Emergency Medical Minute

Contributor: Alec Coston, MD
Educational Pearls:
Disclaimer: this has nothing to do with the ER but is too cool to not talk about.
Condition: Carbamoyl phosphate synthetase 1 (CPS1) deficiency

Rare inborn error of metabolism

Inability to properly break down ammonia

Leads to severe hyperammonemia and hepatic encephalopathy

Natural history:

Without treatment, typically fatal within the first few weeks of life

Even with current standard treatments, life expectancy is often limited to ~5–6 years

Breakthrough treatment:

A team of researchers at the Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania developed the CRISPR-based targeted gene therapy for this patient.

First-of-its-kind precision approach tailored to the patient's specific mutation

Key components of the therapy:

Whole-genome sequencing to identify the exact CPS1 mutation

Creation of a custom base-editing enzyme designed to correct that specific mutation

Design of a guide RNA to direct the base editor to the precise genomic location

Delivery method:

Lipid nanoparticles used to deliver the gene-editing machinery

Nanoparticles can be targeted to specific tissues

Why the liver works well:

CPS1 is primarily expressed in hepatocytes

The liver is relatively easy to target with lipid nanoparticles

Hepatocytes divide frequently, allowing edited genes to be passed on as cells replicate

Long-term impact:

Once edited, cells continue producing functional CPS1 enzyme

Potential for durable, possibly lifelong correction from a single treatment

References
https://www.nih.gov/news-events/news-releases/infant-rare-incurable-disease-first-successfully-receive-personalized-gene-therapy-treatment

Choi Y, Oh A, Lee Y, Kim GH, Choi JH, Yoo HW, Lee BH. Unfavorable clinical outcomes in patients with carbamoyl phosphate synthetase 1 deficiency. Clin Chim Acta. 2022 Feb 1;526:55-61. doi: 10.1016/j.cca.2021.11.029. Epub 2021 Dec 29. PMID: 34973183.

Bharti N, Modi U, Bhatia D, Solanki R. Engineering delivery platforms for CRISPR-Cas and their applications in healthcare, agriculture and beyond. Nanoscale Adv. 2026 Jan 5. doi: 10.1039/d5na00535c. Epub ahead of print. PMID: 41640466; PMCID: PMC12865601.

Summarized and edited by Jeffrey Olson MS4
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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
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:
What is tramadol and how does it work?
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.

What are the concerns with tramadol?
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.

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

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/

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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