What is Theophylline Toxicity?
Theophylline, a drug known as 1,3-dimethylxanthine elsewhere, is frequently used to widen the airways for people with asthma and chronic obstructive pulmonary disease (COPD), making it easier for them to breathe. But in the United States, it is often used to treat slow heart rates and interrupted breathing in premature infants, rather than people with asthma or COPD. Theophylline works by triggering the release of natural substances called catecholamines, which in turn activate certain receptors on airway muscles, leading to relaxation and expansion of the airways.
However, theophylline is a tricky drug to manage. It becomes potentially harmful even if the levels in the body are only slightly above the optimal range. This condition, known as theophylline toxicity, is a serious concern because it can lead to dangerous health problems. These problems are as a result of too many circulating catecholamines in the body. Theophylline can affect various parts of the body, depending on the dosage and mode of administration. It can impact the heart, nerves, metabolism, muscles, and digestive system.
If someone has taken too much theophylline, it’s important for doctors in emergency departments to swiftly recognize and manage theophylline toxicity. This is because very serious complications like irregular heart rhythms, seizures, high blood sugar, and muscle damage (rhabdomyolysis) can occur.
What Causes Theophylline Toxicity?
Theophylline is a drug that needs to be given in very precise dosages. This is because its therapeutic window – that is, the range in which it helps without causing harm – is very narrow. If theophylline levels in the blood go above this range, it can lead to a condition known as theophylline toxicity.
This can happen if a person knowingly takes too much of the medication, or unintentionally due to changes in how the body metabolizes (breaks down) or clears the drug. These changes can sometimes be triggered by certain stressful conditions in the body.
Risk Factors and Frequency for Theophylline Toxicity
The number of people exposed to a toxic substance called theophylline, often used in treating asthma and COPD, has decreased considerably. From 1985 to 1995, there were 49 cases of theophylline poisoning for every one million poison center calls, but this number dropped to just 6 cases per million calls from 1996 to 2005. The American Association of Poison Control Centers reported 133 incidences of exposure to theophylline in 2014.
- Out of these reported incidences, 14 involved children under the age of 6.
- 107 cases involved older patients, aged 19 and above.
- Out of 81 patients who were treated for exposure to theophylline in healthcare facilities that year, there were unfortunately 2 fatalities.
Signs and Symptoms of Theophylline Toxicity
Theophylline toxicity, or overdose, can result in a variety of symptoms, depending on factors such as the amount taken, how it was introduced to the body, and if it was ingested in combination with other substances. Sometimes, the patients may not be able to provide a clear account of their condition, so it’s crucial to get information from paramedics, family members, friends, and witnesses.
- General symptoms: agitation, irritability, restlessness
- Cardiovascular symptoms: rapid heartbeat, irregular heartbeat, low blood pressure, heart arrest
- Respiratory symptoms: rapid breathing, lung damage, respiratory alkalosis
- Gastrointestinal symptoms: nausea, vomiting, stomach pain
- Neurological symptoms: tremors, hallucinations, seizures
Testing for Theophylline Toxicity
If your doctor suspects you might have an issue related to theophylline toxicity, they will perform several tests to confirm this. Theophylline is a medication often used to treat respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD). However, having too much of it in your body can cause serious health problems.
Firstly, your doctor will measure your theophylline level in your blood. Having a high level of theophylline can confirm its toxicity.
Your doctor will also measure your blood glucose levels because having too much sugar in your blood (hyperglycemia) is often common in people with theophylline toxicity.
In addition, your doctor will likely carry out a comprehensive metabolic panel, which is a blood test that evaluates the functioning of your kidneys and liver, the electrolyte and fluid balance, and glucose level. Specifically, these tests are to check for low potassium levels (hypokalemia) and high amounts of acid in your body (metabolic acidosis), as these are signs of theophylline toxicity.
Your doctor will also count the number of blood cells in your blood. This is done through a complete blood count (CBC) test. If your white blood cells are high, it could be a sign of theophylline toxicity.
Calcium is another component that will be checked in your blood since having too much calcium (hypercalcemia) can occur in people with theophylline toxicity.
Furthermore, to rule out the intake of other potentially harmful substances or unknown substances causing similar symptoms, your doctor might test your blood for acetaminophen and salicylate levels, and urine for illicit drugs. They may also check your blood iron level, as excessive iron can cause symptoms similar to theophylline toxicity.
They might test for the enzyme creatine kinase as well because its high presence might suggest muscle injury, or disorder known as rhabdomyolysis.
Liver function tests are important because the liver is responsible for processing theophylline in the body. If the liver isn’t working properly, it could cause an increase in theophylline levels.
Aside from blood tests, your doctor might also use an ECG (Electrocardiogram) to check your heart’s rhythm and electrical activity. This is done to assess any heart issues due to theophylline toxicity or other substances.
Lastly, to rule out other causes of symptoms such as mental state changes or seizures, your doctor may order a CT scan (computed tomography) of your head. This is an imaging procedure that uses special x-ray machines to create detailed pictures of structures inside the body.
Treatment Options for Theophylline Toxicity
Patients suffering from an overdose of theophylline, a medication commonly used to treat conditions such as asthma, are typically helped through supportive care. It’s important for doctors to monitor the patient’s airway, breathing and circulation, and keep track of their heart rate and blood pressure. For severe cases, doctors may need to help the patient breathe using a ventilator, a machine that pushes air into the lungs.
Doctors may also use a method called GI decontamination to remove the drug from the patient’s system. A material called activated charcoal can be given orally or through a tube inserted into the patient’s nose that reaches down to their stomach, but only if it’s safe for the patient. Procedures like gastric lavage, or stomach pumping, and inducing vomiting are typically not recommended. Administering activated charcoal multiple times is suggested for severe cases, again if it’s safe for the patient.
Patients with low blood pressure not responding to fluids given intravenously may need medications like phenylephrine or norepinephrine. These medicines are used to narrow the blood vessels, which can help to increase blood pressure.
If the patient experiences nausea and vomiting, medications like ondansetron or metoclopramide may be given to help provide relief.
In the event of an irregular heartbeat, the medical team will follow specific guidelines to treat the condition, which could involve administering different medications depending on the type of irregular heartbeat.
If seizures occur, medicines from the benzodiazepine family, such as lorazepam, midazolam, or diazepam, are typically used as the first line of treatment. For persistent seizures, heavier sedating medicines like phenobarbital and propofol or a prolonged infusion of midazolam may be used.
For severe cases where a patient has a high level of theophylline in their bloodstream, or where they’re experiencing life-threatening effects, procedures like hemodialysis might be recommended. Hemodialysis is a treatment that uses a machine to clean a patient’s blood. In some situations, if hemodialysis is not available, a similar process called hemoperfusion might be used instead.
Lastly, if the patient is experiencing ventricular arrhythmias (a type of irregular heartbeat) or having low potassium levels, they may be given potassium supplements.
These treatments can vary based on individual patient factors and should always be performed with guidance from a medical professional experienced with managing overdoses.
What else can Theophylline Toxicity be?
- Alcoholic ketosis (a condition caused by excessive alcohol consumption)
- Amphetamine intoxication (overdose from drugs like speed or adderall)
- Anticholinergic poisoning (a reaction to certain medications)
- Atrial fibrillation (an irregular, often rapid heart rate)
- Atrial flutter (a type of abnormal heart rate)
- Bipolar disorder (a mental health condition causing extreme mood swings)
- Cocaine intoxication (overdose from cocaine)
- Carbon monoxide toxicity (poisoning from inhaling too much carbon monoxide)
- Diphenhydramine toxicity (overdose from drugs like Benadryl)
- Delirium tremors (a severe form of alcohol withdrawal)
- Diabetic ketoacidosis (a serious complication of diabetes)
- Encephalitis (inflammation of the brain)
- Hypercalcemia (too much calcium in your blood)
- Hyperthyroidism (an overactive thyroid)
- Hyponatremia (low sodium levels in the blood)
- Hypoxia (lack of oxygen in the body)
- Iron toxicity (overdose from iron supplements)
- Monoamine oxidase inhibitor toxicity (a reaction to certain depression medications)
- Salicylates toxicity (overdose from drugs like aspirin)
- Sepsis (a life-threatening reaction to infection)
- Status epilepticus (a prolonged or repeated seizure)
- Ventricular tachycardia (a type of fast heart rate)
Possible Complications When Diagnosed with Theophylline Toxicity
- Irregular heartbeat
- Sudden stoppage of the heart’s beat
- Sudden injury to the lungs
- Restlessness and seeing or hearing things that aren’t there
- Uncontrolled shaking or seizures
- Failure of the heart to pump blood effectively
- Problems with the liver working properly