Fatal acute intoxication of accidentally ingested nifedipine in an infant - A case report.

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 (40mg/tablet), mistaking it for a ramune confectionery. Despite intensive medical treatment, his death was confirmed at 31h 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 13.0µg/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.

Pilot Trial of Intravenous Lipid Emulsion Treatment for Severe Nifedipine-Induced Shock.

Animal studies and human case reports show promise in using lipid rescue to treat refractory calcium channel antagonist toxicity. However, the majority of research and clinical experience has focused on non-dihydropyridine agents. Thus, we sought to investigate the value of lipid emulsion (ILE) therapy for dihydropyridine-induced shock. This IACUC-approved study utilized seven swine that were sedated with alpha-chloralose, mechanically ventilated, and instrumented for drug delivery and hemodynamic measures. After stabilization and basal measures, nifedipine (0.01875 mg/kg/min) was infused until imminent cardiac arrest (seizure, end tidal CO2 < 10 mmHg, bradydysrhythmia, or pulseless electrical activity). Animals then received a 7 mL/kg bolus of 20% lipid emulsion via central catheter. Lipid circulation was visually confirmed by the presence of fat in peripheral arterial blood. Hemodynamics were continuously monitored until 10 min after lipid bolus. Surviving animals were euthanized. Pre- and post-lipid treatment parameters were analyzed using the Wilxocon signed rank test (p <0.05 significant). Nifedipine toxicity was characterized by vasodilatory hypotension, impaired vascular contractility, and tachycardia with terminal bradycardia. The median time to imminent cardiac arrest from start of nifedipine infusion was 218 min. Lipid treatment did not improve hemodynamics or restore circulation in any animal. There was no benefit from lipid rescue in this model of nifedipine toxicity. Further study of ILE for dihydropyridine toxicity is warranted but initial animal model results are not promising.

Intralipid emulsion treatment as an antidote in lipophilic drug intoxications.

Intravenous lipid emulsion (ILE) is a lifesaving treatment of lipophilic drug intoxications. Not only does ILE have demonstrable efficacy as an antidote to local anesthetic toxicity, it is also effective in lipophilic drug intoxications. Our case series involved 10 patients with ingestion of different types of lipophilic drugs. Intravenous lipid emulsion treatment improved Glasgow Coma Scale or blood pressure and pulse rate or both according to the drug type. Complications were observed in 2 patients (minimal change pancreatitis and probable ILE treatment-related fat infiltration in lungs). In our case series, ILE was used for different lipophilic drug intoxications to improve cardiovascular and neurologic symptoms. According to the results, it was found that ILE treatment is a lifesaving agent in lipophilic drug intoxications and it can be used in unconscious patients who have cardiac and/or neurologic symptoms but no history of a specific drug ingestion.

[The detection of nifedipine in biological materials].

The objective of the present study was to find optimal conditions for the isolation of nifedipine from biological materials by ethylacetate. It was shown that nifedipine can be purified from co-extracted substances of the biological material on a Silasorb C-18 column with the size of the particles 30 microns. The authors propose to use thin-layer chromatography, IR spectrophotometry, and reverse-phase high performance liquid chromatography for the identification and quantitative determination of nifedipine extracted from cadaveric liver samples.

Addition of phenylephrine to high-dose insulin in dihydropyridine overdose does not improve outcome.

INTRODUCTION: Vasopressors are commonly used for calcium channel blocker (CCB)-induced cardiogenic shock after calcium and high-dose insulin (HDI). Vasopressor therapy is frequently used in combination with HDI to increase blood pressure and improve outcome. However, no studies have compared the efficacy of HDI to the combination of a vasopressor and HDI in dihydropyridine overdose. We conducted a study to compare the efficacy of HDI to phenylephrine (PE) plus HDI in a porcine model of dihydropyridine toxicity. METHODS: Cardiogenic shock was induced by administering a nifedipine (NP) infusion of 0.0125 mcg/kg/min until a point of toxicity, defined as a 25% decrease in the baseline product of mean arterial pressure (MAP) × cardiac output (CO). Each arm was resuscitated with 20 mL/kg of saline (NS). The nifedipine infusion continued throughout a 4-h resuscitation protocol. The HDI group was titrated up to 10 units/kg/h of insulin and the HDI/PE group was titrated up to a dose of HDI 10 units/kg/h plus PE 3.6 mcg/kg/min. RESULTS: No baseline differences were found among groups including time to toxicity. Survival was not different between the HDI and HDI/PE arms. When comparing the HDI to the HDI/PE arm no differences were found for cardiac index (CI) (p = 0.06), systemic vascular resistance (p = 0.34), heart rate (HR) (p = 0.95), mean arterial pressure (p = 0.99), pulmonary vascular resistance (PVR) (p = 0.07), or base excess (p = 0.36). CONCLUSION: In this model of nifedipine-induced cardiogenic shock, the addition of PE to HDI therapy did not improve mortality, cardiac output, blood pressure, systemic vascular resistance (SVR), or base excess.

Successful treatment of a massive atenolol and nifedipine overdose with CVVHDF.

The aim of this paper was to describe a case of massive atenol and nifedipine poisoning, complicated by the co-existence of liver cirrhosis, where standard therapies (fluid replacement, vasopressors and inotropic agents, insulin, glucagon, calcium and bowel decontamination) were ineffective in restoring an adequate heart rate, blood pressure, renal and intestinal blood flow. This led to consequent anuric renal insufficiency and incipient multiple organ failure syndrome (MOFS). The patient recovered completely after Continuous Veno-Venous Hemo-Dia-Filtration (CVVHDF); this treatment removed atenolol from blood, with predicted clearance levels. The patient was a 45-year old female with a history of hypertension, liver cirrhosis, neurological and psychiatric disorders, with a massive atenolol (69.6 microg/mL) and nifedipine (63 ng/mL) overdose. CVVHDF at an ultrafiltration rate of 1 500 mL/h was started on day 1. From day 2 onwards, as the plasma atenolol concentration decreased, the blood pressure rose at a slow but constant rate. On day 5, there was restoration of an adequate blood pressure, which restored both renal and intestinal function, and also improved MOFS. The standard therapeutic approach was ineffective at eliminating both substances from the blood, and the clinical picture became worse due to incipient MOFS. CVVHDF was used in order to maintain the fluid and electrolyte balance and also to clear the beta blocker from the blood. The clearance kinetics of atenolol were consistent with the expected clearance values, on the basis of a CVVHDF ultrafiltration flow of 1 500 mL/h, which corresponds to a creatinine clearance of about 25 mL/min.

Bezoar formation requiring endoscopic removal after intentional overdose of extended-release nifedipine.

A 61-year-old Caucasian woman was transported to the emergency department after intentionally ingesting several different prescription drugs. She had been found by her husband in an unconscious state with empty bottles of extended-release venlafaxine, extended-release nifedipine, sertraline, and atorvastatin. She was intubated in the emergency department and transferred to the intensive care unit. After 36 hours in the intensive care unit, she was stabilized and brought to a general medical ward. She later developed profound recurrent hypotension with systolic blood pressures ranging from 40-70 mm Hg and diastolic blood pressures of 0-40 mm Hg. She was readmitted to the intensive care unit, where a computed tomography scan revealed a mass in her stomach. A gastroenterology consultation was obtained, and an esophagogastroduodenoscopy (EGD) was performed, during which a large drug bezoar was discovered and removed. The drugs were identified as extended-release nifedipine with a few granules of extended-release venlafaxine. Unfortunately, the patient died 3 days after the EGD from multisystem organ failure related to the overdose. Clinicians who encounter drug overdoses should be aware of the possibility of drug bezoar formation and should consider endoscopic removal as a potential treatment option.

Hyperinsulinemic-euglycemic therapy for intoxication with calcium channel blockers.

Conventional therapy for intoxication with calcium channel blockers consists of crystalloid solutions, calcium gluconate, glucagon and vasopressor agents. These therapies often fail to improve hemodynamic function in intoxicated patients. The pathophysologic mechanism proposed for intoxication with these agents, suggest hypoinsulinemia as the determinant factor. We will describe the case of a 77 years old man treated for an overdose of nifedipine and atenolol who arrived at our institution with hypotension and bradycardia. After conventional therapy failed to improve the patient's hemodynamic status, hyperinsulinemia and euglycemia contributed to the improvement of the patient's neurologic and hemodynamic condition. Thus, hyperinsulinemic-euglycemic therapy was of benefit in this patient with hemodynamic compromise secondary to intoxication with calcium channel blocker not responding to conventional therapy. We will review the mechanism of action of calcium channel blocker drugs as well as the clinical presentation and treatment options for calcium channel blocker intoxication.

Hyperinsulinemic-euglycemic therapy for intoxication with calcium channel blockers

Conventional therapy for intoxication with calcium channel blockers consists of crystalloid solutions, calcium gluconate, glucagon and vasopressor agents. These therapies often fail to improve hemodynamic function in intoxicated patients. The pathophysologic mechanism proposed for intoxication with these agents, suggest hypoinsulinemia as the determinant factor. We will describe the case of a 77 years old man treated for an overdose of nifedipine and atenolol who arrived at our institution with hypotension and bradycardia. After conventional therapy failed to improve the patient's hemodynamic status, hyperinsulinemia and euglycemia contributed to the improvement of the patient's neurologic and hemodynamic condition. Thus, hyperinsulinemic-euglycemic therapy was of benefit in this patient with hemodynamic compromise secondary to intoxication with calcium channel blocker not responding to conventional therapy. We will review the mechanism of action of calcium channel blocker drugs as well as the clinical presentation and treatment options for calcium channel blocker intoxication.

[Toxicological analysis of selected 1,4-dihydropyridine calcium channel blockers in the diagnosis of intoxications]. / Analiza toksykologiczna wybranych pochodnych 1,4-dihydropirydyny w diagnostyce zatruc.

This study is aimed at evaluating effective techniques of qualitative and quantitative analysis of selected 1,4-dihydropyridine calcium channel blockers, useful both for thanatological diagnosis of intoxications as well as monitoring therapy. The studies took advantage of gas chromatography (GLC) and high performance liquid chromatography (HPLC). Isolation of studied compounds from biological material was performed using classical and solid phase extraction procedures (SPE) such as Bond Elut LRC (Varian), Abselut Nexus (Varian), STRATA C - 18 E (Phenomenex). The program included analysis of nine of the most frequently prescribed derivatives: nifedipine, felodipine, amlodipine, nicardipine, nimodypine, nilvadipine, nitrendipine, nisoldipine, isradipine.

[Acute poisoning with nifedipine and acebutol: two cases]. / Ostre zatrucie nifedypina i acebutolem--dwa przypadki.

In this paper the case of intoxication in two women (19-year-old and 23-year-old), who in suicide attempts ingested at the same time different doses of nifedipine and acebutol. In 23-year-old woman 4 hours post ingestion cardiorespiratory arrest was stated. Resuscitation procedures were ineffective, she died. Acebutol concentration in postmortem blood was 24.1 mg/l and nifedipine-1.8 mg/l. The second one (19-year-old) was treated successfully, only mild cardiac disturbances were observed. Acebutol concentration in blood was 1.8 mg/l, nifedipine was not stated.

[A case of successfully treated nifedipine-poisoning].

Calcium antagonists have been prescribed for treatment of hypertension and several other diseases, and the incidence of poisoning involving these agents is increasing. We encountered and successfully treated a case of nifedipine poisoning. The patient was a 52-year-old man who ingested 76 tablets of nifedipine 20 mg while drinking alcohol. He was brought to a clinic and transferred to our emergency department. Since systolic blood pressure on arrival was 110 mmHg, primary care involved gastric lavage, infusion of lactated Ringer solution, and administration of activated charcoal and cathartics. Hypotension subsequently developed and continuous infusion of dobutamine was initiated. Arrhythmia did not appear during the course of treatment, and the patient was discharged after four days.

Continuous calcium chloride infusion for massive nifedipine overdose.

A 37-year-old woman presented with persistent hypotension and noncardiogenic pulmonary edema after massive nifedipine overdose. Judicious use of continuous and prolonged high-dose IV calcium infusion was administered to provide sustained increases in serum ionic calcium level (approximately 2 mmol/L) and was able to improve the hemodynamic status without any major adverse reaction.

Fatal nifedipine ingestions in children.

Nifedipine is a prototypical dihydropyridine calcium channel "blocker" that can cause hypotension and cardiac conduction abnormalities. When compared to other calcium channel antagonists, overdoses have been reported to be relatively benign with treatment consisting mainly of supportive care. We report two pediatric cases of death secondary to accidental ingestion of long acting nifedipine (Adalat). Both cases did not respond to aggressive supportive care that included calcium, atropine, epinephrine, glucagon, sodium bicarbonate, and transthoracic pacing.

Utilization of a glucagon infusion in the management of a massive nifedipine overdose.

This case report describes a continuous i.v. infusion of glucagon used to reverse the cardiovascular manifestations of a nifedipine overdose in a patient who presented after a massive nifedipine extended-release tablet ingestion. In this patient, glucagon appeared to be effective in the management of this toxicologic emergency.

A suicide attempt with an oral calcium channel blocker.

Calcium channel blockers are widely used in all-aged populations. The drugs are generally safe in therapeutic dosage, but severe side effects with elevated intake are increasingly described, mainly in adult patients. We report an adolescent girl who intentionally ingested an overdose of nifedipine.

The use of glucagon in nifedipine poisoning complicated by clonidine ingestion.

Glucagon has been used to treat the hypotension associated with calcium channel antagonist poisoning in adult patients. We describe the successful use of glucagon in a pediatric patient poisoned with nifedipine and clonidine whose hypotension was unresponsive to fluid resuscitation, calcium chloride, and dopamine.