In this episode I’ll:
1. Discuss an article comparing FEIBA with KCentra.
2. Answer the drug information question “Can intermittent boluses of pantoprazole be used to treat acute GI bleeding rather than continuous infusions?”
3. Share a tip for responding to inpatient medical emergencies.
Activated Prothrombin Complex Concentrate Versus 4-Factor Prothrombin Complex Concentrate for Vitamin K-Antagonist Reversal
Lead author: Shaun Rowe
Published in Critical Care Medicine June 2018
The authors designed this study to compare the INR normalization efficacy of activated prothrombin complex concentrates (FEIBA) and 4-factor prothrombin complex concentrates (KCentra). They also examined the thrombotic complications in patients treated with these products for warfarin-associated hemorrhage.
The study was a retrospective, two-center cohort study. Inclusion criteria were any patient age > 18 years who received FEIBA or KCentra for warfarin-associated hemorrhage. Exclusion criteria were pregnancy, baseline INR <2, massive transfusion, receipt of FFP, and acute warfarin overdose.
Patients in the FEIBA group with an INR < 5 received 500 units and those with an INR > 5 received 1,000 units. Patients in the KCentra group received the Food and Drug Administration approved dosing algorithm based on weight and pretreatment INR.
A total of 118 patients received FEIBA and 40 patients received KCentra. The posttreatment INR was similar between the groups. In addition, even when controlling for differences in the pretreatment INR, there was no difference in the ability to achieve a posttreatment INR of less than 1.4 (odds ratio, 0.753). Those in the FEIBA group did have higher odds of achieving a posttreatment INR of less than 1.2 (odds ratio, 3.23).
The authors concluded:
A low, fixed dose of activated prothrombin complex concentrate was as effective as standard dose 4-factor prothrombin complex concentrate for normalization of international normalized ratio. In addition, we did not see an increase in thrombotic events.
This study is especially timely as many hospitals are faced with a shortage of KCentra, and FEIBA may be more readily available. There was only one post-treatment thrombotic complication reported – an ischemic stroke in a patient who received KCentra. This is encouraging news as the activated nature of FEIBA would theoretically lead to a higher risk of thrombosis, but there were no thrombotic events in the FEIBA group. The study was not able however to capture late thrombosis events, as the monitoring ended after hospital discharge.
FEIBA also has several small advantages over KCentra; The dosing regimen in this study is less costly than KCentra, and the dosing regimen is simplified. It should be noted that this study examined only the surrogate endpoint of INR normalization, and did not evaluate which factor-based product had better hard outcomes related to morbidity and mortality. This choice was made because all patients that received KCentra were treated at the same center, and likewise for the patients treated with FEIBA. Therefore, there could have been other factors that could explain a difference in mortality or hemostasis that would have been impossible to control for.
Drug information question
Q: Can intermittent boluses of pantoprazole be used to treat acute GI bleeding rather than continuous infusions?
The best evidence to support intermittent boluses of PPIs to treat GI bleeding comes from a 2014 meta-analysis. The study compared intermittent doses of PPIs and the regimen of pantoprazole 80-mg intravenous bolus dose of a PPI followed by an infusion of 8 mg/h for 72 hours. The two methods were statistically non-inferior when evaluated for the risk of rebleeding and mortality.
A common intermittent regimen is for a bolus of 80 mg pantoprazole IV followed by 40 mg IV q12 hrs. This regimen uses less than half the amount of pantoprazole than a continuous infusion would over a 72 hour period.
Tip for responding to inpatient medical emergencies
After a patient has undergone successful rapid sequence intubation, a pharmacist can focus on ensuring the continued sedation and comfort of the patient. In the immediate post-intubation period, the rest of the care team is focused on confirming tube placement and gas exchange. During this time period, the induction agents used for intubation are wearing off, sometimes earlier than the paralytic agents, especially if rocuronium was used. This creates the chance of an awake-but-paralyzed scenario occurring.
Without a pharmacist present, one study showed that the time to first sedative after RSI with rocuronium was 55 minutes. In the same study, this time was cut by more than 50% if a pharmacist was physically present at the bedside.
Members of my Hospital Pharmacy Academy have access to my Code Blue Training Program, a 6-module series that will help pharmacists develop the confidence and skills necessary to respond to code blue and rapid response calls. The program covers emergency response, highlights of the BLS/ACLS guidelines, ECG recognition, patient assessment, airway pharmacology, and the care of patients with septic shock. To find out more go to pharmacyjoe.com/academy.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.