Caffeine

Aka: Caffeine, Caffeine Overdose, Caffeine Toxicity, Guaranine, Theine

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II. Indications

  1. Central Nervous System Stimulant
    1. Caffeine is the most widely used psychoactive substance in the world
    2. Daly (1998) Lakartidningen 95(51-52):5878-83 [PubMed]
  2. Idiopathic Apnea of Prematurity
    1. Increases central inspiratory drive
    2. Increases carbon dioxide sensitivity at respiratory centers in Medulla
    3. Increases skeletal Muscle contractility (including respiratory Muscles)
  3. Sports Performance Supplement (Ergogenic Aid)
    1. Athletes are limited to 12-15 mcg/ml urine depending on regulatory agency (NCAA, IOC)
    2. Performance enhancing in endurance sports
  4. Headaches
    1. CNS Arteriole constriction may be palliative in Acute Migraine Headache (component of Excedrin-Migraine)
    2. Risk of Caffeine withdrawal Headache
    3. High dose Caffeine may be effective in Spinal Headache

III. Preparations: Relative Caffeine amounts

  1. 10 mg/serving
    1. Decaffeinated coffee (7 oz, 210 ml)
    2. Milk Chocolate (1.5 oz)
  2. 30 mg/serving
    1. Dark Chocolate (1.5 oz)
  3. 50 mg/serving
    1. Tea (8 oz, 240 ml)
    2. Caffeinated soda (12 oz, 360 ml)
    3. Coffee ice cream (8 oz, 240 ml)
  4. 100 mg/serving
    1. Coffee (8 oz, 240 ml)
  5. 150 mg/serving
    1. Espresso (2 oz, 60 ml)
  6. 250-350 mg/serving
    1. Energy Drinks (8-16 oz, e.g. Redline, Spike, Hyde, Wired, Loud, Java Monster, Rockstar, Bang)

IV. Precautions

  1. Energy drinks contain high levels of stimulants
    1. Combined Caffeine and Methylxanthines may exceed 500 mg total
    2. Higher risk of toxicity
  2. Limit daily Caffeine below maximum
    1. Adults: 400 mg/day
    2. Teens: 2.5 mg/kg/day (up to 400 mg/day)

V. Mechanism

  1. Methylxanthine
  2. Adenosine Receptor Antagonist
  3. At high dose, Phosphodiesterase Inhibitor (increased 3-5 cAMP, increased intracellular Calcium)
  4. Stimulates Catecholamines (increased beta-1 and beta-2 Agonist activity)
    1. Stimulates CNS and cardiac activity
    2. CNS Arteriole constriction
    3. Bronchodilator
    4. Diuretic

VI. Pharmacokinetics

  1. Metabolism: Zero order elimination (very slow elimination)
  2. Hepatic Metabolism
  3. High oral Bioavailability
  4. Oral onset of peak activity <2 hours
  5. Half-Life: 4-5 hours (as long as 60-100 hours in newborns)
  6. Volume of distribution: 0.6 to 0.7 L/kg (0.8 to 0.9 in newborns)
  7. Protein binding: 17%
  8. Concentrations
    1. Toxicity: >35 mg/kg (esp. children)
    2. Lethal Dose: 10-20 grams in an adult (>100 mg/kg)

VII. Adverse Effects: Non-toxic Ingestion

  1. Anxiety
  2. Jitteriness
  3. Arrhythmia
  4. Insomnia
  5. Diuresis

VIII. Adverse Effects: Toxic Levels

  1. General
    1. Hypothermia
  2. Cardiopulmonary
    1. Respiratory Depression
    2. Dysrhythmia (e.g. Multifocal Atrial Tachycardia)
    3. Hypertension
    4. Wide Pulse Pressure (with diastolic Hypotension)
  3. Gastrointestinal
    1. Nausea
    2. Vomiting
  4. Neuropsychiatric
    1. Anxiety
    2. Tremor
    3. Seizures

IX. Labs: Toxicity

  1. Consider evaluation for Unknown Ingestion
  2. Caffeine concentration is not typically available outside tertiary centers
  3. Basic Chemistry Panel
    1. Hypokalemia
    2. Metabolic Acidosis
    3. Hyperglycemia

X. Management: Severe Caffeine Toxicity or Overdose

  1. General
    1. Consider other ingestions
    2. Consider Poison Control Consultation
  2. Antidotes
    1. Consider Activated Charcoal after recent known large ingestion
    2. Consider Intralipid (20% lipid emulsion) 1.5 mg/kg for refractory Hypotension or tachydysrhythmia
  3. Supportive care
    1. ABC Management
    2. Vasopressors for Hypotension (e.g. Norepinephrine, Vasopressin)
    3. Consider Esmolol infusion for tachydysrhythmia (Exercise caution)
    4. Consider Benzodiazepines for Agitation
  4. Hemodialysis Indications
    1. Seizures
    2. refractory Hypotension or tachydysrhythmia
    3. Caffeine concentration at toxic levels (>100 mg/L acutely, >60 mg/L chronically)
  5. Discharge Indications
    1. Asymptomatic at 4-6 hours after ingestion

XI. Resources

  1. FDA News: Investigation into Energy Drinks and Supplements
    1. http://www.fda.gov/Food/NewsEvents/ucm328536.htm

XII. References

  1. Leikin (1996) Poisoning and Toxicology Handbook, Lexicomp, Hudson, Ohio, p. 175-7
  2. Nordt in Herbert (2012) EM: Rap 12(8): 5
  3. Tomaszewski (2019) Crit Dec Emerg Med 33(12): 32

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Cost: Medications

caffeine (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
CAFFEINE 200 MG TABLET Generic OTC $0.08 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

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