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Caffeine toxicity arises from the excessive consumption of caffeine, a widely used stimulant recognized for enhancing mental alertness. With 85% of Americans consuming caffeine daily and an average cup of coffee containing 40 to 150 mg of caffeine, the risk of toxicity increases with inadvertent overuse or intentional overdose. Caffeine is present in various over-the-counter products, including energy drinks, appetite suppressants, stimulants, exercise supplements, decongestants, bronchodilators, and mental stimulants, making unintentional overexposure common.[1][37] This activity reviews the pathophysiology of caffeine toxicity, including its clinical manifestations and diagnostic approaches. Management strategies, including supportive care and targeted interventions, are discussed to address mild, moderate, and severe cases. Emphasis is placed on the role of the interprofessional team in preventing, identifying, and managing caffeine toxicity to improve patient outcomes. Understanding the diverse sources of caffeine and their potential interactions aids healthcare providers in mitigating risks associated with overuse. Objectives: Identify the pathophysiology of caffeine toxicity. Assess the signs and symptoms of caffeine toxicity. Implement appropriate management strategies, including supportive care, activated charcoal, or hemodialysis, for caffeine toxicity. Apply interprofessional team strategies to improve care coordination and communication, advance the treatment of caffeine toxicity, and improve outcomes. Access free multiple choice questions on this topic.

Caffeine is a stimulant that has been used globally for centuries due to its ability to improve mental alertness. Approximately 85% of Americans consume caffeine daily, with an average cup of coffee containing between 40 and 150 mg of caffeine.[1] Caffeine can be found in various over-the-counter products, such as energy drinks, appetite suppressants, stimulants, exercise supplements, decongestants, bronchodilators, and mental stimulants, increasing the risk of toxicity with inadvertent overuse or severe toxicity with an intentional overdose.[2][3] Lethal doses of caffeine have been reported at blood concentrations of 80 to 100 μg/mL, which can result from ingesting approximately 10 g or more of caffeine.[4][5][6][7][8]

Lethal overdoses of caffeine in adults are rare and are commonly caused by an intentional overdose of medications.[9][10][11] Conversely, caffeine toxicity in children is typically caused by accidental ingestion.[12] Toxic ingestions can occur after consuming energy drinks but are rarely observed in patients who have consumed coffee or tea, secondary to the excessive amount of fluid required to reach toxic levels.[13] Over-the-counter products containing large doses of caffeine purchased for their stimulant properties can also contribute to caffeine toxicity. These products include health food items, diet aids, decongestants, bronchodilators, and stay-awake pills.[14]

Each year, Poison Control Centers in the United States receive over 3000 reports of caffeine-related exposures, with pediatric and adult cases occurring at an equal ratio. On average, less than 2 of these reports typically end in fatality.[15]

As caffeine can affect a variety of different receptors, the adverse effects of caffeine overdose can be profound. Caffeine is a natural alkaloid methylxanthine that acts as a nonselective antagonist of adenosine receptors, with A1 antagonism triggering seizures and A2 antagonism triggering cerebral and coronary vasoconstriction. In addition, caffeine inhibits phosphodiesterase, increasing intracellular cyclic AMP and intracellular calcium levels. Caffeine can stimulate the release of catecholamines, especially noradrenaline, with β1 agonist activity resulting in tachycardia and β2 agonist activity resulting in peripheral vasodilation and hypotension.[5][11][16][17] Caffeine also sensitizes dopamine receptors and is a competitive antagonist of benzodiazepine receptors. Furthermore, caffeine increases renin excretion, resulting in initial hypertension, sodium retention, and water retention.[7][11][18][19]

Physical examination findings characteristic of caffeine toxicity include nausea, vomiting, tachycardia, tachypnea, depressed consciousness, irritability, headache, and early-stage hypertension, followed by hypotension. Pupils may demonstrate mydriasis. Muscles may be rigid, and deep tendon reflexes may be accentuated (hyperreflexia). A neurological examination may reveal altered mentation, agitation, delusional thoughts, hallucinations, seizures, or even focal neurological findings thought to be due to ischemia from vasoconstriction. Nausea is the most common symptom, and vomiting is also frequently reported.[18][21][22]

Routine serum laboratory evaluations can be useful in drug overdose cases, especially in patients with unstable vital signs, seizures, or altered sensorium. Serum caffeine levels can guide prognosis and therapy. Although not available in all hospitals, serum caffeine levels are generally measured using an immunoassay.[23][24] Lethal blood levels are typically above 80 to 100 mg/L, although ingestions of 5 to 50 g have resulted in fatalities.[7][9][19][25] Venous blood gas testing may reveal anion gap metabolic acidosis, which can be severe. Lactate levels are commonly elevated.[5] Caffeine toxicity can result in hypokalemia, hypocalcemia, hyponatremia, and hyperglycemia. Clinicians should also obtain serum myoglobin and creatine kinase levels to monitor for rhabdomyolysis. An electrocardiogram may show tachycardia, ST-segment depressions, or T-wave inversions. Cardiac monitoring allows the evaluation of heart rate and the early recognition of dysrhythmias, such as ventricular ectopy or fibrillation.[11][18][21]

Fatal caffeine overdose is relatively rare, and treatment information is limited to case reports. The primary treatment for minor caffeine ingestion is supportive care, including advanced cardiac life support or pediatric advanced life support as needed. Hydration may be oral for minor cases. Patients with severe toxicity benefit from intravenous hydration. Beta-blockers such as esmolol or metoprolol are effective for treating tachycardia. Procainamide, lidocaine, or bicarbonate have also been used to treat tachydysrhythmias.[26] Adenosine and electrical cardioversion in cases of caffeine toxicity have not been shown to have any sustained effect on cardiac dysrhythmias.[27][28] Vasopressors, such as norepinephrine or phenylephrine, can help maintain a goal arterial pressure greater than 65 mm Hg without worsening tachycardia.[17] Activated charcoal can bind caffeine if the ingestion is recent, and repeated doses can help diminish serum levels through enterohepatic circulation. Orogastric lavage using a standard nasogastric tube has also been reported to help aspirate caffeine contents, but only if initiated within 1 h of ingestion. If the patient develops symptomatic hypokalemia, then potassium should be replaced. Hemodialysis has been effective in severe, life-threatening caffeine ingestions. The first-line treatment for seizures includes benzodiazepines, such as lorazepam, diazepam, and midazolam. Phenobarbital and propofol may be used to treat refractory seizures. Both phenytoin and fosphenytoin are not recommended for the treatment of seizures related to caffeine toxicity in response to case reports of increased mortality in animal models with methylxanthine toxicity.[29] Caffeine exhibits ideal characteristics for dialysis, including low protein binding (36%), low molecular size (194 kDa), and a small volume of distribution (0.6 to 0.8 L/kg). Dialysis can be discontinued when clinical improvement is observed or when the serum caffeine concentration is less than 15 mg/L.[30] Imminent cardiac arrest in caffeine toxicity should prompt intralipid therapy to scavenge the free serum caffeine.[18][31] Extracorporeal membrane oxygenation can be considered for patients who are resistant to treatment and are hemodynamically unstable.[32][33]

Caffeine toxicity can present with symptoms similar to those of the following conditions: Amphetamine toxicity Atrial fibrillation/flutter Beta-adrenergic agonist overdose Carbon monoxide toxicity Cathinone toxicity Cocaine toxicity Cyanide toxicity Delirium tremens Diabetic ketoacidosis Disulfiram toxicity Intracranial hemorrhage Iron toxicity Monoamine oxidase inhibitor toxicity Multifocal atrial tachycardia Polysubstance overdose Salicylate toxicity Septic shock Status epilepticus Theophylline toxicity Thyrotoxicosis Ventricular fibrillation Ventricular tachycardia

There are relatively few deaths reported from caffeine overdose; however, the prognosis largely depends on how quickly treatment is implemented.[13] In cases of severe caffeine overdose, the prognosis is directly correlated with the timeliness of caffeine removal from the bloodstream using hemodialysis or intralipid emulsion therapy.[18]

Complications of caffeine overdose include seizure, neurological changes, tachydysrhythmia, ECG changes, hypokalemia, hyperglycemia, and anion gap metabolic acidosis secondary to lactic acidosis. Severe cases can result in acute kidney injury, rhabdomyolysis, and even cardiac arrest.[8][22]

There is no established standard of care or treatment plan for caffeine overdose, but consulting poison control is highly recommended when managing these cases. For severe overdoses requiring hemodialysis, nephrology consultation is necessary.[16][17][19][17][26][30] Cardiology may also need to be consulted for associated dysrhythmias. If an extracorporeal membrane oxygenation team is present, they may need to be consulted for severe cases.[35] These patients likely need to be admitted to the intensive care unit (ICU) and may benefit from consulting critical care.

Caffeine is easily accessible as an over-the-counter medication and component in several products.[2] Patients should be cautioned that caffeine can affect a variety of receptors, and the adverse effects can be profound. Toxic levels can be reached quickly, leading to significant morbidity and mortality if not treated promptly.[7][10]

Considerations for caffeine toxicity are as follows: In cases of sympathomimetic toxidrome of unknown cause, clinicians should consider caffeine toxicity, especially in the setting of hypotension, as caffeine levels can be measured, and specific therapy with activated charcoal, hemodialysis, or intralipid can be instituted. Caffeine overdose does not have an established standard of care treatment plan, but toxic serum caffeine levels can be successfully reversed when recognized and treated early. Caffeine is available over the counter and can quickly reach toxic levels when taken in excess. Seizures and cardiac dysrhythmias are commonly observed in toxic caffeine overdose. Esmolol is the first-line treatment for tachydysrhythmias associated with caffeine overdose.

Managing a caffeine overdose requires a consolidated approach by various healthcare professionals, including nursing staff, phlebotomists, pharmacists, toxicologists, nephrologists, and other healthcare providers. Morbidity and mortality can be high if caffeine overdose is not recognized and treated early. The emergency medicine clinician is responsible for stabilizing the patient and coordinating the patient's care in the emergency department. Some of the responsibilities of the emergency clinician include: Ordering drug levels in the blood and or urine. Monitor the patient for signs and symptoms of respiratory depression, cardiac arrhythmias, electrolyte abnormalities, and seizures. Performing various maneuvers to help limit the absorption of the drug in the body. Consulting poison control specialists and pharmacists regarding the use of activated charcoal, benzodiazepines, supplemental potassium, and esmolol. Consulting toxicologists and nephrologists for further management, which may include dialysis. Consulting the intensivist regarding ICU and monitoring while in the hospital. Patients require continued care from the moment they enter the emergency department until the time of discharge and beyond. If it is determined that the patient intentionally overdosed, a mental healthcare provider should be consulted once the patient has recovered medically. Outcomes The outcomes after caffeine toxicity are excellent. Mortality is very rare for patients who seek treatment. Those who do not seek treatment or the treatment is delayed may develop seizures, arrhythmias, or even aspirate vomitus. Over the past decade, less than 36 deaths have been reported. For those who survive, there are typically no residual sequelae.[36]