POTD: Naloxone

Today, I’ll be touching on the life-saving medication Naloxone.

Epidemiology:

In the US, there are three million people with opioid use disorder (OUD). 68K+ people died from opioid overdoses in 2020, nearly 40% higher than 2019. The deaths were primarily attributed to synthetic opioids.

Patients who have overdosed on opioids will show the classic triad of constricted pupils, decreased respiratory rates, and somnolence. You should consider naloxone administration in OUD patients with RR<8 and GCS<12.

Naloxone:

Naloxone is the antidote for opioid overdose since it is an opioid antagonist. Naloxone is available intranasally, intramuscularly, nebulized, and intravenously.

The onset of action is within 1-2 minutes, but remember that the half-life is 20-90 minutes. The half-life of the opioids are longer, so it’s recommended to observe these patients for at least 3 hours.

The first question you must ask – could this patient die from apnea? If so, you can bolus large amounts of naloxone. If the patient is somnolent but not apneic, you can titrate smaller doses at a time.

In a patient with OUD, there is a higher likelihood that you will precipitate withdrawal through the administration of naloxone. Therefore, start with lower doses of narcan for OUD patients compared to opioid-naive patients. As a side note - some of the doses below are controversial depending on the source that you’re looking at. Remember, the dosing of naloxone depends on the route.

Intranasal narcan:

• 4mg in one nostril intranasally

• Redose as needed

• MMC ED Pharmacy has kits with two 4mg spray bottles

• Available over the counter in New York

IM/IV dosing:

• Apneic/dying patient: administer 2mg-4mg IM/IV off the bat

• OUD patient in overdose: 0.1mg IV (0.4 mg IM) aliquots, q1-2 minutes. Consider larger doses if your patient isn’t responding appropriately. Synthetic opioids may require higher doses (sometimes up to 10mg IV.)

  • Titration: The goal is to titrate to a point of adequate ventilation and airway protection, but not necessarily full arousal. But the patient should be arousable.

• Opioid-naive patient in overdose: 0.4mg IV/IM

Initiating a drip:

• Because the half-life of narcan is short, you may want to consider starting a drip for patients requiring repeat doses.

• Calculate the amount that the patient required to wake up to an appropriate level and then put them on a drip ⅔ of that per hour.

Nebulized naloxone:

• If the drip is taking a while to set up, you can consider administering nebulized naloxone by mixing the 0.4mg vial with NS.

I would recommend having them placed on a monitor in resus with an EtCO2. If your patient develops respiratory distress, consider non-cardiogenic pulmonary edema as a side effect and get a CXR. These patients may require intubation.

EMRAP just did a piece this month about the importance of dispensing Narcan kits in the ED (as opposed to just a prescription for it, which goes largely unfilled.) This is a lifesaving medication, so I highly recommend giving a kit to every OUD patient in the ED.

https://www.emrap.org/episode/emrap20223/takehome

Last couple of pearls and tidbits:

• Check the skin: you may find fentanyl patches which can be causing their overdose. Fentanyl patches come in doses 12mcg-100mcg/hr and require changing q72h. Just keep in mind that the effects may linger after removal.

• Consider making push-dose naloxone. Naloxone comes in 0.4mg vials. If you mix the vial with 10cc of NS, you will be able to give 0.04mg/ml aliquots easily.

• If there’s literally no response to the naloxone at high doses, consider alternate etiologies. Pontine stroke may be a mimic.

• Watch the show “Dopesick” on Hulu. It follows the story of oxycodone coming to market and the Sackler family. It’s crazy.

• You can have your own take-home Narcan kit. Just pick it up from our friendly ED pharmacists. You could save a life!

• Also, as a reminder, Relay for Life is also an amazing service for nonfatal opioid overdoses.

References:

https://wikem.org/wiki/Naloxone

https://emcrit.org/ibcc/opioid/

https://litfl.com/naloxone/

https://www.ncbi.nlm.nih.gov/books/NBK553166/

POTD: Supratherapeutic INR

I’ve maybe had to think about this twice during residency and both times was like ??? so I figured I should at least learn a little about it.

Although slowly dying out in terms of popularity, some providers STILL put their patients on warfarin. One of the last conditions where warfarin is indicated over a DOAC is in the setting of a mechanical valve, which can be a clue into the patient’s past medical history if you see it on their medication list (or that their PCP is old school). And even this may change as data on DOAC’s continues to evolve. There are multiple reasons why warfarin is a very annoying drug to work with.

1)    Narrow therapeutic window – for most indications the target INR is between 2-3

2)    Variable dose response

3)    Multiple drug-diet and drug-drug interactions

4)    Requiring bridging therapy

The main benefit of warfarin is that in the event of bleeding or hemorrhage, there are easy and effective reversal agents.

So, what happens if you shotgun labs on a patient (as one does) and their INR returns at a higher level? Like 4? 7? 10?? It depends on the scenario.

Significant or Life-Threatening Bleeding – very obvious, no thought involved. Obviously do not wait for confirmatory testing before treating.

-       Stop warfarin

-       Give Vitamin K 10mg IV over 20-60min. Some considerations…

o   Vitamin K works by helping the body produce more coagulation factors (no, I won’t go over the mechanism). This takes more than a few hours and does not help immediately

o   If started on vitamin K the patient will usually be refractory to warfarin for some time, but this is less of a problem as a different (and likely better) anticoagulant can be started in the interim

-       4-factor prothrombin complex concentrate (PCC) – Kcentra (what we have at Maimonides). I think this will end up institution specific, but we do…

o   Fixed approach – does not depend on INR. After a lovely discussion with pharmacy, studies appear to show that it is just as effective but lowers cost as overall doses are lower. Preferred if you have a choice.

§  GI/ENT/life-threatening hemorrhage – 1500 IU

§  ICH – 2000 IU 

o   INR-based approach – start off with 1500 IU empirically then add SUPPLEMENTAL dose…

§  INR 2-4: total 25 IU/kg (max 2500)

§  INR 4-6: total 35 IU/kg (max 3500)

§  INR > 6: total 50 IU/kg (max 5000)

-       If no Kcentra, consider FFP (but it honestly sounds like you should never really consider FFP). Per UpToDate…

o   2U FFP. Check INR 15 min after infusion, if >1.5 give another 2IU. Repeat until INR < 1.5.

o   Consider Lasix if infusing large amounts

Luckily, the order set reflects this at Maimonides, and we don’t have to think about it here.

Not really a debate anymore, but Kcentra vs FFP? Kcentra…

-       Is more rapid and effective at correcting INR - ~30 min

-       Can be infused faster with less volume  less likely leading to fluid overload

-       Shorter preparation time

-       Does not require blood-type matching

-       FFP is cheaper though….      +1

For Urgent/Emergent procedures

-       Treat as above in discussion with surgeon or proceduralist

-       If it can wait, don’t need to treat as aggressively

Minor Bleeding (like epistaxis) – very complicated, decided by many factors and heavily decided by physician judgement. Some things to consider

-       Extent of bleeding and risk of progression

-       Previous bleeding history

-       Comorbidities (CKD, HTN)

-       Concomitant anti-platelet therapy

-       INR level

-       Thromboembolic risk of the patient (prosthetic valve, atrial fibrillation, history stroke/DVT/PE, etc.)

-       Therapy will range from holding warfarin, giving vitamin K, and treating as above

Now on to why I actually decided to make this POTD.

Asymptomatic Elevated INR – based on INR

-       INR > 10: oral vitamin K 2.5-5mg  response in 24-48 hours

o   Hold warfarin

o   No role for Kcentra or FFP

o   INR should be checked daily or every other day, repeat oral vitamin K as needed

-       INR 4.5-10

o   Hold warfarin (1-2 doses)

o   Can consider low dose oral vitamin K – 1 - 2.5mg. Again, consider SEVERAL factors

§  Risk of bleeding – older age, prior bleeding, higher INR  consider oral vitamin K

§  Risk of thrombosis

-       INR <4.5

o   Hold next dose of warfarin (or reduce dose, this is generally on the PCP though)

o   Needs more frequent INR checks in the immediate future

Does anyone NEED to be admitted for management of supratherapeutic INR? Likely not. Fortunately, or unfortunately, depends on our clinical judgement. Off the top of my head…

-       Consider calling PCP to ensure follow-up / PCP comfort

-       Consider risk of bleeding vs. risk thrombosis

-       Patient ability to follow up

-       The thousand other things we think about when deciding whether to admit or discharge patients

What about an elevated INR in a liver patient?

-       Do not treat like warfarin-induced elevated INR

-       Patients are usually at baseline PRO-THROMBOTIC from low levels of protein C and S (anticoagulation factors)

-       Nothing to really do for elevated INR in the cirrhotic patient – per UptoDate appears that most attempts to correct lead to adverse events (thrombosis, etc.)

TL;DR

-       Ensure proper patient follow-up for cases of asymptomatic supratherapeutic INR

-       INR > 10 – hold warfarin, consider 2.5 – 5mg oral vitamin K

-       INR 4.5-10 – hold warfarin, consider 1 – 2.5mg oral vitamin K

-       INR < 4.5 – hold a single dose and recheck INR (not in ED)

https://www.nuemblog.com/blog/supratherapeutic-inr

https://www.uptodate.com/contents/management-of-warfarin-associated-bleeding-or-supratherapeutic-inr#H21790898

http://www.emdocs.net/em-cases-liver-emergencies/

POTD: Tinea Pedis (Athlete's Foot)

This PODT is inspired by a recent case I had in while working in Peds and is something we may encounter often in the summer. This is a perfect example of a fast track compliant that we may have not seen a lot of during COVID.

The patient was a young male in his 20s who works in construction and wears heavy boots and socks for about 8 hours of the day in the heat. He presented with 1 days of sloughing of the skin of both of his feet with discharge.

 Lets discuss Tinea Pedis (Athlete’s Foot):

 Tines pedis is a dermatophyte infection of the skin on the foot.

 Etiology and Risk Factors:

• Usually occurs in adults and adolescents and is rare prior to puberty

• Infection is acquired by means of direct contact with the causative organism

• Commonly seen in patients who have a history of walking barefoot in locker rooms or swimming pool facilities

• Also commonly seen in patients who wear occlusive footwear

Predisposing factors to consider

• Diabetes Mellitus

• Immunodeficiency, Systemic corticosteroid use, or use of immune suppressive agents

• Poor peripheral circulation or lymphoedema

• Excessive sweating (hyperhidrosis)

 Who would have know that there are different types of tinea pedis?

•  Types of Tinea Pedis:

  • Interdigital tinea pedis: Manifests as pruritic erosions or scales between the toes, most commonly in the third and fourth digital interspaces

    • More severe form of this is known as Ulcerative tinea pedis. This is generally associated with secondary bacterial infection

  • Hyperkeratotic (Moccasin-Type): Characterized by diffuse hyperkeratotic eruption involving the soles and medial and lateral surfaces of the feet.    

  • Vesiculobullous (inflammatory-type): Pruritic, sometimes painful, vesicular or bullous eruption. Medial foot often affected 

Management:

• Topical antifungal therapy is treatment of choice for most patients.

  1. Example of topical antifungal: Azoles, Allylamines, Butenafine, Ciclopirox, Tolnaftate, and Amorolfine. Recommended to apply once or twice a day for four weeks. (Refer to references for dosages and frequency)

  2. Beneficial and more effective for patients to use the suspension formulation of these medications

• Systemic antifungal agents are primarily reserved for patients who fail topical therapy

  1.   Terbinafine 250mg per day for 2 weeks in adults

     1. Most check LFTs prior to administration and patients need to follow up and have LFTs checked while receiving treatment

     2. Peds dosing:

        • 10 to 20kg: 62.5mg/day

        • 20 to 40kg: 125mg/day

        • Above 40kg: standard adult dosing

  • Itraconazole 200mg per day for two weeks

    •   Peds dosing:

      • 3 to 5 mg/kg per day

  • Fluconazole 150mg once weekly for two to six weeks

    • Peds dosing:

      •   6mg/kg once weekly

• ·Ulcerative Tinea Pedis;

  •   Always treatment with systemic antifungal agents in addition to topical antifungals

  • Make sure to add in addition to your antifungal an antibiotic such as Keflex

  • Outpatient podiatry follow up should be given to patients

• Prevention

  • Use of sock with wick-away material

  • Use of desiccating foot powders

  • Tx of hyperhidrosis if there is history of moist feet

  •   Tx of shoes with antifungal powder

  •   Avoidance of occlusive foot wear

 We diagnosed our patient with ulcerative tinea pedis. We started the patient on Terbinafine, Ciclopriox, and Keflex and arranged for podiatry follow up. Our patients case was unique in the fact that the patient had bilateral involvement normally this occurs unilateral.

 References :

·      https://www.uptodate.com/contents/dermatophyte-tinea-infections?search=tinea%20pedis&source=search_result&selectedTitle=1~103&usage_type=default&display_rank=1#H2658711829

·      https://www.uptodate.com/contents/image?csi=18b425c8-5b1f-4694-a039-5bc8aa27c160&source=contentShare&imageKey=PC%2F76148

·      https://wikem.org/wiki/Tinea_pedis

·      https://www.aafp.org/afp/2014/1115/p702.html

·      https://accessemergencymedicine.mhmedical.com/content.aspx?sectionid=109447903&bookid=1658

·      https://dermnetnz.org/topics/tinea-pedis/