Anti-NMDA Encephalitis

Today we are going to attempt to broaden your differential of altered mental status in the “young” patient.  While we attribute AMS or psychotic/bizarre behavior in many young patients to toxicologic causes or schizophrenia, there are other organic causes which are probably far more common than diagnosed. We are going to focus on one of these causes: Anti-NMDA Encephalitis

Symptoms

• Many different presentations. Typically progresses in four stages.

• Phase 1

o   May be prodrome of URI, flu-like syndrome, or headache.

• Phase 2

o   Typically begins with a behavioral change

o   Cognition, memory, speech problems.

o   Odd behavior, however no prodrome: agitation, paranoia, psychosis.

o   Seizures

• Phase 3

o   Automatisms: Twitching, lip smacking.

o   Catotonia, LOC

• Phase 4

o   Autonomic dysfunction, hypoventiliation

Demographics

• Mean age is 21 years old!

• Mainly affects women (~80%).

• 38% have a paraneoplastic syndrome, almost all of these are women (97%), typically associated with a teratoma (which contain tissue with NMDA receptors).

• It appears to be the most common individual cause of encephalitis in those youngers than age 30, even more common than HSV encephalitis.

Cause

• Thought to be an autoimmune issue caused by an antagonist again the NR1 subunit of the NMDA receptor.

• Some of this autoimmune activity is thought to be invoked by tumors (teratoma, ovarian).

Workup

Rule out other causes ruled out (meningitis, toxicologic causes, herpes, etc).

Should get CSF.  Send for oligoclonnal bands.  You should also send CSF to test for the anti-NMDA antibody (in addition to HSV, etc).

Otherwise patient should get EEG, MRI, CSF (probably already performed) which show non-specific abnormalities.

Treatment

IVIG and Steroids (1G/day methylprednisone).  Consider plasmapheresis. Secondarily immunotherapy (rituximab) or cyclophosphamide.

Prognosis

Many patients take months to get better.  Phases of symptoms are generally reversed as patient improves. Those with masses do better as masses are removed. Additionally those with early treatment  do better.

Hopefully this helps to expand your differential in new onset AMS.  Remember to rule out other causes: meningitis, toxicologic, etc!

EM:RAP, David Carr

Aliem

California Encephalitis Project

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.

UNC Healthcare

UpToDate

Aliem

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