Approach to Calcium Channel Blocker Overdose

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.Welcome to our Episode about a 14- year- old female who presented with hypotension after a suicide attempt.Here's the case:A 14 yo F with PMH of depression and oppositional defiant disorder presents with dizziness. Her mother states she was in her normal state of health when on the day of admission she noticed the patient to be dizzy, slurring speech, and pale. The mother became very concerned about the dizziness as the patient was stumbling and a few hours prior to presentation, became increasingly sleepy. The patient does have a history of depression and is controlled on sertraline. Other medications in the home include Metformin, Amlodipine, and Clonidine. The patient denies ingesting any substance. She does have a prior attempt two years prior, after an argument with her mother; however, her mother was able to “stop” her prior to the attempt. She presents to the ER via EMS. Her vital signs are notable for HR 50 bpm with occasional PACs and non-conducted QRS complexes on telemetry; BP of 75/40. A physical exam is notable for AMS and GCS of 10. She is noted to have clear breath sounds, with a cardiac exam notable for slowed and delayed pulses. Initial laboratory work is notable for serum glucose 180 mg/dL and B HCG negative. Initial resuscitation is begun with IV fluids and atropine. Serum acetaminophen and ASA levels are sent and upon stabilization, the patient presents to the PICU for admission.To summarize key elements from this case, this patient has:A history of depression with prior attemptAn acute bout of altered mental statusBradycardia, hypotension, and hyperglycemia.All of which brings up a concern for an acute ingestionLet’s take a step back and talk about the approach to ingestions in the PICU.What are key aspects to consider in the work-up of these patients?History and physical are key:Stratifying acute or chronic ingestionsBaseline prescription medications a patient may be taking or have access to in the householdWhether the ingestion involves a single drug or co-ingestants are all first steps in evaluating your patient.In an undifferentiated patient, management is paramount. Initial management is focused on pattern recognition and acute stabilization.A brief initial screening examination should be performed on all patients to identify immediate measures required to stabilize and prevent deterioration of the patient. Assess the airway, vital signs, mental status, pupil size, and skin temperature and moisture.These components of your physical exam should help allude to a toxidrome, and these syndromes are frequently tested on board examinations. Any time a patient has hypotension and bradycardia other drugs that should be considered include beta blockers, digoxin, clonidine, as well as ingestion of barbiturates, opioids, and even benzodiazepines.What are some diagnostic studies you will want to send immediately in a patient with suspected ingestion?Immediate diagnostic studies to be performed include pulse oximetry, continuous cardiac monitoring, an electrocardiogram (ECG), and a capillary glucose measurement (in altered patients). Intravenous (IV) access should be obtained in all cases of serious ingestion.You also want to send beta-hcg and acetaminophen and salicylate levels. an extended toxicology screen may be required on a case-by-case basis.One study found detectable serum acetaminophen concentrations in 9.6 percent of all overdose patients; almost one-third of this subset denied ingestion of acetaminophen.Now that you’ve focused on ABCs are there more detailed laboratory studies to send in patients with toxidromes?Symptomatic patients and those with an unreliable or unknown history should, at a minimum, undergo urinalysis and measurement of serum electrolytes, blood urea nitrogen (BUN), creatinine, and glucose. Measurements of serum ketones, creatine kinase, liver function tests, lipase, ionized calcium, and magnesium should also be performed in most significantly ill patients.Additional testing may be useful in specific circumstances, such as serum osmolality in suspected toxic alcohol ingestion. We will discuss these in a separate episode.Patients who continue to be altered may also undergo head CT as head trauma is frequently associated with ingestions.ECG, Echocardiography helps to distinguish refractory hypotension due to vasodilatation from pump failure. CXR may be needed to evaluate pulmonary edema and guide fluid management. Abdominal radiograph or US may be required in cases of suspected bowel ischemia/perforation. Ingestion of a large number of CCB tablets, especially sustained-release tablets, the pills may aggregate to form bezoars and the drug can be continuously absorbed for long periods.To go back to our case, with history and initial diagnostics only, how are we able to stratify whether this patient took a CCB versus a beta-blocker?This is a great question. This patient had an electrocardiogram, which showed changes associated with CCB poisoning including a PR interval prolongation and bradydysrhythmia. Importantly, our patient’s serum glucose was >150 mg/dL and thus, the presence of hyperglycemia in a non-diabetic patient may help to distinguish CCB from beta-blocker poisoning.The mechanism of hyperglycemia in CCB involves the CCB causing inhibition of calcium-mediated insulin release; remember that the serum glucose elevation is rarely clinically significant, and is used for diagnostic purposes to stratify between bb and CCB overdose.Per history, our patient had access to amlodipine which is the likely agent she ingested. Can you shed some light on how non-DHP CCB overdoses are different than DHP overdoses?Let’s review some basic science & pharmacology:Calcium channel blockers (CCBs) can be divided into two major categories based on their predominant physiologic effects: dihydropyridines, which preferentially block the L-type calcium channels in the vasculature; and non-dihydropyridines, such as verapamil and diltiazem which selectively block L-type calcium channels in the myocardium.L-type calcium channels are responsible for myocardial contractility and vascular smooth muscle contractility; they also affect conducting and pacemaker cells.In general DHP (which has the suffix dipine) are potent vasodilators that have little negative effect upon cardiac contractility or conduction at standard doses.In contrast, verapamil and diltiazem are relatively weak vasodilators but have a depressive effect on cardiac conduction and contractility.How does this framework help with our understanding of CCB ingestions?Overdose with dihydropyridine CCBs (amlodipine/nifedipine) causes hypotension coupled with reflex tachycardia, although severe toxicity may result in hypotension and bradycardia. This is what we saw in our patient — severe toxicity.Overdose with non-DHP CCB like verapamil or diltiazem also causes a dangerous combination of hypotension and...