Accidental iron poisoning in children – Experience from a teaching institution

Abstract

Background:

Acute iron toxicity is fatal in children resulting from an accidental overdose of maternal iron tablets at home. There is scanty literature on children looking at the profile and outcome. We report a case series of five children presenting after accidental ingestion of iron tablets. Two presented with fulminant hepatic failure at 48 h, and despite supportive management and plasmapheresis in one child, both succumbed to illness.

Materials and Methods:

This retrospective study was conducted in the pediatric intensive care unit (PICU) of a teaching institution in South India between January 2009 and December 2019. All children with accidental iron poisoning were included in the analysis.

Results:

During the study period, five children presented to our PICU after accidental iron tablet ingestion. The mean age was 25.8 months [standard deviation (SD): 13.9]. All the children had consumed iron tablets from their pregnant mothers. Two children presenting with liver failure succumbed to illness. Treatment included a standard protocol of gastric lavage and desferrioxamine. Most of them (3/5) received whole bowel irrigation. We did plasmapheresis in one child who presented with fulminant hepatic failure. The majority were discharged alive (3/5). The presence of coagulopathy, acute liver failure, and delayed presentation were associated with high mortality.

Conclusion:

Accidental iron poisoning is prevalent in children and associated with significant mortality. Parents and caretakers must be counseled by primary care physicians and made aware of the safe storage of iron tablets.

Introduction

Iron poisoning in children has been described as early as in the 1950’s, attributed to a rising use of iron supplementation in household members.[1] Iron, despite being one of the most important trace metals, has severe negative consequences when consumed in high numbers. Because of the candy-like form of the pills, which makes them enticing to youngsters, the majority of reported cases are in children, providing a significant risk factor for them. Iron poisoning is a common toxicologic emergency in infants and toddlers. Many prenatal vitamins contain significant quantities of iron, and ferrous sulfate tablets (20% elemental iron) are routinely administered to postpartum women, many of whom have children in the family. Children less than 5 years of age are at high risk for accidental poisoning.[2] Primary care physicians play a pivotal role being the first care responders in the community. They can educate the young mothers to store medications safely out of reach of children as even one or two tablets of iron could be lethal for children. Prevention of accidental poisoning can be performed by spreading awareness regarding household poisons.[3]

We present five cases of acute iron consumption and discuss the profile and therapy and focus on plasmapheresis. Our case series had predominantly a toddler age group, with various levels of ingestion; two children died of liver failure because of high-dosage toxicity and late presentation.

Materials and Methods

This is a descriptive retrospective case series of lethal iron toxicity in children, evaluating the spectrum of clinical presentation and outcome. During the 11-year study period (January 2009 to December 2019), all eligible children who presented with iron toxicity were recruited. Data on their demographics, symptoms, laboratory tests, complications, and outcomes were collected. The baseline characteristics are shown in Table 1, laboratory investigations in Table 2, and treatment and outcome in Table 3.

Table 1.

Baseline characteristics and symptoms of iron ingestion

	Case 1	Case 2	Case 3	Case 4	Case 5
Age	1 year 3 months	1 year 3 months	2 year 6 months	2 year 6 months	3 year 7 months
Sex	Female	Female	Male	Male	Male
History of ingestion	Yes	Yes	Yes	Yes	Yes
Dose	120 mg/kg	30 mg/kg	200 mg/kg	80 mg/kg	50 mg/kg
Form of ingestion	Oral	Oral	Oral	Oral	Oral
Time of presentation	<1 h	45 mins	<1 h	3.5 h	100 h
Glasgow Coma Score at presentation	15	15	13	15	13
0-6 h	Vomiting, loose stools	Vomiting, loose stools	Vomiting	Vomiting	Vomiting, loose stools
6-24 h			Low sensorium		Low sensorium
>24 h			Liver failure		Liver Failure

Table 2.

Laboratory investigations of iron ingestion

	Case 1	Case 2	Case 3	Case 4	Case 5
Serum Iron (µg%) Normal range: 60-150 µg%	462	472	868	412	253
TIBC (mcg%) Normal range 300-360 mcg%	472	533	733	429	257
Total bilirubin (mg%) Normal range: 0.05-0.55 mg%	0.5	0.3	0.53	0.2	6.57
Direct bilirubin (mg%) Normal range: 0.05-0.3 mg%	0.2	0.1	0.2	0.1	3.9
SGOT (U/L) Normal range: 9-25 U/L	38	34	40	29	3067
SGPT (u/l) Normal range: 18-40 u/l	15	12	18	11	4093
Albumin (g%) Normal range: 2.8-4.7 g%	3.4	4.8	4.8	4.5	3.3
Alkaline Phosphatase (u/l) Normal range: 156-450 u/l	195	327	318	238	588
Prothrombin Time in seconds/INR	9.9/0.92	10.8/1.01	14.5/1.32	10.5/0.97	90/6.85
Creatinine mg% Normal range: 0.2-0.7 mg%)	0.4	0.6	0.44	0.31	0.35
Glucose (mg/dl) Normal range: 54-150 mg/dl	80	110	60	76	24
Abdomen Xray	Yes	Yes	Yes	Yes	Yes

TIBC=Total iron-binding capacity, SGOT=Serum glutamic-oxaloacetic transaminase, SGPT=Serum glutamic pyruvic transaminase, INR=International normalized ratio

Table 3.

Treatment and complications during PICU stay

Treatment and complications	Case 1	Case 2	Case 3	Case 4	Case 5
Gastric lavage	Yes	Yes	Yes	Yes	Yes (outside)
Whole bowel irrigation	Yes	No	No	No	No
Desferroxime (dose in mg/kg/h)	15	10	15	15	15
Time of infusion	<1 h	<1 h	<1 h	<1 h	101st h
N-Acetyl cysteine	Not given	Not given	Given	Not given	Given
Ventilation	No	No	Yes	No	Yes
Duration	Not applicable	Not applicable	5 days	Not applicable	7 days
Plasma exchange	No	No	No	No	Yes (3 sessions)
DIC	No	No	Yes	No	Yes
ARDS	No	No	Yes	No	Yes
AKI	No	No	Yes	No	No
CNS	No	No	No	No	Yes
MODS	No	No	Yes	No	Yes
Outcome	Alive	Alive	Died	Alive	Died

DIC=Disseminated intravascular coagulation, ARDS=Acute respiratory distress syndrome, AKI=Acute kidney injury, CNS=Central nervous system, MODS=Multi-organ dysfunction syndrome

Case 1

A 1-year-3-month-old girl presented herself with vomiting and loose stools 1 hour after accidentally ingesting iron tablets (120 mg/kg). She was hemodynamically stable at the time of presentation, and her liver and renal function tests were normal. She received stomach lavage and entire bowel irrigation and was started on desferrioxamine. She survived to discharge without any complications.

Case 2

A 1-year-3-month-old girl presented with vomiting and loose stools within 45 minutes of accidental ingestion of iron tablets (30 mg/kg). She was hemodynamically stable at the time of presentation, and her liver and renal function tests were normal. She was given stomach lavage as well as the start of desferrioxamine. She made it to discharge without incident.

Case 3

A 2-year-6-month-old boy presented with vomiting and lethargy within 1 hour of accidental ingestion of iron tablets (200 mg/kg). He had low sensorium, hypotension, and normal liver and renal function tests at the time of presentation. Gastric lavage, desferrioxamine, N-acetyl cysteine (NAC) infusion, fluid bolus, and ventilation were all administered to him. He died on day 5 of his sickness after developing disseminated intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), and liver failure with multi-organ dysfunction syndrome (MODS).

Case 4

A 2-year-6-month-old boy presented with vomiting at 3.5 hours of accidental ingestion of iron tablets (80 mg/kg). At the presentation, he was hemodynamically stable, and his liver function tests and renal function tests were normal. He was given gastric lavage along with the initiation of desferrioxamine. He survived to discharge without any complications.

Case 5

A 3-year-7-month-old boy presented with vomiting, loose stools, and altered sensorium at 100 hours (4 days) after accidental ingestion of iron tablets (50 mg/kg). At presentation, he had low sensorium and hypotension, and his liver function tests were deranged with coagulopathy and hypoglycemia. He was given gastric lavage, desferrioxamine, NAC infusion, ventilation, and three cycles of single-donor plasmapheresis. He developed acute liver failure secondary to iron overload, complicated with multi-organ failure, ARDS, and coagulopathy. Despite all efforts, he succumbed on day 7 of illness.

Discussion

Our case series revealed a high mortality rate. Although the fatal dose in children is stated to be 900 mg/kg, we discovered that our child who presented with ingestion of 200 mg/kg and one child who presented late (100 hours) were the ones who died from the sickness.[1]

Iron is one of the most important trace elements in the body, playing an important role in oxygen transport and cellular respiration. Because of its pathophysiologic impact, iron poisoning causes severe organ damage.[4,5]

The systemic insult is predicted by the serum iron content at presentation. Iron poisoning was described by Robertson et al. as a serum iron concentration greater than 300 g/dL (55 mol/L) within 12 hours of consumption, and they emphasized that serum iron levels can be misleading in late presentation because iron is re-distributed intra-cellularly. This was observed in our patients, who all had high levels upon presentation, except for one youngster who presented at 100 hours.[6] Serum iron levels more than 500 g/dL indicate a risk of severe manifestation, as seen in our cohort, where the infant with the highest level died. When children present to a primary care center, it is crucial to recognize the symptoms and initiate on antidotes if available.

Desferrioxamine is a particular antidote and the first iron chelator to be licensed. Desferrioxamine binds to iron, forming a ferrioxamine complex that is easily removed by the kidneys. Desferrioxamine binds to 9 mg of elemental iron in 100 mg. Desferrioxamine was given to all our children. According to Sane et al., early commencement of desferrioxamine has a favorable effect, which was observed in our children who presented within 1 hour of consumption. The presence of vinrose urine with remission of this color can be considered the therapy’s endpoint.[5,6,7] Hence, immediate referral for early initiation of treatment by a primary care physician is essential, especially in resource-limited settings.

NAC infusion is used to avoid hepatotoxicity, a major consequence of iron poisoning that has a 50% fatality rate.[7] Daram et al. reported that liver failure requires urgent care, including the early administration of NAC.[10] NAC was started in two of our youngsters who experienced deadly hepatotoxicity. In such extreme situations, as documented by Kozaki K et al., baby liver transplantation would be advantageous.[7,8,9,10] We were unable to provide the same because both our children with liver failure were extremely unwell.

Multi-organ dysfunction syndrome (MODS) is because of free unbound iron in the circulation which results in death even in adults as reported by Abhilash et al.[8] Iron toxicity can result in myocardial injury, pulmonary involvement, and disseminated intravascular coagulation.[5,6,8] Two of our children with fatal toxicity had MODS, resulting in death.

Plasmapheresis as a method of detoxification has been mentioned in clinical toxicology with a significant role in life-threatening intoxication. Highly protein-bound drugs with a low volume of distribution are eliminated with plasmaphereses.[11,12,13] Aslan N reported a successful case of plasmapheresis in a toddler with iron toxicity and liver failure.[13] We started plasmapheresis as a bridge to a liver transplant, but our child died. Nye R et al. proposed continuous venovenous hemofiltration in conjunction with plasmapheresis, which resulted in enhanced survival.[14]

Conclusion

Iron poisoning, although rare, is fatal in children with hepatotoxicity and MODS being a dose-related manifestation of delayed presentation. Early recognition by primary care physicians with initiation of treatment and prompt referral of children with toxicity, especially those needing intensive care management, is crucial for survival. In the presence of liver failure, early initiation of NAC and plasmapheresis could improve survival.

Key points

• Iron poisoning in children is mostly accidental with high mortality.

• Improving awareness among families can help in prevention of toxicity.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.