Elsevier

Legal Medicine

Volume 24, January 2017, Pages 12-18
Legal Medicine

Case Report
Fatal acute intoxication of accidentally ingested nifedipine in an infant – A case report

https://doi.org/10.1016/j.legalmed.2016.11.002Get rights and content

Highlights

  • We report a death caused by acute nifedipine intoxication in two years old infant.

  • He orally ingested nifedipine which had been prescribed to his grandfather.

  • It was considered that he ingested nifedipine in mistake for ramune confectionery.

  • Blood concentration of nifedipine was higher than that of past infant fatal case.

  • There was a few fatal report of accidental ingestion of nifedipine in infant.

Abstract

A fatal case of acute nifedipine intoxication in a two-year-old boy is presented. The boy accidentally orally ingested an unknown amount of his grandfather’s nifedipine (40 mg/tablet), mistaking it for a ramune confectionery. Despite intensive medical treatment, his death was confirmed at 31 h after the accidental ingestion. The forensic autopsy revealed that there were neither pathological alterations or injuries in all of the organs. Toxicologically, nifedipine could be detected at the concentrations of 0.463, 0.669 and 13.0 μg/g in cardiac blood, peripheral blood and stomach contents, respectively. These concentrations were evaluated as fatal levels, and the cause of death was diagnosed as acute nifedipine intoxication. Recently, the number of infants and children who accidentally ingest drugs in the home is increasing. This case report prompts forensic pathologists and toxicologists to emphasize that children are always exposed to the risk of accidental drug ingestion in daily life.

Introduction

Dihydropyridine demonstrates greater selectivity for the calcium channels of vascular cells than for those of cardiac cells. Inhibiting calcium entry or release by blocking calcium channel suppresses the increase of the cytoplasmic calcium ion concentration, and causes relaxation of vascular smooth muscles and vasodilation [1]. Nifedipine is one dihydropyridine calcium channel blocking agent that is widely used as a first treatment of hypertension and angina pectoris [2], [3], [4] because it rapidly and effectively decreases blood pressure compared with other drugs [5].

As for the pharmacokinetics, nifedipine reaches peak concentration at 3 h after oral ingestion, and its biological half-life is 2–5 h [6], [7], [8], [9]. The drug is supplied as the free base in 10 and 20 mg normal-release capsules. The initial oral dose is 10 mg given 3 times daily, and the effective daily dosage is 30–120 mg. The total daily dose should not exceed 180 mg [10]. In adult cases, oral administration of 10 mg of nifedipine resulted in a serum concentration of 0.05 μg/ml at 1.6 h [10]. Moreover, chewing of the tablet increased serum concentration of nifedipine [11].

Recently, the number that infants and children who accidentally ingest drugs prescribed to their family members is increasing based on the report from the Japan Poison Information Center. Accidental ingestion of psychotropic drugs, hypoglycemic agents, bronchodilators and antihypertensive agents cause especially serious health damage. Herein, we reported a fatal case of acute nifedipine intoxication due to accidental oral ingestion in a 2-year-old boy.

Section snippets

Case report

At noon on a certain day, a two-year-old healthy boy accidentally orally ingested nifedipine, which had been prescribed to his grandfather. Immediately, the grandfather consulted his attending doctor by telephone, and was told to observe the boy without doing anything. Approximately 1 h after the ingestion, the boy complained of dizziness, and was transported to a hospital by an ambulance. Upon arrival at 13:45, his blood pressure was unmeasurable and heart rate was 169 bpm. Consciousness level

Autopsy and histopathological findings

The deceased was 88 cm in height and 11.5 kg in weight. The rectal temperature was 16 °C (room temperature: 25 °C). Postmortem rigidity was markedly observed in all of the joints. Postmortem lividity, dark, reddish-purple in color, was apparent on the back. There was no mechanical injury leading to death. Internally, the heart weighed 60 g, and there were many petechial hemorrhages on the epicardium. The amount of heart blood, dark red in color, was 45 ml including a small amount of hemocoagula. In

Materials

Intracardiac blood, peripheral blood from the femoral vein and stomach contents were obtained at the autopsy and subjected to toxicological analysis.

GC–MS apparatus and conditions

Nifedipine analysis (screening and quantitative) was performed using the Agilent 7890 GC-5975 MSD system (Agilent Technologies, Santa Clara, CA, USA). The system was operated in the positive electron impact (EI) mode. The ionization voltage and ionization current were set 70 eV and 0.15 mA, respectively. A fused-silica capillary column, DB-1MS (15 m × 

Results

Toxicological screening test demonstrated positive results of nifedipine, lidocaine and phenobarbital. Mass chromatograms and mass spectra of nifedipine in the authentic sample and extracts of peripheral blood are shown in Fig. 1. In each sample, the concentrations of nifedipine were determined (Table 1), indicating that the boy orally ingested nifedipine as evidenced by the higher nifedipine concentration in the stomach contents than in the intracardiac and peripheral blood. Toxicologically,

Discussion

In the forensic autopsy, there were no significant findings contributing to the cause of death. In toxicological analyses, the nifedipine concentrations in the intracardiac and peripheral blood samples were much higher than the therapeutic level for adults (0.025–0.15 μg/ml) [14]. Ramoska and colleagues [15] reported that the mean non-toxic dose was 19 mg, while the mean toxic ingestion was 340 mg in the past 31 cases of nifedipine ingestion with toxicity developing in seven patients. There were

Conflict of interest

The authors have declared that no conflict of interest exists.

References (27)

  • V.F. Challenor et al.

    The trans-hepatic of nifedipine

    Br. J. Clin. Phamacol.

    (1987)
  • R.C. Baselt

    Disposition of Toxic Drug and Chemicals in Man

    (2011)
  • T. Tanaka et al.

    Safety and pharmacokinetics of Adalat CR after administration of crunched tablet

    Jpn. J. Clin. Pharmacol. Ther.

    (1997)
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