The Poor Man's Tox Screen: ECG Findings in the Acute Overdose


In the middle of a busy ED shift the tech runs up to you with an ECG. Just prior to signing the top “No STEMI” you think: “wait, why do the QRS complexes look like that?”

Figure 1 EKG.png

You walk back to triage with the tech to see a 86 year old male patient who looks unwell. Dry mucus membranes, mumbling to himself and not making sense, not responding to your questions, febrile, diaphoretic. You know something is wrong, and a quick review of his nursing home paper work gives you the answer: digoxin toxicity.

Figuring out what medication is causing problem for an altered patient can be challenging for any physician. Luckily, there are some classic ECG changes that will help clue to into what a patient may have overdosed on.

Beta Blocker

Beta blockers (such as metoprolol, propranolol, carvedilol) interfere with catecholamine effect on beta adrenergic receptors (principally Beta-1 on heart muscle cells) leading to a decreased heart rate and contractility (Yates & Manini 2012). This leads to low heart rate and blood pressure, as well as an increased probability of sinus bradycardia on ECG.

There are a few main-stays of treatment, all of which try to counteract the drugs activity at the cell. High dose insulin therapy (1U/kg/hr) with high dose glucose (0.5g/kg/hr) is thought by some to be first line for beta blocker overdose (Nelson et al. 2016). Hypoglycemia is coming in these patients, so make sure that highly concentrated (≥5% dextrose solutions) glucose is given before the insulin. If this fails to correct the hypotension, beta-selective pressers such as dobutamine and isoproterenol may help, but carry the risk of paroxysmal hypotension due to the high doses that are often required (Nelson et al. 2016). Glucagon is the classic first line treatment for beta blocker overdose, but has high rates of vomiting and requires large doses, so most hospitals will exhaust their supply before the beta blocker has time to wear off (Nelson et al. 2016). Additionally, phosphodiesterase inhibitors (inamrinone, milrinone, enoximone) can help prevent cAMP breakdown and thereby increase calcium activity within the cell to increase frequency and strength of contract (Nelson et al. 2016). Vasopressin (Holger et al. 2007), levosimendan (Archan & Toller 2008), pyruvate (Hermann et al. 2004), and fat emulsion are also possible treatment options, but only have animal trials or case reports to support their use, so it is unclear if these actually work.

Calcium channel blocker

Calcium channel blockers (such as amlodipine, nifedipine, diltiazem, verapamil) have similar effects to beta blockers (lower heart rate), but calcium channel also usually block sodium channels, causing conduction delays and QRS widening. This key difference may clue you to a calcium channel blocker overdose in a bradycardia patient.

Common treatment for both beta blockers are calcium channel blockers include high dose insulin and glucose, pressors, glucagon, and phosphodiesterase inhibitors. Calcium channel blockers toxicity can also be treated with calcium itself (3mg/kg/min of CaCl2) (Reikeras et al. 1985)

Sodium Channel Blockers

EKG Na Blocker.jpg

Sodium channels are responsible for depolarization of myocytes in the atria and ventricles, so blockade of these channels will lead to prolong depolarization and widen the QRS complex (Nelson et al. 2016). There is also a classic ECG finding of a prominent r-wave and a rightward axis of the terminal deflection of the r-wave that is seen in lead aVR of a 12-lead ECG.

This finding is a result of sodium channel blocker’s preference for blocking the right bundle of the bundle of Hiss (Yates & Manini 2012). Drugs that block this channel include lidocaine, procainamide, and flecainide.

Overdose treatment for sodium channel blockade may vary slightly depending upon the specific xenobiotic that is causing toxicity. In general, a prolonged QRS from a drug known to cause sodium channel blockade is treated with sodium bicarbonate at a rate of 1-2meq/kg as an initial bolus, followed by a drop of 150 met in 1L D5W at twice maintenance. Keep the ECG attached while doing this so a quick ECG can be done to assess for narrowing of QRS. Any overdose with a QRS longer than 100ms (Nelson et al. 2016) should be treated because of the risk of arrhythmia and death (Boehnert & Lovejoy 1985).

Potassium Channel Blockers

Potassium channels mediate cardiac repolarization, so cause lengthening of the QT interval on ECG (Barrett et al. 2016). This QT prolongation is thought to increase the risk of developing a polymorphic wide complex tachycardia known as Torsades de Pointes (Kurita et al. 1992). Many drugs can have this affect, though few use this effect therapeutically. Some examples include anti-nausea medication, anti-psychotic medication, macrolide and fluoroquinolone antibiotics, and antihistamines.

The mainstay of treatment for most potassium channel blocker xenobiotic overdoses is observation and symptomatic care. While there are not many specific treatments known for potassium channel blockade, IV magnesium (2mg) is used for treatment of prevention of Torsade’s de Pointes (Brady 2016). Electrical cardioversion and overdrive pacing are also treatment options for unstable patient in Torsades (Brady 2016).

Na/K/ATPase Blockers

Digoxin and other cardiac glycoside plants exert both therapeutic and toxic effects by blocking the action of Na/K/ATPase pump. By increasing the intracellular concentration of calcium, contractions of the heart are stronger and occur at a faster rate (Nelson et al. 2016). All this extra calcium causes makes the gives the heart cells a lower activation energy, and makes they more prone to random contraction. Blocking this pump also causes AV nodal blockade by lowering the gradient for calcium influx and thus AV nodal depolarization. These combined effects lead to the classic ECG findings of digoxin toxicity: increased automaticity with block and rhythms such as bi-directional VT (Nelson et al. 2016), atrial flutter with ventricular bradycardia, and the “scooped out” t-wave (the QRS terminates into a depressed and down-sloping ST segment with a short QT interval) known as Salvador Dali’s mustache (Ma et al. 2001).

Image caption: Life in the Fast Lane: Digoxin Effect.

Image caption: Life in the Fast Lane: Digoxin Effect.

Treatment includes digoxin-specific antibody fragment (DSFab) (acute toxicity dose = (mg ingested / 0.5mg/vial * 80% bioavailability; chronic toxicity dose = (serum digoxin concentration in ng/L) x (weight in kg) ÷ 100), usually 10-20 vials for acute poison and 3-6 vials for chronic poisoning in adults, 1-2 vials in children). This antidote is effective for cardiac glycosides other than digoxin (such as oleander) (Nelson et al. 2016). Atropine, phenytoin, and lidocaine have also been used, but are often not needed due to DSFab efficacy (Nelson et al. 2016).

Xenobiotic ECG Findings ECG Image Physiology Treatment
Beta-blocker (e.g. propranolol, labetalol) Sinus bradycardia Blockage of cardiac beta receptors Glucagon, high dose insulin and glucose, Pressors
Ca2+ Channel Blocker (e.g. diltiazem, verapamil) Sinus bradycardia, wide QRS Prolongation of phase 0 of nodal action potential, slowing rate of depolarization and thus heart rate High dose insulin, Pressors, glucagon, and phosphodiesterase inhibitors, calcium
Na+ Channel Blocker (e.g. TCA, local anesthetics) Wide QRS, negative deflection of terminal R wave in aVR Prolongation of phase 0 of myocyte action potential, prolonging depolarization phase of cardiac myocytes Sodium bicarbonate to pH <7.55 if QRS > than 100ms, pressors, lidocaine
K+ Channel Blocker (e.g. antipsychotics) Long QT Prolongation of phase 3 of action potential, prolonging time for repolarization Magnesium to treat or prevent Torsades de pointes
Na/K/ATPase Blocker (e.g. cardiac glycoside, digoxin) Biphasic QRS, Increased automaticity with AV block Increased calcium in cardiac myocytes increasing sensitivity to multiple signals and increasing automaticity Digoxin Immune Fab

Table 1: Summary of xenobiotic effects and associated ECG findings. 

These ECG tracings were use with the permission of Dr. Mike Cadogan, and additional images, summary, and description of ECG changes seen in overdose can be seen on his website

Faculty Reviewer: Dr. Jason Hack


Archan S, Toller W. “Levosimendan: current status and future prospect.” Current Opinions in Anesthesiology. 21:78-84. 2008.

Barrett K, Barman S, Boitano S, Brooks H. Ganong’s Review of Medical Physiology, 25th Edition. 2016

Boehnert MT, Lovejoy FH Jr. “Value of the QRS duration verses the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressant.” NEJM. 313:474-479. 1985.

Brady WJ, Laughrey TS, Ghaemmaghami CA. Cardiac Rhythm Disturbances. In: Tintinalli JE, Stapczynski J, Ma O, Yealy DM, Meckler GD, Cline DM. eds.Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e. New York, NY: McGraw-Hill; 2016. 

Graudins, A., Lee, H. M., and Druda, D. (2016) Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies. Br J Clin Pharmacol, 81: 453–461.

Hermann HP, Arp J, Pieske B, et. al. “Improved systolic and diastolic myocardial function with intracoronary pyruvate in patients with congestive heart failure.” Cardiovascular Drugs and Therapies. 15:405-411. 2004.

Holger JS, Engebreten KM, Fritzlar SJ, Patten LC, Harris CR, Flottemesch TJ. “Insulin vs vasopressin and epinephrine to treat beta-blocker toxicity.” Clinical Toxicology. 45:396-401. 2007.

Holstege C, Eldridge D, Rowden A. “ECG Manifestations: The Poisoned Patient.” Emergency Medicine Clinics of North America. 24:159-177. 2006.

Kurita T, Ohe T, Marui N, Aihara N, et al. “Bradycardia-induced abnormal QT prolongation in patients with complete atrioventricular block with torsades de pointes.” American Journal of Cardiology. 69(6):628-33. 1992.

Ma G, Brady W, Pollack M, Chan T. “Electrocardiographic manifestations: Digitalis toxicity.” Journal of Emergency Medicine. 20:145-152. 2001.

Nelson L, Lewin N, Howland M, Hoffman R, Goldfrank L, Flomenbaum N. Goldfrank’s Toxicologic Emergencies. 9th Edition. McGraw-Hill Companies Inc. 2011.

Reikeras O, Gunnes P, Sorlie D, Ekroth R, Jorde R, Mjos OD. Metabolic effects of high doses of insulin during acute left ventricular failure in dogs. European Heart Journal. 6:451-457. 1985.

Image Credit

Images Courtesy of Life in the Fast Lane blog and are used with permission:

AEM Early Access 14: Cannabis and Mental Health ED Visits in Colorado

Welcome to the fourteenth 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 recent AEM Article or Article in Press, with an author interview podcast and suggested supportive educational materials for EM learners.

Find this podcast series on iTunes here.

A FOAM Collaboration: Academic Emergency Medicine Journal and Brown EM

A FOAM Collaboration: Academic Emergency Medicine Journal and Brown EM

DISCUSSING:(Click title for open access through may 31, 2018)

Mental Health-Related Emergency Department Visits Associated with Cannabis in Colorado. Katelyn E. Hall MPH, Andrew A. Monte MD, Tae Chang, Jacob Fox, Cody Brevik, Daniel I. Vigil MD, MPH,  Mike Van Dyke PhD, CIH,  Katherine A. James PhD, MSPH. Academic Emergency Medicine, 2018.


Monte head shot-2014.jpg

Andrew A. Monte, MD

Associate Professor, Departments of Emergency Medicine & PharmaceuticaLSciences
University of Colorado Denver-Anschutz Medical Center Aurora, CO and Rocky Mountain Poison & Drug Center
Denver Health & Hospital Authority
Denver, CO


Across the United States, the liberalization of marijuana use has resulted in a rapid increase in the social acceptability of its use.  Colorado has been at the forefront of marijuana legalization, allowing recreational use beginning in 2014.  Since then, Colorado has positioned itself as the optimal environment to study health-related impacts from marijuana use.  Cannabis use is well-known to exacerbate mental health illness such as schizophrenia, mood disorders, anxiety, and depression.  Since legalization in Colorado, increased healthcare utilization has been associated with acute and chronic marijuana use.  It is currently unknown if cannabis use is associated with increased ED visits in patients with mental illness.  The primary objective of this study was to determine the prevalence ratios of mental health diagnoses among ED visits with cannabis-associated diagnosis compared to those without cannabis-associated diagnoses in Colorado.

The study was cross-sectional in design, with discharge diagnostic codes collected from Colorado emergency departments from 2012 to 2014.  Diagnosis codes identified visits associated with both mental health conditions and cannabis.  Prevalence ratios of mental health ED discharges were calculated to compare cannabis-associated visits to those without cannabis.  Rates of mental health and cannabis-associated ED discharges were examined of the study period.  

State-wide data demonstrated a five-fold higher prevalence of mental health diagnoses in cannabis-associated ED visits (PR: 5.35, 95% CI: 5.27-5.43) compared to visits without cannabis. In the study’s secondary outcome, state-wide rates of ED visits associated with both cannabis and mental health significantly increased from 2012 to 2014 from 224.5 to 268.4 per 100,000 (p<0.0001).

In Colorado from 2012 to 2014 the prevalence of mental health conditions in ED visits with cannabis-associated diagnostic codes is higher than in those without cannabis.  Due to the nature of the study design, it is unclear if these findings are attributable to cannabis or coincident with increased use and availability.  Per the authors of the paper, ED physicians nationwide should be aware of the detriments of marijuana use on pre-existing mental health conditions and ED management should include counseling on cessation and rehabilitation.

AEM Early Access 10: Air Ambulance Delivery and Administration of 4-Factor PCC

Welcome to the tenth 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 recent AEM Article or Article in Press, with an author interview podcast and suggested supportive educational materials for EM learners.

Find this podcast series on iTunes here.

A FOAM Collaboration: Academic Emergency Medicine Journal and Brown EM

A FOAM Collaboration: Academic Emergency Medicine Journal and Brown EM


Air Ambulance Delivery and Administration of Four-Factor Prothrombin Complex Concentrate is Feasible and Decreases Time to Anticoagulation Reversal. Claire Vines, PharmD, Stephanie J. Tesseneer, PharmD, Robert D. Cox, MD, PhD,
Damon A. Darsey, MD, Kristin Carbrey, PharmD, BCPS and Michael A. Puskarich, MD

(click on title for full text; open access through February 1, 2018)     

LISTEN NOW: INTERVIEW WITH corresponding AUTHOR DR.michael puskarich

Dr. Michael Puskarich

Michael Puskarich, MD

Associate Professor and Research Director

Department of Emergency Medicine

University of Mississippi Medical Center


Objectives: The objective was to evaluate the feasibility, safety, and preliminary efficacy of four-factor prothrombin complex concentrate (4-factor PCC) administration by an air ambulance service prior to or during transfer of patients with warfarin-associated major hemorrhage to a tertiary care center for definitive management (interventional arm) compared to patients receiving 4-factor PCC following transfer by air ambulance or ground without 4-factor PCC treatment (conventional arm).

Methods: This was a retrospective chart review of patients presenting to a large academic medical center. All patients presenting to the emergency department (ED) treated with 4-factor PCC from April 1, 2014, through June 30, 2016, were identified. For this study, only transfer patients with an International Normalized Ratio (INR) > 1.5 actively treated with warfarin were included. The primary outcome was the proportion of patients with an INR ≤ 1.5 upon tertiary care hospital arrival, and the secondary efficacy outcome was difference in time to achievement of INR ≤ 1.5. Additional safety and efficacy objectives included difference in thromboembolic complications, length of stay, intensive care unit length of stay, and inpatient mortality between groups.

Results: Of the 72 included patients, a higher proportion of patients in the interventional group had an INR ≤ 1.5 on ED arrival (proportion difference = 0.82, 95% confidence interval = 0.64–0.92, p < 0.0001) and significantly reduced time to observed INR ≤ 1.5 (181 minutes vs. 541 minutes, p = 0.001). No differences were observed in thromboembolic complications or patient-centered outcomes with the exception of mortality, which was significantly higher in patients in the interventional group. This group was also observed to have lower Glasgow Coma Scale score and higher intubation rates prior to transfer and treatment.

Conclusions: Dispatch of an air ambulance carrying 4-factor PCC with administration prior to transfer is feasible and leads to more rapid improvement in INR among patients with warfarin-associated major hemorrhage.


Race against the clock: overcoming challenges in the management of anticoagulant-associated intracerebral hemorrhageJ Neurosurg. 2014 Aug;121 Suppl:1-20. doi: 10.3171/2014.