关键词: Caffeine esmolol norepinephrine poisoning toxicodynamics toxicokinetics

Mesh : Administration, Oral Adrenergic alpha-Agonists / administration & dosage Adrenergic beta-1 Receptor Antagonists / administration & dosage Caffeine / administration & dosage pharmacokinetics poisoning Cardiotoxicity Central Nervous System Stimulants / administration & dosage pharmacokinetics poisoning Electric Countershock Half-Life Heart Rate / drug effects Humans Hyperlactatemia / chemically induced Infusions, Intravenous Intubation, Intratracheal Male Metabolic Clearance Rate Middle Aged Norepinephrine / administration & dosage Powders Propanolamines / administration & dosage Suicide, Attempted Tachycardia / chemically induced diagnosis physiopathology therapy Treatment Outcome Ventricular Fibrillation / chemically induced diagnosis physiopathology therapy

来  源:   DOI:10.1080/15563650.2021.1891243   PDF(Sci-hub)

Abstract:
UNASSIGNED: Caffeine poisoning may cause life-threatening arrhythmias and hemodynamic failure. We aimed to investigate the toxicokinetics (TK), toxicodynamics (TD) and TK/TD relationships of caffeine in a case of poisoning.
UNASSIGNED: A 47-year-old male ingested pure anhydrous caffeine powder (70 g) in a suicide attempt. He developed agitation, tachycardia, and two episodes of ventricular fibrillation treated with defibrillation and tracheal intubation. He was successfully managed using intravenous infusions of esmolol and norepinephrine.
UNASSIGNED: We modelled the time-course of plasma caffeine concentration (TK study using online liquid chromatography-tandem mass spectrometry), the time-course of blood lactate concentration and infusion rates of esmolol and norepinephrine (TD studies) and the TK/TD relationships.
UNASSIGNED: Caffeine TK was of first-order peaking at 258 mg/L with an elimination half-life of 46.2 h and clearance of 2.2 L/h. Caffeine-related effects on blood lactate (peak, 10 mmol/L at 1.25 h postingestion) were described by a Bateman-type equation (formation rate, 0.05 mmol/mg.h; elimination rate, 0.9 mmol/mg.h). Esmolol and norepinephrine infusion rates to reverse caffeine-related cardiovascular effects (peaks at 51-h postingestion) fitted well with a sigmoidal Emax model (EC50, 180.0 and 225.9 mg/L, respectively; Hill coefficient, 10.0).
UNASSIGNED: Massive caffeine ingestion is characterized by prolonged caffeine elimination. TK/TD relationships are helpful to quantify caffeine-related catecholaminergic effects.
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