In vitro study of pharmacobezoar formation in simulated acetaminophen overdose.

Objectives: There have been few studies of pharmacobezoar formation, but they can be an important contributor to overdose toxicity. Pharmacobezoars may explain the delayed peak or "double hump" pharmacokinetics, which were noted in previous case reports with delayed toxicity of acetaminophen (APAP). We validated the presence of APAP bezoar formation in a controlled modified in vitro environment simulating acute APAP overdose.Methods: This study involved the APAP and control groups (ferrous sulfate and chlorpheniramine). The APAP study group contained three subgroups of APAP with different dosage, i.e., 25 g (50 tabs)/37.5 g (75 tabs)/50 g (100 tabs). The positive control group containing ferrous sulfate, i.e., 15 g (50 tabs), has been reported previously to form pharmacobezoars in overdose. The negative control group containing chlorpheniramine, i.e., 200 mg (50 tabs), has not been reported to form pharmacobezoars in previous case studies. Tablets from each study group were placed into a separate pig stomach. Each stomach contained 28 ml USP standard simulated gastric acid. The stomach was placed in a plastic box filled with water maintaining at 37 °C. Each test group was examined for 4 h in the stomach. The primary outcome was the presence of clump formation. Positive clump formation was defined as tablets sticking together and the ability to maintain shape upon dissecting the pig stomach and lifting with fingers. Tablet clumps would then undergo dissolution testing with subsequent analysis of dissolution profiles.Results: Formation of tablets clumps was confirmed in APAP overdose in the in vitro environment. Clumps were noted to be present in the 37.5 g and 50 g APAP groups, while 25 g APAP was unlikely to form clumps. The dissolution profile of clump demonstrated slower release without reaching plateau at 60 min, as compared to corresponding individual tabs of APAP. f1 and f2 analyses showed the dissolution profile of clump was different compared to that of referenced individual tab.Conclusions: APAP clump formation was confirmed in acute overdose of 37.5 g or more. Dissolution tests revealed delayed and steady release of tablet residue from the clumps, which could explain prolonged or delayed toxicity in large APAP overdose.

Childhood Drug and Non-Drug Poisoning in Nigeria: An Economic Appraisal.

BACKGROUND: The dearth of information on the economic cost of childhood poisoning in sub-Saharan Africa necessitated this study. OBJECTIVE: This study has investigated the prevalence of childhood drug and non-drug poisoning, treatment modalities and economic costs in Nigeria. METHOD: A retrospective study of childhood drug and non-drug poisoning cases from January 2007 to June 2014 in the University of Port Harcourt Teaching Hospital (UPTH), Port Harcourt, Nigeria was carried out. Medical records were analysed for demographic and aetiological characteristics of poisoned children (0-14 years of age), as well as fiscal impact of poisoning cases. FINDINGS: Of the 100 poisoned patients, 46% were male and 54% female, with female/male ratio of 1.17:1. Most of the children were under five years of age. Paracetamol, amitriptyline, chlorpromazine, ferrous sulphate, kerosene, organophosphates, carbon monoxide, snake bite, alcohol and rodenticides were involved in the poisoning. The average cost of poison management per patient was about $168, which is high given the economic status of Nigeria. CONCLUSION: Childhood poisoning is still a significant cause of morbidity among children in Nigeria and accounts for an appreciable amount of health spending, therefore preventive strategies should be considered.

Pediatric liver transplantation for fulminant hepatic failure secondary to intentional iron overdose.

Acute iron poisoning may lead to life-threatening hepatotoxicity. We present the cases of two pediatric patients with hepatotoxicity following intentional iron ingestion that progressed rapidly to fulminant hepatic failure despite treatment with deferoxamine. Liver transplantation was lifesaving in both patients. These cases emphasize the need for a high index of suspicion for iron ingestion, close monitoring for liver toxicity, and timely consideration for liver transplantation.

[Iron intoxication--poisoning with easily accessible medicines]. / Järnintoxikation - förgiftning med läittillgängligt läkemedel.

A 20-year-old woman was found semiconscious on the floor in a pool of black diarrhea with an empty 100 jar of ferrous sulphate beside her (100 mg Fe2+/tablet), 160 mg/kg. She was brought to the hospital an estimated 4 hours after ingestion and presented with irritability and a fluctuating CNS depression. Her blood pressure was 190/85 mmHg and pulse 130 bpm. An arterial blood gas analysis showed pH 7.17, pCO2 5.4 kPa, pO2 16.7 kPa and BE ­14 mmol/l. Deferoxamine was started immediately with a dose of 15 mg/kg/h intravenously. The patient was intubated in the ICU and whole bowel irrigation was performed. Due to technical problems with the venous blood sampling, a correct measurement of the serum iron concentration (s-Fe2) was not at hand until 15 hours post ingestion and showed 131 µmol/l. At that point her condition deteriorated with circulatory instability, hepatic failure, coagulopathy and renal insufficiency. Despite full treatment including continuous renal replacement therapy she died after 4 Days.

Iron autointoxication in a 16-year-old girl: a protective role for hepcidin?

Intentional iron overdose appears to be an increasingly common form of attempted suicide. We present a case of iron overdose in a 16-year-old girl who was found unconscious in her bed and brought to our emergency department. The most remarkable diagnostic findings were the patient's comatose condition, divergent eye position and positive Babinski foot pad reflexes. Laboratory tests showed hyperglycaemia and mild metabolic acidosis. A computed tomography scan of the cerebrum showed no signs of intracerebral haemorrhage or elevated intracerebral pressure. Toxicology screening showed no use of acetaminophen, ethanol or drugs of abuse. The patient was stabilized and monitored on the intensive care ward. When she woke up, she confessed to having taken Fero-Gradumet(®). Retrospectively analysed, the serum iron concentration in the first blood sample (seven hours after ingestion) was 62 µmol/L which corresponds with moderate iron intoxication. The patient received whole bowel irrigation with 2 L polyethyleneglycol solution and de-ironing treatment with intravenous deferoxamine 20 mg/kg in eight hours. She was discharged from the hospital after three days in a good clinical condition. Retrospectively, serum hepcidin concentrations were determined and evaluated in conjunction with serum iron concentrations and the installed treatment. Before medical de-ironing interventions were started, we saw that the serum iron concentration in our patient was already declining. At the same time, we observed a sharp increase in the serum hepcidin concentration. After normalization of serum iron concentrations, hepcidin normalized as well.

Intraperitoneal N-acetylcysteine for acute iron intoxication in rats.

Free radical formation and release of oxidant agents have been suggested as possible mechanisms for tissue damage in acute iron intoxication. N-acetylcysteine (NAC), a glutathione substitute and an antioxidant, is widely used as an antidote for various intoxications. Our aim was to determine whether intraperitoneal (i.p.) NAC would reduce the mortality of rats after acute, toxic oral doses of iron. Male Wistar rats were studied in three phases. In the first phase, animals were assigned to groups 1 (distilled water by gavage) and 2 (i.p. NAC) and observed for survival. In the second phase, rats were assigned to groups 3 (400 mg/kg elemental iron orally) and 4 (400 mg/kg elemental iron, followed by 150 mg/kg i.p. NAC). Survival was observed. Because most rats in Group 3 died within 90 minutes after iron administration, a third phase was conducted in order to allow for comparison of iron and transaminase serum levels after the administration of iron and NAC (group 5: n = 10). Mortality was significantly lower in rats treated with iron and NAC, compared to those treated with iron (P = 0.016). Median serum iron level was significantly lower among rats treated with iron and NAC, compared with rats treated with iron alone (P = 0.002). In a rat model of acute iron intoxication, i.p. administration of NAC may decrease serum iron levels and mortality.

[Ferrous sulfate: acute poisoning with a frequent use drug]. / Sulfato ferroso: intoxicación grave con un medicamento de empleo frecuente.

The iron is the main component of hemoglobin and is also part of myoglobin and enzymes. Its deficit is the most common cause of nutritional anemia in humans. The use of iron salts is very common in children, because they are indicated for prophylaxis and treatment of iron deficiency anemia. The availability in households and the emergence of flavored formulations that promote adherence to treatment, greatly assist in this type of poisoning. Usually, the overdose is considered a low hazard, because it is a mineral supplement added in many of the baby food. Iron in free state is able of producing toxicity, disrupting multiple cellular processes by catalyzing redox reactions with lipid peroxidation and free radical formation. We report a case of serious toxicity by iron salts, in which early intervention and management with specific chelator, allowed a favorable evolution.

Fulminant hepatic failure in woman with iron and non-steroidal anti-inflammatory drug intoxication.

A 17-year-old, previously healthy female ingested 16,000 mg iron sulphate (96.15 mg of iron ions per kg of b.wt.) with a suicidal intent. The patient was admitted to a toxicology unit 10 hours after the drug ingestion. Serum iron concentration at admission was 2351 µg% (421.0 µmol/L). In the course of the intoxication, hemorrhagic gastritis, renal insufficiency and increasing signs of fulminant hepatic failure complicated with coagulopathy and encephalopathy were observed. Treatment with deferoxamine was started immediately after admission to the hospital and continued for 15 hours until the serum concentration of iron decreased to 145 µg% (25.9 µmol/L). Patient was qualified for liver transplant, therefore albumin dialysis as a bridge to liver transplantation was performed. In spite of two procedures of albumin dialysis using the Prometheus system, deep coma, shock and respiratory insufficiency developed. The patient died 80 hours after iron ingestion. In the presented case, the ingestion of a very high dose of iron and late introduction of deferoxamine treatment contributed to fulminant liver failure and fatal outcome of the intoxication.

The use of haemofiltration for severe iron overdose.

A toddler who had ingested a significant amount of ferrous sulphate was admitted to the regional paediatric intensive care unit for supportive treatment. He received gastric lavage, bowel irrigation and intravenous desferrioxamine. He had a very high serum iron level of 700 micromol/l and was commenced on continuous veno-venous haemofiltration. His serum iron levels quickly returned to normal and he made a good recovery, with no permanent sequelae from the ingestion.

Infantile iron poisoning: challenges in diagnosis and management.

OBJECTIVE: To describe the clinical course and treatment of an infant with iron poisoning. DESIGN: Case report. SETTING: Pediatric intensive care unit in a tertiary care children's hospital. PATIENT, INTERVENTION, AND RESULTS: A 7-week-old, ex-28-week premature infant, was accidentally poisoned with ferrous sulfate. She recovered completely from metabolic acidosis and shock after treatment with inotropes and chelation with deferoxamine, but her management was complicated by challenges of physiologic immaturity of developing organs. This is the youngest infant reported, to date, with iron poisoning resulting in metabolic acidosis and shock. CONCLUSIONS: This case illustrates the importance of including toxic exposure in the differential diagnosis of neonatal shock of unknown etiology. Because of physiologic immaturity, iron poisoning in young infants poses special diagnostic and therapeutic challenges.

Emergency laparoscopic-assisted gastrotomy for the treatment of an iron bezoar.

Iron ingestion accounts for approximately 3% of calls to poison control centers. The profound local and systemic effects of an iron overdose have an associated mortality rate of 5%. Laparotomy and gastrotomy has been reported as a life-saving maneuver to extract the retained iron aggregates that are notoriously resistant to, removal by conventional emesis or lavage techniques. In this paper, we describe, for the first time, the use of laparoscopic-assisted gastrotomy in the treatment of an iron overdose. A 14-year-old girl attempted suicide by means of a polydrug drug overdose, which included ferrous fumarate, at a calculated potentially lethal dose of 70 mg/kg. A gastric iron bezoar was seen on plain radiograph. The regional poison control center recommended surgical removal of the retained iron tablets. Upper endoscopy confirmed the retention of iron and showed its dense adherence to the gastric mucosa. A 5-mm laparoscope was introduced at the umbilicus, and the stomach was grasped by an instrument introduced through a left-upper quadrant incision. The incision was then enlarged to allow the formation of a gastrotomy. The iron bezoar was removed with the aid of digital disimpaction and copious saline irrigation. The patient made a rapid postoperative recovery prior to undergoing psychiatric treatment. We conclude that laparoscopic-assisted gastrotomy is a simple and safe option in the acute management of a retained iron bezoar.