Cardiology

AEM Early Access 05: The Role of Prehospital ACLS for Potential E-CPR Candidates

Welcome to the fifth episode of AEM Early Access, a FOAMed podcast collaboration between the Academic Emergency Medicine Journal and Brown Emergency Medicine. Each month, we'll give you digital open access to an AEM Article in Press, with an author interview podcast and links to curated FOAMed supportive educational materials for EM learners.

Find previous podcasts and subscribe to this series on I tunes here.

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Dr. Alexis Cournoyer, MD   Universite de Montreal, Montreal, Quebec, Canada Hospital du Sacre-Coeur de Montreal, Montreal, Quebec, Canada Institut de Cardiologie de Montreal, Montreal, Quebec, Canada

Dr. Alexis Cournoyer, MD

Universite de Montreal, Montreal, Quebec, Canada
Hospital du Sacre-Coeur de Montreal, Montreal, Quebec, Canada
Institut de Cardiologie de Montreal, Montreal, Quebec, Canada

 

 

 

Listen now: Interview with Dr. Alexis Cournoyer, lead author, interviewed by Dr. Thomas Ross

Open Access Through September 30th. Click below:

Prehospital Advanced Cardiac Life Support for Out-of-Hospital Cardiac Arrest: A Cohort Study. Cournoyer A, et. al

Article Summary:

Objectives: Out-of-hospital advanced cardiac life support (ACLS) has not consistently shown a positive impact on survival. Extracorporeal cardiopulmonary resuscitation (E-CPR) could render prolonged on-site resuscitation (ACLS or basic cardiac life support [BCLS]) undesirable in selected cases. The objectives of this study were to evaluate, in patients suffering from out-of-hospital cardiac arrest (OHCA) and in a subgroup of potential E-CPR candidates, the association between the addition of prehospital ACLS to BCLS and survival to hospital discharge, prehospital return of spontaneous circulation (ROSC) and delay from call to hospital arrival. 

Methods: This cohort study targets adult patients treated for OHCA between April 1010 and December 2015 in the city of Montreal, Canada. We defined potential E-CPR candidates using clinical criteria previously described in the literature (65 years of age or younger, initial shockable rhythm, absence of return of spontaneous circulation after 15 minutes of prehospital resuscitation and emergency medical services witnessed collapse or witnessed collapse with bystander cardiopulmonary resuscitation). Associations were evaluated using multivariate regression models.

Results: A total of 7134 patients with OHCA were included, 761 (10.7%) of whom survived to discharge. No independent association between survival to hospital discharge and the addition of prehospital ACLS to BCLS was found in either the entire cohort [adjusted odds ratio (AOR) 1.05 (95% confidence interval 0.84-1.32), p=0.68] or amongst the 246 potential E-CPR candidates [AOR 0.82 (95% confidence interval 0.36-1.84), p=0.63]. The addition of prehospital ACLS to BCLS was associated with a significant increase in the rate of prehospital ROSC in all patients experiencing OHCA (AOR 3.92 [95% CI 3.38-4.55], p<0.001) and in potential E-CPR candidates (AOR 3.48 [95% CI 1.76-6.88], p<0.001) as compared to isolated prehospital BCLS. Delay from call to hospital arrival was longer in the ACLS group than in the BCLS group (difference=16 min [95% CI 15-16], p<0.001). 

Conclusions:  In a tiered-response  urban emergency medical service setting, prehospital ACLS is not associated with an improvement in survival to hospital discharge in patients suffering from OHCA and in potential E-CPR candidates, but with an improvement in prehospital ROSC and with longer delay to hospital arrival. 

Suggestions for Further Reading: 

Open Access:

RAGE Podcast: E-CPR by Vincent Pellegrino

EM Docs: ECMO in the ED

Subscriptions/Abstracts:

Sanghavi P, Jena AB, Newhouse JP, Zaslavsky AM. Outcomes after out-of-hospital cardiac arrest treated by basic vs advanced life support. JAMA Intern Med 2015;175:196-204. 

Ma MH, Chiang WC, Ko PC, et al. Outcomes from out-of-hospital cardiac arrest in Metropolitan Taipei: does an advanced life support service make a difference? Resuscitation 2007;74:461-9.

Bakalos G, Mamali M, Komninos C, et. al. Advanced life support versus basic life support in the pre-hospital setting: a meta analysis. Resuscitation 2011;82:1130-7.

Stub D, Bernard S, Pellegrino V, et. al. Refractory cardiac arrest treated with mechanical CPR, hypothermia, ECMO and early reperfusion (the CHEER trial). Resuscitation 2014. 

Siao FY, Chiu CC, Chiu CW, et al. Managing cardiac arrest with refractory ventricular fibrillation in the emergency department: Conventional cardiopulmonary resuscitation versus extracorporeal cardiopulmonary resuscitation. Resuscitation 2015;92:70-6. 

Faculty Editors/Reviewers: Dr. Gita Pensa and Dr. Kristy McAteer 

Podcast credits: Used under creative commons license: intro music by freemusicarchive.org , sound effect from freesound.org, exit music by bensound.com

AEM Early Access 04: A 0h/1h Chest Pain Protocol

Welcome to the fourth episode of AEM Early Access, a FOAMed podcast collaboration between the Academic Emergency Medicine Journal and Brown Emergency Medicine. Each month, we'll give you digital open access to an AEM Article in Press, with an author interview podcast and links to curated FOAMed supportive educational materials for EM learners.

Find previous podcasts and suscribe to this series on iTunes here.

 

 

 

 

 

LISTEN NOW: Interview with Dr. Arash Mokhtari, lead author, interviewed by Dr. Michael Prucha.

Dr Arash Mokhtari, MD, PhD   Department of Internal and Emergency Medicine, Skåne University Hospital, Lund Department of Cardiology, Lund University, Skåne University Hospital, Lund

Dr Arash Mokhtari, MD, PhD

Department of Internal and Emergency Medicine, Skåne University Hospital, Lund
Department of Cardiology, Lund University, Skåne University Hospital, Lund

Open Access Through August 31st. Click here:

A 0-Hour/1-Hour Protocol for Safe, Early Discharge of Chest Pain Patients. Mokhtari A, et al. 

Article Summary:

Objective: To investigate the effectiveness of a rapid ACS rule-out protocol using 0h and 1h high-sensitivity troponin in conjunction with EKG changes and a modified TIMI risk score in order to safely and quickly discharge patients presenting with chest pain.

Methods: A secondary data analysis was performed on data collected from a prospective observational study on patients presenting to the Emergency Department at the Skåne University Hospital in Lund, Sweden. Evaluation included 0h and 1h troponin, including the absolute change, EKG changes as interpreted by Emergency physicians, as well as a modified TIMI risk score to decide whether patients could be discharged.  Adverse outcomes were defined as major adverse cardiac events (MACE) at 30 days including myocardial infarction, unstable angina, ventricular arrhythmia, atrioventricular block, cardiac arrest, or death of cardiac or unknown cause.

Results: This study included 1,020 patients who were evaluated on the above parameters, and discharged only if their modified TIMI risk score was less than, or equal to 1, the EKG was non-ischemic, and the 0h troponin was < 5 ng/L or 0 h <12 ng/L with a 1h troponin increase < 3 ng/L.  Using these criteria 432 (42.4%) patients were defined as “very low risk.”  Of those only 2 patients had MACE, both of which were unstable angina.  This produced a negative likelihood ratio of 0.04 for 30-day MACE.

Conclusion: While validation of this study needs to take place in other settings, the results of this study suggest that possibly greater than 40% of patients presenting to the ED could be discharged quickly and safely, after the result of a 1h high-sensitivity troponin or sooner, with a very small risk of missing 30-day MACE. Of course, this study was performed at one unique site in Sweden, but the results provide promising prospects for new accelerated diagnostic protocols.

 

Suggestions for further readinG:

Open access:

The Fast and the Furious: Low Risk Chest Pain and the Rapid Rule Out Protocol, a review, West JEM, February 2017

ERCast: Which Chest Pain Patients Can Be Discharged? February 20, 2016

REBEL EM: Management and Disposition of Low Risk Chest Pain, February 2016

Subscription/Abstracts:

Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement Below the Limit of Detection: A Collaborative Meta-analysis. Ann Intern Med. 2017 May 16;166(10):715-724. 

Present and Future of Cardiac Troponin in Clinical Practice: A Paradigm Shift to High-Sensitivity Assays.Am J Med. 2016 Apr;129(4):354-65. 

High-sensitivity cardiac troponin assays and unstable angina.Eur Heart J Acute Cardiovasc Care. 2016 Jul 7

State-of-the-Art Evaluation of Emergency Department Patients Presenting With Potential Acute Coronary Syndromes.Hollander J et al, Circulation. 2016 Aug 16;134(7):547-64.

High-sensitivity cardiac troponin assays: answers to frequently asked questions. Arch Cardiovasc Dis. 2015 Feb;108(2):132-49

 

Faculty Editors/Reviewers: Dr. Kristy McAteer and Dr. Gita Pensa

Podcast credits: Used under creative commons license: intro music by freemusicarchive.org , sound effect from freesound.org, exit music by bensound.com

Cardiotoxicity of Opioids

Background:

Loperamide, sold over-the-counter as Imodium among others, is a medication to decrease the frequency of diarrhea. The medication was first synthesized in 1969, first used medically after FDA approval in 1976, and first sold OTC in 1988. Loperamide was recently listed on the WHO’s List of Essential Medicines, due to its affordability and widespread use for patients with inflammatory bowel disease, gastroenteritis, irritable bowel syndrome, and traveler’s diarrhea.

Mechanism:

Loperamide is an opioid-receptor agonist, decreasing the tone of intestinal smooth muscles, and subsequently allowing more water to be absorbed from fecal matter. The effects of loperamide are limited by the actions of P-glycoprotein (P-gp), a cell membrane protein that pumps xenobiotics back into the intestinal lumen, preventing further absorption. This effect is also noticed in the blood-brain barrier where P-gp prevents loperamide from affecting the central nervous system.

Misuse/abuse: 

Appropriate dosing is 4 mg initially, followed by 2 mg after each subsequent loose stool, with a recommended daily maximum of 16 mg. When taken in large quantities, the levels of P-gp in the CNS and gut are overwhelmed, and the medication is able to cross the blood-brain barrier, eliciting opiate-like effects. A report from the National Poison Data System showed a 91% increase in loperamide exposures from 2010-2015, notable for 23 ingestion deaths, with 8 being solely attributed to loperamide. During this timeframe, on-line drug forums with user-generated content noted significant opportunity for misuse by patients seeking euphoria or withdrawal symptom relief. Furthermore, the low cost, legal status, and lack of social stigma also precluded this medication to misuse.

An FDA June 2016 report linked the abuse/misuse of loperamide to serious cardiac events, and urged health care providers to ‘consider loperamide as a possible cause of unexplained cardiac events including QT interval prolongation, torsades de pointes or other ventricular arrhythmias, syncope, and cardiac arrest.

Cardiac Effects of Loperamide: 

In cardiac tissue, loperamide has been shown to inhibit the human Ether-a-go-go Related Gene (hERG) product, a slow K channel. Resultantly, this prolongs phase 3 of the action potential, preventing repolarization, and lengthening the QTc interval.

Cardiotoxicity of Other Opioids: 

Propoxyphene (Darvocet when combined with acetaminophen) is a synthetic weak opioid introduced in 1957, that has subsequently been withdrawn from the US market after multiple black box warnings regarding cardiac effects. Propoxyphene exhibits Vaughn-Williams class Ic antiarrhythmic effects (more potent than lidocaine) and promotes cardiac Na channel blockade, subsequently prolonging phase 0 of the action potential, and prolonging the QRS interval. 

Methadone, commonly used in the treatment of opioid dependence since the 1960s in the US, also exhibits QTc prolongation effects. Similar to loperamide, methadone has been shown to also block the same slow K channel, precluding patients to risk of torsades de pointes.

Figure 1: Borrowed from https://www.pinterest.com/krazeniq/diastolic-dysfunction/?lp=true

Figure 1: Borrowed from https://www.pinterest.com/krazeniq/diastolic-dysfunction/?lp=true

Treatment/conclusions:

When presented with ingestions of loperamide or the other aforementioned opioids with cardiac effects, after appropriate resuscitation, an ECG should be collected to assess the QRS and QTc intervals. The QTc prolongation effects of loperamide and methadone should be treated supportively with magnesium sulfate to prevent torsades de pointes. If TdP develops, the provider should consider isoproterenol (if there is intermittent bradycardia), and further transcutaneous/transvenous pacing.

Faculty Reviewer: Dr. Jason Hack 

References:

Marraffa J, Holland M, Sullivan R, et al. Cardiac conduction disturbance after loperamide abuse. Clin Toxicol. 2014;52,952-957.

Daniulaityte R, Carlson R, Falck R. “I just wanted to tell you that loperamide WILL WORK”: a web-based study of extra-medical use of loperamide. Drug Alcohol Depend. 2013;130,241-244.

Dierksen J, Gonsoulin M, Walterscheid J. Poor man’s methadone: a case report of loperamide toxicity. Am J Forensic Med Pathol. 2015;36,268-270.

Vakkalanka J, Charlton N, Holstege C. Epidemiologic trends in loperamide abuse and misuse. Ann Emerg Med. 2017;69,73-78.

Uphadyay A, Bodar V, Malekzadegan M, et al. Loperamide induced life threatening ventricular arrhythmia. Case Rep Cardiol. 2016;1-3.

Lasoff D, Schneir A. Ventricular dysrhythmias from loperamide misuse. J Emerg Med. 2012;508-509.

Aschenbrenner D. Loperamide abuse or misuse triggers cardiac events. AJN. 2016;116,26-27.

Eggleston W, Clark K, Marraffa J. Loperamide abuse associated with cardiac dysrhythmia and death. Ann Emerg Med. 2017;69,83-86.

Gussow L. Opioid abusers using loperamide to get high or alleviate withdrawal, with fatal consequences. Emergency Medicine News. 2016;38,8.

Adler A, Viskin S, Bhuiyan Z, et al. Propoxyphene-induced torsades de pointes. Heart Rhythm. 2011;8,1952-54.

Jang D, Hoffman R, Nelson L, et al. Fatal outcome of a propoxyphene/acetaminophen (Darvocet) overdose: should it still be used in the United States? Ann Emerg Med. 2011;57,421-22.

Barkin R, Barkin S, Barkin D. Propoxyphene (Dextropropoxyphene): a critical review of a weak opioid analgesic that should remain in antiquity. Am J Ther. 2006;13,534-542.

Latta K, Ginsberg B, Barkin R. Meperidine: a critical review. Am J Ther. 2002;9,53-68.

Song M, Bae E, Baek J. QT prolongation and life threatening ventricular tachycardia in a patient injected with intravenous meperidine (Demerol). Korean Circ J. 2011;41,342-45.

Alinejad S, Kazemi T, Zamani N, et al. A systematic review of the cardiotoxicity of methadone. EXCLI Journal. 2015;14,577-600.

Caffrey C, Pinchbeck C. Methadone Induced Torsades. NUEM Blog. Retrieved from http://nuemblog.com/blog/methadone-torsades.

Chen A, Ashburn M. Cardiac effects of opioid therapy. Pain Medicine. 2015;16,S27-S31.