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Calcium channel blocker poisoning

Author: Fermin Barrueto, Jr, MD, FACEP, FAAEM, FACMT

Section Editor: Stephen J Traub, MD
Deputy Editor: Jonathan Grayzel, MD, FAAEM

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2017. | This topic last updated: Feb 22, 2017.

INTRODUCTION — Calcium channel blockers (CCBs) are used in the treatment of hypertension,
angina pectoris, cardiac arrhythmias, and other disorders. These medications are available in both
immediate-release and extended-release preparations; the latter are in wide clinical use (figure 1) [1].

The potential toxicity of these agents is substantial, and is often under appreciated by the public. As
an example, over 9500 cases of CCB intoxication, caused by intentional or unintentional overdosage,
were reported to poison centers in the United States during 2002 [2]. Although only 16 percent of all
cardiovascular drug exposures were due to CCBs, this class accounted for 38 percent of deaths [2].

The management of CCB intoxication will be reviewed here. A summary table to facilitate emergent
management is provided (table 1). An overview of the major side effects of CCBs is presented
separately. (See "Major side effects and safety of calcium channel blockers".)

PATHOPHYSIOLOGY — The calcium channel blockers (CCBs) can be divided into two major
categories based upon their predominant physiologic effects: the dihydropyridines, which preferentially
block the L-type calcium channels in the vasculature; and the nondihydropyridines, such as verapamil
and diltiazem, which selectively block L-type calcium channels in the myocardium [1,3].

The L-type calcium channels are responsible for myocardial contractility and vascular smooth muscle
contractility; they also affect conducting and pacemaker cells. The dihydropyridines (including
nifedipine, amlodipine, felodipine, nicardipine, nisoldipine, isradipine, and lacidipine) are potent
vasodilators that have little negative effect upon cardiac contractility or conduction at standard doses.
In contrast, verapamil and, to a lesser extent, diltiazem are weak vasodilators but have a depressive
effect on cardiac conduction and contractility [3].

Dihydropyridine intoxication generally results in arterial vasodilation and reflex tachycardia, whereas
diltiazem and verapamil toxicity cause peripheral vasodilation, decreased cardiac inotropy, and
bradycardia [4]. However, as the dose is increased, this selectivity can be lost, and dihydropyridine
CCBs (including nifedipine and amlodipine) may affect the myocardium and conducting system like
verapamil and diltiazem (ie, decreased inotropy and bradycardia).
PHARMACOKINETICS — Most calcium channel blockers (CCBs) are highly protein bound, have a
large volume of distribution, and are metabolized in the liver. As the dose is increased, the rate of CCB
clearance decreases, prolonging the half-life [5]. Extended-release preparations slowly release the
drug from a matrix to facilitate once-daily dosing. In overdose, this property makes absorption
unpredictable, and prolongs the duration of toxicity.

CLINICAL FEATURES

History — Whenever possible, determine the time of ingestion, as well as the type, amount, and
preparation (immediate or sustained release) of drug ingested. The identity of the drug ingested will
help predict toxicity, and the type of preparation will help determine the appropriate approach to
gastrointestinal decontamination. Patients ingesting more than 5 to 10 times the usual dose can
develop signs of severe intoxication.

It is important to clarify whether the ingestion was accidental or intentional, and to assess the patient
for suicidality; however, this determination is often made after resolution of the acute episode. (See
"Suicidal ideation and behavior in adults".)

Physical examination — Vital sign abnormalities include hypotension, which may be seen in any
calcium channel blocker (CCB) overdose, and bradycardia, which usually is seen only in verapamil or
diltiazem overdose. However, bradycardia may also be seen with severe dihydropyridine (eg,
nifedipine) poisoning. Jugular venous distension, pulmonary crackles, and other signs of heart failure
may be noted in some cases. Despite hypotension, CCB-poisoned patients may maintain a
surprisingly clear mental status, possibly due to the neuroprotective effects of CCBs. However,
neurologic status may deteriorate precipitously once cerebral perfusion becomes critically limited.

DIAGNOSTIC EVALUATION — An electrocardiogram (ECG) should be obtained in patients with

known or suspected calcium channel blocker (CCB) intoxication [6]. ECG changes associated with
CCB intoxication include PR interval prolongation and any bradydysrhythmia. A finger stick blood
glucose measurement may reveal hyperglycemia, which is caused by inhibition of calcium-mediated
insulin release; however, this elevation is rarely clinically significant, except for diagnostic purposes
[7,8]. The presence of hyperglycemia in a non-diabetic patient may help to distinguish CCB from beta
blocker poisoning. Serum toxicology can confirm coingestion of acetaminophen or salicylates, which
should be excluded in suicidal patients [6].

Serum electrolytes, blood urea nitrogen (BUN), creatinine, calcium, and glucose concentrations
should be assessed. A chest radiograph should be obtained if there are any signs of pulmonary
edema, hypoxia, or respiratory distress. (See "General approach to drug poisoning in adults".)

MANAGEMENT

Initial resuscitation — Circulation is the main focus of the treatment of calcium channel blockers
(CCB) exposures. Hypotension and bradycardia can be profound and refractory even to maximal
treatment. Intravenous fluids are the initial therapy for hypotension, and atropine the initial treatment
for bradycardia, but both may be insufficient.

CCB-poisoned patients may maintain a clear mental status despite hypotension and bradycardia.
However, clinicians need to reassess these patients frequently, as precipitous deterioration is
common, and many will eventually require intubation and mechanical ventilation.

Approach to the selection of specific therapies — Although it is ideal to institute treatments

individually to assess their success or failure, this is often not possible in patients who are severely
poisoned with calcium channel blockers (CCBs), especially verapamil or diltiazem. These patients are
frequently moribund on presentation, but even when initially well-appearing may deteriorate rapidly
and disastrously. Our suggested approaches to therapy, based upon the severity of clinical signs, are
described below; a summary table to facilitate emergent management is provided (table 1). Studies of
therapies for CCB poisoning consist primarily of case series and animal studies, and thus, the
approaches to treatment that we describe below are based upon limited evidence and our clinical
experience [9].

Severely symptomatic patients — Our suggested approach to patients manifesting signs of

severe CCB poisoning (profound hypotension and/or bradycardia) consists of multiple simultaneous
interventions, including all of the following treatments [4,10]:

● Stabilization of the airway as necessary (avoid induction agents that exacerbate hypotension)

● Additional IV boluses of isotonic crystalloid

● IV calcium salts

● IV glucagon

● IV high-dose insulin and glucose

● IV vasopressor (eg, norepinephrine)

● IV lipid emulsion therapy

Dosing for each of these therapies is provided below. (See 'Specific therapies' below.)

Mildly symptomatic patients — Our suggested approach to patients with mild hypotension or
bradycardia begins with IV boluses of isotonic crystalloid and atropine respectively. However, these
therapies often do not reverse the cardiotoxic effects of CCB poisoning. In such cases, we add the
following treatments in succession based upon patient response. As an example, we begin treatment
with a calcium salt if IV crystalloid is ineffective, but if hypotension resolves following treatment with a
calcium salt, we do not proceed to IV glucagon or any other treatment.

● IV boluses of isotonic crystalloid

● IV calcium salts

● IV glucagon

● IV high-dose insulin and glucose

● IV vasopressor (eg, norepinephrine)

● IV lipid emulsion therapy

A period of 15 minutes is reasonable to determine the effectiveness of a specific therapy before
proceeding to the next treatment. Dosing for each of these therapies is provided below. (See 'Specific
therapies' below.)

Asymptomatic patients — Some patients with an isolated CCB overdose remain asymptomatic
(primarily those with dihydropyridine [eg, nifedipine] poisoning) and may be discharged after a period
of observation, unless the overdose was intentional. (See 'Disposition' below.)

Gastrointestinal decontamination — Orogastric lavage may be necessary in patients who present

within one to two hours of a potentially dangerous ingestion. Vagal stimulation from orogastric lavage
may exacerbate CCB-induced hypotension and bradycardia [11].

Activated charcoal (AC) should be administered to patients with CCB overdose, even if they are
asymptomatic. AC is maximally effective if administered within one hour of ingestion, but patients with
delayed presentation after CCB exposure may still benefit. Charcoal should be withheld in patients
with a depressed mental status who may not be able to protect their airway, unless endotracheal
intubation is performed first. AC is given as a single dose of 1 g/kg for children up to the adult dose of
50 g. (See "Gastrointestinal decontamination of the poisoned patient" and "Enhanced elimination of
poisons".)

Whole bowel irrigation (WBI) may be implemented if a sustained-release or extended-release

preparation has been used or is strongly suspected [12]. If the history is in doubt, WBI may be delayed
until the patient develops signs or symptoms of toxicity. If the ingestion is certain, particularly if the
drug is verapamil or diltiazem, WBI should be started even in the asymptomatic patient. Whole bowel
irrigation involves the administration of polyethylene glycol/electrolyte lavage solution by mouth at a
rate of 2 L per hour for adults (up to 500 mL per hour in children) until the rectal effluent is clear
[13,14]. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Whole bowel
irrigation'.)

Specific therapies

Atropine — Atropine should be administered to any patient with symptomatic bradycardia;

however, it is often ineffective after significant CCB exposure [15]. Atropine is administered in a dose
of 0.5 to 1.0 mg intravenously every two to three minutes to a maximum of 3 mg. Pediatric dosing is
0.02 mg/kg intravenously, with a minimum dose of 0.1 mg to avoid the paradoxical bradycardia that
may result from very small doses of this medication. (See "Primary drugs in pediatric resuscitation",
section on 'Atropine'.)

Intravenous calcium — Calcium salts are often used to overcome the cardiovascular effects of
CCBs. However, treatment with calcium salts is often ineffective. This is because CCB poisoning
interferes with both the serum concentration and the intracellular handling of calcium.

Calcium gluconate may be administered via peripheral or central venous access; calcium chloride is
more irritating, and should be administered via central venous access, if at all possible. In adults,
calcium chloride, 10 to 20 mL of a 10 percent solution, can be administered over 10 minutes; if no
effect is noted, the dose can be repeated up to four times approximately every 20 minutes. If calcium
gluconate is used, the dose must be adjusted (30 to 60 mL of 10 percent calcium gluconate), as
calcium gluconate has only one third the calcium of calcium chloride [16].
A high-dose continuous infusion of calcium has been used anecdotally with success [17-19]; we
believe a reasonable infusion is 0.5 meq of calcium/kg per hour (or 0.2 to 0.4 mL/kg per hour of 10
percent calcium chloride; or 0.6 to 1.2 mL/kg per hour of 10 percent calcium gluconate). Close
monitoring of the serum or ionized calcium concentration (measurements every two hours) and serial
ECGs is necessary to avoid clinically significant hypercalcemia, which has been reported with
intensive calcium therapy [20]. (See "Clinical manifestations of hypercalcemia" and "Treatment of
hypercalcemia".)

Glucagon — Glucagon increases intracellular levels of cyclic AMP and, in animal models, has
been shown to increase heart rate in calcium channel blocker toxicity [21]. However, it has minimal
effects on the mean arterial pressure. Glucagon has been effective in treating human cases of CCB
toxicity [22-24].

The dosing regimen for glucagon in the treatment of CCB has not been established in human clinical
trials. For the adult patient, an initial 5 mg intravenous bolus is a reasonable start, and may be
repeated twice at 10 minute intervals. A glucagon infusion can be started at the total dose at which a
response is noted. Nausea and vomiting are common side effects of this medication.

Vasopressors — The ideal vasopressor in CCB poisoning would be a direct-acting agent with
positive inotropy, positive chronotropy, and vasoconstrictive effects. Based on these criteria, we
believe that norepinephrine is the initial vasopressor of choice. We start the infusion at a rate of 2
mcg/minute, but titrate rapidly upwards with the goal of achieving a mean arterial pressure of 65
mmHg. Check the blood pressure every few minutes, increasing the infusion liberally (one reasonable
approach is 10 mcg/minute increments) if hypotension persists.

In patients who remain hypotensive at maximal doses of an initial vasopressor, we suggest the
addition of a second vasopressor. Invasive hemodynamic monitoring (with a pulmonary artery
catheter) or echocardiography may point to a selective failure of inotropy or vascular resistance, thus
helping to refine the choice of catecholamine and the titration rate. We believe that such information is
particularly important to guide the choice of a second agent. (See "Pulmonary artery catheterization:
Interpretation of hemodynamic values and waveforms in adults" and "Echocardiographic assessment
of the right heart".)

Patients with profound CCB toxicity may require higher doses of vasopressors than those typically
used in the treatment of severe sepsis or other causes of shock. In one series, patients with severe
diltiazem or verapamil toxicity received vasopressor doses as high as 100 mcg/minute of
norepinephrine, 150 mcg/minute of epinephrine, and 100 mcg/kg per minute for dopamine [25].
However, the arrhythmogenic effects of these drugs become more prominent at higher doses and thus
the risk of such high doses, particularly with multiple agents, may outweigh the benefits. (See "Use of
vasopressors and inotropes".)

Insulin and glucose — High-dose insulin therapy has positive inotropic effects in patients with
CCB toxicity. Its effectiveness and safety have been noted in animal models and an increasing
number of case reports [26-29].

Relative hypoglycemia and hypokalemia must be corrected prior to initiating high-dose insulin therapy.
For patients with a serum glucose concentration below 150 mg/dL (8.25 mmol/L), we administer 50
mL of 50 percent dextrose (D50W) intravenously (IV). In young children the initial dose of dextrose is
0.25 g/kg body weight, usually given as 2.5 mL/kg of 10 percent dextrose solution (see "Approach to
hypoglycemia in infants and children", section on 'Treatment'). For patients with a serum potassium
concentration below 3 mEq/L (3 mmol/L), we administer 20 mEq of potassium IV.

We initiate high-dose insulin therapy with a bolus of 1 unit/kg of regular, short-acting insulin given IV.
Following this bolus, we begin a continuous infusion at 0.5 units/kg per hour IV and titrate upwards
until hypotension is corrected or a maximum dose of 10 units/kg per hour is reached. One approach is
to increase the infusion rate by 50 percent every 20 minutes until either target is met. High doses of
insulin may be necessary and are appropriate in some cases, and the accepted range is 1 to 10
units/kg per hour given IV of regular, short-acting insulin. Even higher doses may be given under the
direction of a medical toxicologist or poison control center.

CCB overdose often causes hyperglycemia that is refractory to high dose insulin. Therefore, not all
patients require supplemental dextrose. Nevertheless, if necessary, euglycemia can be maintained by
means of a continuous IV infusion of 5 to 10 percent dextrose. A reasonable initial rate for such an
infusion is 0.5 to 1 g of dextrose/kg per hour. Titration of the dextrose infusion and additional boluses
of 50 percent dextrose are provided based upon serum glucose measurements (finger stick glucose),
which are obtained every 15 to 30 minutes until the concentration is stable, and every hour thereafter
until several hours after therapy is complete.

The serum potassium concentration is measured every 30 minutes until it is stable, and every one to
two hours thereafter. Supplementation is given as necessary to maintain a potassium concentration in
the low normal range. Magnesium replacement is often needed in hypokalemic patients. (See "Clinical
manifestations and treatment of hypokalemia in adults".)

A hemodynamic response to high-dose insulin therapy is delayed for 30 to 60 minutes; therefore,

simultaneous implementation of other therapies to support the patient's pulse and blood pressure are
generally required.

Animal studies of CCB toxicity have shown improved survival associated with
hyperinsulinemia/euglycemia therapy compared with calcium, epinephrine, or glucagon [26,30].
Clinical experience with this approach is limited [27,28]; in one case series of four verapamil-poisoned
patients, hyperinsulinemia/euglycemia therapy improved blood pressure and ejection fraction without
changing heart rate [28]. High-dose insulin therapy is also used in beta blocker poisoning. (See "Beta
blocker poisoning".)

The mechanism by which hyperinsulinemia-euglycemia therapy works remains unclear, though there
are several theories. Though the mechanism is not completely understood, CCBs appear to disrupt
fatty acid metabolism and create relative insulin resistance within the myocardium. This state of
carbohydrate dependence and insulin resistance can theoretically be overcome with high-dose insulin
[31,32]. In addition, calcium is needed to facilitate exocytosis of insulin from the beta-islet cells of the
pancreas. CCBs block the influx of calcium and prevent insulin release from the beta-islet cells. High-
dose insulin therapy is thought to compensate for this impaired secretion of insulin.

Lipid emulsion therapy — Lipid emulsions are the fats used in total parenteral nutrition (TPN).
Initially used to treat overdoses of local anesthetics, such as bupivacaine, intravenous lipid emulsion
(ILE) is being studied as a therapy for poisonings involving a number of lipophilic medications. Studies
of ILE therapy are preliminary. Systematic reviews of lipid emulsion therapy for acute poisoning have
found the overall quality of studies supporting this treatment to be low or very low but included human
case reports provide some evidence of benefit in patients with toxicity from verapamil, beta blockers,
some tricyclic antidepressants, bupivacaine, chlorpromazine, and some antidysrhythmics (eg,
flecainide) [33-35]. ILE may have a useful role in the treatment of patients who are hemodynamically
unstable from such poisonings [36-39].

We suggest consultation with a medical toxicologist or poison control center to determine whether ILE
therapy is appropriate. The dosing protocol most widely reported consists of an intravenous bolus of 1
to 1.5 mL/kg given over one minute of a 20 percent lipid emulsion solution [36,37,40]. If there is no
response, the same dose may be repeated in cases of cardiac arrest every three to five minutes, for a
total of three bolus doses. Following the initial bolus, an infusion is started at a rate of 0.25 to 0.5
mL/kg per minute until hemodynamic recovery occurs. The infusion is generally maintained for 30 to
60 minutes. The infusion rate may be increased if the patient’s blood pressure drops.

Possible adverse effects from standard ILE treatment include hypertriglyceridemia, fat embolism,
infection, and hypersensitivity reactions. Although these and other potential complications from ILE
treatment have been reported, further study is needed to determine the risk of complications from
circumscribed treatment in the setting of acute overdose.

ILE therapy interferes with some laboratory measurements and may affect therapeutic drug monitoring
[41,42]. As examples, serum glucose concentrations when determined by colorimetric testing and
serum magnesium concentrations become inaccurate following the administration of ILE, while
creatinine and lipase become unmeasurable. Potassium and troponin-I are not affected.
Centrifugation of blood samples substantially reduces any interference.

Two mechanisms are believed to account for the effectiveness of ILE. The first is that the emulsion
acts as a “lipid sink,” surrounding a lipophilic drug molecule and rendering it ineffective. The second is
that the fatty acids from the ILE provide the myocardium with a ready energy source, thereby
improving cardiac function [40].

Phosphodiesterase inhibitors — Phosphodiesterases inhibitors, such as inamrinone (formerly

known as amrinone) increase cyclic AMP levels by preventing intracellular degradation of cyclic AMP.
Although there are reports of successful treatment with inamrinone in combination with glucagon after
amlodipine poisoning [43], phosphodiesterases inhibitors may exacerbate hypotension and should
NOT be used routinely. We recommend that inamrinone not be considered unless therapy with a
readily titratable vasopressor has been instituted, and a pulmonary artery catheter is in place to help
guide management. (See "Use of vasopressors and inotropes".)

Other proposed treatments — Some have proposed levosimendan as a treatment for CCB
poisoning [44]. However, studies of levosimendan are limited and we do not recommend its use for
this purpose. Levosimendan sensitizes the calcium channels and promotes the influx of calcium into
the cell. Theoretically this would appear beneficial in a calcium channel blocker overdose, but results
from animal models are conflicting and the drug has some phosphodiesterase activity which may
exacerbate hypotension [45-48].
 Invasive treatment measures — A transvenous pacemaker can be inserted to assist with
electrical conduction. However, pacing does not counteract the negative inotropic effects of these
drugs, and successful capture may not correct the patient's hypotension [49]. Intraaortic balloon
insertion can be considered in the absence of contraindications [50]. (See "Temporary cardiac pacing"
and "Intraaortic balloon pump counterpulsation".)

There are anecdotal reports of complete recovery in severely poisoned pediatric and adult patients
placed on prolonged cardiopulmonary bypass or extracorporeal membrane oxygenation [51-54]. (See
"Extracorporeal membrane oxygenation (ECMO) in adults".)

Extracorporeal removal — CCBs are highly protein bound; therefore, extracorporeal removal by
hemodialysis is not effective.

Disposition — A patient who ingests or claims to have ingested an immediate-release CCB but
remains asymptomatic after six to eight hours may be considered medically cleared. If the CCB
preparation was a sustained or extended-release preparation, admission and cardiac monitoring for
24 hours is warranted. In the symptomatic patient, continuous hemodynamic monitoring is required
until the patient does not require any pharmacologic assistance to maintain blood pressure. If multiple
agents are being utilized, invasive monitoring with a pulmonary artery catheter should be strongly
considered to help guide therapy. If an intentional overdose is known or suspected, psychiatric
evaluation is needed.

ADDITIONAL RESOURCES — Regional poison control centers in the United States are available at
all times for consultation on patients who are critically ill, require admission, or have clinical pictures
that are unclear (1-800-222-1222). In addition, some hospitals have clinical and/or medical
toxicologists available for bedside consultation and/or inpatient care. Whenever available, these are
invaluable resources to help in the diagnosis and management of ingestions or overdoses. The World
Health Organization provides a listing of international poison centers at its website:
www.who.int/gho/phe/chemical_safety/poisons_centres/en/index.html

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from

selected countries and regions around the world are provided separately. (See "Society guideline
links: Treatment of acute poisoning caused by specific agents other than drugs of abuse" and "Society
guideline links: General measures for acute poisoning treatment".)

SUMMARY AND RECOMMENDATIONS

● Severe calcium channel blocker (CCB) poisoning is life threatening and management is often
challenging. Patients may be moribund at presentation and those who are not may deteriorate
precipitously. A summary table to facilitate emergent management is provided (table 1). Diltiazem
and verapamil are the most cardiotoxic of the CCBs, although any of these agents can be
dangerous when large doses are ingested.

● Patients ingesting more than 5 to 10 times the usual dose can develop signs of severe
intoxication, including drowsiness and confusion. Vital sign abnormalities can include hypotension
and bradycardia. Jugular venous distension, pulmonary crackles, and other signs of heart failure
may be noted. (See 'Clinical features' above.)
● ECG changes associated with CCB intoxication include PR interval prolongation and any
bradydysrhythmia. A finger stick blood glucose measurement may reveal hyperglycemia. (See
'Diagnostic evaluation' above.)

● Treatment varies according to the severity of symptoms and may include gastrointestinal
decontamination, possibly including gastric lavage, and the administration of intravenous calcium,
glucagon, catecholamines, and high-dose insulin therapy may be necessary. Intralipid therapy
may be of benefit in critically ill, hemodynamically unstable patients resistant to standard medical
therapies. A transvenous pacemaker, intraaortic balloon pump, and extracorporeal membrane
oxygenation are treatment options for the severely poisoned. (See 'Initial resuscitation' above and
'Approach to the selection of specific therapies' above.)

● For patients with severely symptomatic CCB poisoning, we suggest simultaneous treatment with
all of the following therapies (Grade 2C). Dosing is provided in the text and the rapid overview
table (table 1). Severe beta blocker poisoning can be difficult to manage and consultation with a
medical toxicologist or regional poison control center is prudent (see 'Severely symptomatic
patients' above and 'Specific therapies' above):

• Stabilization of the airway as necessary (avoid induction agents that exacerbate

hypotension)

• IV boluses of isotonic crystalloid

• IV calcium salts (see 'Intravenous calcium' above)

• IV glucagon (see 'Glucagon' above)

• IV high-dose insulin and glucose (see 'Insulin and glucose' above)

• IV vasopressor (norepinephrine) (see 'Vasopressors' above)

• IV lipid emulsion therapy (see 'Lipid emulsion therapy' above)

● A suggested treatment approach for patients with mild hypotension or bradycardia caused by
CCB toxicity is provided in the text. (See 'Mildly symptomatic patients' above.)

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Topic 331 Version 28.0

GRAPHICS

Increasing use of longer-acting dihydropyridines

Introduction and growth of new prescriptions of differing formulations of

nifedipine and of amlodipine since 1986. Nifedipine was only available in the
United States as a short-acting formulation in the late 1980s. The slow-
release GITS (gastrointestinal therapeutic system) formulation of nifedipine
was not introduced until 1989, and its usage did not increase appreciably
until 1991-1992; the usage of amlodipine began to increase in 1993.

Data from Epstein, M, Am J Hypertens 1996;9:110.

Graphic 51498 Version 1.0

Calcium channel blocker poisoning: Rapid overview

To obtain emergent consultation with a medical toxicologist, call the United States Poison Control
Network at 1-800-222-1222, or access the World Health Organization's list of international poison
centers (www.who.int/gho/phe/chemical_safety/poisons_centres/en/index.html).

Clinical features
Hypotension and bradycardia are prominent

Electrocardiogram may show PR prolongation or any bradydysrhythmia

Patients with a significant calcium channel blocker (CCB) ingestion can deteriorate rapidly

Diagnostic evaluation
Assays for CCBs are not routinely available

Diagnosis depends on the history and clinical presentation

Differential diagnosis for unexplained bradycardia includes toxicity from medications including CCBs,
beta-blockers, clonidine, and digoxin

Structural cardiac disease and active myocardial ischemia must be excluded

Treatment
Assess and stabilize airway, breathing, and circulation

For patients with severe calcium channel blocker (CCB) poisoning (eg, profound
hypotension refractory to crystalloid boluses and atropine), give ALL of the following:
calcium salts, glucagon, high dose insulin and dextrose, vasopressor, and lipid emulsion
therapy

For patients with mild CCB poisoning, give the following treatments in succession based upon
patient response (see topic text for details): IV crystalloid, atropine, calcium salts, glucagon, high
dose insulin and dextrose, vasopressor, and lipid emulsion therapy

Initiate treatment for hypotension and bradycardia, if present:

Intravenous crystalloid (hypotension): isotonic saline 500 to 1000 mL boluses

Atropine (bradycardia): 1 mg IV; may repeat for 3 total doses

Intravenous calcium (hypotension and/or bradycardia)

Bolus therapy:
Calcium chloride - 10 to 20 mL of 10 percent solution (via central venous access if possible)

Calcium gluconate - 30 to 60 mL of 10 percent solution

Continuous infusion of 0.5 meq calcium/kg per hour

Monitor serum calcium and ECG for evidence of hypercalcemia

Glucagon (bradycardia)

Bolus therapy:
1-5 mg IV push, may repeat up to 15 mg total

Continuous infusion:
Determine bolus amount needed to obtain response; give this "response dose" every hour as continuous
infusion

Vasopressor support (hypotension)

Norepinephrine: begin 2 mcg/minute IV, titrate rapidly to systolic blood pressure 100 mmHg
 Hyperinsulinemia with euglycemia (hypotension)

Bolus therapy:

Regular insulin 1 Unit/kg IV

Dextrose 25-50 grams IV; repeat for hypoglycemia; give potassium for hypokalemia

Maintenance infusions:
Regular insulin: start infusion at 0.5 Units/kg per hour IV; titrate upwards until hypotension corrected or
maximum dose of 2 Units/kg per hour reached

Dextrose 0.5 grams/kg per hour; titrate to euglycemia

Gastrointestinal decontamination

Activated charcoal: 1 gram/kg up to 50 grams

Whole bowel irrigation: 2 L/hour by mouth; for extended-release preparations only

Consider the following therapies if the above measures fail:

Transvenous cardiac pacing

Intraaortic balloon pump

Cardiopulmonary bypass

Extracorporeal membrane oxygenation

Graphic 63193 Version 11.0

Contributor Disclosures
Fermin Barrueto, Jr, MD, FACEP, FAAEM, FACMT Nothing to disclose Stephen J Traub,
MD Nothing to disclose Jonathan Grayzel, MD, FAAEM Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found,
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