Emergency Medical Minute

Contributor: Aaron Lessen, MD
Educational Pearls:
What is anaphylaxis and what are its treatments? 
Anaphylaxis is a broad term for potentially life threatening allergic reactions that can progress to cardiovascular collapse (anaphylactic shock). 
It is triggered by IgE and antigen cross-linking on mast cells to induce degranulation and the release of histamines, which can cause diffuse vasodilation and respiratory involvement with end-organ hypoperfusion.
First line treatment is the immediate administration of epinephrine at 0.01 mg/kg (max dose for pediatrics is 0.3 mg and for adults is 0.5 mg) as well as removal of the offending agent causing the reaction.
Additional pharmacologic treatments such as anti-histamines and steroids should be considered but not used instead of epinephrine when anaphylactic shock is evident as the sole therapy.
What is biphasic anaphylaxis and what is its occurrence?
Biphasic anaphylaxis is the return of anaphylactic symptoms after the initial anaphylactic event. Previous studies have reported an incidence ranging from 1-20% of patients having an initial anaphylactic reaction having biphasic anaphylaxis, at a range of time from 1-72 hours.
The mechanism of biphasic anaphylaxis is not completely known, but can be contributed to by initial interventions wearing off (and why patients will be monitored for 2-4 hours after initial symptoms and treatment), or delayed immune mediators beginning to take effect.
Recent studies show that the rate of biphasic anaphylaxis may be closer to 16% occurrence with a median time of occurrence being around 10 hours.
What is the key take away and patient education on biphasic anaphylaxis?
After patients have been observed for the initial 2-4 hours in the emergency room, they are generally safe to go home.
Patients should be informed of the need to carry an Epi-Pen for similar anaphylactic reactions, and informed that there is a chance within the next day (10-20 hours) that they may have the symptoms occur once again.
The biphasic reaction may be more mild, and patients should be educated on how to treat it and to seek immediate emergency care if the symptoms do not improve.
References
Golden DBK, Wang J, Waserman S, et al. Anaphylaxis: A 2023 practice parameter update. Annals of Allergy, Asthma & Immunology. 2024;132(2):124-176. doi:10.1016/j.anai.2023.09.015
Rubin S, Drowos J, Hennekens CH. Anaphylaxis: Guidelines From the Joint Task Force on Allergy-Immunology Practice Parameters. afp. 2024;110(5):544-546.
Weller KN, Hsieh FH. Anaphylaxis: Highlights from the practice parameter update. CCJM. 2022;89(2):106-111. doi:10.3949/ccjm.89a.21076
Gupta RS, Sehgal S, Brown DA, et al. Characterizing Biphasic Food-Related Allergic Reactions Through a US Food Allergy Patient Registry. The Journal of Allergy and Clinical Immunology: In Practice. 2021;9(10):3717-3727. doi:10.1016/j.jaip.2021.05.009
Summarized by Dan Orbidan OMS2 | Edited by Dan Orbidan & Jorge Chalit OMS4
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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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