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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POTD: Droperidol

CODE WHITE AMBULANCE TRIAGE. The patient is at imminent risk of harming themselves and your staff. Verbal deescalation was attempted but has failed. Everyone is looking to you for your OK for chemical sedation. You dig your heels in and are about to mutter the first thing that comes to mind: "5 of haldol and 2 of ativan."

But hold up. Because this POTD is about droperidol.

Background: Droperidol is a dopamine antagonist, and is a first generation antipsychotic. It used to be a favorite of ED doctors to treat agitation in the ED and was used for more than 30 years for acute agitation. It was removed from market 20 years ago because of a black box warning due to QTC prolongation and risk of torsades/sudden cardiac death. This was based off a study looking at 273 case reports over a 4 year period. In the deaths reported, the doses used were 25mg-250mg per dose, doses MUCH higher than what we would typically give in the ED for agitation. Adverse cardiac events or death occurred in 10 patients who received a dose less than 2.5mg. From this study, the FDA placed a black box warning on droperidol. Upon further review of these cases by multiple authors, all of these cases had confounding factors that could have accounted for the adverse event. Overwhelming evidence after the FDA black box warning was issued has showed that droperidol is both safe and effective, especially when used at typical dosing for agitation.

Why Droperidol: Comparatively to other sedatives, namely haloperidol, droperidol is more potent, is faster onset, and has a shorter duration. According to Cressman et. al who examined absorption, metabolism, and excretion of droperidol, absorption via IM is near equivalent to IV administration. Onset of action is 3-10 minutes, and peaks at 30 minutes. Duration of effect is 2-4 hours, and effects may last up to 12 hours. Undergoes hepatic metabolism.

In the DORM study, 10mg droperidol IM was compared to 10mg IM Midazolam. Droperidol, compared to Midazolam, reduced the duration of violent behavior (20 min vs 24 min), required less additional sedation (33% vs 62%), and has less respiratory distress among intoxicated agitated patients.

If single agent droperidol is not enough, it was found in a study authored by Taylor et al that combination 5+5 droperidol and midazolam was more effective at sedation than droperidol or olanzapine alone.

Uses: Typical dosing ranges between 5mg -10mg for agitation, and can be administered IM or IV.

In addition, it can be used to treat headaches, vertigo, nausea, and pain, usually at half the agitation dose.

Side effects: Sedation, extrapyramidal effects, hypotension, prolongation of QT interval. Obtain an EKG if possible before administration, but if not possible, can be obtained after if the patient is agitated. Be mindful of using droperidol in the setting of patients with known prolonged QT interval and patients at risk given their medication history (e.g. methadone).

Sources:

https://vimeo.com/180991859

https://pubmed.ncbi.nlm.nih.gov/4707581/

http://www.emdocs.net/droperidol-use-in-the-emergency-department-whats-old-is-new-again/

http://www.emdocs.net/the-art-of-the-ed-takedown/

https://www.tamingthesru.com/blog/2019/4/20/the-return-of-droperidol

https://pubmed.ncbi.nlm.nih.gov/12707137/

https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=147e033d-d997-4ef6-8bb5-a9ba372590b2&type=display

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Prescription Drug Prices

Prescription drug prices are highly variable and out of control in the United States. Often times, we will find ourselves telling a patient they should see their PMD and take all their medications, or we’ll be prescribing a medication for a newly diagnosed chronic condition. Whether or not our patients follow our advice is dependent on dozens of socioeconomic factors, but one of those is the price of prescription medications.

 

I was curious about the prices our patients face for some of the common medications we often send them home with or expect them sometimes for the rest of their lives. Of course, insurance is a whole other issue, but these are just some of the upfront costs that particularly our most vulnerable and socioeconomically destitute patients may face:

 

*prices listed are the lowest price at a pharmacy within 5 miles of the hospital

Albuterol HFA inhaler, $22.14

Amlodipine 5mg, 30 tabs, $5.20

Amoxicillin 400mg/5mL, 100mL bottle, $9.45

Atorvastatin 10, 30 tabs, $6.27

Azithromycin 250, Z pack with 6 tablets, $9.49

Cephalexin 500mg, 30 tabs, $10.86

Ciprofloxacin 500mg, 20 tabs, $17.42

Clopidogrel 75mg, 30 tabs, $6.60

Doxycycline 100mg, 30 tabs, $19.46

Divalproex 500mg, 30 tabs, $14.41

Furosemide 40mg, 30 tabs, $5.10

Gabapentin 300mg, 30 tabs, $6.07

HCTZ 12.5, 30 tabs, $5.58

Ibuprofen 400mg, 30 tabs, $6.65

Levothyroxine 50mcg, 30 tabs, $10.72

Lisinopril 20mg, 30 tabs, $4.99

Metformin 500mg 30 tabs, $4.99

Nitrofurantoin 100mg, 14 tabs, $18.64

Omeprazole 20mg, 30 tabs, $7.47

Prednisone 10mg, 21 tabs, $14.29

Tamsulosin 0.4mg, 30 tabs, $7.77

 

Drug prices are extremely hard to track down. For instance, the NYS DOH website for searching drug prices hasn’t updated their list of prices for our MMC Pharmacy since 2013.

Our wonderful ED pharmacist Ankit Gohel also pointed out to me that you can look up the average wholesale price of any medication on uptodate in the ‘price’ section.

The Epocrates app will also list average retail prices.

Hope this can be some food for thought.

 

Source: www.communitycaresrx.com

https://apps.health.ny.gov/pdpw/SearchDrugs/Home.action

https://www.goodrx.com/

 

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