Tranexamic Acid vs. Amicar

** Updated June 2022**

Over the years, our hospital has been using Amicar… until there was a drug shortage.  With that drug shortage came a different drug called tranexamic acid.  We’ve been using it for awhile and I can’t seem to tell a difference in coagulation between the two drugs.  Let’s break down each one and also discuss cost-effectiveness.

Amicar

What is it?


From MedPage Today

Tranexamic Acid

What is it?

Tranexamic acid acts by reversibly blocking the lysine binding sites of plasminogen, thus preventing plasmin activation and, as a result, the lysis of polymerised fibrin.12 Tranexamic acid is frequently utilised to enhance haemostasis, particularly when fibrinolysis contributes to bleeding. In clinical practice, tranexamic acid has been used to treat menorrhagia, trauma-associated bleeding and to prevent perioperative bleeding associated with orthopaedic and cardiac surgery.13–16 Importantly, the use of tranexamic acid is not without adverse effects. Tranexamic acid has been associated with seizures,17 18 as well as concerns of possible increased thromboembolic events, including stroke which to date have not been demonstrated in randomised controlled trials.

Fibrinolysis is the mechanism of clot breakdown and involves a cascade of interactions between zymogens and enzymes that act in concert with clot formation to maintain blood flow.25 During extracorporeal circulation, such as cardiopulmonary bypass used in cardiac surgery, multiplex changes in haemostasis arise that include accelerated thrombin generation, platelet dysfunction and enhanced fibrinolysis.26 Tranexamic acid inhibits fibrinolysis, a putative mechanism of bleeding after cardiopulmonary bypass, by forming a reversible complex with plasminogen.

Dosing:

  • Ortho/Spine
  • OB
  • Trauma

Currently at our hospital (June 2022):

TXA DOSING AND ADMINISTRATION OVERVIEW

How supplied from PharmacyTXA 1000mg/10mL vials Will not provide premade bags like with Amicar; Amicar is a more complex mixture than TXA Will take feedback on this after go-live and reassess
Where it will be supplied from PharmacyPOR-SUR1 Omnicell (in HeartCore Room)   Perfusion Tray (will replace aminocaproic acid vials 6/7)  
Recommended Dosing (see below for evidence)~20 mg/kg total dose Can give as: 20 mg/kg x 1, OR 10 mg/kg x 1, followed by 1-2 mg/kg/h*   Perfusion may also prime bypass solution with 2 mg/kg x 1*
Preparation & AdministrationIV push straight drug (1000mg/10mL) from vial   AND/OR   Mix vial of 1000mg/10mL TXA with 250mL NS for continuous infusion*

TXA & Amicar ADRs

  • Seizure risk may be increased also by duration of prolonged open-chamber surgery based on findings from Zuffery, et al. Anesthesiology 2021.
  • Per OR pharmacist at Scripps Mercy, they have not seen an increased incidence of seizures in their patient-population (anecdotally)

DOSING EVIDENCE

There are a number of dosing strategies in the literature. What I recommend for maximal safety and efficacy is taken from Zuffery, et al. Anesthesiology 2021 meta-analysis and is practiced at Scripps Mercy.

  • ~ 20 mg/kg total dose recommended in this meta-analysis.
  • Two dosing strategies they report that were as effective as high-dose but with lower seizure risk than high dose:

Methadone: perioperative pain use

Methadone for perioperative pain #methadone #pain #ERAS

There’s a lot of great data that methadone use decreases postoperative narcotics use in cardiac surgery patients, and I believe it would really be a beneficial drug in an ERAS pathway for early extubation, decreased LOS in ICU and hospital, and better patient satisfaction.  Please see the articles below/attached for references.

Methadone for cardiac surgery: 0.2-0.3 mg/kg prior to incision – perhaps different metabolism on CPB so consider split dosing pre-pump and post-pump. Dose adjustment with age and other co-morbidities. At induction, one half of the study opioid (either 0.15 mg/kg of methadone or 6 μg/kg of fentanyl) was administered via an infusion pump over 5 min. The remainder of the study opioid (0.15 mg/kg of methadone or 6 μg/kg of fentanyl) was infused over the next 2 h. Either 0.3 mg/kg of methadone (maximum dose of 30 mg) or 12 μg/kg of fentanyl (maximum dose of 1200 μg) was added to 100-ml bags of normal saline (total volume 100 ml).

Methadone for non-cardiac surgery: 0.2mg/kg prior to incision. REVIEW: Intraoperative Methadone in Surgical Patients: A Review of Clinical Investigations. Anesthesiology 9 2019, Vol.131, 678-692.

Methadone for obesity: 0.15 mg/kg IBW+20% at induction. J Pain Res. 2018; 11: 2123–2129. Intraoperative use of methadone improves control of postoperative pain in morbidly obese patients: a randomized controlled study.

Methadone for outpatient surgery: 0.15 mg/kg ideal body weight. Anesth Analg. 2019 Apr; 128(4): 802–810. Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study.

OVERALL: A variety of doses have been used in clinical trials, ranging from 0.1 to 0.3 mg/kg, with the majority of studies using a dose of either 0.2 mg/kg or a fixed dose of 20 mg.

Methadone has a long elimination half-life (1–2 days). It is cleared predominantly by hepatic metabolism, primarily via N-demethylation to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), which is pharmacologically inactive, and thence secondarily to 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP).

Together these investigations established that a) CYP3A has no influence on single-dose intravenous or oral methadone plasma concentrations, b) CYP3A plays a minimal (if any) role clinically in single-dose methadone N-demethylation and clearance, c) methadone is not a clinical CYP3A substrate, and d) clinical guidelines stating that methadone is a CYP3A4 substrate and warning about CYP3A4 drug interactions needed revision. In addition, CYPs 2C9, 2C19, and 2D6 do not appear to contribute materially to clinical methadone N-demethylation and clearance.

In summary, it is now obvious that CYP2B6 a) is a predominant catalyst of methadone metabolism in vitro; b) mediates clinical methadone metabolism, clearance, stereoselective disposition, and drug-drug interactions; and c) genetic polymorphisms influence methadone disposition. Thus, both constitutive variability due to CYP2B6 genetics, and CYP2B6-mediated drug interactions, can alter methadone disposition, clinical effect, and drug safety. Rewritten clinical guidelines stating that methadone is a CYP2B6 substrate and warning about CYP2B6 drug interactions may improve methadone use, treatment of pain and substance abuse, and patient safety.

FDA Drug Datasheet

From Anesthesiology 5 2015, Vol.122, 1112-1122.
From Anesth Analg. 2019 Apr; 128(4): 802–810.

What I’m doing these days:

  • March 2021
    • Cardiac: Ketamine current pt weight (non-adjusted) 0.2mg/kg/hr start after induction (after lines placed) + 0.35 mg/kg 5-10 minutes prior to incison. Change from 0.2mg/kg/hr to 0.1mg/kg/hr when rewarming. Infusion off when driving sternal wires. Methadone currently not available.
    • Non-cardiac (cases 2+ hours duration) Ketamine: 0.3mg/kg (non-adjusted, current weight) at induction. Methadone currently not available.
    • Outpatient: ketamine not currently available for use.
  • July 2020
    • Cardiac: Ketamine IBW 0.3mg/kg total: 0.2mg/kg prior to incision + 0.1mg/kg when separate from CPB
    • Excel spreadsheet dosing


Adult Cardiothoracic

Adult Non-Cardiac

From Perioperative Methadone and Ketamine for Postoperative Pain Control in Spinal Surgical Patients: A Randomized, Double-blind, Placebo-controlled Trial. Anesthesiology Newly Published on March 2021. doi: https://doi.org/10.1097/ALN.0000000000003743.

Adult Outpatient

Pediatric Surgery

Methadone Pharmacology & Effects

Prescription of Controlled Substances: Benefits and Risks. [Updated 2020 Jun 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537318/

The role of methadone in opioid rotation-a Polish experience. Support Care Cancer. 2009 May;17(5):607-12.

Methylene Blue

Case: 65 yo male with septic endocarditis and septic emboli with + valve vegetations. Severe MR, mod AI, mod TR, no PFO, EF 60-70%. Mild pericardial effusion. Large bilateral pleural effusions.

Vasoplegic syndrome—the role of methylene blue. European Journal of Cardio-Thoracic Surgery, Volume 28, Issue 5, 1 November 2005, Pages 705–710.

OpenAnesthesia: Methylene Blue

Dose:
2 mg/kg bolus –> 0.5 mg/kg/hr x 12 hours
Worked wonderfully for vasoplegia unresponsive to levophed or vasopressin.

Intraoperative cystoscopy and ureteral visualization

Over the years, I’ve been asked to inject various dyes to help light up the urine for visualization of the ureters.  Now, we’ve moved to fluorescein because it “lights up” quicker than other previous dyes.  Why are we always switching?  Drug shortages.

Dosing: 0.25 – 1.0 ml of 10% preparation of sodium fluorescein

Dose: 5 ml. bolus of 10% fluorescein intravenously.