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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