In this episode I’ll:
1. Discuss an article about the prothrombin time and bleeding in hospitalized patients receiving rivaroxaban.
2. Answer the drug information question “Is melatonin associated with physical dependence or addiction?”
3. Share a tip for responding to inpatient medical emergencies.
Article
Association between prothrombin time and bleeding in hospitalized patients receiving rivaroxaban
Lead author: Ashley Woodruff
Published in American Journal of Health-System Pharmacy July 2018
Background
The prothrombin time (PT) may provide a qualitative assessment of the pharmacodynamic effect of rivaroxaban. The manufacturer has reported that prothrombin time is influenced by rivaroxaban in a dose-dependent way with a close correlation to plasma concentrations, although this depends on the reagent used. The authors of this study sought to report on the pharmacodynamic effect of rivaroxaban anticoagulation, as measured by prothrombin time, on bleeding risk and other outcomes in hospitalized patients.
Methods
The study was a retrospective, single-center, cohort study of adult inpatients who had a PT measured within 24 hours after rivaroxaban administration. A comparison was made between patients who experienced in-hospital bleeding with those who did not. A multivariable logistic regression model was used to quantify the association between PT and bleeding events while adjusting for albumin levels and use of nonsteroidal anti-inflammatory drugs and/or antiplatelet agents. A secondary outcome was the rate of thromboembolic events.
Results
The study included 199 patients of which 41 experienced a bleeding event. Among patients with a PT of ≥30 seconds versus a PT of <30 seconds, the overall rate of bleeding events was more than double (38.7% vs. 17.3%) and this was statistically significant ( p = 0.0067). After multivariable regression modeling was applied, a PT of ≥30 seconds correlated with an approximately 3-fold higher bleeding risk. Additionally, hypoalbuminemia was also a positive predictor of bleeding risk. For each increase in albumin concentration of 1 g/dL, starting at 2 g/dL, the risk of bleeding dropped by 75%. There was no significant between-group difference in thromboembolic events.
Conclusion
The authors concluded:
In hospitalized patients receiving rivaroxaban who had coagulation tests performed, a PT of ≥30 seconds was associated with a higher risk of bleeding. Hypoalbuminemia was also associated with bleeding in this population.
Discussion
Therapeutic monitoring of rivaroxaban is not practical due to the test not being readily available. However, patients at the extremes of body weight or close to renal dosing cutoff limits may benefit from the PT being taken into account when deciding if rivaroxaban is dosed correctly. This study also provides a foundation that could be applied to real-time clinical surveillance of hospitalized patients on rivaroxaban with an elevated PT and/or hypoalbuminemia. If the patients could be readily identified, a pharmacist could evaluate the bleeding risk prospectively, potentially preventing bleeding before it occurs.
Drug information question
Q: Is melatonin associated with physical dependence or addiction?
A: Probably not.
There are no case reports in PubMed that describe melatonin addiction or dependence. Multiple review articles consider that melatonin has little potential for dependence, especially compared to other medication classes used to treat insomnia. In addition, there are several articles that examine the potential for melatonin to be used in substance abuse disorders. If melatonin did have a potential for dependence, it would likely have been recognized in that patient population already.
Tip for responding to inpatient medical emergencies
When treating anaphylaxis, remember that epinephrine is the drug of choice. There is no evidence that supports the use of other medications such as antihistamines, glucocorticoids, or bronchodilators. Their use is extrapolated from other disease states. The pharmacist responding to inpatient medical emergencies can help prioritize the order of administration of medications by ensuring that epinephrine is administered first. The recommended adult dose of epinephrine (1 mg per mL) is 0.3 to 0.5 mg per single dose, injected IM into the mid-outer thigh. If needed, this dose may be repeated every 5 to 15 minutes.
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.
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