CME REVIEW ARTICLE
Calcium Channel Blocker Toxicity
Anna Maria Arroyo, MD* and Louise W. Kao, MDÞ
Abstract: Calcium channel blockers continue to be used for the
management of a wide variety of adult and pediatric conditions including
hypertension, angina pectoris, atrial arrhythmias, Raynaud phenomenon,
and migraine headaches. With increased use comes increased potential
for misuse and abuse. This article serves as a review of calcium channel
blocker physiology with emphasis on presentation and management of
the pediatric patient with calcium channel blocker toxicity.
Key Words: calcium channel blocker, poisoning, insulin, glucagon,
lipid emulsion
(Pediatr Emer Care 2009;25: 532Y541)
TARGET AUDIENCE
This CME review article is intended for emergency medi-
cine physicians and residents interested in the evaluation and care
of acute pediatric calcium channel blockers (CCB) ingestion.
LEARNING OBJECTIVES
After completion of this article, the reader should be able to:
1. Describe the function of CCB and identify differences
between the classes.
2. Identify the clinical signs and symptoms of acute CCB
poisoning, and describe the care of an asymptomatic toddler
who possibly ingested 1 or 2 pills of a CCB.
3. Compare and contrast treatment modalities including
gastrointestinal decontamination, extracorporeal life sup-
port (ECLS), and insulin therapy in the setting of CCB
poisoning.
BACKGROUND
Of the 9 CCB currently sold commercially in the United
States, only verapamil and amlodipine are approved by the Food
and Drug Administration (FDA) for use in the pediatric
population1 (Table 1). Despite the limited number of FDA-
approved pediatric indications, a significant number of CCB
exposures continue to be reported to the US Poison Control
Centers yearly.4Y6 In 2006, the American Association of Poison
Control Centers recorded approximately 2.4 million human
exposures, of which 50.9% were in children younger than 6
years. Calcium channel blocker exposures in 2006 numbered
From the *Fellow (Arroyo), Medical Toxicology, and †Director (Kao), Depart-
ment of Emergency Medicine, Indiana University School of Medicine,
Indianapolis, IN.
Reprints: Anna Maria Arroyo, MD, Washington University School of
Medicine Hospital Medicine Division, Campus Box 8058, 660 South
Euclid Avenue, St. Louis, MO 63110 (email: aarroyo@neoucom.edu).
The authors have disclosed that they have no significant relationship with or
financial interests in any commercial companies that pertain to this
educational activity.
All staff in a position to control the content of this CME activity have
disclosed that they have no financial relationships with, or financial
interests in, any commercial companies pertaining to this educational
activity.
Lippincott CME Institute, Inc. has identified and resolved all faculty conflicts
of interest regarding this educational activity.
No funding or support was received for this work.
Copyright * 2009 by Lippincott Williams & Wilkins
ISSN: 0749-5161
532 www.pec-online.com
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10,031 overall, with 1363 exposures in children younger than 6
years and 234 exposures in children 6 to 19 years.5 Increased
access to these medications may increase the potential for
exploratory and intentional poisoning. As such, it is important
for emergency medicine physicians to recognize and effectively
treat patients who present with potential CCB poisoning.
CALCIUM CHANNEL PHYSIOLOGY
Calcium plays a critical role for many physiologic
functions. Muscle contraction and myocardial conduction
depend on an interaction between intracellular and extracellular
calcium. Voltage sensitive L-type calcium channels located on
the cellular plasma membrane regulate this interaction.2
Vascular smooth muscle contraction begins with calcium entry
into the cells through these L-type channels. Once inside,
calcium binds calmodulin which stimulates the phosphorylation
of myosin by myosin light-chain kinase.2 Phosphorylated
myosin becomes active and binds actin leading to muscular
contraction.
Myocardial contraction depends on Bcalcium-induced
calcium release.[2 Here, phase 2 of the action potential is
created by the slow influx of calcium through L-type channels,
which serves as an intracellular second messenger. This calcium
binds to receptors on the sarcoplasmic reticulum causing the
release of stored calcium. Cytosolic calcium binds troponin C,
freeing actin from troponin and tropomyosin through confor-
mational change.2 Actin is then able to bind myosin leading to
myocardial muscle contraction.
Cardiac conduction is also dependent on calcium.2 Spon-
taneous depolarization during phase 4 of the action potential in
the sinoatrial (SA) node is mediated through calcium influx.
Normal propagation of electrical impulses through myocardial
conduction tissues such as the atrioventricular (AV) node is also
dependent on this calcium influx.2
In addition, calcium plays a vital role in skeletal muscle
contraction. However, CCB preferentially affect cardiac and
vascular smooth muscle. Even so, CCB exposure has been
associated with tetany in adults and myoclonic seizures in an 18-
month-old child.7
Pharmacology/Toxicokinetics of CCB
Oral CCB are well absorbed and undergo first pass
metabolism.2,8 The enzymes responsible for hepatic oxidative
metabolism may become saturated in cases of overdose.9 This
serves to decrease the effects of first pass metabolism, allowing
increased quantities of active drug to reach the systemic cir-
culation and may prolong the half-life of the CCB.2 In addition,
CCB are highly protein bound, and most have large volumes of
distribution.10
The currently available CCB are divided into 4 classes,
each with different affinities for myocardial and vascular smooth
muscle L-type calcium channels.2,8 These differing affinities are
responsible for the diverse physiologic effects seen with
therapeutic dosing. At therapeutic doses, dihydropyridines
preferentially bind vascular smooth muscle L-type channels
and produce the most potent vasodilatory effects of the CCB.2,8
Vasodilation is seen less with verapamil and least with diltiazem.
Pediatric Emergency Care & Volume 25, Number 8, August 2009
Pediatric Emergency Care & Volume 25, Number 8, August 2009
TABLE 1. CCB Available in the United States
Class1,2 Drug Pediatric FDA Approval
Phenylalkylamine Verapamil Yes
Benzothiazepine Diltiazem
Dihydropyridines Nifedipine
Isradipine
Amlodipine Yes
Felodipine
Nimodipine
Nisoldipine
Nicardipine
*In hours.
SR indicates sustained-release; ER, extended-release; CR, controlled-release; IR, immediate-release.
Dihydropyridines have only slight direct myocardial effect,
whereas verapamil causes profound inhibition at the SA and AV
nodes.2 Diltiazem also affects nodal tissue, but to a lesser extent.
Calcium channel blockers selectivity may be lost in overdose.11
Table 2 lists the suggested pediatric dosing of the FDA-approved
CCB. Pediatric dosing has been summarized elsewhere for the
nonYFDA-approved CCB.12 Kinetic information, including
elimination half-life and time to peak serum concentration for
therapeutic oral dosing, is listed in Table 1.
CCB POISONING
Clinical Manifestations
Most children are asymptomatic after exploratory expo-
sure, as small ingestions present little or no risk.12,13 However,
deaths after the ingestion of 1 or 2 tablets have been reported,
and symptomatic exposures may be rapidly fatal.12 Serious
toxicity can be delayed after the ingestion of a sustained-release
preparation.14 Cardiovascular instability may be seen with
significant ingestions and is manifested by hypotension,
bradycardia, conduction abnormalities of the SA/AV nodes,
and idioventricular arrhythmias. Sinus tachycardia has also been
reported in cases of CCB overdose. Patients may present with
altered mental status, seizures, respiratory depression, hyper-
glycemia, and metabolic acidosis. Non-cardiogenic pulmonary
edema, possibly due to selective precapillary vasodilation and
aggressive fluid resuscitation, has been reported after CCB
ingestion.9,15 Patients with underlying renal or hepatic dysfunc-
tion may manifest signs of toxicity with therapeutic doses. The
different pharmacological affinities seen may also lead to some
agent-specific effects with ingestion. At high doses, verapamil
can block sodium channels, aggravating the hypotension and
depressed cardiac output seen with calcium channel blockade.
Initial Emergency Department Evaluation
Unfortunately, it can be difficult to risk stratify patients,
particularly pediatric patients, after CCB exposure. Severity is
difficult to predict based on prodromal events and history,
TABLE 2. Therapeutic Dosing of CCB in Pediatric Patients1
Verapamil No FDA-approved oral dose for patients younger than 18 y
For atrial arrhythmia or paroxysmal supraventricular tachycardia: aged G1 y, 0.1Y0.2 mg/kg IV over 2 min. Aged 1Y15 y,
0.1Y0.3 mg/kg IV over 2 min (maximum: 5 mg)
Amlodipine For hypertension: aged 6Y17 y, 2.5Y5 mg orally per day
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Calcium Channel Blocker Toxicity
Time to Serum Peak* Elimination Half-Life*
5.21 (SR) 11 (ER) 3Y7
4Y6 (CR) 10Y18 (ER) 3.5Y6 (5Y7 SR)
0.5 2Y5
7Y18 (CR) 1.5 (IR) 8
6Y12 30Y50
2.5Y5 11Y16
1 1Y2
6Y12 (ER)3 7Y12
0.5Y2 2Y4
particularly in toddlers where the ingestion is often not
witnessed. Documented cases have demonstrated significant
overlap between toxic and nontoxic doses, and current data do
not support a precise definition. In addition, delayed clinical
deterioration is possible after sustained-release CCB exposures.
Every patient with a potential CCB overdose should be placed
on a cardiac monitor and undergo electrocardiogram evaluation
for possible conduction abnormalities as this may be an early
sign of significant poisoning. Asymptomatic toddlers should be
monitored for 6 hours after ingesting a regular release for-
mulation and for at least 24 hours if a sustained-release for-
mulation is involved.2,12 All symptomatic patients, and those
who have ingested sustained-release CCB formulations, should
be admitted and placed on cardiopulmonary monitoring.2,14
Measurement of plasma levels can be considered in the eval-
uation of possible child abuse, but are not readily available and
do not influence short-term patient management. Calcium
channel blockers also affect L-type calcium channels in the
pancreas, preventing the release of insulin. This, in addition
to CCB-induced insulin resistance, produces a hyperglycemic
state which has been shown to correlate with poisoning sever-
ity in the adult population.16
TREATMENT
Although there is no consistently reliable antidote, initial
management should focus on cardiovascular stabilization.2,14,17
Trendelenberg positioning may help alleviate pre-syncopal
symptoms. Hypotension unresponsive to isotonic volume ex-
pansion and intravenous vasoactive medications can be second-
ary to CCB-induced bradycardia and decreased contractility.
Careful clinical evaluation should allow for supportive therapy
to be directed at the physiological derangement, which may be
either at the level of systemic vascular resistance or at the cardiac
pump. Hypotension and bradycardia may respond to routine
advanced cardiac life support measures using atropine, dopa-
mine, isoproterenol, or other vasoactive medications which
should be titrated to maintain adequate blood pressure and urine
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Arroyo and Kao Pediatric Emergency Care & Volume 25, Number 8, August 2009

TABLE 3. Specific Therapy for CCB Toxicity

Dosing
Agent Bolus Infusion Adverse Effects
Calcium 10Y20 mg/kg IV over 10Y15 min, 20Y50 mg/kg/hr Extravasation, hypercalcemia, hypophosphatemia
may repeat every 10Y15 min
Glucagon 50 Kg/kg over 1Y2 min 70Y100 Kg/kg/h Nausea, vomiting, hyperglycemia, hypokalemia
Insulin (HIE)* 1.0 IU/kg 0.5Y1.0 IU/kg/h Hypoglycemia, hypokalemia
Lipid Emulsion 20% 1 mL/kg over 1 min, repeated 0.25 mL/kg/min Fat emboli, thrombophlebitis, seizures
(adult dosing) every 3Y5 min to a maximum
of 3 mL/kg
Amrinone 750 Kg/kg 1Y20 Kg/kg/min Vasodilation
*Clinical response may be delayed 30 to 45 min after initiating therapy. Dextrose infusion may be required.

output.8 Cardiac pacing can be considered for significant
bradycardia and conduction blocks.2 More specific therapies
such as calcium, glucagon, and insulin/glucose are discussed in
more detail below and in Table 3. Suggested treatment
guidelines are presented in Figure 1.
Gastrointestinal Decontamination
Early gastrointestinal decontamination may be considered
in any patient with a potentially life-threatening ingestion. Pro-
longed absorption has been reported with CCB ingestion, par-
ticularly when sustained-release preparations are involved,
therefore, delayed gastrointestinal decontamination may be of
benefit.9 Lapatto-Reiniluoto et al19 demonstrated decreased
absorption of a therapeutic dose of sustained-release verapamil
using activated charcoal with and without whole-bowel irriga-
tion, 1 hour after ingestion. When given alone, activated char-
coal decreased verapamil absorption detected by the area under
the curve by 63%. The addition of whole-bowel irrigation leads
to an 85% reduction. Early use of whole-bowel lavage9,20 and
multidose activated charcoal21 may decrease initial drug ab-
sorption and interrupt enterohepatic circulation,9 lowering se-
rum drug levels.
Although uncommon, bezoar formation has been reported
with therapeutic use and with intentional ingestion and may
result in delayed or prolonged toxic effects.9,22 The possibility of
a bezoar should be considered in any patient with persistent or
recurrent symptoms suggestive of continued exposure to a CCB
or with an unexplained mass seen within the gastrointestinal
tract on diagnostic imaging such as computed tomography.
Polyethylene glycol solution has been associated with bezoar

FIGURE 1. Calcium channel blocker exposure algorithmVasymptomatic child.12,18

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Pediatric Emergency Care & Volume 25, Number 8, August 2009
passage,9 but a conservative approach is not ideal if a potential
bezoar is felt to contain active medication. A gastrointestinal
consult for possible endoscopic removal versus a surgical
consult may also be considered.22
Calcium
Calcium can be used to treat cardiac symptoms from mild
to moderate intoxications and is often used as a first-line
therapy.8 Hemodynamic improvement because of increased
inotropy has been demonstrated in animal studies as well as
human case reports.2 However, calcium does not significantly
affect peripheral vascular resistance or heart rate. The required
dose and route of calcium administration is unclear, and clinical
effect is inconsistent.11,15 In addition, patients treated with intra-
venous calcium risk extravasation and skin necrosis. This can be
minimized with dilution or with administration through a central
venous catheter.15 Calcium chloride is preferred to calcium glu-
conate in the non-acidemic patient because of the higher per-
centage of calcium available (13.4 mEq vs 4.3 mEq in 10 mL of
10% solution, respectively).2 Calcium gluconate may be pref-
erable if the patient is acidemic as calcium chloride may worsen
existing acidosis. Pediatric patients may receive an initial 10 to
20 mg/kg intravenous dose of calcium over 10 to 15 minutes
(0.1Y0.2 mL/kg of 10% calcium chloride or 1Y2 mL/kg of 1%
calcium chloride).8 If necessary, intravenous dosing may be
repeated every 10 to 15 minutes or followed by an infusion of 20
to 50 mg/kg/h. The dose for larger children and adolescents
should not exceed the adult dose of 10 mL (1 g) of 10% calcium
chloride. Calcium and phosphorus should be monitored closely,
and ionized calcium should not exceed twice normal.
Glucagon
Glucagon, because of its inotropic, chronotropic, and dromo-
tropic effects, has been used in the treatment of the myocardial
depression seen with CCB poisoning. Its mechanism is via acti-
vation of adenylate cyclase and increased production of cAMP,
independent of myocardial > and A receptors.2,23 Glucagon may
be particularly beneficial in mixed ingestions with other car-
dioactive agents, such as A blockers. Glucagon increases heart rate
and cardiac output in addition to reversing the second- and third-
degree AV block seen in animal models of CCB poisoning.24
Animal studies do not show a consistent increase in mean arterial
pressure or improved survival.24 It is unclear whether glucagon
use would confer any additional benefit over traditional
vasopressors in pure CCB toxicity.2
Glucagon should be considered in the treatment of CCB
toxicity when other inotropic agents have been optimized.24
A suggested loading dose is 50 Kg/kg intravenously over 1 to
2 minutes.8 Because of the short half-life of glucagon, a
maintenance infusion may be required and can be initiated at
50 to 100 Kg/kg/h and titrated to effect.2,8
Dose-dependent adverse effects seen with glucagon ad-
ministration include nausea, emesis, hypoglycemia and hyper-
glycemia, and hypokalemia. Hypersensitivity reactions may also
occur.25 In addition, glucagon is known to cause pheochromo-
cytoma catecholamine release and is contraindicated in these
patients.26
Hyperinsulinemia/Euglycemia
In addition to the cardiac effects normally attributed to
CCB, these medications bind L-type calcium channels on
pancreatic A-islet cells, inhibiting insulin release and altering
tissue insulin sensitivity. This leads to impaired cellular glucose
uptake and hyperglycemia. A shift from free fatty acid oxidation
to dependence on glucose use is also seen in cardiac myocytes.
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Calcium Channel Blocker Toxicity
The combined effects of hypoinsulinemia, insulin resistance,
and decreased glucose delivery caused by decreased perfusion
prevent adequate energy production, further compromising car-
diac function. The use of hyperinsulinemia/euglycemia (HIE)
therapy can break this cycle of hemodynamic deterioration. The
improvements seen in cardiac inotropy, peripheral vascular
resistance, and acidosis are likely related to changes in cellular
metabolism and can be delayed 30 to 45 minutes after initiating
therapy.17
Currently reported adult and pediatric doses used and du-
ration of HIE therapy vary. Existing recommendations sug-
gest the intravenous administration of 1 IU/kg of regular
insulin as a bolus followed by a continuous infusion of 0.1
to 1 IU/kg/h.10,17 Insulin infusion may be adjusted based on
clinical improvement with a goal minimal systolic blood pres-
sure of 100 mm Hg and a minimal heart rate of 50 beats per
minute. Blood glucose levels should be monitored every 30 to
60 minutes to minimize the risk of hypoglycemia. An infu-
sion of dextrose may be initiated and titrated to maintain blood
glucose at the upper limits of normal. Patients who initially
present hyperglycemic may not require supplemental dextrose.
In addition, insulin-induced intracellular potassium transfer
may lead to intravascular hypokalemia in patients treated with
HIE. Total body potassium stores are normal and most patients
remain asymptomatic without supplementation. In addition, the
acidosis seen with hemodynamic compromise may serve to
counteract intravascular hypokalemia through an outward flux of
potassium ions. Still, mild hypokalemia has been suggested to
improve insulin-induced inotropy and promote intracellular
calcium entry.
Clinical response with the return of hemodynamic stability
and withdrawal of vasoactive medications should dictate the
length of HIE therapy. Although not an ideal single agent, HIE
therapy should be used as an adjunct in the treatment of severe
CCB toxicity. Early initiation has been recommended to
maximize clinical benefit.17,27
Lipid Emulsion
Lipid emulsion is used as a component of total parenteral
nutrition and has been used as nutritional supplementation in
pediatrics.28 Animal models and human case reports have
demonstrated benefit from the use of lipid emulsion in the
treatment of local anesthetic toxicity, even when other resusci-
tative measures have been unsuccessful (also known as lipid
rescue).29Y34 These findings have prompted study on other
lipophilic agents such as CCB. Tebbutt et al35 evaluated the use
of lipid emulsion for the treatment of verapamil poisoning in
the rat. They were able to demonstrate prolonged survival in
addition to an increase in the median lethal verapamil dose.
Bania et al36 also demonstrate benefit from adding lipid
emulsion to initial therapy of atropine, calcium chloride, and
saline in a canine model of verapamil toxicity.
Although the exact mechanism for lipid emulsion therapy
remains to be elucidated, there are a number of possible
explanations. Lipid emulsion may sequester lipophilic drugs in a
separate intravascular lipid compartment, reducing the amount
of available free drug (also known as lipid sink). Lipid emulsion
may also promote clearance of drug through the hepatic delivery
of compound-laden chylomicrons. In addition, cardiac myocytes
undergo a switch from lipid to glucose metabolism in times of
stress and ischemia, and increased availability of fatty acids
provided by the lipid emulsion may reverse this metabolic
change.35,36 Nitric oxide and A-ketoacids are also increased with
lipid emulsion infusions. These compounds stimulate insulin
secretion and may serve to reverse the CCB-induced blockade
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Arroyo and Kao
of pancreatic insulin release, facilitating myocyte carbohydrate
use.35 Long-chain fatty acids also produce a dose-dependent rise
in calcium flux by activating myocyte calcium channels.37
Although more study is needed, early data on the potential ben-
efit of lipid emulsion for CCB poisoning appear promising.
One suggested dosing regimen for lipid emulsion is 20%
solution, 1 mL/kg over 1 minute, repeated every 3 to 5 min-
utes to a maximum of 3 mL/kg, followed by an infusion of
0.25 mL/kg/min.38 There is one case report of lipid rescue being
used successfully in a pediatric patient (13 years) with cardiac
arrhythmia from local anesthetic toxicity.31 However, lipid
rescue therapy has not been reported in a pediatric patient for the
treatment of CCB toxicity.
Adverse events from the use of lipid emulsion for rescue
therapy have not been reported to our knowledge, and in the
setting of refractory cardiac arrest, the potential benefits likely
outweigh the risks. However, the potential risks may include
allergy, anaphylaxis, fat emboli, thrombophlebitis, increased
susceptibility to infection, and seizures.28,39
Extracorporeal Drug Removal and Life Support
The high protein binding of all CCB, in addition to the
large volume of distribution seen with most, limits the use of
extracorporeal mechanisms of drug removal.2,8 However, hemo-
dialysis and hemoperfusion have been used to treat patients who
have failed to respond to intensive care measures including
artificial pacing and pharmacologic therapy.40 ter Wee et al41 did
not see a significant decrease in serum levels of verapamil and
norverapamil after 6 hours of hemodialysis in their patient.
Anthony et al42 demonstrate enhanced elimination of a CCB
with improved symptoms using charcoal hemoperfusion, in the
treatment of a combined diltiazem and metoprolol ingestion.
However, benefit is not consistent.43,44 In general, extracorporal
removal measures would not be expected to remove large
amounts of drug but can be considered as an adjunct in a
severely poisoned patient.14
Plasmapheresis is an additional option for the treatment of
severely poisoned patients.21,23,45 High CCB protein binding
allows for significantly lower plasma levels through the use of
plasmapheresis, potentially limiting cardiotoxicity. However, the
large volume of distribution seen with CCB makes net drug
removal poor.23 Still, plasmapheresis may serve as a bridge
allowing time for hepatic decontamination in severely poisoned
patients.45
Extracorporeal life support has been used to treat pediatric
and adult patients with severe cardiovascular compromise from
CCB poisoning, alone or in combination with other cardioactive
medications.20,23,46 Blood flow to vital organs is maintained by
ECLS, allowing time for drug redistribution as well as renal and
hepatic metabolism. By augmenting drug clearance, plasma-
pheresis may reduce the length of time needed for ECLS
therapy.23 Extracorporeal life support should be considered early
in potentially fatal CCB poisoning, especially when combined
with the ingestion of other synergistically active cardiovascular
medications.
Additional options for mechanical support for cardiac
compromise may include intraaortic balloon pumps and cardiac
pacing. Although pediatric data are limited regarding the use of
these therapies, abstracts and case reports primarily from adult
literature suggest benefit.44,47Y50 Pacemaker devices can be
considered for the treatment of refractory bradycardia or
complete heart block and may be the treatment of choice in
this situation. Intraaortic balloon pumps may also support
patients unresponsive to more conventional therapies because
these devices help preserve cardiac blood flow and may improve
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Pediatric Emergency Care & Volume 25, Number 8, August 2009
cardiac output in patients with severe cardiac compromise.
However, their use may be limited to larger children and ad-
olescents because vascular size can impede pump placement.
Alternative Therapies
Acidic conditions can decrease cellular calcium influx,
possibly through pH-dependent changes in channel conforma-
tion or affinity for the CCB. Administration of sodium bi-
carbonate may reverse this blockade, aiding in recovery. Cardiac
contractility has been shown to improve with an increase in the
pH of the calcium channel microenvironment. In addition,
verapamil has been suggested to have sodium channel blocking
activity that may be reversed with the administration of sodium
bicarbonate.51
Phosphodiesterase inhibitors, such as amrinone, inhibit the
breakdown of cAMP and have been used as adjunctive therapy
for CCB poisoning with limited success, possibly because of the
concomitant peripheral vasodilation which may result.2 Sug-
gested dosing for amrinone is 750 Kg/kg followed by an infusion
of 1Y20 Kg/kg/min.8
Metaraminol, a sympathomimetic amine, has been sug-
gested for use in the management of refractory hypotension
and bradycardia due to CCB poisoning because of its cardiac
inotropic effects and ability to increase systolic and diastolic
blood pressure while promoting peripheral vasoconstriction.
Wood et al52 report the successful use of metaraminol in the
treatment of a patient with amlodipine ingestion unresponsive to
intravenous fluids, calcium, glucagon, norepinephrine, and epi-
nephrine. However, metaraminol is not currently FDA-approved
for use in the pediatric population.1 Although metaraminol has
been used to treat CCB poisoning in the United States,48 it may
not be available in all institutions.
Vasopressin and terlipressin have been used in the
management of catecholamine-resistant septic shock in adult
and pediatric patients.53,54 When compared with vasopressin,
terlipressin has a prolonged half-life, which may help avoid the
rebound hypotension seen with discontinuation of vasopressin
therapy. The exact timing and dose for vasopressin and
terlipressin administration is unclear, with these medications
often being used as rescue therapy. The successful use of
terlipressin for CCB poisoning has been demonstrated in the
adult literature, but not in the pediatric literature. Currently,
terlipressin is not available in the United States.55 However,
vasopressin (and terlipressin where available) may be considered
for the treatment of severe CCB poisoning.
Fampridine has also been reported to aid in the successful
treatment of verapamil poisoning.41 This medication appears to
serve as a competitive verapamil antagonist,1,55 possibly through
enhanced transmembrane calcium influx.41 This medication is
currently only available in the United States for unlabeled and
investigational use.55
CONCLUSIONS
Calcium channel blocker poisoning can result in serious
morbidity and mortality, and toxicity may be delayed after
ingestion of sustained-release preparations. Some specific
supportive therapies exist and were discussed. Here we reviewed
CCB physiology and discussed patient presentation and
management to aid the emergency physician in identifying and
successfully treating a patient with an acute CCB ingestion.
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overdose with verapamil. Intensive Care Med. 1999;25(12):1473.
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Pediatric Emergency Care & Volume 25, Number 8, August 2009 Calcium Channel Blocker Toxicity

CME EXAM
Instructions for the Pediatric Emergency Care CME Program Examination

To earn CME credit, you must read the designated article and complete the examination below, answering at least 80% of the
questions correctly. Mail a photocopy of the completed answer sheet to the Lippincott CME Institute Inc., 770 Township Line Road,
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Education to provide continuing medical education for physicians.

CME EXAMINATION
AUGUST 2009
Please mark your answers on the ANSWER SHEET.

Calcium Channel Blocker Toxicity, Arroyo and Kao

1. The parents of a 2-year-old boy bring him to the emergency discharge the child at this point, when you find out that the
department with a report that he swallowed 1 to 2 of his medication is?
grandmother’s Bheart pills[ about 90 minutes ago. They a. Amlodipine
know that the grandmother takes a calcium channel blocker, b. Diltiazem
but they do not have the name of the drug. Which of the c. Felodipine
following issues will contribute to your management d. Nifedipine
decisions? e. Verapamil
a. Metabolic alkalosis is likely to ensue
b. Toxicity may not occur for 12 hours 4. You are monitoring an 18-month-old boy in the emergency
c. Ingestion of G 2 tablets is harmless department after the presumed ingestion of both diltiazem
d. Hypertension is a common complication and propanolol. Initially, his pulse is 110/min and his blood
e. The boy shows no signs of lethargy pressure is 95/55 mm Hg. After 2 hours of observation, the
nurse reports that his vital signs as a pulse of 70/min and a
blood pressure of 70/40 mm Hg. In addition to supportive
2. A 15-year-old girl ingested a handful of verapamil after her care and dopamine, you administer:
parents Bgrounded[ her for the weekend. When she emerged
a. Ca chloride
from the bathroom at home crying and confessed her
misdeed, her mother immediately called EMS. She appears b. Ca gluconate
well and has a pulse of 95 beats/min and a blood pressure of c. Glucagon
105/50 mm Hg. Your first priority is to? d. Insulin
e. Lipids
a. Measure oxygen saturation
b. Obtain a metabolic panel 5. A depressed 17-year-old girl who ingested multiple
c. Arrange an ICU admission amlodipine tablets develops severe hypotension while
d. Perform an electrocardiogram being monitored in your emergency department. She
e. Send serum for a drug level appears confused and her peripheral perfusion is poor.
Because you want to stanch her hemodynamic deterioration
3. The father of toddler reports that the child ingested 3 to 4 in the next 5 to 10 minutes, you would not rely on which
tablets that he took from his aunt’s pocketbook. When the therapy?
father asked the aunt what the pills were, she told him that a. Ca chloride
she was using a calcium channel blocker. After observing the b. Dopamine
boy for 6 hours, during which time you observe no c. Glucagon
hemodynamic changes, the father is finally able to track d. Insulin
down the aunt. You are most likely to cancel your plans to e. Normal saline

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Arroyo and Kao Pediatric Emergency Care & Volume 25, Number 8, August 2009

ANSWER SHEET FOR THE PEDIATRIC EMERGENCY CARE

CME PROGRAM EXAM
August 2009

Please answer the questions on page 539 by filling in the appropriate circles on the answer sheet below. Please mark the one best
answer and fill in the circle until the letter is no longer visible. To process your exam, you must also provide the following
information:
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Specialty
1. A B C D E
2. A B C D E
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4.

A
A
B C
B C
D
D
E
E
5. A
B C D E

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future planning of CME activities. Please respond to the following questions:
1. Did the content of this CME activity meet the stated learning objectives?
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[]5 []4 []3 []2 []1
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Please explain your answer.

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Pediatric Emergency Care & Volume 25, Number 8, August 2009 Calcium Channel Blocker Toxicity

CME EXAM ANSWERS

Answers for the Pediatric Emergency Care CME Program Exam

Below you will find the answers to the examination covering the review article in the May 2009 issue. All participants
whose examinations were received by June 15, 2009 and who achieved a score of 80% or greater will receive a certificate
from Lippincott CME Institute, Inc.

EXAM ANSWERS
May 2009
1. a
2. d
3. b
4. a
5. c

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