AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Sales of calcium channel blockers (CCBs) have increased over the last decade. Newly developed CCBs include ultralong-acting medications and sustained-release forms of existing preparations. Increased availability in the home has led to an increase in the number and severity of CCB ingestions by children.

Many CCBs are marketed today. As of June 2007, 7 drugs in 3 classes in multiple immediate and sustained-release preparations are available in the United States. These classes are as follows:

• Phenylalkylamines (eg, verapamil): These agents poison both the atrioventricular (AV) node and peripheral vasculature equally.
• Benzothiazines (eg, diltiazem): These agents are more chronotropic than vasoactive.
• Dihydropyridines (eg, nifedipine, amlodipine): These agents exert blood pressure–lowering effects almost entirely on the peripheral vasculature.

The generic preparations of these medicines currently available include amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nimodipine, and verapamil. Each preparation has its own pharmacologic properties and has a slightly different effect and duration of action. These medications have different onsets of action, and many are available in sustained-release forms, which complicates the physician's decision regarding the most appropriate time to release patients with CCB ingestion.

The current range of indications for CCBs is broad. Although most of the disease processes that respond to CCBs affects adults, pediatricians have used CCBs to treat children with congenital heart malformations, arrhythmias, hypertension, subarachnoid hemorrhage, and/or congestive heart failure.

Pathophysiology

CCBs function by binding to the L-subtype, voltage-sensitive, slow calcium channels in cell membranes. This binding decreases the flow of calcium into the cell, which leads to an inhibition of the phase 0 depolarization in cardiac pacemaker cells and leads to the phase 2 plateau of Purkinje cells, cardiac myocytes, and vascular smooth muscle cells. Some CCBs may also demonstrate weak cross-reactivity with fast sodium channels, partially blocking these voltage-gated ion pores, which are responsible for rapid membrane depolarization.

Different CCBs work by slightly different mechanisms. Nifedipine likely "plugs" the slow calcium channel, whereas drugs such as diltiazem and verapamil are use-dependent. That is, they interact with the calcium channel after it has been depolarized to its inactivated recovery state.

Each CCB has a certain degree of tissue specificity, but they do have common properties. CCBs are all absorbed early in the GI system, are substantially bound by plasma proteins, and are predominantly metabolized by the liver. Therefore, impaired renal function should not alter CCB metabolism.

Frequency

United States

The American Association of Poison Control Centers (AAPCC) collects data annually from regional poison control centers throughout the country. In 2005, 61 regional sites contributed information, and almost 2.4 million exposures were recorded from these sites; 38.1% of the reported cases occurred in children younger than 3 years, and 50.9% of the cases occurred in children younger than 6 years.¹ Only 14% of exposures occurred in youth aged 6-19 years. 

Of the 2.4 million exposures logged in 2005, 10,500 of these cases were due to various CCBs.¹ Approximately 2,340 (22%) of the CCB exposures occurred in children younger than 6 years, and 482 (4.5%) occurred in children aged 6-19 years.

Mortality/Morbidity

According to the 2005 AAPCC data, 9% of adolescent exposures were fatal, whereas only 1.9% of cases occurring in children younger than 3 years were fatal.¹ This likely reflects the fact that accidental small ingestions or tasting occurs in toddlers, whereas intentional overdoses of various sizes are responsible for cases in the adolescent population.

In 2005, CCBs resulted in 75 (0.7%) fatalities and 384 (3.6%) major poisonings among the 10,500 individuals exposed to CCBs, although the AAPCC report does not stratify that data by age.¹ Koren reviewed the literature and considered sustained-release CCBs to be one of the medications considered to be lethal to infants with the ingestion of a single pill.² Therefore, whenever a physician or parent suspects that a child has taken a CCB, aggressive treatment in a well-equipped hospital setting should be rapidly initiated.

Race

Although CCB ingestion has no racial predilection among young children, racial trends mirror statistics of suicide attempts by adolescents.

Sex

Among young children, a male predilection for CCB toxicity is observed. In adolescence, the incidence mirrors suicide attempt statistics, with more female adolescents ingesting CCB agents than male adolescents.

Age

CCB ingestions show a bimodal distribution in the pediatric age range.

• Infants and toddlers often unintentionally ingest tablets that they mistake for food or candy.
• Teenagers ingest CCB agents as a suicide gesture.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Whenever a patient presents with bradycardia, hypotension, and an altered mental status, gather a short and AMPLE (ie, allergies, medications, past medical history, last meal, and events of the incident) medical history.

• If the patient ingested medications, ascertain type, dose, and number or amount.
• • Determine the number of tablets that are missing from the bottle. If the number of pills in the bottle at the time of the ingestion is unknown, determine the number of pills that the bottle initially contained (ie, the maximum number of pills the child could have taken).
  • Ascertain whether the ingestion is a sustained-release preparation. Ask the patient's family members what medications they are taking because these are most likely the substances that the patient ingested.
  • Finally, try to determine the time between the ingestion and presentation to the emergency department (ED) because this interval provides an indication of how long the calcium channel blockers (CCBs) have had to be absorbed in the patient's digestive system.
• If a suicide attempt is suspected, try to determine whether other medications or alcohol could have been co-ingested. Acetaminophen or aspirin ingestion is especially important to determine because both have known medical treatment modalities.
• When CCB ingestion is suspected, specifically question the patient or family about cardiac or pulmonary manifestations of CCB toxicity.
• • Did the patient exhibit chest pain, diaphoresis, flushing, palpitations, weakness, peripheral edema, dyspnea, or cough?
  • Does the patient exhibit any signs of CNS involvement?
  • Does the patient have a history of drowsiness, confusion, seizure, dizziness, headache, tremor, nausea, vomiting, or syncope?

Physical

Pay particular attention to the cardiac, vascular, and neurologic examinations because CCB toxicity manifests most physical findings in these systems. According to one study, maximal elapsed time to onset of symptoms ranged from 3 hours (seen with normal preparations) to 14 hours (in the setting of sustained-release medications).³ These onset times should be considered when discharging home patients that may or may not have ingested CCBs.

• Begin the physical examination of the patient who has ingested an unknown amount of a CCB by checking vital signs. The heart rate may be decreased if the sinoatrial (SA) node is poisoned or may be increased if the patient is experiencing reflex tachycardia secondary to peripheral vasodilation and hypotension. Hypotension may last up to 24 hours with some sustained-release, long-acting medications.
• When examining the head, eyes, ears, nose, and throat, ensure that the patient's pupils are equal, round, reactive to light, and not pinpoint. Specifically look for signs of focal neurologic deficits.
• A detailed, 6-part neurologic examination should be performed, and the findings should be documented. With the exception of nimodipine, CCBs have poor CNS penetration. Therefore, drowsiness, seizures, or altered mental status in the absence of hemodynamic collapse should alert the physician to the possibility of co-ingestions.
• Examine the abdomen, paying particularly close attention to the right upper quadrant. With CCB toxicity, venous congestion can lead to hepatic engorgement and stretching of the hepatic capsule, causing hepatic tenderness and hepatomegaly. Hepatojugular reflux may also be observed. Listen for bowel sounds because CCBs may cause enteric dysmotility. Bowel perforation secondary to CCB ingestions has been reported. Peritoneal signs of rebound and guarding are ominous findings.
• Hyperglycemia may result from impaired insulin release in addition to insulin resistance. Although beta-antagonist toxicity may resemble CCB toxicity in most aspects of the physical examination, the serum glucose level may help identify which cardiovascular toxin was ingested because beta-antagonists often lower the glucose level.

Causes

CCB agents are some of the most widely prescribed drugs in America. They are marketed under many brand names and many doses in many colors. They look appealing to children, resembling candy, and are found in many households; therefore, these drugs are commonly unintentionally ingested.

• Verapamil (Calan, Isoptin), a phenylalkylamine, has a higher affinity for calcium slow channels in the cardiac conducting system than in peripheral smooth muscle cells; therefore, it causes a greater negative inotropic effect than other CCB agents. Several sustained-release formulations are available (eg, Calan SR, Isoptin SR, Verelan, Covera HS). Patients who ingest any of these preparations should be observed longer than those who consume other preparations to guard against a delayed onset of toxicity. Verapamil almost exclusively undergoes hepatic metabolism, yielding a single active metabolite, norverapamil. This compound has 20% of the pharmacologic activity of the parent drug.
• Nifedipine (Procardia, Procardia XL, Adalat, Adalat CC) is a dihydropyridine. Nifedipine has relatively high affinity for the calcium channels in the smooth muscle cells of vascular tissue and causes little to no AV nodal interference. The primary manifestation of nifedipine-related toxicity is hypotension secondary to loss of systemic vascular resistance. This agent has no active metabolites after hepatic metabolism and attains peak drug levels 2-6 hours after ingestion.
• Nicardipine (Cardene, Cardene SR) and nimodipine (Nimotop) are similar to nifedipine. They demonstrate greater peripheral vascular smooth muscle effects. The selectivity of nimodipine is directed at cerebral vasculature because of its high lipid solubility and ability to cross the blood-brain barrier. Nimodipine has been approved for use in the treatment of cerebral ischemia after subarachnoid hemorrhage. Nicardipine and nimodipine may have small negative inotropic effects. These compounds are predominantly metabolized by the liver. They do not exhibit a large first-pass effect, as is observed with other CCBs.
• Diltiazem (Cardizem, Cardizem CD, Cardizem SR, Dilacor XR, Teczem, Tiazac) has properties from the drug categories mentioned above. Although diltiazem demonstrates an affinity for both cardiac conductive tissues and vascular smooth muscle cells, its clinical response more closely resembles that of verapamil than nifedipine. Diltiazem mainly undergoes hepatic metabolism with a large first-pass effect that may differ from patient to patient. Its peak plasma concentration in non–sustained-release preparations is 2-8 hours.
• Amlodipine (Norvasc) is one of the newer CCB agents. It has a long half-life of 30-58 hours.⁴ Clinical effects of amlodipine are similar to those of nicardipine. Because of its long effect time, amlodipine ingestion increases the risk of morbidity and mortality.
• Bepridil (Vascor) is a unique CCB with some sodium channel-blocking activity. It is used for refractory angina and may prolong the QT interval corrected for heart rate (QTc) through a potassium channel-blocking effect. Similar to other drugs with this property, Bepridil can cause torsades de pointes. Bepridil is no longer available in the United States.
• Mibefradil (Posicor) was taken off the market after adverse drug reactions were reported. It was a selective T-channel CCB that was supposed to have less negative inotropy than earlier drugs in its category.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Beta-blocker ingestion
Ingestion of any sedative hypnotics, including benzodiazepines, barbiturates, and nonbarbiturate sedative hypnotics (eg, glutethimide)
Ingestion of any alcohols or cyclic esters
Clonidine ingestion
Ingestion of any plants containing digoxin-like compounds (eg, grayanotoxin, oleander, foxglove)
Narcotic toxicity
Septicemia
Septic shock
Spinal shock
Typhoid
Allergic reaction
Trauma resulting in tamponade and tension pneumothorax
Respiratory arrest (infants)

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Basic chemistries: Look for hyperglycemia, hypokalemia, and a decreased serum bicarbonate level secondary to acidosis. Obtain a baseline calcium level before intravenously (IV) administering calcium, unless the patient requires immediate detoxification due to severe poisoning.
• ABG: Consider this test in severely affected patients. In patients with significant toxicity, ABGs can be used to assess the acid-base status and respiratory function.
• CBC count: An elevated WBC count may suggest infection.
• Aspirin level: Determine the aspirin level of all patients who present to the ED after a suicide attempt.
• Acetaminophen level: Determine the acetaminophen level of all patients who present to the ED after a suicide attempt.
• Serum level of ingested medication: Determining the serum drug level of the ingested medication is not always feasible and is usually not helpful.
• Urine toxicology: Look for co-ingestions with illicit substances that may alter treatment protocols.

Imaging Studies

• Chest radiography is not routinely indicated unless physical findings suggest lung pathology.
• An abdominal flat plate may be obtained if a co-ingestion with a radio-opaque tablet is also suspected.

Other Tests

• Perform ECG in all patients who present to the ED who may have ingested any cardiac medication.
• Perform ECG in every patient who presents with a suicide gesture to evaluate for the signs of tricyclic antidepressant (TCA) overdose. This results in a positive deflection in the augmented voltage unipolar right arm lead (aVR) in the terminal 40 microseconds of the complex. TCA toxicity can rapidly progress to malignant arrhythmia if left untreated.
• ECG changes are neither sensitive nor specific for calcium channel blocker (CCB) toxicity.
• ECG may reveal bradycardia; tachycardia; first-, second-, or third-degree AV block; any type of bundle-branch block; and nonspecific ST-T wave changes.

Procedures

• Gastric lavage
• • The usefulness of gastric lavage is still debated.
  • Weigh the risk of aspiration against the probability of removing undigested medications remaining in the stomach.
  • CCB agents slow gastric motility; therefore, gastric lavage may be advisable. Lavage is especially important for patients who may have taken a large dose of medication or for those who have ingested sustained-release preparations.
  • After gastric lavage is completed, the nasogastric (NG) or orogastric (OG) tube can also deliver activated charcoal and a cathartic.
  • An endotracheal tube cuff protects the airway during the lavage, thus placing patients at lower risk of aspiration by intubating them.
• Foley catheter placement: This may be indicated to monitor urine output in severely poisoned patients.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Patients with calcium channel blocker (CCB) toxicity should be treated in a well-equipped emergency facility or an intensive care setting. Numerous strategies for treating patients who have ingested CCBs are available.

• Basic supportive care is the first and possibly most important mode of management.
• Blood pressure can be augmented with isotonic sodium chloride solution or Ringer lactate solution. Both are efficient volume expanders.
• • Deliver fluid in 20-mL/kg boluses, which may be repeated 1, 2, or even 3 times if the patient remains hypotensive.
  • If blood pressure normalizes with these fluid challenges, start IV fluid at 1-2 times the normal maintenance rate. If this does not raise the blood pressure to the desired level, positive inotropes (eg, dopamine, norepinephrine, epinephrine) can be added.
  • If hypotension persists, administer oxygen with a nasal cannula and place the patient in Trendelenburg position to perfuse the brain with well-oxygenated blood.
  • Correction of acid-base disturbances and electrolyte abnormalities is also important to optimize cardiac function.
• Gut decontamination may be considered because CCBs delay gastric emptying. Perform gastric lavage with a large-bore OG hose.
• • Use of a wide-diameter tube is necessary because sustained-release tablets are large and resistant to breakdown.
  • Sustained-release tablets may not fit through a simple Salem sump NG tube. A small tube diameter decreases the effectiveness of lavage.
• If the child has ingested a large number of CCB tablets, especially sustained-release tablets, consider whole-bowel irrigation with polyethylene glycol or a cathartic, such as sorbitol, which is included in some activated charcoal products. Under these circumstances, the pills may aggregate to form bezoars and can be continuously absorbed for long periods.
• • Administer polyethylene glycol at a rate of 0.5 L/h for 4-6 hours or until rectal effluent becomes clear.
  • Administer activated charcoal in a 1-g/kg initial dose; this administration can be repeated every 4 hours at half the initial dose. Because gastric emptying may be delayed, administer activated charcoal even if the patient presents well after the ingestion. In children, care must be used not to administer a significant amount of sorbitol-containing products because of the potential to induce electrolyte disturbances. Some package inserts recommend not using sorbitol-containing charcoal products in children who weigh less than 32 kg and recommend not to use these products as multiple-dose agents.
• Ipecac syrup always is contraindicated in CCB toxicity because the patient may rapidly lose consciousness and may develop seizures. The added vagal tone of emesis can also worsen cardiovascular status. For this reason, an antiemetic can be administered to prevent vomiting secondary to the initial CCB ingestion.
• Many pharmacologic therapies have been proven beneficial in CCB toxicity.
• • Calcium administered IV theoretically creates a concentration gradient large enough to partially overcome the channel blockade, driving calcium into the cells. Calcium is usually administered IV as calcium gluconate or calcium chloride; either form is acceptable to manage CCB overdose if an equal amount of ionized calcium is administered. Administer a calcium bolus if the patient is symptomatic at presentation. A high-dose IV bolus of calcium can be repeated, or a slow calcium infusion can be implemented if the response to the initial bolus begins to diminish.
  • Under extreme circumstances, consider drugs such as 4-aminopyridine or its more potent cousin 3,4-diaminopyridine to increase calcium entry into the cell. Their exact mechanism is not fully understood, but they may indirectly promote calcium entry by blocking voltage-sensitive potassium channels. Although these medications have reversed verapamil toxicity in feline, canine, and rabbit experiments, their value and safety in human CCB toxicity has not been established.
  • Positive inotropes (eg, dopamine, epinephrine) stimulate myocardial contractility and cause vasoconstriction by activating adrenergic receptors on the cell membrane. These receptors then activate adenylyl cyclase to produce the second messenger, cyclic adenosine monophosphate (cAMP). This intracellular intermediary causes calcium to enter the cell and causes its release from the endoplasmic reticulum. Calcium then effects conformational changes to cellular machinery and initiates smooth and cardiac muscle contractions.
  • Other agents that raise intracellular cAMP levels indirectly cause an increased cellular response by promoting calcium entry into the cell. Glucagon, a polypeptide hormone, is thought to have its own receptor that is separate from adrenergic receptors. Stimulation of this receptor is also believed to increase cAMP production. Glucagon is supplied as a lyophilized powder and must be reconstituted. The manufacturer includes an ampule of propylene glycol that can be used for single injections. However, if an excessive amount is administered, propylene glycol (the same diluent that comes with phenytoin) causes hypotension and arrhythmias. For this reason, glucagon infusions and repeat doses should be reconstituted in 5% dextrose in water (D5W) to avoid administering large doses of propylene glycol.
  • Another method of increase intracellular cAMP concentrations is to prevent its breakdown. This can be accomplished with certain phosphodiesterase inhibitors. Inamrinone (formerly amrinone) is a bipyridine that inhibits phosphodiesterase isoenzyme III, specific for cardiac and vascular tissue. Exercise caution using this drug. Although it increases cardiac contractility, it also causes peripheral vasodilation and may worsen the patient's clinical condition; this is not an insignificant concern, especially given the relatively long half-life of phosphodiesterase inhibitors. Careful consideration should be given to the decision to use this type of medication in the face of hypotension or potential hypotension. One study of inamrinone in patients with congestive heart failure showed that inamrinone had a 3% risk of causing cardiac arrhythmias. However, this rate was significantly lower than that of arrhythmias caused by sympathomimetic agents in the same patient population.
  • High-dose insulin is the most recently proposed remedy for CCB toxicity. Insulin has an intrinsic positive inotropic effect. Insulin appears to promote calcium entry into the cells by means of an unknown mechanism. Because CCB agents inhibit insulin production or release and also decrease the ability of the heart to use free fatty acids, it seems intuitive that exogenous insulin administration improves the clinical picture in CCB toxicity. Note that 2 opposing hormones, such as insulin and glucagon, both have beneficial effects in treating CCB toxicity. Although the therapeutic efficiency of high-dose insulin has been effective in animal models, no human trial has been completed. One must always closely monitor serum potassium and glucose levels when administering high doses of insulin.
  • Intralipid has recently been studied in a rat model of verapamil toxicity.⁵ Because this drug is quite lipophilic, pulling the active drug into the lipid microspheres from the plasma is theorized to reduce the drug's toxicity. Although this rat experiment has met with some success in lowering mortality, human trials need to be performed to confirm this positive effect.

Surgical Care

As with medical care for CCB overdose, many surgical modalities can be used.

• A transvenous pacemaker may be placed if the transthoracic cutaneous pacer fails to capture in the face of symptomatic bradycardia. Pacing may decrease the need for pressors in a patient who may not tolerate a positive cardiac inotrope because of cardiac ischemia, although this likely is not a concern for pediatric patients. Cardiac pacing is typically required for 12-48 hours.
• Consider temporary placement of an intra-aortic balloon pump for hypotension that is refractory to all other medical and surgical treatments.
• Cardiopulmonary bypass can be a last resort to support the blood pressure long enough for the body to clear the ingested toxin.
• Extracorporeal membrane oxygenation (ECMO) has also been attempted in patients who have hypotension refractory to all pharmacologic therapies. One case reported by Durward described a massive diltiazem ingestion (12 g Cardura CD) that resulted in prolonged cardiac standstill.⁶ However, after 48 hours of ECMO and 15 days in the critical care unit, the patient made a very good recovery and was discharged home "fit and well and showed no evidence of neurologic dysfunction."
• Hemodialysis or charcoal hemoperfusion may provide a method of drug removal in cases of severe toxicity when the patient's condition appears to be worsening or if the ingestion is known to be large. Although CCBs are highly protein bound, some physicians believe that hemodialysis or charcoal hemoperfusion may be used as a last resort in severely toxic patients who have no other hope. These treatment modalities are debatable.

Consultations

Many different specialists can help the physician care for a patient who has ingested a CCB.

• A hemodynamically unstable child who has ingested a CCB requires prolonged care in a pediatric intensive care unit (PICU); arrange for consultation with this service soon after starting treatment in the ED. If the hospital does not have a PICU, transfer to a more specialized hospital should be considered sooner rather than later when severe toxicity has already developed.
• Request consultation with a cardiologist or pediatric cardiologist to place a transvenous pacemaker if capture cannot be accomplished with transthoracic cutaneous pacing pads.
• Even if the ED personnel do not need care advice for the patient with CCB overdose, notify the hospital's regional poison control center to document the overdose characteristics and help create an accurate database for epidemiologic studies. In general, working in partnership with regional poison control centers on all ingestions is a good practice.
• After any patient who has attempted suicide is medically stable, request a psychiatric consultation.

Diet

Do not allow patients with CCB toxicity to eat after the ingestion because they risk rapid mental status deterioration, including seizures, and may require intubation. Placement of an endotracheal tube when the patient has an empty stomach decreases the risk of aspiration. For these same reasons, do not administer ipecac syrup.

Activity

Orthostatic hypotension is a particular concern in patients who ingest CCBs. Limit the activity level of these patients to bed rest at the first clinical signs of CCB toxicity.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Initial management for a symptomatic calcium channel blocker (CCB) overdose includes cardiovascular support with IV fluids and positive inotropy. Calcium administration can partially overcome channel blockade and, in all but the most severe cases, should improve the clinical condition. By increasing intracellular cAMP concentrations, glucagon and inamrinone (formerly amrinone) also reportedly improve blood pressure and heart blockade. High-dose insulin coadministered with dextrose to maintain euglycemia is the most recent addition to the treatment plan for CCB overdose. Always use basic GI decontamination in overdose situations.

Drug Category: Calcium

These agents theoretically increase calcium's concentration gradient, overcoming the channel blockade and driving calcium into the cells. Calcium is given to reverse hypotension and improve cardiac conduction defects.

Drug Category: Sympathomimetics

These agents augment blood pressure by stimulating dopamine, alpha-adrenergic receptors, and beta-adrenergic receptors. This extracellular effect is transduced across the cell membrane and activates adenylyl cyclase in the cell to form cAMP. The activation induces calcium inflow from the endoplasmic reticulum and the extracellular space, which initiates muscle cell contraction. Sympathomimetics lead to vasoconstriction and increased cardiac inotropy, chronotropy, and dromotropy.

Drug Category: Antihypoglycemic agent

Glucagon uses a different receptor than that used by sympathomimetics to stimulate intracellular cAMP production, increasing cardiac conduction and contractility. Glucagon has positive inotropic and chronotropic effects, which may be useful for treating bradycardia caused by calcium channel blockers.

Drug Category: Phosphodiesterase inhibitors

Inamrinone, a bipyridine, inhibits the phosphodiesterase isoenzyme III specific for cardiac and vascular tissue and decreases the rate of cAMP breakdown, increasing contractility.

Drug Category: Muscarinic receptor blocking agents

Atropine, an anticholinergic medication, works by blocking muscarinic acetylcholine receptors. Use of this drug theoretically lets the sympathetic characteristics of the autonomic nervous system prevail over the parasympathetic system. This action includes vasoconstriction and increased cardiac inotropy and chronotropy.

Drug Category: Insulin

Case reports of patients treated with high-dose insulin are beginning to support use of this drug in CCB toxicity. Insulin increases cardiac output and may increase survival as long as plasma glucose levels are monitored and supplemented with exogenous dextrose. To date, no prospective human trials have been published supporting this practice.

Drug Category: GI decontaminants

Activated charcoal adsorbs ingested medication remaining in the GI system and creates a concentration gradient to "pull back" medication circulating in the blood stream. Cathartics increase GI transit time.

Drug Category: Aminopyridines

These drugs inhibit the voltage-sensitive potassium channels.

Drug Category: Fluids for fluid resuscitation

Augmenting the intravascular volume may help move the patient to a more favorable Starling curve, in addition to filling dilated peripheral vascular structures.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• The need to hospitalize patients who have mild calcium channel blocker (CCB) ingestions is debated.
• • Most physicians believe that adults who have potentially severe CCB toxicity and toddlers who have ingested as little as one sustained-release CCB tablet should be observed in the hospital for 24 hours for arrhythmias and hypotension.
  • Some groups of physicians and toxicologists are beginning to debate this practice. They state that when a few tablets are ingested, poison centers may reasonably recommend observation at home rather than refer patients for prolonged (24-h) in-hospital monitoring if the child is asymptomatic. This argument places the burden on the physician to prove that these ingestions are safe enough to be treated at home.
• Obtain a psychiatric evaluation for all suicidal patients after they have been medically stabilized.

Further Outpatient Care

• Most poison control centers recommend discharge and home monitoring of the patient if they are asymptomatic after 6-12 hours of ED observation, as long as they did not ingest a sustained-release CCB preparation.
• Patients who have exhibited suicidal ideations should have a psychiatric consultation before discharge home from the ED.

Transfer

• Some patients may present with overwhelming bradycardia and hypotension that is unresponsive to available medical management. Patients with these complications may require cardiopulmonary bypass, ECMO, or an intraaortic balloon pump to maintain peripheral perfusion until the CCB has cleared their system; transferring these patients to a facility offering such services may be reasonable.
• Not all community hospitals offer a pediatric ICU for inpatient care of the hemodynamically unstable child. This may also be an indication to transfer the patient.

Deterrence/Prevention

• Parents should keep all medicine out of reach of children.
• Use childproof bottles for all medications, especially those that are potentially dangerous to youngsters.
• All homes should have the number of the local poison control center posted on or near their telephones for use in an emergency. The number for the New York City poison control center is 212-POISONS (212-764-7667); the center offers advice to anyone who calls from anywhere in the world. The new national poison control number is 800-222-1222; calling this number connects the caller to their regional poison control center.

Complications

• Seizure
• Coma
• Death
• Anoxic encephalopathy from prolonged CNS hypoxia
• Ileus
• Bowel infarction or perforation from mesenteric hypotension
• Noncardiogenic pulmonary edema
• Aspiration pneumonia

Prognosis

Prognosis depends on the following:

• Amount and formulation of drug ingested
• Co-ingestions
• Patient's age
• Time elapsed before treatment begins
• Underlying disease states
• Specific treatments
• Initial rhythm
• Use of a pacemaker and time before it is placed

Patient Education

• Educate parents who take CCB medications about child safety.
• For excellent patient education resources, visit eMedicine's Drug Overdose Center and Poisoning - First Aid and Emergency Center. Also, see eMedicine's patient education articles Poisoning, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Few medical or legal concerns are specifically associated with calcium channel blocker (CCB) toxicity.
• However, failure to recognize co-ingestion of a substance that has an antidote or simple treatment can result in litigation if the failure contributes to a negative outcome.

Special Concerns

• Data collection and case reporting through regional poison control centers are necessary to direct further investigations and to determine the epidemiology of substance ingestions.
• When calling a poison control center, be prepared to give as much information as possible during the initial call.
• Estimate amount and type of drug ingested, elapsed time since ingestion, and time treatment was started.
• Many poison control centers make follow-up calls to learn patient outcomes; the physician can supply additional information at that time.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Lai MW, Klein-Schwartz W, Rodgers GC, Abrams JY, Haber DA, Bronstein AC. 2005 Annual Report of the American Association of Poison Control Centers' national poisoning and exposure database. Clin Toxicol (Phila). 2006;44(6-7):803-932. [Medline].
2. Koren G. Medications which can kill a toddler with one tablet or teaspoonful. J Toxicol Clin Toxicol. 1993;31(3):407-13. [Medline].
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