versus $1; P < 0.001). CONCLUSIONS: Intravenous APAP use in EENT ambulatory surgery is not associated with decreased PACU length of stay. However, it may decrease postoperative pain following EENT procedures.

Patient safety challenges in treprostinil therapy.

Treprostinil (Remodulin) is a new therapy for pulmonary hypertension. A multidisciplinary plan for safely managing the drug is described, and includes a flow chart to guide practice through high-risk issues.

Comparison of blood product use and costs with use of 3-factor versus 4-factor prothrombin complex concentrate for off-label indications.

PURPOSE: Results of a comparison of blood product use and cost outcomes with use of 3-factor versus 4-factor prothrombin complex concentrate (PCC) for indications other than warfarin reversal are presented. METHODS: Consecutive patients who received 3-factor PPC (PCC3) or 4-factor PCC (PCC4) for non-warfarin-related indications at 2 U.S. hospitals during a 19-month period were identified. The primary outcome was in-hospital blood product use, with a focus on plasma use. Total hemostasis costs, intensive care unit (ICU) and hospital lengths of stay, and other outcomes were evaluated. RESULTS: Indications for PCC3 use (n = 118) or PCC4 use (n = 64) included intraoperative bleeding, nonintraoperative bleeding, coagulopathy of liver disease, and reversal of direct-acting oral anticoagulant effects. The proportion of patients who received plasma was 56.8% with PCC3 use versus 53.1% with PCC4 use (p = 0.643); the corresponding median volumes of plasma received were 638 mL (interquartile range [IQR], 550-1,355 mL) and 656 mL (IQR, 532-1,136 mL), respectively. The median total hemostasis costs were $5,559 (IQR, $3,922-$8,159) with PCC3 use and $7,771 (IQR, $6,366-$9,205) with PCC4 use (p < 0.001). CONCLUSION: PCC3 use and PCC4 use were associated with similar blood product use, ICU length of stay, hospital length of stay, and in-hospital mortality when given for non-warfarin-related indications. However, relative to PCC3 use, PCC4 use was associated with an increase in costs that was primarily due to drug costs.

Implementation of a pharmacy-managed program for the transition of chemotherapy to the outpatient setting.

PURPOSE: Implementation of a pharmacy-managed program for the transition of chemotherapy to the outpatient setting is described. SUMMARY: The University of Arizona Cancer Center and Banner-University Medical Center Tucson are affiliated not-for-profit academic medical centers in Tucson, Arizona, whose facilities include a hospital and ambulatory care clinics that maintain 3 outpatient infusion centers. The cancer center pharmacy currently employs 25 pharmacists, with 4 clinical pharmacists serving both the inpatient and outpatient treatment sites. A multidisciplinary team of staff members was assembled to address the transition of chemotherapy from inpatient to outpatient that included physicians, ambulatory clinical oncology pharmacists, finance, social workers, pharmacy staff, nursing staff, and information technology. The program was initiated in May 2014, with a 2-year postimplementation evaluation of our transition of chemotherapy to the outpatient setting. Chemotherapy order sets were developed in our electronic medical record for transitioning rituximab to the outpatient setting for inpatient chemotherapy orders as well as transitioning leukemia, lymphoma, and solid tumor chemotherapy regimens to be administered in the outpatient setting. Eighteen rituximab-containing regimens and 14 chemotherapy protocols were switched to the outpatient setting, with numerous variants of these regimens also created for outpatient only administration. The realized savings for high-cost chemotherapy transitioned to the outpatient setting with rituximab and clofarabine was $1,902,890. Over 747 inpatient bed days were saved, with an approximated cost savings to the health system of $1,402,866, with a cumulative cost savings to our health system of $3,305,756. CONCLUSION: This model for transitioning chemotherapy from the hospital to the outpatient setting enhanced access to care, decreased bed utilization in the hospital, and improved clinical and financial metrics.

Impact of delayed initiation of erythropoietin in critically ill patients.

BACKGROUND: The purpose of this study was to evaluate the impact of recombinant human erythropoietin (rHuEPO) use for anemia of critical illness at a practice site where delayed initiation is common. METHODS: Retrospective medical record review involving patients treated with rHuEPO for anemia of critical illness. Those patients given rHuEPO or diagnosed with end-stage renal disease (ESRD) prior to ICU admission were excluded. The primary endpoints were rHuEPO use and RBC transfusion patterns. RESULTS: Complete data were collected for consecutive admissions of 126 patients. Average age (SD) and APACHE II score were 56.5 (18.6) years and 25 (7.8), respectively. The median ICU (IQR) and hospital length of stay (LOS) were 24 (11.25, 39) and 29 (17, 44.75) days, respectively. Treatment with rHuEPO was started an average of 12.5 +/- 10.5 days after ICU admission and given for 3.8 +/- 3.8 doses. Eighty percent of patients were transfused with an average total of 5.42 +/- 5.08 units received. RBC exposure inversely correlated with a lower mean hemoglobin response to rHuEPO. ICU LOS (p < 0.0001), hemoglobin at 24 hours (p = 0.055), transfusion within 48 hours of admit (p < 0.0001), and postoperative status (p = 0.019) were the best predictors of transfusion requirements (r2 = 0.37). CONCLUSION: Delayed initiation of rHuEPO for anemia of critical illness resulted in comparable hemoglobin and transfusion benefits. Future studies are needed to establish clinical benefit and role in therapy. RBC exposure may blunt the erythropoietic effects of rHuEPO, potentially frustrating benefits to those of greatest apparent need.

Retrospective evaluation of inhaled prostaglandins in patients with acute respiratory distress syndrome.

STUDY OBJECTIVES: To determine whether use of inhaled alprostadil (PGE 1 ) or epoprostenol (PGI 2 ) significantly improved oxygenation in patients with acute respiratory distress syndrome (ARDS), and to determine whether differences between the two drugs exist with regard to oxygenation, duration of mechanical ventilation and hospitalization, adverse effects, and survival. DESIGN: Retrospective chart review. SETTING: A 360-bed tertiary care teaching facility with medical and surgical intensive care units. PATIENTS: Twenty-seven patients admitted to the hospital who received either PGI 2 or PGE 1 for a primary or secondary diagnosis of ARDS. MEASUREMENTS AND MAIN RESULTS: Seventeen patients received inhaled PGE 1 and 10 received inhaled PGI 2 . There were no significant changes in the ratio of arterial partial pressure of oxygen (PaO 2 ):fraction of inspired oxygen (FiO 2 ) and in the PaO 2 , from baseline to any time point that was analyzed during treatment, for patients receiving either PGE 1 (p=0.2120 and 0.3399, respectively) or PGI 2 (p=0.1655 and 0.0784, respectively). CONCLUSION: No statistically significant improvement in oxygenation was observed in patients receiving either PGE 1 or PGI 2 . In addition, no significant differences were found between the two prostaglandins for the variables studied. Until positive results from large, prospective studies are available, we recommend that these inhaled prostaglandins not be used to treat ARDS.

Cost savings with interventions to reduce aerosolized bronchodilator use in mechanically ventilated patients.

PURPOSE: The purpose of this evaluation is to describe the cost savings associated with multimodal interventions aimed at reducing aerosolized bronchodilator use in mechanically ventilated patients without adversely affecting costs associated with length of stay (LOS). MATERIALS AND METHODS: Subjects were included in the analysis if they were aged more than 18 years, on mechanical ventilation in the intensive care unit, and received aerosolized bronchodilators. Patients were excluded if they had reversible airway disease, an indication needing bronchodilator therapy. Patient data were obtained using the University Health System Consortium Clinical Data Base/Resource Manager (Chicago, IL) to compare outcomes during two 6-month periods separated by a 4-month intervention phase aimed to reduce bronchodilator use. RESULTS: There were no significant differences in age, sex, and LOS (observed and expected) between the preintervention and postintervention phases. Based on whole acquisition costs, the total cost of bronchodilators dispensed to the adult intensive care units over the 6-month postintervention phase was reduced by $56960 compared with the 6-month preintervention phase ($120562 vs $63602, respectively). CONCLUSIONS: Multimodal efforts to restrict aerosolized bronchodilator therapy in mechanically ventilated patients were successful and led to sustained reductions in use that was associated with substantial reductions in cost, without affecting LOS.

Evaluation of discontinuation of atypical antipsychotics prescribed for ICU delirium.

A number of trials suggest that short-term use of atypical antipsychotics may be useful in the treatment of delirium associated with critical illness. However, long-term use of such agents for this indication has not been studied and may be associated with risks of adverse effects as well as unnecessary health care costs. A retrospective study of prescribing patterns of atypical antipsychotics initiated for the treatment of intensive care unit (ICU) delirium was performed to identify whether these agents were being discontinued prior to or upon hospital discharge. Of the 59 patients who met inclusion criteria and survived to hospital discharge, 28 (47%) were continued on the atypical antipsychotic upon discharge from the medical ICU. For those continued on the agent, 20 patients (71.4%) were prescribed continued therapy as an outpatient. Inpatient costs for atypical antipsychotics during the 9-month study period were increased by approximately $888. Annual cost of the medication as outpatient therapy is assessed at approximately $45,107. Although short-term trials of atypical antipsychotics may be useful for ICU delirium, caution is advised regarding potential adverse effects and added health care costs when use is prolonged.

Use of epoetin alfa in critically ill patients.

OBJECTIVE: To discuss the controversies regarding the use of epoetin alfa (EPO) for reducing red blood cell (RBC) transfusions in critically ill patients with anemia. DATA SOURCES: A MEDLINE search (1966-July 2003) was conducted using the search terms anemia; critical illness; erythropoietin; epoetin alfa; and erythropoietin, recombinant. References of selected articles were reviewed for studies that may have been missed by the computerized search. STUDY SELECTION AND DATA EXTRACTION: Studies pertaining to the use of EPO for anemia of critical illness with an emphasis on data obtained from controlled trials. DATA SYNTHESIS: Anemia is a common complication in patients admitted to the intensive care unit (ICU). Two prospective, randomized studies have demonstrated decreased transfusion requirements associated with EPO administration in medical/surgical patients who were in the ICU for at least 3 days and had hematocrit concentrations <38%. No differences were found in length of stay or mortality. A multicenter trial found that a restrictive strategy of RBC transfusion (hemoglobin goal 7-9 g/dL) was associated with in-hospital mortality lower than that with a more liberal approach, which calls into question the 38% hematocrit goal in the EPO trials. Furthermore, preliminary results from an economic analysis of EPO use in the ICU setting have demonstrated that EPO is not cost-effective. CONCLUSIONS: Given the controversies surrounding EPO administration in critically ill patients, institutions are encouraged to develop EPO guidelines to help ensure the most appropriate use of this expensive product. Additional studies regarding patients most likely to benefit from EPO therapy, the most effective dosing regimen, and use of adjunctive therapies are needed.