Prospective Evaluation of a Fixed-Dose 4-Factor Prothrombin Complex Concentrate Protocol for Urgent Vitamin K Antagonist Reversal.

BACKGROUND: Four-factor prothrombin complex concentrate (4F-PCC) is the standard of care for reversal of vitamin K antagonists (VKAs). Research has demonstrated noninferior efficacy with the use of lower, fixed-dose strategies for 4F-PCC dosing. OBJECTIVES: We compared a fixed-dose 4F-PCC protocol to weight-based dosing at our institution. METHODS: This was a multicenter, noninferiority, interventional, quasiexperimental cohort study including subjects who were administered 4F-PCC for VKA reversal. The retrospective cohort consisted of subjects given a weight-based dose of 4F-PCC dependent on international normalized ratio (INR). The prospective cohort was managed with a fixed-dose protocol. The fixed dose was 1500 units of factor IX unless subjects weighed >100 kg or had a baseline INR >7.5, in which case the dose was 2000 units of factor IX. The primary endpoint was achievement of a postinfusion INR of <2. Secondary endpoints included achievement postinfusion INR <1.5, mean 24-h INR, 7-day mortality, and 7-day venous thromboembolic events. RESULTS: Twenty-four subjects were enrolled in the prospective cohort and 30 in the retrospective cohort. A postinfusion INR <2 was achieved in 96% of subjects in the retrospective cohort and 95% in the prospective cohort (p = 0.0035 for noninferiority). A postinfusion INR <1.5 occurred in 90% of subjects in the retrospective cohort and 75% in the prospective cohort (p > 0.4 for noninferiority). There were no significant differences in 24-h postinfusion INRs, mortality, or venous thromboembolic events. CONCLUSION: The use of a fixed-dose 4F-PCC protocol is safe and effective for the rapid reversal of VKA-associated anticoagulation.

Alvimopan use in laparoscopic and open bowel resections: clinical results in a large community hospital system.

BACKGROUND: Alvimopan has received Food and Drug Administration approval to accelerate the time to upper and lower gastrointestinal recovery following partial large or small bowel resection with primary anastomosis. OBJECTIVE: To assess the efficacy, safety, and economic benefit of alvimopan in patients undergoing open or laparoscopic bowel resection in a community hospital system setting. METHODS: This 6-month, open-label, multi-hospital, prospective study combined with a retrospective chart review compared postoperative length of stay and postoperative ileus-related morbidity (nasogastric tube insertion, hospital readmission) for patients undergoing open or laparoscopic bowel resection who received alvimopan 12 mg (n = 108) versus historical control bowel resection patients (n = 91) who would have been eligible to receive alvimopan. Multivariate analysis assessed the effects of age and surgery type on postoperative length of stay. Additional-day hospital costs were estimated using ordinary least-squares regression to calculate costs based on length of stay in the control cohort. RESULTS: Compared with historical controls, patients receiving alvimopan had a mean 1.8-day shorter postoperative length of stay (p = 0.01) and lower rates of nasogastric tube insertion (2% vs 15%, p < 0.001). Multivariate analysis revealed a statistically significant reduction in postoperative length of stay in the alvimopan group of approximately 1.2 days (p = 0.01), regardless of age or surgery type, with an even larger difference (3.2 days) observed in patients ≥70 years old. Mean cost savings associated with alvimopan use ranged from $531 (laparoscopic bowel resection) to $997 (open bowel resection) per patient. CONCLUSIONS: Consistent with clinical trial data, alvimopan use resulted in an approximately 1 day shorter postoperative length of stay and was associated with substantial cost savings.

Tramadol use in pediatric sickle cell disease patients with vaso-occlusive crisis.

AIM: To evaluate whether the addition of scheduled oral tramadol to intravenous morphine and intravenous ketorolac reduces morphine requirements. METHODS: This single-centered, Institutional Review Board-approved, retrospective study at Moses Cone Memorial Hospital included pediatric patients who were ≥ 2 years old with vaso-occlusive crisis (VOC) caused by sickle cell disease (SCD), were on morphine patient-controlled analgesia (PCA), and had scheduled oral tramadol added to their standard pain regimen. The study population was admitted between March 2008 and March 2011. The data was collected from electronic records and included age, weight, morphine use, tramadol use, hemoglobin, pain scores, number of days on PCA, length of hospital stay, respiratory rate, and polyethylene glycol use. Thirty patients were analyzed as independent admissions and seven patients as paired admissions. RESULTS: Eighteen pediatric SCD patients with VOC received morphine PCA and intravenous ketorolac and twelve patients received morphine PCA and intravenous ketorolac and scheduled oral tramadol. Baseline characteristics were similar between both groups with the exception of the average weight, which was greater in the tramadol group than in the morphine group. The average morphine requirements in patients with and without the use of tramadol were similar, both for the independent admissions [0.58 mg/kg per day vs 0.65 mg/kg per day (P = 0.31)] and the paired admissions [0.71 mg/kg per day vs 0.77 mg/kg per day (P = 0.5)]. The daily polyethylene glycol requirement was less in the tramadol group for both the independent [0.5 g/kg per day vs 0.6 g/kg per day (P = 0.64)] and paired admissions analyses [and 0.41 g/kg per day vs 0.55 g/kg per day (P = 0.67)]. CONCLUSION: The addition of scheduled tramadol in patients receiving concomitant morphine and ketorolac demonstrates a trend toward decreased morphine and polyethylene glycol use.

Evaluation of the accuracy of different methods used to estimate weights in the pediatric population.

OBJECTIVES: The purpose of this study was to compare the predictive accuracy of 3 methods (Broselow tape, Leffler formula, and Theron formula) for pediatric weight estimation to identify factors that can influence weight estimation, and to derive alternative models for such estimation if indicated. METHODS: This was a prospective, nonblinded observational study. Every patient in the cohort was < or =10 years of age. The patients' age and height were used to estimate their weight by using the 3 previously mentioned methods. These estimated weights were compared with the patients' actual weight by using the modified Bland-Altman method. RESULTS: One thousand eleven subjects were included. Percent differences between predicted and actual weight were significantly less using the Broselow tape compared with other methods for patients weighing <10 or 10 to 25 kg and for the Theron formula compared with other methods for patients weighing >40 kg. For patients weighing 25.1 to 40 kg, performance of the Broselow tape and Leffler method were similar, and both were superior to the Theron formula. Three weight predictors (age, gender, and ethnicity) were identified, and 2 new weight-estimation models were derived from the cohort. CONCLUSIONS: The Broselow tape is accurate for weight estimation in children < or =25 kg, but the Theron formula performs better with patients weighing >40 kg. The Broselow tape was not statistically superior to the Leffler formula in subjects weighing 25.1 to 40 kg. A separate cohort is needed to evaluate the validity of the alternative predictive formulae.

Patient-specific factors predictive of warfarin dosage requirements.

OBJECTIVE: To identify patient-specific factors predictive of maintenance warfarin dosage requirements >5 mg/d. METHODS: One hundred forty-six adults taking warfarin were identified from a community hospital and an outpatient anticoagulation clinic. Patient demographics and data on warfarin doses, laboratory results, and medication use were obtained by abstracting patient records. Estimates of vitamin K intake were obtained using a questionnaire and structured interview. Multiple logistic regression was used to identify patient characteristics independently predictive of warfarin maintenance requirements >5 mg/d. An assessment tool for estimating an individual patient's likelihood of requiring warfarin maintenance doses >5 mg/d was derived from the logistic regression model and was assessed in both the study cohort and a separate historical validation cohort of 125 patients. RESULTS: Five factors were independently associated with warfarin requirements >5 mg/d: age <55 years, male gender, African American ethnicity, vitamin K intake >400 micro g/d, and body weight >or=91 kg. The assessment tool derived from these factors correctly classified semiquantitative warfarin requirements as non-high-dose in 84 of 93 study cohort patients and 71 of 78 validation cohort patients, and correctly classified requirements as high-dose in 10 of 13 study cohort patients and 11 of 15 validation cohort patients. CONCLUSIONS: African American ethnicity is a newly identified predictor of warfarin requirements >5 mg/d and is independent of dietary vitamin K intake. An assessment tool incorporating this and other predictors can estimate a patient's likelihood of requiring such dosages.