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Don’t let the beat drop: management of refractory bradycardia in suspected xylazine ingestion

By Holly Everett


 

CASE


Presentation:

BM is a 44-year-old female with a past medical history of IVDU (cocaine, heroin, xylazine) complicated by recurrent abscesses, alcohol use disorder complicated by withdrawal seizures, and bipolar disorder who initially presented to the ED for increasing pain and swelling of her bilateral upper extremity wounds.   

 

At triage, vital signs were HR 80, BP 134/87, RR 16, SpO2 98% on room air, and T36.2C. After several hours, the patient was roomed, an IV was placed and she received doses of her home gabapentin and quetiapine as well as IV antibiotics for her infected wounds.

 

An hour later she was noted to be somnolent and have slurred speech, with blood pressure 70/44 and HR 38, which increased to 55 with ambulation. She denied ingestion or injection of any substance and refused an EKG or repeat vitals, attributing her sleepiness to her home meds.  

 

Over the next 30 minutes she became increasingly obtunded and only intermittently responsive to noxious stimuli. Her pupils were pinpoint, but she maintained a respiratory rate of 11-12 breaths per minute with SpO2 100% on room air. Her belongings were searched and revealed several capsules, some empty and others with an unknown white powder. An EKG at that time revealed marked sinus bradycardia with T wave inversions in the anterolateral leads.

Initial EKG: Sinus bradycardia at 37 bpm (12:30 am)

Due to her bradycardia and hypotension, she was started on IV fluids and received 1 mg IV x2 atropine pushes with no improvement in her heart rate or blood pressure. Naloxone was considered but held in the setting of her adequate respiratory drive and oxygen saturation. Norepinephrine was started at 0.05 mcg/kg/min and her blood pressure quickly rose to 175/103. Her heart rate, however, remained in the mid 40s. Norepinephrine was titrated to a normotensive blood pressure with MAP goal of >65. She was transferred to the ICU for further management of her unstable bradycardia.

 

Given the patient’s known history of both opioid and xylazine use and the unknown powder found on her person, it was presumed that she ingested either or both drugs while in the department. Given her respiratory rate and oxygen saturation were reassuring and her presentation was dominated by marked bradycardia, xylazine ingestion with or without concomitant opioid ingestion was thought to be most likely.


Clinical question: How should the patient with unstable vitals due to suspected xylazine exposure be managed in the ED?


Background: Xylazine (“tranq”) is a veterinary sedative and analgesic that has become an increasingly common adulterant in the unregulated opioid supply in the US over the past 10 years (4, 8, 9, 11). More recently, there are increasing reports of intentional use of xylazine as a solo agent (5). Xylazine acts as an alpha-2 agonist, causing sedation, vasodilation, muscle relaxation, bradycardia, hypotension, chronic skin ulcers, and can have synergistic effects with opioids (5, 7). Unstable bradyarrhythmia is defined as HR <50 with hypotension and signs of poor perfusion, including altered mental status, ischemic chest pain, or dyspnea from pulmonary congestion (1, 2). 


Summary of Evidence:


  • The mainstay of treatment is supportive care with IV fluids, atropine, and vasopressors to promote hemodynamic stability. Transcutaneous or transvenous pacing should be used in patient unresponsive to these measures (1, 2, 3, 4, 10)

  • In a case series, naloxone was not effective for reversing the effects of xylazine. Since given patients are often exposed in conjunction with fentanyl or other opioids, naloxone should be given for signs and symptoms of CNS depression suspected to be driven by opioids (3, 4, 7, 9, 10)

  • Withdrawal from xylazine can produce a syndrome to opioid withdrawal with symptoms including restlessness, dysphoria and rigors. Withdrawal can be managed with the structurally similar alpha-2 agonist clonidine (5)

  • Specific alpha-2 antagonists, including atipamezole and yohimbine, have been used to reverse alpha-2 agonists in veterinary medicine. These drugs are not approved for use in humans but preliminary studies suggest 100 mg atipamezole IM is safe for humans (4, 6).

  • Other causes of unstable bradycardia should be considered and treated per the American Heart Association Adult Bradycardia Algorithm, including hypo/hyperkalemia, hypomagnesemia, hypo/hypercalcemia, hypoglycemia, sepsis, acute coronary syndrome, beta blocker or calcium channel blocker overdose and intrinsic AV node dysfunction (1, 2)


RECOMMENDATIONS

In patients with unstable vital signs in the setting of suspected xylazine ingestion, management should include:

  • Supportive care with IV fluids and oxygen supplementation for SpO2 <92% (1, 2, 10)

  • Consider naloxone for RR <8 and/or concern for mixed ingestion with opioids leading to respiratory depression (3, 4, 9, 10)

  • 1 mg IV atropine up to 3 times for unstable bradycardia, though unlikely to be effective in the setting of xylazine ingestion (1, 2, 3, 4)

  • Vasopressors for maintaining MAP >65 to ensure adequate tissue perfusion (1, 2, 3, 4)

  • Consider transcutaneous or transvenous pacing for patients not responding to atropine and vasopressors (1, 2)

  • Monitoring for signs and symptoms of xylazine withdrawal which can be treated with clonidine (5)

  • In the future, alpha-2 antagonists (such as atipamezole) may be appropriate as a specific reversal agent if approved by the FDA for this indication (4, 6)


REFERENCES


  1. Adult bradycardia algorithm. American Heart Association. (2020). https://cpr.heart.org/-/media/cpr-files/cpr-guidelines-files/algorithms/algorithmacls_bradycardia_200612.pdf 

  2. Alblaihed L, Tewelde S. Bradydysrhythmias. In: Johnson W, Nordt S, Mattu A and Swadron S, eds. CorePendium. Burbank, CA: CorePendium, LLC. https://www.emrap.org/corependium/chapter/recSdHpVvdD2oAbVe/Bradydysrhythmias. Updated July 13, 2021. Accessed June 14, 2024.

  3. Choon LK, Khiruddin AI, Annuar WMWM, Shamsuddin SR. A case series of accidental xylazine intoxication in humans; Is there a role of naloxone as an antidote? Turk J Emerg Med. 2023 Jan 2;23(2):119-122. doi: 10.4103/tjem.tjem_198_22. PMID: 37169031; PMCID: PMC10166292.

  4. Edinoff AN, Sall S, Upshaw WC, Spillers NJ, Vincik LY, De Witt AS, Murnane KS, Kaye AM, Kaye AD. Xylazine: A Drug Adulterant of Clinical Concern. Curr Pain Headache Rep. 2024 May;28(5):417-426. doi: 10.1007/s11916-024-01211-z. Epub 2024 Mar 20. PMID: 38507135; PMCID: PMC11126434.

  5. Ehrman-Dupre, Rachel MD; Kaigh, Caroline MD; Salzman, Matt MD; Haroz, Rachel MD; Peterson, Lars-Kristofer MD; Schmidt, Ryan MD. Management of Xylazine Withdrawal in a Hospitalized Patient: A Case Report. Journal of Addiction Medicine 16(5):p 595-598, 9/10 2022. DOI: 10.1097/ADM.0000000000000955

  6. M Greenberg, A Rama, J R Zuba. A Protocol for the Emergency Treatment of Alpha-2 Agonist Overdose using Atipamezole, a Selective Alpha-2 Antagonist. The Internet Journal of Toxicology. 2017 Volume 12 Number 1.

  7. Hochheimer M, Strickland JC, Rabinowitz JA, Ellis JD, Dunn KE, Huhn AS. Knowledge, Preference, and Adverse Effects of Xylazine Among Adults in Substance Use Treatment. JAMA Netw Open. 2024;7(2):e240572. doi:10.1001/jamanetworkopen.2024.0572

  8. Kazandra Ruiz-Colón, Carlos Chavez-Arias, José Eric Díaz-Alcalá, María A. Martínez, Xylazine intoxication in humans and its importance as an emerging adulterant in abused drugs: A comprehensive review of the literature, Forensic Science International, Volume 240, 2014, Pages 1-8, ISSN 0379-0738,https://doi.org/10.1016/j.forsciint.2014.03.015.

  9. Love JS, Levine M, Aldy K, Brent J, Krotulski AJ, Logan BK, Vargas-Torres C, Walton SE, Amaducci A, Calello D, Hendrickson R, Hughes A, Kurt A, Judge B, Pizon A, Schwarz E, Shulman J, Wiegan T, Wax P, Manini AF. Opioid overdoses involving xylazine in emergency department patients: a multicenter study. Clin Toxicol (Phila). 2023 Mar;61(3):173-180. doi: 10.1080/15563650.2022.2159427. PMID: 37014353; PMCID: PMC10074294.

  10. Thornton S, Rianprakaisang T. Opioid Toxicity and Poisoning. In: Johnson W, Nordt S, Mattu A and Swadron S, eds. CorePendium. Burbank, CA: CorePendium, LLC. https://www.emrap.org/corependium/chapter/reczO71T3dCQWXjNF/Opioid-Toxicity-and-Poisoning. Updated February 6, 2024. Accessed June 14, 2024.

  11. Zhu DT, Friedman J, Bourgois P, Montero F, Tamang S. The emerging fentanyl-xylazine syndemic in the USA: challenges and future directions. Lancet. 2023 Nov 25;402(10416):1949-1952. doi: 10.1016/S0140-6736(23)01686-0. Epub 2023 Aug 24. PMID: 37634523; PMCID: PMC10842070.

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