Podcast production, editing and sound design by Anton Helman
Podcast content, written summary & blog post by Brit Long, Michelle Klaiman, Ian Walker and Anton Helman
Cite this podcast as: Helman, A. Klaiman, M. Long, B. Walker, I. Myers, V. Reid, S. Morgenstern, J. EM Quick Hits 27 – Colchicine for COVID, Bicarb in Cardiac Arrest, Troponin in CKD, GHB Withdrawal, Iloprost for Frostbite, Patient Complaints. Emergency Medicine Cases. March, 2021. https://emergencymedicinecases.com/em-quick-hits-march-2021/. Accessed [date].
Colchicine for COVID – COLCORONA RCT
Design – COLCORONA is an RCT that enrolled 4488 patients age > 40, with either PCR confirmed or clinical criteria for COVID pneumonia and one of the following high-risk criteria: age >70, obesity, diabetes, uncontrolled hypertension, known respiratory disease, known heart failure, known coronary disease, fever of at least 38.4°C within the last 48 hours, dyspnea at the time of presentation, bicytopenia, pancytopenia, or the combination of high neutrophil and low lymphocyte counts; patients were randomized to either colchicine 0.5mg bid x 3 days, then once daily x 27 days or placebo
Outcome was a composite of death OR hospitalization due to COVID
Results – no significant difference in death; no significant difference in hospitalization, no significant difference in mechanical ventilation; however, intention to treat analysis: Odds ratio of protection from death OR hospitalization: , 0.79 (95% CI 0.61 to 1.03); Prespecified subgroup analysis: PCR confirmed cases only: Odds ratio of protection from death from hospitalization, 0.75 (95% CI, 0.57 to 0.99), mostly driven by prevention of hospitalization; patients on colchicine had significant side effects (eg., GI bleed) and increased rates of pneumonia and PE
Problems with this trial
Trial stopped early (not because of major harm or significant benefit), because of difficulty recruiting patients, and may be underpowered
The odds ratio crosses 1 therefore there is no clear protective benefit from colchicine
Conclusion – There is presently no role for colchicine for COVID-19 in ambulatory patients with high risk factors
Tardif J-C, Bouabdallaoui N, L’Allier PL., et al. Efficacy of Colchicine in Non-Hospitalized Patients with COVID-19. Infectious Diseases (except HIV/AIDS); 2021.
IV Sodium Bicarbonate in Cardiac Arrest
Administration of sodium bicarbonate in cardiac arrest is likely to increase serum pH (which is generally lower the longer a patient is in cardiac arrest), however it does not lower serum potassium as is commonly believed, and it adds a potentially detrimental sodium and volume load as well as shifts the oxygen-Hb curve and decrease serum calcium; it may lead to intracellular acidosis
An RCT of 50 cardiac arrest patients randomized to bicarb vs placebo there was no increased rate of ROSC or survival with good neurologic outcome
A prospective observational study of 15 601 out-of-hospital cardiac patients in British Columbia, Canada found that pre-hospital bicarb administration administration was associated with worse survival rate and neurological outcomes to hospital discharge
Administering bicarb may have a detrimental effect on resuscitation economics, whereby more effective treatments may be a better use of the resuscitation team’s time
Bottom line: IV sodium bicarbonate should not be used routinely in cardiac arrest patients, and should be reserved for ASA overdose and sodium-channel blockade overdoses such as TCAs and cocaine
Update 2021: Double-blind, placebo-controlled RCT with 397 adult patients with out-of-hospital cardiac arrest in Denmark, assessing IV/IO doses of calcium chloride versus sodium chloride. With regards to impact on sustained ROSC and outcomes of survival and favorable neurological outcomes at 30 and 90 days, found no significant improvement of sustained ROSC in IV/IO calcium group, and study was halted early due to concerns about harm in calcium group. Abstract
Standards for cardiopulmonary resuscitation (CPR) and emergency cardiac care (ECC). 3. Advanced life support. JAMA. 1974; 7 Suppl(7): 852–860.
Panchal AR, Bartos JA, Cabañas JG, Donnino MW, Drennan IR, Hirsch KG, Kudenchuk PJ, Kurz MC, Lavonas EJ, Morley PT, O’Neil BJ, Peberdy MA, Rittenberger JC, Rodriguez AJ, Sawyer KN, Berg KM; 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; 142: S366-S468.
Ahn S, Kim YJ, Sohn CH, Seo DW, Lim KS, Donnino MW, Kim WY. Sodium bicarbonate on severe metabolic acidosis during prolonged cardiopulmonary resuscitation: a double-blind, randomized, placebo-controlled pilot study. J Thorac Dis. 2018; 10(4): 2295-2302.
Kawano T, Grunau B, Scheuermeyer FX, Gibo K, Dick W, Fordyce CB, Dorian P, Stenstrom R, Straight R, Christenson J. Prehospital sodium bicarbonate use could worsen long term survival with favorable neurological recovery among patients with out-of-hospital cardiac arrest. Resuscitation. 2017; 119: 63-69.
Mathieu D, Neviere R, Billard V, et al. Effects of bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic acidosis: a prospective, controlled clinical study. Crit Care Med. 1991; 19: 1352–6.
Shapiro JI. Functional and metabolic responses of isolated hearts to acidosis: effects of sodium bicarbonate and Carbicarb. Am J Physiol 1990; 258: H1835–H1839.
Troponin interpretation in chronic kidney disease
Patients with chronic kidney disease (CKD) are at high risk for acute coronary syndrome (ACS), which is the most common cause of death in this patient population; patients with CKD also more commonly present atypically with fatigue or shortness of breath
An elevated troponin in this patient population is not due to renal disease alone, as intact troponin has a molecular weight close to albumin; other causes of troponin elevation in CKD include uremic skeletal myopathy, microinfarctions, left ventricular hypertrophy, sepsis, and PE, and unrecognized CHF
Whatever the cause of troponin elevation, this elevation is associated with higher risk of poor outcome, including mortality, in patients with CKD
Be cautious using a single standard troponin level to rule in or rule out ACS in patients with renal disease; sensitivity for diagnosis of ACS in CKD using troponin T is 71-100% and 43-94% for troponin I, while specificity is 31-86% for troponin T and 48-100% for troponin I
Repeat troponin testing and use of the whole clinical picture and ECG are recommended; in patients with an elevated troponin, those with new EKG findings or ischemic symptoms should be admitted for further evaluation
In patients without ischemic symptoms and elevated troponin, think about other causes of troponin elevation (sepsis, PE, CHF, etc.)
Thygesen K,Alpert JS, Jaffe AS, et al; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). 2018 Nov 13;138(20):e618-e651.
Michos ED, Wilson LM, Yeh HC, et al. Prognostic value of cardiac troponin in patients with chronic kidney disease without suspected acute coronary syndrome: a systematic review and meta-analysis. Ann Intern Med. 2014;161:491-501.
Freda BJ, Tang WH, Van Lente F et al. Cardiac troponins in renal insufficiency: review and clinical implications. J Am Coll Cardiol. 2002;40:2065–2071.
Stacy SR,Suarez-Cuervo C, Berger Z, et al. Role of troponin in patients with chronic kidney disease and suspected acute coronary syndrome: a systematic review. Ann Intern Med. 2014 Oct 7;161(7):502-12.
GHB withdrawal management
Gamma-hydroxybutyrate (GHB) is a “party” drug used for its euphoric and sedative effects, a date rape drug and is used by bodybuilders
Tolerance and physical dependence develops quickly (within 7 days) due to rapid onset and short half-life
Its effects are initially stimulating, then progresses to a mixed picture of stimulation and sedation as serum levels increase
GHB is undetectable in standard urine drug screens
GHB withdrawal is similar to alcohol withdrawal (anxiety, tremor, insomnia progressing to confusion, delirium, psychosis, paranoia, autonomic instability) typically develops within the first 6 hours (up to 72hrs) after cessation, can be severe, life-threatening, and is ideally managed in an inpatient setting
Initial treatment of GHB withdrawal is with benzodiazepines; initiate CIWA protocol, but consider dose escalation and more frequent dosing as needed; low dose baclofen has been shown to be an effective adjunctive therapy
For benzodiazepine resistant withdrawal, consider phenobarbital 120-450mg IV
Cornelis F. Vos, Monica Pop-Purceleanu, Maarten J. W. van den Berg & Arnt F. A. Schellekens (2021) Successful treatment of severe, treatment resistant GHB withdrawal through thiopental-coma, Substance Abuse, 42:1, 33-38, DOI: 10.1080/08897077.2020.1827124
Kamal, R.M., van Noorden, M.S., Wannet, W. et al. Pharmacological Treatment in γ-Hydroxybutyrate (GHB) and γ-Butyrolactone (GBL) Dependence: Detoxification and Relapse Prevention. CNS Drugs 31, 51–64 (2017).
McDonough, M., Kennedy, N., Glasper, A., & Bearn, J. (2004). Clinical features and management of gamma-hydroxybutyrate (ghb) withdrawal: A review. Drug and Alcohol Dependence, 75(1), 3-9. doi:10.1016/j.drugalcdep.2004.01.012.
Iloprost may have promise for treatment of frostbite
Iloprost is a synthetic prostaglandin, platelet aggregation inhibitor and vasodilator traditionally used for pulmonary hypertension and Raynaud’s phenomenon, and has been used in Europe widely for treatment of frostbite, but has not been approved by the FDA for this indication, yet is available in Canada through Health Canada’s Special Access Program
Iloprost came to North American attention when an open label randomized trial of 47 patients was described in a letter to the editor of the NEJM in 2010; patients were randomized to Iloprost, Iloprost plus IV TPA or Bluflomidil (which has subsequently been removed from the market due to safety concerns); Iloprost alone, or Iloprost with TPA resulted in the near complete avoidance of amputation (in patients with frostbite extending proximal to the PIP or MCP / MTP, where amputation rates of 60% and 100% respectively would have been expected, the actual rates ranged from zero to 12%)
A 6hr IV Iloprost infusion for 5 days is a reasonable treatment for patients with severe frostbite that would otherwise be at risk of amputation and presenting within 72 hours of rewarming
Summary of the Whitehorse General Hospital (Yukon Hospital Corporation) frostbite protocol*
Rapid rewarming of the affected digits in hot water (39°C) with chlorhexidine and isopropyl alcohol
Immersion of affected parts in hot water (39°C) in a hydrotherapy whirlpool daily (starting the day after rewarming)
Debridement and aspiration of clear blisters
Application of aloe vera protective ointment and porous low-adherent wound dressings
Elevation of affected parts
Avoidance of tobacco and alcohol
Oral ibuprofen every 6 hours
For grade 3 or higher frostbite:
IV iloprost 2 ng/kg per min infusion, 6 h/d, for 5 days
For grade 4 frostbite:
After administration of iloprost, concurrent intravenous infusion of alteplase (for one day; weight-based dosage, progressively increased to a maximum total dose of 100 mg) and heparin (for 72 hours; dosage based on weight and prothrombin time)
Cauchy E, Cheguillaume B, Chetaille E. A controlled trial of a prostacyclin and rt-PA in the treatment of severe frostbite. N Engl J Med 2011;364:189-90.
Cauchy E, Chetaille E, Marchand V, et al. Retrospective study of 70 cases of severe frostbite lesions: a proposed new classification scheme. Wilderness Environ Med 2001;12:248-55.
Groechenig E. Treatment of frostbite with iloprost. Lancet 1994; 344:1152-3.
Lorentzen AK, Davis C, Penninga L. Interventions for frostbite injuries. Cochrane Database of Systematic Reviews 2020, Issue 12. Art. No.: CD012980. DOI: 10.1002/14651858.CD012980.pub2.
McIntosh SE, Hamonko M, Freer L, et al. Wilderness Medical Society practice guidelines for the prevention and treatment of frostbite. Wilderness Environ Med 2011;22:156-66.
Poole, A., Gauthier, J., Treatment of Severe Frostbite with Iloprost in Northern Canada. CMAJ 188(17-18), 2016. 1255-1258
Tips on how to avoid patient and parent complaints
A common patient/parent complaint about EM care is of them feeling that they were dismissed by the physician; to prevent this:
check your mood before you enter the examining room and walk in with the intent to help no matter how minor or chronic the complaint
validate the patient/parent’s feelings (eg., “I can see that you’re worried; what are you most worried about?”)
set the tone for the visit by reassuring the patient/parent that you will address any serious causes of their chief complaint in this visit and that you will ensure appropriate followup
Avoid telling patients/parents that you are 100% sure about anything, as diagnostic errors are sometimes made
Take a minute to see eye to eye with the child/patient/parent and make an empathetic statement to build rapport
If you sense conflict with the patient/parent starting to build, stop, and ask “Is there something else you were worried about?”, “What other questions do you have for me?”, “Was there something else you were expecting from this visit?”
Shared decision making is paramount, especially with patients who have rare/complex diagnoses/illnesses that they have years of experience dealing with; ask them what has worked in the past for them and what treatments they were envisioning
Be aware of your body language and facial expression and avoid “the benevolent smile”; body language and facial expression should ideally reflect the patient/parent mood
Dr. Anton Helman is an Emergency Physician at North York General in Toronto. He is an Assistant Professor at the University of Toronto, Division of Emergency Medicine and the Education Innovation Lead at the Schwartz-Reisman Emergency Medicine Instititute. He is the founder, editor-in-chief and host of Emergency Medicine Cases.