Severe iron intoxication treated with exchange transfusion

Abstract

An 18-month-old previous healthy girl who had ingested 442 mg elemental iron/kg was admitted to a paediatric intensive care unit. The child was treated with gastric lavage, whole bowel irrigation and intravenous deferoxamine. After 2 h of standard therapy serum iron had risen threefold to 1362 µg/dl (244 µmol/l). The child was treated with exchange transfusion (ET; 52 ml/kg) and serum iron fell to 134 µg/dl (24 µmol/l). The patient made an uncomplicated recovery. ET should be considered in severe iron poisoning when standard therapy is inadequate.

BACKGROUND

Life-saving treatment of severe iron intoxication, when standard therapy is inadequate

Accidental iron intoxication is common in childhood. The severity of intoxication depends on the amount of elemental iron (Fe²⁺) ingested; a dose of 40 mg Fe²⁺/kg is associated with serious toxicity and doses higher than 100 mg Fe²⁺/kg can be fatal (table 1).¹

Table 1.

Toxic doses and serum levels of Fe²⁺

Ingested dose (mg Fe2+/kg)	Serum level, μg/dl (µmol/l)	Toxicity
Less than 20 mg	50–190 (8.95–34.01)	Normal, no toxicity
20–30 mg	190–350 (34.01–62.65)	Self limiting intoxication
40–50 mg	350–500 (62.65–89.50)	Serious toxicity
60 mg	500–1000 (89.50–179)	Potentially lethal
100 mg or more	>1000 (179)	Lethal

Iron poisoning has four clinical stages¹:

(1) Local corrosive stage (0–6 h) with gastrointestinal symptoms

(2) Latent asymptomatic stage (6–24 h), which can be missing

(3) Organ failure stage (12 h–5 days) with hepatic, renal, pulmonary and cardiac failure

(4) Gastrointestinal scarring stage (2–6 weeks).

We report a case of survival after ingestion of 442 mg Fe²⁺/kg treated by early exchange transfusion (ET) in addition to standard treatment.

CASE PRESENTATION

An 18-month-old previous healthy girl (weight 12 kg) was admitted to the emergency department (ED) 3 h after ingestion of 5300 mg Fe²⁺ (442 mg Fe²⁺/kg).

In the ED the girl was lethargic and vomiting dark, but not bloody, material containing lots of dark tablet remnants. Her vital signs (VS) were temperature 36.0°C (95.2°F), respiratory rate 26, regular pulse 128, blood pressure 86/63 mm Hg and oxygen saturation 96%. The abdomen was slightly tender, with active bowel sounds and no guarding.

The patient was treated with gastric lavage and large numbers of pills were aspirated. An abdominal x ray showed many visible radiopaque pills within the small intestine. Whole bowel irrigation (WBI) using dinatriumphosphate was initiated and continued until the rectal effluent was clear.

Continuous intravenous deferoxamine treatment was started. In our hospital it takes 2 h to analyse the level of serum iron, which turned out to be 447 µg/dl (80 µmol/l) at ED admission.

The child was admitted to the paediatric intensive care unit (ICU). She was drowsy and responded to pain with spontaneous sufficient breathing and unchanged VS. Laboratory tests revealed persistent metabolic acidosis with a positive anion gap. After 2 h of standard therapy serum iron had risen to 1362 µg/dl (244 µmol/l). The National Poison Control Centre advised us to perform ET, possibly followed by plasmapheresis (PP).

The girl was prepared for ET. Under uncomplicated general anaesthetic (thiomebumal, fentanyl, rocuronium, sevoflurane), a haemodialysis catheter and an intra-arterial line were inserted. The child was on a ventilator and sedated with midazolam and fentanyl infusions. The ET was performed 9 h after the iron ingestion. Over 30 min, group B Rhesus-positive (patient’s blood type) reconstituted donor blood was exchanged in rapid 50 ml increments. A volume of 625 ml blood was removed from the patient, whose estimated blood volume was 840 ml. Around two-thirds of the blood volume was exchanged, equivalent to 52 ml/kg. The patient remained circulatory stable during the procedure. Arterial blood gas results 2 and 4 h after ET showed normal values without acidosis.

After ET, treatment was continued with PP for the following 5 h as the serum iron level was not known at that time. A total of 2580 ml plasma was exchanged with 1250 ml 5% human albumin and 1330 ml fresh frozen plasma. Serum iron after ET fell to 134 µg/dl (24 µmol/l) and further after PP to 40 µg/dl (7 µmol/l) and deferoxamine infusion was stopped. Iron content in the exchanged blood and plasma volumes was not measured.

The child had a diuresis of 1355 ml during the first 18 h (6 ml/kg/h).

Figure 1 summarises the course of the treatment using deferoxamine, exchange transfusion and plasmapheresis and the correlation with iron sample values.

Figure 1.

The course of the treatment (deferoxamine, exchange transfusion, plasmapheresis) and serum iron values. Bulleted numbers are serum iron values during the course of treatment. WBI, whole bowel irrigation.

OUTCOME AND FOLLOW-UP

The child improved quickly and was extubated 18 h after ET. Serum iron remained normal 12 h after ET at 34 µg/dl (6 µmol/l). The girl was observed in the paediatric ICU for another 24 h, which were uneventful. Serum phosphorus was elevated, probably as a side-effect of the WBI.

The child was discharged from the paediatric department on day 4 asymptomatic with normal biochemistry and remained well at follow-up after 7, 14 days and 3 months.

DISCUSSION

Two cases: one in 1958 and another in 1964

Iron is well absorbed in the proximal small bowel and peak serum level occurs 2–6 h after ingestion. Iron is transported in the blood bound to transferrin and the body has no specific way to excrete it. Intracellular toxicity starts approximately 12 h after ingestion. Iron is supposed not to be absorbed by charcoal and is not dialysable.

Deferoxamine has been used over the past four decades as a therapeutic agent for the treatment of both acute and chronic iron overload, and remains the drug of choice for the treatment of significant iron intoxication. The recommended maximal dose of deferoxamine is 80 mg/kg over 24 h. However, in severe iron poisoning this dose may not be sufficient as 100 mg deferoxamine chelates 8.5 mg of iron. Only 81.6 mg Fe²⁺ could have been chelated by the maximal recommended dose of deferoxamine in this patient. The child was treated with intravenous deferoxamine at a dose 15 mg/kg/h for 14 h to a total amount of 2520 mg, so the given dose was 210 mg/kg. No side-effects of deferoxamine were observed in the child despite the high dose.

ET as a successful treatment for iron poisoning was described in 1958² and in 1964³ in case reports describing two children aged 18 and 16 months. An animal study from 1969⁴ showed that significant quantities of iron (30 times greater than by deferoxamine treatment) could be removed by two-blood volume ET over 1 h. To our knowledge there are no other references to ET as a treatment for iron poisoning.

In the case reports mentioned above, the ET procedures were accomplished in 2 h² and 3 h.³ In both cases blood was exchanged in 20 ml amounts to a total volume of more than 100 ml/kg. In our case ET was accomplished in 30 min and we exchanged 50 ml amounts to a total volume of 52 ml/kg. The exchanged volume was sufficient to remove Fe²⁺ and serum iron fell from 1362 µg/dl (244 µmol/l) to 134 µg/dl (24 µmol/l). We used reconstituted donor blood of the patient’s own blood type. Group O Rhesus-negative blood was used in the report by Tomlinson,³ but there is no record of blood type used for ET in the report by Amerman et al.² In our case, ET was performed 9 h after iron ingestion. Previously, ET had been performed 12 h² and more than 24 h³ after ingestion.

In general, ET has been used as a successful treatment for other types of poisoning since 1955. PP is effective in removing highly protein bound drugs with a low volume of distribution, but there are no controlled studies on the effectiveness of PP in any specific intoxication.⁵

LEARNING POINTS

• Accidental iron intoxication is common in childhood; the severity of the toxicity depends on the amount of iron ingested.

• A dose of greater than 40 mg/kg is seriously toxic and greater than 100 mg/kg often fatal.

• Iron toxicity causes gastric irritation followed by renal, hepatic and cardiac failure.

• Standard treatment is with gastric lavage and intravenous iron chelation.

• In this report, exchange transfusion was used to treat a near fatal case of iron intoxication.