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2. Beta-Blocker Overdose: “You know, the green pill.”
Keywords
Beta-blockerBradycardiaAltered mental statusCase
Sad, Young, Bradycardic and Hypotensive
Pertinent History
A 28-year-old male with no past medical history presented to triage with report of a suicide attempt by ingestion of his grandmother’s medications. This was witnessed by his girlfriend approximately 20 minutes prior to arrival. He does not know what medications his grandmother takes, but he reports he took all of the “green ones.” Neither he nor his girlfriend knows how many pills were in the bottle. He currently denies chest pain or shortness of breath. He has no known psychiatric history or history of suicide attempts.
His girlfriend shares that he has stopped exercising and meeting with friends, since he was laid off about 3 weeks ago.
Pertinent Physical Exam
Pulse 45 | Respiratory rate 16 | SpO2 100% on RA | Blood pressure 116/85 | Temperature 98.1F/36.7ºC.
Constitutional: Well-appearing male patient sitting in bed.
HEENT: Normocephalic, atraumatic. Moist mucous membranes.
Cardiac: Bradycardic, regular rhythm. No murmurs, rubs or gallops.
Pulmonary: Clear lung sounds bilaterally.
Abdomen: Soft, nondistended and nontender.
Neuro: A&O x3. No CN deficits. No tremors. 5/5 strength of bilateral UE and LEs.
Skin: No rashes. No wounds.
No PMH, FH related to presentation.
SH
Denies tobacco, alcohol, and drug use.
Pertinent Test Results
CBC
Chem 10
Hepatic function panel
Acetaminophen level
Salicylate level
Venous blood gas
UA
Urine drug screen
Chest radiograph
EKG: Sinus bradycardia
ED Management
This patient presented reporting an overdose of a “green pill.” Pharmacy was called but without having the pills, it was hard to narrow what he took. As he was well-appearing, our differential remained wide, but with the reported overdose in mind ordered: CBC, chem 10, hepatic function panel, acetaminophen level, salicylate leve1, urine or blood drug screen, blood gas, EKG. We placed him on the monitor, ordered suicide precautions, and requested that our nurses alert us immediately of any changes.
Update 1
While awaiting the initial workup, the nurse called to report that the patient’s pulse was now 30. When we arrived at the bedside, he was newly hypotensive with a blood pressure of 64/palp. As we walked into the room, patient’s girlfriend handed us a sheet of paper with the grandmother’s medication list on it:
Medication List
Published with kind permission of © Colin G. Kaide 2019. All Rights Reserved
With this medication list and the turn of events, a beta-blocker overdose was at the top of the differential. Our pharmacist was also able to confirm that Inderal (propranolol) 40 mg is a green pill.
Because the overdose was reported to have occurred so recently, the patient was given 50 grams of activated charcoal and 1 mg of atropine. He then received 5 mg of glucagon. Shortly after that, he sat up and vomited a black cloud of charcoal and little green pills. He remained hypotensive and bradycardic and received 5 mg of glucagon and an infusion was started at 5 mg/h along with 3 grams of calcium gluconate. High-dose insulin was ordered as a 1 unit/kg bolus, followed by an infusion of 1 unit/kg/h. After epinephrine was started at 5 mcg/minute, his pressure increased to 100 systolic and his heart rate to 70.
We considered lipid emulsion therapy, since propranolol is lipid soluble but held off initially after the poison center recommended against it.
Update 2
After an initial stabilization of vital signs, the patient again became bradycardic and hypotensive (40 and 60/p). We initiated 1.5 mL/kg of 20% Intralipid followed by an infusion of 0.25 mL/kg/minute. Shortly after starting lipids and titrating the epinephrine drip, the patient stabilized and was admitted to the ICU. After starting lipids and titrating the epinephrine drip, the patient improved and was stabilized. He was subsequently admitted to the ICU.
Learning Points
Priming Questions
- 1.
What is the workup for a suspected beta blocker overdose?
- 2.
How do beta blockers cause toxicity?
- 3.
How do you treat a stable beta blocker overdose?
- 4.
How do you treat an unstable beta blocker overdose?
Introduction/Background
- 1.
The first beta-blocker was synthesized in 1958 (pronethalol). It was never used clinically. Propranolol was introduced in the USA in 1973.A(1)
Today, there are about 20 beta-blocker agents that are approved for use in the USA.
- 2.
Each year, there are approximately 25,000 overdose cases that include a beta-blocker that are reported to poison centers across the USA.1(2)
Owing to the wide range of diagnoses for which it is prescribed (including anxiety, stress, and depression), propranolol accounts for a disproportionate number of overdoses and deaths [1].
- 3.
In only about half of the cases (10,500) was beta-blocker was the only drug ingested [2]. Therefore, one must always consider a coingestion, especially if the patient’s presentation is atypical for a beta-blocker overdose.
Physiology/Pathophysiology
- 1.
Beta-blockers are class II antiarrhythmic agents commonly prescribed for tachydysrhythmias, cardiovascular disorders, and elevated blood pressure. They are also used for congestive heart failure, migraine headaches, benign essential tremor, panic attacks, stage fright, hyperthyroidism, and topically for ophthalmic conditions.
Therapeutic effects
They cause a decrease blood pressure, heart rate, cardiac contractility, and cardiac depolarization through effects on both the SA and AV nodes.
They also block the peripheral manifestations of catecholamine stimulation such as tremor, sweating, and anxiety.
Overdose effects
Hypotension, hypoglycemia, respiratory depression, CNS depression bronchospasm, seizures, and arrhythmias.
- 2.
Sotalol has class III antidysrhythmic properties along with beta-blocking effects. This leads to prolongation of QTc interval, increasing the risk of developing Torsades de Pointes. Unlike other beta-blockers, sotalol poisoning can present in a delayed fashion with symptoms developing up to 24 h after overdose.
- 3.
Propranolol has significant membrane-stabilizing effects, acts to block sodium channels, and can cause a prolonged QRS, leading to arrhythmias [3].
A “Brugada-like” EKG pattern has been reported in some cases of propranolol overdose [4].
Propranolol is concentrated in synaptic vesicles and can interfere with synaptic function by inhibiting membrane ion pumps (sodium, potassium, and magnesium ATPase). This may be the reason propranolol can cause more significant CNS symptoms such as delirium, coma, and seizures than other beta-blockers [5].
One study looked at propranolol compared to other beta-blockers in overdose and found 29% of the propranolol overdoses experienced seizures verses none in the nonpropranolol group [6].
EKG findings can mimic a tricyclic overdose.
- 4.
In overdose, beta-selectivity is lost and both beta-1 and beta-2 receptors are affected.
- 5.
Lipophilicity can indicate the possible usefulness of lipid therapy in overdose.
Lipid Solubility of Beta-Blockers
High Lipophilicity:
Propranolol, labetalol
Intermediate Lipophilicity:
Metoprolol, bisoprolol, carvedilol, acebutolol, timolol, pindolol
Low Lipophilicity (hydrophilic beta-blockers):
Atenolol, nadolol, and sotalol
Making the Diagnosis
Differential Diagnosis (Bradycardia)
Sinus bradycardia
Primary cardiac events
Metabolic derangements
Hypothyroidism
Ingestion (beta blockers, calcium channel blockers, digoxin, cholinergic medications, clonidine)
- 1.
Most importantly, think of beta-blocker overdose as a cause for a a patient presenting with significant bradycardia.
This patient presented with a reported ingestion. Not all patients will volunteer this history!
- 2.
Always consider overdose as the cause for presentation in an altered and/or unstable patient.
- 3.
The history provided by potential overdose patients can be is unreliable [7, 8] and you MUST consider beta-blocker overdose in order to treat it.
Related posts:
Delirium: “I’m So Excited … I Just Can’t Hide It”
Syndrome: “I Need Somebody HELLP, Not Just Anybody…”
Widow Spider Bite: “Can’t We Just Get a Divorce?”
Blast Crisis/Hyperviscosity Syndrome: Blasting Off!
Storm of the Heart: A Shocking Experience!
Surprise Attack!: Chest Pain and the “Forgotten Lead”
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