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Colchicine Toxicity: A New Threat from COVID-19 Treatments

In the continued fight against COVID-19, a January 22, 2021 press release from the Montreal Heart Institute touted the potential of colchicine, citing results from the COLCORONA trial [1, 2]. We’ve learned to be especially skeptical of any study results reported only via press release before undergoing full peer-review and publication. Nevertheless, the authors claim a non-significant (p=0.08) relative risk reduction of 19% (absolute risk reduction 1.1%) in hospitalizations, mechanical ventilation, and death. Note that the pre-print of the study has still not been peer-reviewed [3]. This study comes on the heels of the much smaller GRECCO-19 study published in June 2020 [4].

Early in 2020, promising results on hydroxychloroquine for treatment of COVID-19 led to a large increase in its use in outpatients and inpatients. It is now known that there is virtually no role for hydroxychloroquine and that this spike in use led to serious toxicity both from therapeutic use and overdose [5, 6]. The same may be anticipated for colchicine. And, if there is a drug that toxicologists fear more than hydroxychloroquine in overdose, it’s colchicine.

5 things to know about colchicine toxicity

1. Colchicine inhibits microtubule formation and function, thereby inhibiting mitosis.

  • It also is a GABA-A antagonist.

2. Acute toxicity occurs in 3 phases.

  • 0-24 hours: Nausea, vomiting, diarrhea, salt and water depletion, and  leukocytosis
  • 1-7 days: Sudden cardiac death (24-48 hours), pancytopenia, acute kidney injury, sepsis, acute respiratory distress syndrome, rhabdomyolysis, and electrolyte imbalance
  • >7 days: Alopecia, myopathy, neuropathy, and myoneuropathy

3. Colchicine levels are not helpful.

  • They also aren’t readily available at most institutions.

4. Hemodialysis doesn’t remove the toxin.

  • Colchicine’s volume of distribution is large.
  • Extracorporeal treatment can be employed if kidney toxicity results from the poisoning.

5. There is no antidote.

  • Management is largely supportive with IV fluids, vasopressors, and colony-stimulating factors.
  • Experimental anti-colchicine Fab fragments are being studied [7].

This 2010 Clinical Toxicology review article provides further information and education on colchicine toxicity.

Want to learn more about EM Pharmacology?

Read other articles in the EM Pharm Pearls Series.

References:

  1. Montreal Heart Institute. Colchicine reduces the risk of COVID-19-related complications. GlobalNewswire website. January 22, 2021. Accessed January 26, 2021.
  2. Montretal Heart Institute. ColCorona. Accessed January 26, 2021.
  3. Tardif J-C, Bouabdallaoui N, L’Allier PL, et al. Efficacy of colchicine in non-hospitalized patients with covid-19. medRxiv. doi: 10.1101/2021.01.26.21250494. Epub 2021 Jan 27.
  4. Deftereos SG, Giannopoulos G, Vrachatis DA, et al. Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019: the grecco-19 randomized clinical trial. JAMA Netw Open.  2020;3(6):e2013136. doi: 10.1001/jamanetworkopen.2020.13136. PMID: 32579195.
  5. Mahan KM, Hayes BD, North CM, et al. Utility of hypertonic saline and diazepam in covid-19–related hydroxychloroquine toxicity. The Journal of Emergency Medicine. doi: 10.1016/j.jemermed.2020.10.048. Epub 2020 Oct 2020. PMID: 33353811.
  6. Chai PR, Ferro EG, Kirshenbaum JM, et al. Intentional hydroxychloroquine overdose treated with high-dose diazepam: an increasing concern in the covid-19 pandemic. J Med Toxicol. 2020;16(3):314-320. doi: 10.1007/s13181-020-00790-8. PMID: 32514696.
  7. Eddleston M, Fabresse N, Thompson A, et al. Anti-colchicine Fab fragments prevent lethal colchicine toxicity in a porcine model: a pharmacokinetic and clinical study. Clinical Toxicology. 2018;56(8):773-781. doi: 10.1080/15563650.2017.1422510. PMID: 29334816.

 

By |2021-01-29T10:38:07-08:00Jan 30, 2021|EM Pharmacy Pearls, Tox & Medications|
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2020 ACLS Guidelines on Medications for Toxicology-Related Conditions

ACLS 2020 toxicology

The 2020 ACLS guidelines provide recommendations on the medication-specific management recommendations for toxicology [1]. Although the name of the guidelines emphasize they are ‘Advanced,’ these are still relatively basic toxicology recommendations and largely apply to patients in cardiac arrest or refractory shock. There are also our 2020 ACLS guideline summaries on vasopressor and non-vasopressor medications used during cardiac arrest and arrhythmia management.

Benzodiazepines

  • Flumazenil if NOT recommended in undifferentiated coma (COR3, LOE B-R)

Cocaine

  • Benzodiazepines, alpha blockers, calcium channel blockers, nitroglycerin, and/or morphine can be beneficial for hypertension, tachycardia, agitation, or chest discomfort (COR 2a, LOE B-NR)
  • Pure beta-adrenergic blockers may be reasonable to avoid, although “contradictory evidence exists (COR 2b, LOE C-LD)

Local Anesthetics

  • IV lipid emulsion may be reasonable (COR 2b, LOE C-LD)

Sodium Channel Blockers (e.g. tricyclic antidepressants)

  • Sodium bicarbonate can be beneficial for cardiac arrest or life-threatening conduction delays, such as QRS >120 msec (COR 2a, LOE C-LD)
  • Extracorporeal membrane oxygenation (ECMO) may be considered for cardiac arrest or refractory shock (COR 2b, LOE C-LD)

Digoxin

  • Antidigoxin Fab should be administered in severe toxicity (COR 2b, LOE B-R)

Carbon Monoxide

  • Hyperbaric oxygen may be helpful in severe toxicity (COR 2b, LOE B-R)

Cyanide

  • Hydroxocobalamin can be beneficial, along with oxygen +/- sodium thiosulfate (COR 2a, LOE C-LD)

Atrioventricular Nodal Blockers

Intervention Beta-adrenergic blocker Calcium channel blocker Evidence (COR/LOE)
High-dose insulin Reasonable Reasonable 2a/C-LD
Glucagon IV Reasonable May be considered 2a/C-LD and 2b/C-LD
Calcium May be considered Reasonable 2b/C-LD and 2a/C-LD
ECMO Might be considered Might be considered 2b/C-LD

Table: Medications and interventions in the management of beta-adrenergic and calcium channel blocker toxicity (COR: class of recommendation, LOE: level of evidence, ECMO: extracorporeal membrane oxygenation)

Reference

Panchal AR, Bartos JA, Cabañas JG, et al; Adult Basic and Advanced Life Support Writing Group. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020 Oct 20;142(16_suppl_2):S366-S468. doi: 10.1161/CIR.0000000000000916. Epub 2020 Oct 21. PMID: 33081529.
By |2026-06-16T16:16:51-07:00Jan 23, 2021|Critical Care/ Resus, EM Pharmacy Pearls, Tox & Medications|
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2020 ACLS Guidelines on Medications for Management of Specific Arrhythmias

ACLS 2020 arrhythmias

The 2020 ACLS guidelines provide recommendations on the medication-specific management for arrhythmias including wide-complex tachycardia, regular narrow-complex tachycardia, atrial fibrillation/flutter, and bradycardia [1]. There are also our 2020 ACLS guideline summaries on vasopressor and non-vasopressor medications used during cardiac arrest and toxicology-related conditions.

Wide-complex tachycardia (WCT)

Wide-complex tachycardia Medication(s) Evidence
Hemodynamically stable Adenosine COR 2b, LOE B-NR
Amiodarone, procainamide, or sotalol COR 2b, LOE B-R
NOTE: Verapamil is harmful COR 3, LOE B-NR
Polymorphic VT with long QT (torsades de points) Magnesium COR 2b, LOE C-LD
Polymorphic VT without long QT Lidocaine or amiodarone COR 2b, LOE C-LD

Regular narrow-complex tachycardia

  1. Vagal maneuvers (COR 1, LOE B-R)
  2. Adenosine (COR 1, LOE B-R)
  3. Diltiazem or verapamil (COR 2a, LOE B-R)
  4. Beta-blockers (COR 2a, LOE C-LD)

Atrial fibrillation/flutter with rapid ventricular rate

  1. Beta-blocker or diltiazem or verapamil (COR 1, LOE B-NR)
  2. Amiodarone (COR 2a, LOE B-NR)

Note that medications can be harmful in these settings:

  1. Preexcitation: Digoxin, non-dihydropyridine calcium channel blockers, beta-blockers, or amiodarone (COR 3, LOE C-LD)
  2. LV systolic dysfunction and decompensated heart failure: Non-dihydropyridine calcium channel blockers or beta-blockers (COR 3, LOE C-EO)

Bradycardia

  1. Treat reversible causes (COE 1, LOE C-EO)
  2. Atropine if hemodynamic compromise (COR 2a, LOE B-NR)
  3. Epinephrine or transcutaneous pacing if unresponsive to atropine (COR 2b, LOE C-LD)

Reference

Panchal AR, Bartos JA, Cabañas JG, et al; Adult Basic and Advanced Life Support Writing Group. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020 Oct 20;142(16_suppl_2):S366-S468. doi: 10.1161/CIR.0000000000000916. Epub 2020 Oct 21. PMID: 33081529.

By |2021-01-20T14:10:34-08:00Jan 23, 2021|Cardiovascular, Critical Care/ Resus, EM Pharmacy Pearls, Tox & Medications|
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2020 ACLS Guidelines on Vasopressors and Non-Vasopressors During Cardiac Arrest

The 2020 ACLS Guidelines were published in October 2020 [1]. This first of 3 blog posts will focus on vasopressor and non-vasopressor medications during cardiac arrest. Part 2 will focus on specific arrhythmia management and Part 3 will focus on toxicologic interventions.

Summary

There were no major updates for vasopressors and non-vasopressors used during cardiac arrest. The American Heart Association (AHA) published Highlights of the 2020 Guidelines [PDF] as a clear and concise summary. Now that the AHA is releasing focused updates in the 5-year period between guidelines (like this one on lidocaine), fewer major changes likely will be needed when the full guidelines are published.

 

Vasopressor Non-Vasopressor

Epinephrine

  • Recommended for patients in cardiac arrest (COR 1, LOE B-R)
  • Reasonable to administer 1 mg every 3-5 minute (COR 2a, LOE B-R)
  • Reasonable to administer as soon as feasible in non-shockable rhythm (COR 2a, LOE C-LD)
  • May be reasonable to administer after initial defibrillation attempts have failed in shockable rhythm (COR 2b, LOE C-LD)

Amiodarone or lidocaine

  • May be considered for VF/pVT unresponsive to defibrillation (COR 2b, LOE B-R)

 

 

 

Vasopressin

  • Offers no advantage over epinephrine (COR 2b, LOE C-LD)

Steroids

  • During CPR, are of uncertain benefit in OHCA (COR 2b, LOE C-LD)
 

Calcium

  • Routine use NOT recommended (COR 3, LOE B-NR)
 

Sodium bicarbonate

  • Routine use NOT recommended (COR 3)
 

Magnesium

  • Routine use NOT recommended (LOE B-R)

Table: Vasopressors and non-vasopressors used during cardiac arrest (VF: ventricular fibrillation, pVT: pulseless ventricular tachycardia)

 

Reference:

Panchal AR, Bartos JA, Cabañas JG, et al; Adult Basic and Advanced Life Support Writing Group. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020 Oct 20;142(16_suppl_2):S366-S468. doi: 10.1161/CIR.0000000000000916. Epub 2020 Oct 21. PMID: 33081529.

By |2021-01-20T13:44:43-08:00Jan 23, 2021|Critical Care/ Resus, EM Pharmacy Pearls, Tox & Medications|
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Buprenorphine prescribing: The Get Waivered Initiative makes it easier to get your DEA-X Waiver

A major development in curbing the opioid epidemic is the introduction of the medication buprenorphine to address opioid addiction. Being able to prescribe this medication, however, requires a special DEA-X Waiver in the United States. Dr. Alister Martin, the Founder of the Get Waivered initiative, is working to reduce the barriers for clinicians to obtain the training and paperwork necessary to obtain this waiver. Dr. Michelle Lin talks with Dr. Martin on this podcast about the backstory of the Get Waivered program, the lowered barriers to obtaining training, and some sneak peaks on what is new on the launching pad for his program.

Interesting fact: Medical students can participate in the free DEA-X waiver training now. The certificate of completion has no expiration date and can be submitted, when eligible for this waiver license.

Podcast with Dr. Alister Martin on the Get Waivered program

Visit the Get Waivered site to learn of their upcoming online training events and hot off the press news.

Additional Reading

  • A Tale of Two Epidemics: COVID-19 and the Opioid Crisis

ACEP E-QUAL podcasts on the opioid epidemic

  1. Opioid Use Disorder (OUD) Access in the Time of COVID
  2. Transitioning to Outpatient Care in OUD
  3. Substance Use Disorder Chat
  4. Pain Management for Patients with Opioid Use Disorder
  5. Opioid Overdose Prevention & Naloxone Distribution
  6. Opioid Withdrawals & Buprenorphine in the ED
  7. Buprenorphine after Opiate Overdose Part 1
  8. Buprenorphine After Opiate Overdose Part 2
  9. Supercharging Medication Assisted Therapy (MAT) with PAs and APRNs

 

buprenorphine suboxone OUD get waivered

Disclosure: ALiEM is proud to be a collaborator with the Get Waivered Initiative. This work was funded by the Foundation for Opioid Response Efforts (FORE). The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies or stance, either expressed or implied, of FORE. FORE is authorized to reproduce and distribute reprints for Foundation purposes notwithstanding any copyright notation hereon.

By |2026-06-16T16:16:40-07:00Dec 2, 2020|Podcasts, Tox & Medications|
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