Contributors: Travis Barlock MD, Ian Gillman PA, Jacob Altholz MD, Jeffrey Olson MS4

In this episode, EM attending Travis Barlock and medical student Jeffrey Olson listen in to the two remaining cases presented from EMM's recent event, Tox Talk 2025.

Talk 1- Methemoglobinemia- Ian Gillman

• Cyanosis + chocolate-colored blood + normal PaO₂ + pulse ox stuck at ~85% = Methemoglobinemia → Treat with methylene blue

• The medications that can cause it can be remembered with…

• Watch out with methylene blue as it can cause serotonin syndrome

• While treating with methylene blue the pulse ox can drop dramatically but this is not a real drop in oxygenation but rather an effect of how the methylene blue affects the sensor

• BADNAPS: causes of methemoglobinemia

• • Benzocaine

  • Aniline Dyes

  • Dapsone

  • Nitrites/Nitrates (Found in meds, preservatives, and well water)

  • Antimalarials

  • Pyridium

  • Sulfonamides
    

Talk 2- Intratecal TXA and Hierarchy of Controls for Error Avoidance - Jacob Altholz

• Hierarchy of Controls in terms of error prevention includes all of the layers of protection which can be categorized as elimination, substitution, engineering controls, administration controls, and PPE

References

• Centers for Disease Control and Prevention. (2022, April 28). Hierarchy of controls. National Institute for Occupational Safety and Health. https://www.cdc.gov/niosh/learning/safetyculturehc/module-3/2.html

• Pushparajah Mak RS, Liebelt EL. Methylene Blue: An Antidote for Methemoglobinemia and Beyond. Pediatr Emerg Care. 2021 Sep 1;37(9):474-477. doi: 10.1097/PEC.0000000000002526. PMID: 34463662.

Produced by Jeffrey Olson, MS4

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Contributor: Alec Coston, MD

Educational Pearls:

• BiPAP is often effective in severe asthma, but many patients struggle with mask tolerance due to intense air hunger–driven anxiety, often compounded by hypoxia.

• Benzodiazepines are commonly used for anxiety, but they can depress respiratory drive, making clinical improvement difficult to interpret (a lower RR may reflect sedation rather than true physiologic improvement).

• Low-dose fentanyl is a useful alternative when patients cannot tolerate BiPAP despite coaching.

• • Opioids blunt the perception of dyspnea and are well established for treating air hunger.

  • When carefully titrated, fentanyl provides anxiolysis without significant respiratory suppression.

  • It is rapidly titratable (e.g., 25 mcg IV every 5 minutes).

• Evidence primarily comes from palliative and oncology literature, but growing clinical experience supports its use in severe asthma to improve BiPAP tolerance.

• Failure of fentanyl should prompt escalation to ketamine, often signaling impending need for intubation.

References

1. Pang GS, Qu LM, Tan YY, Yee AC. Intravenous Fentanyl for Dyspnea at the End of Life: Lessons for Future Research in Dyspnea. Am J Hosp Palliat Care. 2016 Apr;33(3):222-7. doi: 10.1177/1049909114559769. Epub 2014 Nov 25. PMID: 25425740.

Summarized and edited by Meg Joyce, MS2

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Contributor: Aaron Lessen, MD

Educational Pearls

BRASH Syndrome:

• Bradycardia

• Renal Failure

• AV Nodal Blockade

• Shock

• Hyperkalemia

Clinical Features:

• Profound bradycardia and shock in patients on AV nodal blockers:

• • Commonly, Beta Blockers or Calcium Channel Blockers

Etiology:

• Caused by an inciting kidney injury:

• • Common triggers include precipitating illness, dehydration, or medications

  • Results in hyperkalemia

• The enhanced effect of the combination of AV nodal blockade and hyperkalemia leads to a more profound presentation of shock.

Treatment:

• IV Fluids, unless volume overloaded

• Epinephrine for bradycardia

• Lasix for volume overload, only if the patient is still making urine

• Low threshold to dialyze for hyperkalemia

• Focus on treating early and more aggressively.

References:

Farkas JD, Long B, Koyfman A, Menson K. BRASH Syndrome: Bradycardia, Renal Failure, AV Blockade, Shock, and Hyperkalemia. J Emerg Med. 2020 Aug;59(2):216-223. doi: 10.1016/j.jemermed.2020.05.001. Epub 2020 Jun 18. PMID: 32565167.

Summarized by Ashley Lyons OMS3

Editting by Ashley Lyons OMS3 and Jeffrey Olson MS4

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Contributor: Taylor Lynch, MD

Educational Pearls:

• Tramadol is a Schedule IV opioid analgesic used for moderate pain and is often perceived as safer than other opioids due to lower abuse potential.

• It is a prodrug with weak direct μ-opioid receptor activity.

• The parent compound also inhibits serotonin and norepinephrine reuptake, giving it SSRI/SNRI-like properties.

• Tramadol is metabolized by CYP2D6 into O-desmethyltramadol (ODT), which has significantly stronger μ-opioid receptor agonism than the parent drug.

• Ultrarapid CYP2D6 metabolizers (more common in Middle Eastern and North African populations) rapidly convert tramadol to ODT, increasing the risk of opioid toxicity.

• Poor CYP2D6 metabolizers generate little ODT and may experience primarily serotonergic effects, increasing the risk of serotonin syndrome, especially when combined with SSRIs or SNRIs.

• CYP2D6 inhibitors (e.g., bupropion, paroxetine, terbinafine, celecoxib) can block tramadol's conversion to ODT, potentially precipitating opioid withdrawal or increasing serotonergic toxicity.

• Tramadol is also associated with an increased risk of first-time seizures, even at therapeutic doses.

• Tramadol's effects are highly unpredictable, varying from minimal analgesia to exaggerated opioid effects depending on metabolism.

• Drug–drug interactions can lead to serotonin syndrome or opioid withdrawal.

• Despite its Schedule IV classification and reputation for safety, alternative analgesics may be preferable in many patients.

References

1. DailyMed - TRAMADOL HYDROCHLORIDE tablet, coated. Accessed January 10, 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=61fb5ba7-6896-4ee4-83de-caee69b06a8e#ID57

2. Dean L, Kane M. Tramadol Therapy and CYP2D6 Genotype. In: Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, eds. Medical Genetics Summaries. National Center for Biotechnology Information (US); 2012. Accessed January 10, 2026. http://www.ncbi.nlm.nih.gov/books/NBK315950/

3. Aly SM, Tartar O, Sabaouni N, Hennart B, Gaulier JM, Allorge D. Tramadol-Related Deaths: Genetic Analysis in Relation to Metabolic Ratios. J Anal Toxicol. 2022;46(7):791-796. doi:10.1093/jat/bkab096

Summarized and edited by Dan Orbidan OMS2

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Contributor: Aaron Lessen, MD

Educational Pearls:

The Case

• 24F brought in for anxiety. Patient is tearful, not talking, and potentially hyperventilating. History from boyfriend is that she suddenly stopped talking and started crying and it was hard to understand what she was saying. On exam, patient appears anxious and has a gaze preference for the right side and is still having difficulty speaking.

• Decision is made to stroke alert patient.

• CT shows early MCA stroke and M2 occlusion.

• Patient is treated by IR with mechanical thrombectomy.

What are the risk factors for strokes in young people (<50 y.o.)?

• Traditional risk factors still matter

• • Hypertension

  • • Most important modifiable risk factor, present in 30-50% of young stroke patients

  • Diabetes

  • • Especially insulin dependent type 1

  • HLD

  • Smoking

• Substance use

• • Cocaine

  • Meth

  • Alcohol, especially binge drinking

  • IV drug use

• Structural heart disease

• • PFO

  • Valvular heart disease like rheumatic disease

• Hypercoagulable states

• • Factor V Leiden

  • Protein C or S deficiency

  • Antithrombin III deficiency

• Vertebral dissections

• • Recent trauma

References

• Aigner A, Grittner U, Rolfs A, Norrving B, Siegerink B, Busch MA. Contribution of Established Stroke Risk Factors to the Burden of Stroke in Young Adults. Stroke. 2017 Jul;48(7):1744-1751. doi: 10.1161/STROKEAHA.117.016599. Epub 2017 Jun 15. PMID: 28619986.

• Ekker MS, Boot EM, Singhal AB, Tan KS, Debette S, Tuladhar AM, de Leeuw FE. Epidemiology, aetiology, and management of ischaemic stroke in young adults. Lancet Neurol. 2018 Sep;17(9):790-801. doi: 10.1016/S1474-4422(18)30233-3. PMID: 30129475.

• Khan M, Wasay M, O'Donnell MJ, Iqbal R, Langhorne P, Rosengren A, Damasceno A, Oguz A, Lanas F, Pogosova N, Alhussain F, Oveisgharan S, Czlonkowska A, Ryglewicz D, Yusuf S. Risk Factors for Stroke in the Young (18-45 Years): A Case-Control Analysis of INTERSTROKE Data from 32 Countries. Neuroepidemiology. 2023;57(5):275-283. doi: 10.1159/000530675. Epub 2023 May 17. PMID: 37231971.

Summarized and edited by Jeffrey Olson MS4

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Contributor: Aaron Lessen, MD

Educational Pearls:

A 2025 multistate outbreak of infant botulism has been linked to ByHeart infant formula

• As of December 10-17th, there have been at least 51 infants with suspected or confirmed botulism who were exposed to this formula across 19 states

• All reported cases resulted in hospitalization but no deaths reported to date

Infant botulism

• Occurs when C. botulinum spores germinate in the infant's intestine, producing toxin

• • Spores are classically found in honey but can also be in dirt or contaminated in infant formula

  • Infants are particularly susceptible because their body can't neutralize the spores

• Symptoms may include initial constipation, poor feeding, weak cry, floppy movements, loss of head control, difficulty swallowing, generalized weakness, and respiratory compromise if progressive

• Can be treated with antitoxin

• Maintain a high index of suspicion for infant botulism in infants fed the recalled formula presenting with neuromuscular symptoms.

References

1. Human Foods Program. Outbreak Investigation of Infant Botulism: Infant Formula. U.S. Food and Drug Administration. Published 2025. https://www.fda.gov/food/outbreaks-foodborne-illness/outbreak-investigation-infant-botulism-infant-formula-november-2025

Summarized by Meg Joyce, MS2 | Edited by Meg Joyce & Jeffrey Olson, MS4

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Carepoint Journal Club is a quarterly series with discussions about a medical topic, brought to you by Carepoint's Emergency Physicians.

Contributor: Meghan Hurley, MD

Educational Pearls:

OTC Medications

• Dextromethorphan (DM)
  • Most common OTC cough suppressant
  • Minimal efficacy: Little evidence that it shortens the duration or severity of cough.
  • Potential side effects:
    • At recommended doses: Mild dizziness, drowsiness, GI symptoms
    • Higher doses: Decreased consciousness, dissociative effects
• Guaifenesin
  • Found in Mucinex and other severe cough/cold products
  • Thins secretions and loosens mucus in airways
  • No more effective than increasing oral fluid intake

Prescription Medications

• Codeine-containing products
  • Suppresses cough center in the medulla
  • Metabolized via CYP2D6 with significant differences in metabolism between individuals:
    • Low metabolizers experience little effect, high metabolizers have risk of increased toxicity
• Benzonatate (Tessalon Perles)
  • Topical anesthetic; inhibits pulmonary stretch receptors and reduces cough reflex.
  • Efficacy is mixed; no clear benefit over placebo.
  • Precautions: do not bite or chew; dangerous in children <2 years if chewed (risk of seizures, tremors, cardiac arrest)
• Inhaled/Nebulized Lidocaine
  • Used for chronic or refractory cough (patients with lung cancer, COPD)
  • Side effects: bitter taste, perioral numbness
  • Precautions: Keep patient NPO with continuous monitoring due to aspiration risk
  • Improvement usually within a few hours; duration of effect unclear

Children Over 1 Year

• Many children's OTC cough products are naturopathic and not FDA-approved.
• Other remedies:
  • Honey (only age >1 year; risk of botulism in infants), Vicks VapoRub on chest, thyme/honey/lemon tea mixture

Prolonged Cough

• Cough >2 weeks or post-tussive emesis → consider pertussis.
• Tdap immunity wanes over time; risk increases if Tdap is not received routinely.
• If pertussis is suspected, consider trial of a macrolide antibiotic.

References

1. Chong CF, Chen CC, Ma HP, Wu YC, Chen YC, Wang TL. Comparison of lidocaine and bronchodilator inhalation treatments for cough suppression in patients with chronic obstructive pulmonary disease. Emerg Med J. 2005 Jun;22(6):429-32. doi: 10.1136/emj.2004.015719. PMID: 15911951; PMCID: PMC1726806.
2. Havers FP, Moro PL, Hunter P, Hariri S, Bernstein H. Use of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccines: Updated Recommendations of the
3. Lam SHF, Homme J, Avarello J, Heins A, Pauze D, Mace S, Dietrich A, Stoner M, Chumpitazi CE, Saidinejad M. Use of antitussive medications in acute cough in young children. J Am Coll Emerg Physicians Open. 2021 Jun 18;2(3):e12467. doi: 10.1002/emp2.12467. PMID: 34179887; PMCID: PMC8212563.
4. Malesker MA, Callahan-Lyon P, Ireland B, Irwin RS; CHEST Expert Cough Panel. Pharmacologic and Nonpharmacologic Treatment for Acute Cough Associated With the Common Cold: CHEST Expert Panel Report. Chest. 2017 Nov;152(5):1021-1037. doi: 10.1016/j.chest.2017.08.009. Epub 2017 Aug 22. PMID: 28837801; PMCID: PMC6026258.
5. Singu B, Verbeeck RK. Should Codeine Still be Considered a WHO Essential Medicine? J Pharm Pharm Sci. 2021;24:329-335. doi: 10.18433/jpps31639. PMID: 34192509.
   U.S. National Library of Medicine. Benzonatate capsule. DailyMed. Updated July 31, 2023. Accessed December 13, 2025. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c21afd18-3b04-4f15-874b-25e0c768f801

Summarized by Ashley Lyons, OMS3 | Edited by Ashley Lyons and Jorge Chalit, OMS4

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