Fondaparinux (Arixtra) and neuraxial anesthesia

[Planktonmd]

The ASRA guidelines concerning neuraxial anesthesia on patients receiving this anticoagulant are ambiguous to say the least.
This is a long acting thrombin inhibitor with a half life close to 21 hours.
I would like to hear how people are approaching neuraxial anesthesia when patients are on this drug?
How long should you wait?
How about indwelling catheters?

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[proman]

Fondaparinux is actually a synthetic anti-Xa (via ATIII) inhibitor. The direct thrombin inhibitors are another drug class.

 

[Planktonmd]

Fondaparinux is actually a synthetic anti-Xa (via ATIII) inhibitor. The direct thrombin inhibitors are another drug class.

You are right.
It is an indirect Xa inhibitor.
So, how do we do Neuraxial anesthesia when patients are receiving it?

 

[BLADEMDA]

Sorry for taking so long to post about Arixtra. Plankton, this is a very good thread. The few times I have seen Arixtra used preoperatively
my partners refused to administer Neuraxial anesthesia. I was using 72 hours since last dose of arixtra vs. 24 hours for Lovenox. However, perhaps 48 hours "off" Arixtra is sufficient?

In addition, Arixtra may need to be started 12 hours AFTER your spinal/epidural/lumbar plexus blocks. Some studies show increased bleeding from the sutgical site if Arixtra is started within 6 hours of major surgery. Hence, most surgeons wait 6-12 hours after surgery before giving Arixtra. I prefer at least 12 hours after Spinal injection before first dose of Arixtra.

Finally, what about indwelling Lumbar Plexus or Epidural Catheters. The experts seem to recommend pulling these catheters out after being "off" Arixtra for 36 hours and then waiting 12 more hoyrs before restarting the drug.

Based on available evidence Neuraxial/Lumbar Plexus blocks should be performed only if the patient has not been given any Arixtra for 36-48 hours. I prefer greater than 48 hours for my practice.

What do you think?

Blade

 

[BLADEMDA]

1: Anesth Analg. 2007 Dec;105(6):1540-7, table of contents. Links

Comment in: Anesth Analg. 2009 Feb;108(2):670-1; author reply 671-2. The safety and efficacy of extended thromboprophylaxis with fondaparinux after major orthopedic surgery of the lower limb with or without a neuraxial or deep peripheral nerve catheter: the EXPERT Study.

Singelyn FJ, Verheyen CC, Piovella F, Van Aken HK, Rosencher N; EXPERT Study Investigators.
Department of Anesthesiology, Clinical Center, Soyaux, France. [email protected]
BACKGROUND: The benefit-risk ratio of extended fondaparinux therapy has not been assessed in patients undergoing major lower limb joint arthroplasty. Few data on the concomitant use of fondaparinux and continuous neuraxial or deep peripheral nerve blockade are available. We performed a prospective intervention study in patients undergoing major orthopedic surgery primarily designed to assess the efficacy of fondaparinux when drug administration was withheld for 48 h to permit removal of a neuraxial or deep peripheral nerve catheter. The safety and efficacy of extended fondaparinux therapy for the prevention of venous thromboembolism were also evaluated. METHODS: Patients received a daily subcutaneous injection of 2.5 mg fondaparinux for 3 to 5 wk postoperatively. In patients with a neuraxial or deep peripheral nerve catheter, the catheter was removed 36 h after the last fondaparinux dose. The next fondaparinux dose was administered 12 h after catheter removal. The primary end points were symptomatic venous thromboembolism and major bleeding up to 4-6 wk after surgery. RESULTS: We recruited 5704 patients. A neuraxial or deep peripheral nerve catheter was inserted in 1553 (27%) patients and 78 (1.4%) patients, respectively. The rate of venous thromboembolism was 1.0% (54 of 5387). There was no difference between patients without (1.1%) or with (0.8%) a catheter (the upper limit of the 95% confidence interval of the odds ratio, 1.49, being below the predetermined noninferiority margin of 1.75). The incidence of major bleeding was 0.8% (42 of 5382). No neuraxial or perineural hematoma was reported. CONCLUSIONS: Once-daily subcutaneous injection of 2.5 mg fondaparinux given for 3 to 5 wk was effective and safe for prevention of venous thromboembolism after major orthopedic surgery. Temporary discontinuation of fondaparinux for 48 h permitted safe removal of a neuraxial or deep peripheral nerve catheter without decreasing thromboprophylatic efficacy.
PMID: 18042845 [PubMed - indexed for MEDLINE]

 

[Planktonmd]

Your approach makes sense but there is really no established guidelines.
Our hospital just added this drug to formulary and they are encouraging surgeons and others to prescribe it since it is cheaper than Lovenox and it only requires a once a day injection.
The long half life is a problem though and would make it really complicated to do neuraxial anesthesia on these patients.

Sorry for taking so long to post about Arixtra. Plankton, this is a very good thread. The few times I have seen Arixtra used preoperatively
my partners refused to administer Neuraxial anesthesia. I was using 72 hours since last dose of arixtra vs. 24 hours for Lovenox. However, perhaps 48 hours "off" Arixtra is sufficient?

In addition, Arixtra may need to be started 12 hours AFTER your spinal/epidural/lumbar plexus blocks. Some studies show increased bleeding from the sutgical site if Arixtra is started within 6 hours of major surgery. Hence, most surgeons wait 6-12 hours after surgery before giving Arixtra. I prefer at least 12 hours after Spinal injection before first dose of Arixtra.

Finally, what about indwelling Lumbar Plexus or Epidural Catheters. The experts seem to recommend pulling these catheters out after being "off" Arixtra for 36 hours and then waiting 12 more hoyrs before restarting the drug.

Based on available evidence Neuraxial/Lumbar Plexus blocks should be performed only if the patient has not been given any Arixtra for 36-48 hours. I prefer greater than 48 hours for my practice.

What do you think?

Blade

 

[Planktonmd]

Thanks for the study Blade.

1: Anesth Analg. 2007 Dec;105(6):1540-7, table of contents. Links

Comment in: Anesth Analg. 2009 Feb;108(2):670-1; author reply 671-2. The safety and efficacy of extended thromboprophylaxis with fondaparinux after major orthopedic surgery of the lower limb with or without a neuraxial or deep peripheral nerve catheter: the EXPERT Study.

Singelyn FJ, Verheyen CC, Piovella F, Van Aken HK, Rosencher N; EXPERT Study Investigators.
Department of Anesthesiology, Clinical Center, Soyaux, France. [email protected]
BACKGROUND: The benefit-risk ratio of extended fondaparinux therapy has not been assessed in patients undergoing major lower limb joint arthroplasty. Few data on the concomitant use of fondaparinux and continuous neuraxial or deep peripheral nerve blockade are available. We performed a prospective intervention study in patients undergoing major orthopedic surgery primarily designed to assess the efficacy of fondaparinux when drug administration was withheld for 48 h to permit removal of a neuraxial or deep peripheral nerve catheter. The safety and efficacy of extended fondaparinux therapy for the prevention of venous thromboembolism were also evaluated. METHODS: Patients received a daily subcutaneous injection of 2.5 mg fondaparinux for 3 to 5 wk postoperatively. In patients with a neuraxial or deep peripheral nerve catheter, the catheter was removed 36 h after the last fondaparinux dose. The next fondaparinux dose was administered 12 h after catheter removal. The primary end points were symptomatic venous thromboembolism and major bleeding up to 4-6 wk after surgery. RESULTS: We recruited 5704 patients. A neuraxial or deep peripheral nerve catheter was inserted in 1553 (27%) patients and 78 (1.4%) patients, respectively. The rate of venous thromboembolism was 1.0% (54 of 5387). There was no difference between patients without (1.1%) or with (0.8%) a catheter (the upper limit of the 95% confidence interval of the odds ratio, 1.49, being below the predetermined noninferiority margin of 1.75). The incidence of major bleeding was 0.8% (42 of 5382). No neuraxial or perineural hematoma was reported. CONCLUSIONS: Once-daily subcutaneous injection of 2.5 mg fondaparinux given for 3 to 5 wk was effective and safe for prevention of venous thromboembolism after major orthopedic surgery. Temporary discontinuation of fondaparinux for 48 h permitted safe removal of a neuraxial or deep peripheral nerve catheter without decreasing thromboprophylatic efficacy.
PMID: 18042845 [PubMed - indexed for MEDLINE]

 

[sevoflurane]

At my institution we recommend to stop it one month before the procedure due to it's long half life. Neuraxial or peripheral.

 

[BLADEMDA]

At my institution we recommend to stop it one month before the procedure due to it's long half life. Neuraxial or peripheral.

Half life is like 17 hours. Usually, all you need is 3-4 half lives for the drug to be reduced significantly; I was using 72 hours but will reduce to 48 hours based on current study listed above and utilize a non-cutting needle.

But, for Epidural Placement I still am likely to use 72 hours because of higher risk of blood vssel puncture with catheter compared to single shot spinal. Until more studies are published or ASRA makes its recommendation a 48-72 hour interval seems reasonable.

Blade

 

[BLADEMDA]

ARIXTRA is 100% synthetic.

• ARIXTRA is not a heparin.
• Unlike heparins and LMWHs, no part of the manufacturing process for ARIXTRA involves animal products, including pork by-products.
• ARIXTRA is the first and only synthetic Factor Xa inhibitor, representing an important evolution in antithrombotic DVT therapy.

Pharmacokinetics/Pharmacodynamics

1. Pharmacologic Class: ARIXTRA is a synthetic and specific inhibitor of activated Factor X (Xa).
2. Absorption: Fondaparinux sodium administered by subcutaneous injection is rapidly and completely absorbed (absolute bioavailability is 100%). Following a single subcutaneous dose of fondaparinux sodium 2.5 mg in young male subjects, Cmax of 0.34 mg/L is reached in approximately 2 hours. In patients undergoing treatment with fondaparinux sodium injection 2.5 mg, once daily, the peak steady-state plasma concentration is, on average, 0.39-0.50 mg/L and is reached approximately 3 hours post-dose. In these patients, the minimum steady-state plasma concentration is 0.14-0.19 mg/L. In patients with symptomatic deep vein thrombosis and pulmonary embolism undergoing treatment with fondaparinux sodium injection 5 mg (body weight <50 kg), 7.5 mg (body weight 50-100 kg) and 10 mg (body weight >100 kg) once daily, the body-weight-adjusted doses provide similar mean steady-state peaks and minimum plasma concentrations across all body weight categories. The mean peak steady-state plasma concentration is
   in the range of 1.20-1.26 mg/L. In these patients, the mean minimum steady-state plasma concentration is in the range of 0.46-0.62 mg/L.
   
3. Distribution: In healthy adults, intravenously or subcutaneously administered fondaparinux sodium distributes mainly in blood and only to a minor extent in extravascular fluid as evidenced by steady state and non-steady state apparent volume of distribution of 7-11 L. Similar fondaparinux distribution occurs in patients undergoing elective hip surgery or hip fracture surgery. In vitro, fondaparinux sodium is highly (at least 94%) and specifically bound to antithrombin III (ATIII) and does not bind significantly to other plasma proteins (including platelet Factor 4 [PF4]) or red blood cells.
4. Metabolism: In vivo metabolism of fondaparinux has not been investigated since the majority of the administered dose is eliminated unchanged in urine in individuals with normal kidney function.
5. Elimination: In individuals with normal kidney function fondaparinux is eliminated in urine mainly as unchanged drug. In healthy individuals up to 75 years of age, up to 77% of a single subcutaneous or intravenous fondaparinux dose is eliminated in urine as unchanged drug in 72 hours. The elimination half-life is 17-21 hours.

If you have additional questions regarding ARIXTRA, please call us at 1-866-ARIXTRA (1-866-274-9872).

 

[Licoricestick]

While we're at it - what about Rivaroxaban? We've recently had it introduced at our hospital. Our acute pain service hasn't yet been confronted with the issue of epidural removal in a patient on it - what're people doing?

 

[BLADEMDA]

While we're at it - what about Rivaroxaban? We've recently had it introduced at our hospital. Our acute pain service hasn't yet been confronted with the issue of epidural removal in a patient on it - what're people doing?

It just got approved this month. I would follow the same guidelines as listed above for Arixtra. Rivaroxaban has Anti-Factor Xa activity for at least 24 hours and is given P.O. once a day. The half life may be only 8 hours or so but the manufacturer claims the drug works for at least 24 hours.

The studies show that Arixtra and Rivaroxaban are superior in preventing DVT's compared to Lovenox. I suspect we will see more patients on them in the very near future.