Lethal suicidal intoxication with propafenone, after a history of self-inflicted injuries

A Tissue Distribution Study of Propafenone in an Intentional Fatal Poisoning Case

“…Similar manifestations of intoxication as in the abovementioned studies were also observed by Gil et al [15] at a dose of 4500 mg PPF and by Keramari et al [16] in a suicide attempt with a dose of 2250 mg or a dose of 1800 mg PPF, where the PPF concentration in the blood, measured 6 h after intake, was 4.9 µg/mL [35]. Fatal cases of PPF intoxication are rarer, and the blood concentrations reach slightly higher values, i.e., 4.18 and 9.42 µg/mL [19]; 5.27 µg/mL [17]; 2.50 µg/mL in the serum, probably after a dose of 1500-3000 mg [20]; and 12 µg/mL in the blood, probably after a dose of 6000 mg PPF [18]. In the current case, the concentration of PPF in the serum was 17.4 µg/mL (Table 3) approximately 12 h after the ingestion of the tablets and significantly exceeded the toxic plasma concentrations observed in clinical poisonings with a successful recovery.…”

“…In these cases, symptoms such as collapse, vomiting and unresponsiveness, different levels of the Glasgow Coma Scale, a ventricular escape rhythm and intraventricular conduction, delayed bradycardia, hypotension, QRS prolongation and a corrected QT interval, generalized tonic-clonic seizures and cardiac arrest have been observed [13][14][15][16]. Fatal cases of PPF intoxication (five were intentional suicides and one was accidental) are rarer, characterized by significantly higher PPF concentrations in the blood than during therapy [17][18][19][20][21]. All studied cases had similarities in heart function failure, leading to cardiac arrest, as well as in the method of respiratory depression, ECG patterns (prolongation QT and QRS intervals), hypotension, bradycardia and other symptoms (vomiting, decreased consciousness, etc.).…”

“…In many publications, especially in the case of PPF poisoning, the validation parameters and necessary details that are essential for the correct execution and reproducibility of the extraction and separation are missing. Most publications [13,[17][18][19][20]24,25] report on the use of liquid-liquid extraction (LLE) to isolate PPF from biological matrices (mainly from blood), but it is not apparent which analytical quantification procedure was applied. As PPF extraction is not standardized, the guidelines [28,29] recommend the use of the standard addition method (SAM) over the conventional matrix-matched calibration method (MMCM) as the preferred quantitation approach for complex matrices.…”

“…As PPF extraction is not standardized, the guidelines [28,29] recommend the use of the standard addition method (SAM) over the conventional matrix-matched calibration method (MMCM) as the preferred quantitation approach for complex matrices. Separation techniques are usually applied for quantitative analysis-most frequently, either high-performance liquid chromatography (HPLC) [13,[18][19][20]24,25] or gas chromatography (GC) [17] combined with spectrometric detection (e.g., UV or diode-array detection). The published methods, however, suffer from a poor resolution as they benefit from the use of highly selective mass spectrometric (MS) detection.…”

Clinical Management of Severe Propafenone Intoxication

“…This is unclear and may be related to a toxic effect or secondary to cerebral hypoperfusion caused by arrhythmia and conduction disturbance (2). Review of the literature revealed 55 cases of propafenone intoxication with ingested doses from 1800 to 9000 mg (1,2,5,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). The main clinical warning signs are cardiac insufficiency, conduction disturbance, and seizures.…”