Diltiazem is a prescription medication used to manage conditions like high blood pressure, chronic stable angina, and certain heart rhythm abnormalities such as atrial fibrillation. As a non-dihydropyridine calcium channel blocker, it works by relaxing the muscles of the heart and blood vessels, which lowers the heart rate and blood pressure. An overdose of diltiazem is a serious medical event where the drug’s intended effects become exaggerated, leading to systemic cardiovascular collapse. This situation requires immediate intervention to prevent life-threatening complications.
The Mechanism of Toxicity
Diltiazem exerts its effect by binding to the alpha-1 subunit of L-type calcium channels found in the heart, blood vessels, and pancreas. Blocking these channels prevents the necessary influx of calcium ions into the cells. This excessive blockade disrupts the heart’s electrical and mechanical functions, leading to toxicity.
The heart’s ability to contract and conduct electrical signals slows significantly due to the lack of intracellular calcium. This results in a decreased force of contraction (negative inotropy) and a reduction in heart rate (negative chronotropy). Simultaneously, the blockade causes significant dilation of the peripheral blood vessels, leading to a severe drop in systemic blood pressure.
Beyond the cardiovascular system, diltiazem impairs the function of the pancreas’s beta-islet cells, which rely on calcium influx to release insulin. The resulting hypoinsulinemia, combined with insulin resistance, prevents the heart muscle from properly utilizing glucose for energy, compounding cardiac depression. This combination of slowed heart function and profound low blood pressure leads to reduced systemic perfusion and eventual organ failure due to lack of oxygen.
Recognizing the Clinical Signs
The signs of a diltiazem overdose can manifest rapidly with immediate-release formulations or be delayed up to 12 to 16 hours with extended-release versions. Cardiovascular symptoms are the most prominent and life-threatening. These include severe bradycardia (abnormally slow heart rate) and profound hypotension (extremely low blood pressure).
These cardiac effects can quickly progress to signs of shock, such as a weak or absent pulse, cool and clammy skin, and a lack of urine output. The heart’s electrical system may also show serious disturbances, including various degrees of atrioventricular (AV) block, where signal transmission between the heart chambers is delayed or completely blocked.
Neurological symptoms often develop as a consequence of reduced blood flow to the brain. An individual may experience dizziness, lightheadedness, and confusion. In severe cases, this lack of oxygenated blood can lead to altered mental status, lethargy, loss of consciousness, or coma.
Gastrointestinal symptoms are common following a diltiazem overdose, including complaints such as nausea and vomiting. A metabolic effect often observed in calcium channel blocker toxicity is hyperglycemia (high blood sugar), which is a marker of overdose severity due to the drug’s effect on insulin release.
Initial Emergency Response and Stabilization
A suspected diltiazem overdose is a time-sensitive medical emergency requiring immediate action. The first step is to call emergency services and the national Poison Control Center for guidance. While waiting for help, the person should be positioned safely, and continuous monitoring of vital signs should be maintained.
Upon arrival at the emergency department, initial treatment focuses on the fundamental principles of life support: securing the airway, ensuring adequate breathing, and supporting circulation. Intravenous (IV) fluids are administered to address hypotension and increase circulating volume. Clinicians must be cautious with fluid administration to avoid fluid overload, which can worsen heart failure during severe cardiac depression.
Gastrointestinal decontamination may be considered if ingestion occurred recently and the patient has a protected airway. Activated charcoal, which binds to the drug in the stomach and prevents absorption, can be given shortly after ingestion, particularly with immediate-release formulations. For extended-release formulations, whole bowel irrigation may be used to physically flush the unabsorbed medication from the digestive tract.
Advanced Treatment Protocols
Once initial stabilization is achieved, medical teams implement specialized treatments to counteract diltiazem’s toxic effects. Intravenous calcium salts, such as calcium chloride or calcium gluconate, are administered early. This therapy attempts to overcome the blockade by increasing the concentration gradient of calcium outside the cell, promoting the small amount of calcium influx that is still possible.
High-Dose Insulin Euglycemia Therapy (HIET) is an effective treatment for severe calcium channel blocker toxicity. HIET involves administering a large bolus of insulin followed by a continuous infusion, which improves myocardial contractility and helps the heart shift its energy source. Insulin facilitates the uptake of carbohydrates by the heart muscle, providing a readily available fuel source to a heart struggling with reduced blood flow.
Glucagon is another medication used, as it works by a different mechanism than calcium channels to increase heart rate and contractility. It achieves this by activating receptors on the heart muscle cells, leading to a rise in cyclic AMP (cAMP) levels independent of the diltiazem blockade. Glucagon is often given as an initial bolus followed by a continuous infusion, though its effectiveness can be variable.
If low blood pressure persists despite these therapies, vasopressors such as norepinephrine are administered to constrict blood vessels and raise systemic blood pressure. In refractory cases where the patient remains in profound cardiogenic shock, advanced life support techniques may be required. These include temporary cardiac pacing to regulate the heart rhythm or extracorporeal membrane oxygenation (ECMO), which acts as an artificial heart and lung to maintain circulation and oxygenation while the body clears the drug.
Recognizing the Clinical Signs
The signs of a diltiazem overdose can manifest rapidly with immediate-release formulations, or be delayed up to 12 to 16 hours with extended-release versions. Cardiovascular symptoms are typically the most prominent and life-threatening. These include severe bradycardia, which is an abnormally slow heart rate, and profound hypotension, or extremely low blood pressure.
These cardiac effects can quickly progress to signs of shock, such as a weak or absent pulse, cool and clammy skin, and a lack of urine output. The heart’s electrical system may also show serious disturbances, including various degrees of atrioventricular (AV) block, where the signal transmission from the upper to the lower chambers of the heart is delayed or completely blocked. This lack of proper signaling can rapidly lead to cardiac arrest.
Neurological symptoms often develop as a consequence of the reduced blood flow to the brain. An individual may experience dizziness, lightheadedness, and confusion. In more severe cases, this lack of oxygenated blood can lead to altered mental status, lethargy, or a loss of consciousness and coma.
Gastrointestinal symptoms are common following a diltiazem overdose. These may include complaints such as nausea and vomiting. A metabolic effect often observed in calcium channel blocker toxicity is hyperglycemia, or high blood sugar, which is a marker of the severity of the overdose due to the drug’s effect on insulin release.
Initial Emergency Response and Stabilization
A suspected diltiazem overdose is a time-sensitive medical emergency that requires immediate action. The first step is to call emergency services, such as 911, and the national Poison Control Center for expert guidance. While waiting for help, the person should be positioned safely, and continuous monitoring of vital signs should be maintained if possible.
Upon arrival at the emergency department, initial treatment focuses on the fundamental principles of life support: securing the airway, ensuring adequate breathing, and supporting circulation. Intravenous (IV) fluids are administered to address hypotension and increase circulating volume. However, clinicians must be cautious with fluid administration to avoid fluid overload, which can worsen heart failure in the setting of severe cardiac depression.
Gastrointestinal decontamination may be considered if the ingestion occurred recently and the patient has a protected airway. Activated charcoal, a substance that binds to the drug in the stomach and prevents its absorption, can be given within one hour of ingestion for standard preparations. For extended-release formulations, whole bowel irrigation may be used to physically flush the unabsorbed medication from the digestive tract.
Advanced Treatment Protocols
Once initial stabilization is achieved, medical teams implement specialized treatments to directly counteract the diltiazem’s toxic effects. Intravenous calcium salts, such as calcium chloride or calcium gluconate, are often administered early in the process. This therapy attempts to overcome the blockade by increasing the concentration gradient of calcium outside the cell, promoting the small amount of calcium influx that is still possible.
High-Dose Insulin Euglycemia Therapy (HIET) is a highly effective treatment for severe calcium channel blocker toxicity. HIET involves administering a large bolus of regular insulin followed by a continuous infusion, which improves myocardial contractility and helps the heart shift its energy source. Insulin facilitates the uptake of carbohydrates by the heart muscle, providing a more readily available fuel source to a heart struggling with reduced blood flow.
Glucagon is another medication that may be used, as it works by a different mechanism than calcium channels to increase the heart rate and contractility. It achieves this by activating receptors on the heart muscle cells, leading to a rise in cyclic AMP (cAMP) levels independent of the diltiazem blockade. Glucagon is often given as an initial bolus followed by a continuous infusion, though its effectiveness can be variable.
If low blood pressure persists despite these therapies, vasopressors such as norepinephrine are administered to constrict blood vessels and raise systemic blood pressure. In extremely refractory cases where the patient remains in profound cardiogenic shock, advanced life support techniques may be required. These include temporary cardiac pacing to regulate the heart rhythm or extracorporeal membrane oxygenation (ECMO), which acts as an artificial heart and lung to maintain circulation and oxygenation while the body clears the drug.