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/


Salicylate Poisoning

Welcome to today's POTD: Aspirin overdose, and by extension, salicylate poisoning!

Background: Salicylates are found in a lot of over the counter drugs and "natural" remedies. Most commonly in the form of Aspirin (acetylsalicylic acid, or ASA), it also exists in Pepto-Bismol, Maalox, Alka-seltzer, and the classic stem question, Oil of Wintergreen. Aspirin is rapidly converted to salicylic acid in the body. Fun fact: Aspirin used to exist as Aspergum, with each stick dosed at 227mg of aspirin. You even had your choice between orange and cherry flavors. Discontinued in 2006.

Normally, at therapeutic levels, aspirin is ingested and absorbed in the stomach. It makes its way to the blood stream, and almost all of it is bound to protein. It is first metabolized by the liver, and these metabolites are then excreted by the kidneys into the urine.

This method of metabolism is quickly overwhelmed in overdose. More free salicylate exists unbound by protein, and the liver's ability to detox becomes saturated. Elimination then proceeds via renal elimination, which is much slower.

Pathophysiology and Symptoms:

The effects salicylates have on specific organs and generalized metabolism are what produce its toxicity.

Acid Base Abnormality

-Salicylates directly stimulates the medullary respiratory center, causing hyperventilation. This hyperventilation blows off CO2 and leads to a respiratory alkalosis. This is usually the first acid-base disturbance.

-This is followed by an anion gap metabolic acidosis. Salicylates uncouple oxidative phosphorylation in the mitochondria, leading to a reliance on anaerobic metabolism and a resultant increase in lactic acid. Build up of organic acids lead to a metabolic acidosis. This is on top of the original respiratory alkalosis, leading to a mixed acid-base picture.

Uncoupling oxidative phosphorylation produces heat; patients are usually hyperthermic.


Tinnitus: Salicylate is ototoxic, and can cause temporary hearing loss and reversible tinnitus. Symptoms usually subside 1-3 days following cessation of salicylate cessation.


Vomiting:

Aspirin and salicylates are gastric irritants, and in overdose, leads to direct stimulation of the chemoreceptor trigger zone in the medulla that causes vomiting. Large amounts of emesis may also create a metabolic alkalosis.


AMS and seizures: Salicylates can cross the blood brain barrier, and can build up in the CNS. This can cause AMS in three different ways: through direct toxicity to CNS through acidemia, neuroglycopenia (through increased demand in CNS), and cerebral edema.


Pulmonary edema and acute lung injury: Salicylate toxicity leads to increased pulmonary vascular permeability.


Arrhythmia: Acidosis and electrolyte disturbances lead to cardiac arrhythmia through altering membrane permeability of cardiac myocytes. 

Bleeding: Acidosis lead to thrombocytopenia and platelet dysfunction.

Word to the wise: Aspirin as a means to suicide is often accompanied by a coingestion of one or more medications. Have a low threshold to check levels/treat for other common overdoses.


Workup:

ASA, Acetaminophen, and levels of any other suspected measureable coingestant

BGM, CBC, BMP, repeated blood gas, mag, phos, UA, utox, coags, LFTs

CT head, EKG, CXR, KUB

Treatment:

These patient are potentially SICK. As always, start with you ABCs.

Airway and Breathing: These patients are tachypneic and may go on to develop respiratory distress when they can no longer compensate for their metabolic acidosis. However, for similar reasons to your DKA patients, avoid intubating if possible. It will be difficult to match the patient's respiratory drive, and the short period of apnea occurring when intubating may spell disaster for your patient.

Circulation: These patients are usually volume down from insensible losses and from vomiting. Help them out with some IVF. Be wary if there are signs of cerebral edema pulmonary edema.

Consider activated charcoal and whole bowel irrigation for decontamination.

Administer glucose. There is a real risk of neuroglycopenia, even if plasma levels are normal.

Alkalinize that urine: Providing sodium bicarb helps alkalinize the urine, facilitating renal clearance and also helps with decrease in CNS/plasma levels of salicylic acid. Alkalinization (increasing pH) increases conversion of salicylic acid to its base form.

Dosing is 1-2meq per kg bolus followed by infusion of 100 to 150meq in 1L sterile water with 5% dextrose.


Correct electrolyte abnormalities.

DIALYSIS: Indications are as follows:

AMS or cerebral edema, pulmonary edema, AKI/chronic kidney disease as this will impair salicylate clearance, salicylate level >90, pH <7, or if patient continues to get worse despite care.

Keep your nephro, tox, and ICU friends handy.

Special notes:

AVOID ACETAZOLAMIDE: though it may make sense to try to alkalinize urine via acetazolaminde, it does it at the cost of reducing bicarb reabsorption.

Chronic Salicylate poisoning: Occurs in patients who routinely take salicylates, and sometimes to the point of excess. More common in young children and elderly patients. Symptoms may be all of the above, but the levels of salicylate may be normal or only mildly elevated. Have a lower threshold for dialysis.

Sources:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341117/

https://wikem.org/wiki/Salicylate_toxicity

https://www.uptodate.com/contents/salicylate-aspirin-poisoning-in-adults

https://www.ncbi.nlm.nih.gov/books/NBK499879/

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The Fish Diseases

Hey all,

Scombroid. Ciguatera. Tetrodotoxin. Histamine poisoning.

Tired of getting these questions wrong on Rosh Review? Didn't realize that scombroid and histamine poisoning are the same thing?

Then this POTD is for you. Let's break down this topic together.

Scombroid: Think of histamine, and you'll get most questions correct regarding scombroid poisoning.

Background: Accounts for 40% of seafood borne illness in the US and Europe, most common states in Hawaii, California, Florida. Occur in outbreaks where everyone is eating the same batch of fish.

Symptoms: Flushing of face and neck, urticaria/pruritic erythematous rash, palpitations, dizziness, perioral burning and itching, edema, diarrhea, headache. Length of symptoms: 1-12 hours. Involves other members of family/friends who all ate the same food. Patients note that the fish has a "peppery" taste.

Rarely, upper airway edema, hypotension, or bronchospasm. 

Delicious Jerks Responsible: Typically fish of the Scombridae families, including tuna, mackeral, bonito, skip jack. Also happens with mahi mahi, swordfish, marlin, herring, sardine, anchovies, salmon, tilapia, and trout. Also swiss cheese for some reason (more on that later).

Pathophysiology: Caused by consuming fish which have not been properly refrigerated after being caught. Poor refrigeration leads to bacterial overgrowth in the fish capable of decarboxylating histidine into histamine. Histamine builds up in the fish over time, and post ingestion gives the histaminergic symptoms described above. Foods with histamine concentrations exceeding 50mg/100g of food are considered to be hazardous. Accumulation of histamine oftentimes happens before the fish becomes "spoiled" and thus is approved for consumption. Scombroid is associated with swiss cheese because it is thought the raw milk used in the production of the cheese can be contaminated with the same bacteria able to produce histamine from histidine.

Histamine is NOT destroyed when cooking the fish.

Treatment: Antihistamines- H1 and H2 Antihistamines

Treatment is focused on combating the excess histamine-

H1: Diphenhydramine

H2 for moderate to severe symptoms: famotidine/cimetidine

For patients presenting with enough histamine to appear as if they are in anaphylaxis, treat them as your would any anaphylaxis patient. 

Who is at risk for anaphylaxis like reaction? Patients taking something that inhibit histamine metabolism. This includes patients on isoniazid and MAO inhibitors.

Contact local public health to report scombroid poisoning.

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Ciguatera: Why do my teeth hurt? Why is my ice cream so HOT? The one with all the weird neuro-symptoms

Background:

Common on coastal regions; accounts for 20% of fish related foodborne illness in the US.

Fish containing ciguatera toxin appear normal. They do not taste or smell different than their non-ciguatera containing counterparts.

Symptoms: Vomiting, diarrhea, abdominal pain;

paresthesias, painful teeth, reversal of hot and cold sensation, perioral paresthesias, painful urination, cerebellar dysfunction including ataxia and vertigo, ;

rarely cardiorespiratory symptoms of bradycardia, heart block, hypotension, shortness of breath, respiratory distress.

Patients in multiple case studies report relapsing of symptoms. Though symptoms usually resolve in days to weeks, some report relapsing symptoms months and years down the line. 

Delicious Jerks Responsible: The reefers (moray eel, amberjack, grouper, snapper, parrot fish, sea bass, and ooh, barracuda).

Pathophysiology: Fish eat dinoflagellates of the Gambierdiscus family that grow on coral reefs. These dinoflagellates produce ciguatera toxin that accumulates in the fish. The fish are not affected by the ciguatera. The toxin is also heat stable, meaning it will not be destroyed during cooking.

The toxin works by opening voltage-dependent sodium channels on cell membranes, triggering cell depolarization.

Treatment: Symptomatic treatment.

Start at your ABCs as always, as these patients rarely, though sometimes, require airway maintenance. Atropine if needed for bradycardia, pacing. 

Antiemetics, IV hydration.

Sometimes recommended to use mannitol if neurological symptoms are present, though in an RCT of 50 patients by Schnorf et al, mannitol shown to have no benefit over normal saline in treating symptoms.

Gabapentin for neuropathic pain.

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Tetrodotoxin: The dangerous one; the one that can kill you

Background: Also known as pufferfish poisoning. Question stems usually involve someone eating fugu at a sushi restaurant.

Symptoms: Occur shortly after ingestion: parasthesia, headache, vomiting, diarrhea, abdominal pain

dysarthria, dysphagia, ascending paralysis, respiratory failure, and death.

Delicious Jerks Responsible: Pufferfish, angelfish, blue ringed octopus.

Pathophysiology: Produced by an endosymbiotic bacteria, tetrodotoxin is a neurotoxin that binds sodium channels, preventing sodium influx and preventing depolarization. Can cause paralysis; affects skeletal muscle interfering with respiration, causing respiratory failure, and with vascular smooth muscle, causing hypotension.

Treatment: Supportive care. ABCs, and if progressing to respiratory failure: intubation.

IVF

Can consider GI decontamination with stomach lavage and WBI if presenting to ED soon enough.

Some evidence suggests using anticholinesterases like neostigmine, though the evidence is weak and not shown to be effective in all patients.

Sources:

https://pubmed.ncbi.nlm.nih.gov/2689658/

https://wikem.org/wiki/Scombroid

https://pubmed.ncbi.nlm.nih.gov/11914401/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626696/

https://pubmed.ncbi.nlm.nih.gov/25410493/




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