Life Threatening Anticoagulation Reversal May 2018 Update

Anticoagulation Reversal Updates and Review I’ll begin with the heavy hitting news first that Andexanet alfa (Andexxa) was approved by the FDA this month as a reversal agent for factor Xa inhibitors (specifically approved for apixaban and rivaroxaban).

Note this is not approved for other Xa inhibitors or indirect inhibitors (i.e. Lovenox).

The drug should be available Summer of 2018 in limited supply with broader commercial launch in early 2019.

This comes after the drug was declined approval in 2016

MOA: Recombinant modified human factor Xa molecule which servces as a decoy binding with Xa inhibitors in the patient’s blood.

For Life-Threatening Bleeding

Anticoagulant Reversal Agent Warfarin (Coumadin) K-centra (4 Factor PCC) + Vit K * Lovenox Protamine Sulfate (partial) Heparin Protamine Sulfate Direct Thrombin Inhibitors Dabigatran (Pradaxa) Dabigatran (Pradaxa) Argatroban, Bivalirudin, Lepirudin K-centra/Supportive Factor Xa Inhibitors Apixaban and Rivaroxaban Praxbind (idarucizumab) Edoxaban, Fondaparinux K-centra

*Note for non-life threatening bleeding refer to guides; may administer Vit K, etc.

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Bipap Settings

BIPAP Principles:This one goes out to our rising Resus Residents: Bipap has settings that can ameliorate the two primary causes of respiratory failure: oxygenation (CHF, pneumonia) and ventilation (COPD, etc).

Improve hypoxemia two ways: 1. FiO2 2. PEEP (recruit more alveoli) Improve ventilation (hypercarbia) 1. Tidal Volume 2. Respiratory Rate

Settings on Bipap: IPAP – Inspiratory positive airway pressure (e.g. the high number) EPAP – Expiratory positive airway pressure (e.g. the low number) FiO2 – Fraction of inspired O2 (%) There are more, mentioned below, however lets touch on these first.

It is important to understand the cause of your respiratory failure to apply the proper settings. Physiology! Time to move on to practical application:

For HYPOXEMIA generally start with IPAP of 10cmH2O. EPAP can generally start at 5cmH2O

Example:

• CHF (hypoxemia): Start at IPAP of 10cmH2O with an EPAP of 5cmH20 (remember you want EPAP here to prevent atelectasis. o Pressure will improve oxygenation o May always increase FiO2 as well to improve oxygenation Conversely, for HYPERCARBIA (COPD) start with a similar IPAP of 5-10cmH20 however EPAP may not even be necessary. o Remember the difference in IPAP and EPAP is related to tidal volume, and this is one thing that effects hypercarbia!! Greater the difference = greater tidal volume. o You may also change the respiratory rate (described below)

Other settings/points: • Respiratory rate as well as I:E (inspiratory:expiratory) ratio can also be adjusted (however these settings may or may not be as helpful in a patient who is breathing on their own). I don’t want to get into this too much, but a couple points: • For HYPERCARBIA increased ventilation is desired with a HIGHER respiratory rate to blow off CO2. • For asthma keep EPAP lower (blow out more air in expiration) and setup a lower I:E ratio (e.g. 1:5) to prevent “breath stacking.” • Titrate by 2 – 3 cmH20 every 5 – 10 minutes. • Max IPAP is generally considered 20cmH2O (this is because lower esophageal sphincter tone is roughly 23 – 25cmH20, don’t over insufflate the stomach). • Remember to get a blood gas.

Sources: JB Life in the Fast Lane Rebel EM UpToDate

Targeted Temperature Management

Targeted temperature management refers to temperature management after cardiac arrest where there was decreased or paused blood flow to the brain in an attempt to preserve neurological tissue/function. Indications

Patients not following commands or showing purposeful movements following resuscitation from cardiac arrest should have their temperature managed.

Although there are not true contraindications, here are some commonly recommended institutional indications

• Post cardiac arrest (any cause)

• Time < 6 hours from ROSC

• Patient is comatose

• MAP >=65 (with or without pressors)

Timing: As soon as possible (certainly within first couple hours) and for a duration of 48 hours.

Proposed Mechanism:

Decreasing the brain's oxygen demand (metabolic demand dec. up to 7% for every degree celcius)

Reducing the production of neurotransmitters (glutamate) and free radicals

Maintaining cell wall function

Methods:

• Intravenous infusion of 30 mL/kgof cold (4°C [39°F]) isotonic saline, using a pressure bag to increase the rate of administration, reduces the core temperature by >2°C per hour

o   However may cause pulmonary edema (at recommended 30ml/kg)

• Proper sedation

• Cold water blankets

• Ice packs (groin, axilla)

• Ice Bath

• Other invasive: bladder, peritoneal fluid lavage; ecmo, etc.

Target:

• 2010 AHA guidelines recommend 32-34*C, however more recent trials show similar outcomes reducing temperature to 36*is just as effective.

o   However comparison between trials shows more fevers at the temperature target, and more fever following cardiac arrest is linked to higher mortality.

• Per up to date 36*C for uncomplicated and 33°C for at least 24 hours when coma is deep (loss of motor response or brainstem reflexes)

Monitoring:

• Remember minute ventilation requirements, decrease as body temperature falls and therefore a blood gas should be obtained at target temperature or every few hours (also some machines don’t correct for hypothermia – institution specific).

• Post cardiac arrest patients should have routines labs including coagulation studies and hypoglycemia and hyperglycemia should be avoided.

• Length of cooling is institutional specific, however most recommendations say 48 hours before rewarming.

o   Of note, over 24 hours may be linked to increase risk of infection and other adverse events.

Sources:

Bray JE, Stub D, Bloom JE, Segan L, Mitra B, Smith K, Finn J, Bernard S

Resuscitation. 2017;113:39. Epub 2017 Jan 31.

Nielsen, Niklas, et al. “Targeted temperature management at 33 C versus 36 C after cardiac arrest.”

New England Journal of Medicine 369.23 (2013): 2197-2206. PMID: 24237006; Altmetric

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