Acute iron toxicity in childrenDr Hanan Fathy Abdel Aziz Prof of clinical toxicology Ain Shams University

First Clinical Sinario Four years old child presented to the ER

complaining of blood tinged vomitus , abdominal colic and diarrhea of sudden onset started tow hours ago . Past and family history were negative as well as neonatal history.

General examination was negative except for hypotension, 90 over 55 mmHg .

Abdominal examination revealed lax abdomen with no guarding rigidity , and generalized tenderness all over the abdomen more in the upper quadrant.

what is your first differential diagnosis?

Keep it in mind

The ER physician prescribed anti emetic and analgesic.

The child was put under observation then discharged after stabilization of his clinical condition after 4 hours. Before discharge the pediatrician advised the mother to do stool analysis.

Eight hours later the child presented again by his mother by severe diarrhea and disturbed consciousness, on examination , T 35 , P 135 regular rate and rhythm , B.P was 65 over 30 mmHg. Skin was cold and sweaty with cold extremities and very weak distal pulsations , and Inspite of pale mucous membranes jaundice could be noticed.

Lab workup revealed PH 7.0 , HCO3 was 8 mlEq/l ALT and AST , elevated more than 3 folds of normal , both direct and indirect bilirubin are elevated and K level was 2.5 mlEq/l.

The child was admitted to the ICU and resuscitated but his condition deteriorated within hours ended by death.

Second Clinical Sinario A similar case was presented to another hospital

but in this time the pediatrician put the patient under observation and after 4 hours he performed liver enzymes test. Liver enzymes were double normal elevated.

From the history he suspected iron toxicity. By taking detailed drug history form the mother,

she said that she has multivitamin tablets in the home pharmacy and she is not sure if her child ingested some of these tablets or not.

The physician asked for blood iron level , the result was 520 microgram/dl.

After this result the mother told the truth.

The mother was tending to her newborn infant when the child grabbed his mom's bottle of iron pills (ferrous sulfate 325 mg) from the counter. The iron pill contains 65 elemental iron per pill. He ate them thinking they looked like candy. There were 15 tablets missing this means 975 elemental iron ingested.

Physician performed abdominal plain x ray that revealed radiopaque tablets in the stomach and intestine.

What are The Pediatrician Mistakes in The First Case?

Keep it in your mind

Management of Acute Iron Toxicity

First Step in Management is Diagnosis

To diagnose acute poisoning you have firstly to be minded

by acute poisoning

Diagnostic Work up:

Patients Requiring Assessment Ingestion of > 40 mg/kg elemental iron.

(approximately  > ½ tablet/kg or 6.5 ml syrup/kg).

Ingestion of an unknown quantity.Any symptomatic patients

The following investigations should be done:

Diagnostic investigation: Abdominal XR (if tablets ingested). Serum iron.Serum iron level: Serum iron levels generally correlate with clinical

severity and are as follows: Mild - Less than 300 µg/dl Moderate - 300-500 µg/dl Severe - More than 500 µg/dl

Difficulties in interpretation of serum iron levels

Serum iron level reaches its peak at 4-6 hours post ingestion, and time from ingestion is often unknown.

Serum levels obtained more than 8-12 hours post ingestion may not be useful because iron redistributes into the tissues.

In case of slow release or enteric coated tablets, levels should be repeated at six to eight hours as absorption may be erratic.

Once Desferoxamine is started , it interferes with standard assays and leads to falsely decreased iron levels.

Is TIBC Useful In Diagnosis Of Acute Iron Toxicity?

TIBC should not be used to evaluate cases of iron overdose. It measures iron bound to transferrin so, This is because lab method used to measure it are inaccurate in overdose and desferoxamine interferes with its measurement

Prognostic investigations: ABG (acidosis). Glucose (hyperglycaemia). Complete CBC. Serum electrolytes, blood urea nitrogen (BUN),

and glucose. ALT , AST and bilirubin. Prothrombin and partial thromboplastin time. Clotting (reversible early coagulopathy and late

coagulopathy secondary to hepatic injury)

Parameters of Severity: Anion gap metabolic acidosis is an important, but

nonspecific, predictor of iron toxicity. Although leukocytosis and hyperglycemia   are

non specific for acute iron toxicity , they are only associated with serum iron levels greater than 300 mcg/dl. Consequently , their absence doesn’t exclude acute iron toxicity but their presence indicates severity of the case.

Treatment of Acute Iron Toxicity

Decontamination:Charcoal is of no benefit.Decontamination of choice is whole bowel

irrigation (WBI) with naso-gastric colonic lavage solution 30 ml/kg/hr until rectal effluent clear.

WBI is contraindicated if there are signs of bowel obstruction or hemorrhage.

Poly ethylene glycol

Antidote: Desferoxamine is a chelating agent which forms

with iron a water soluble complex. Consider desferoxamine if:

Serum iron  levels > 90 micromol/l. Level 60- 90 micromol/l but tablets are visible

on X ray . Symptomatic patient e.g nausea, vomiting,

hematemesis, fever, altered consciousness, acidosis etc…

Worsening symptoms irrespective of ingested dose or serum iron level in this case Do not wait for iron level start Desferroxamine without delay.

Dose: It is given 15 mg/kg/hr I.V. maximum

35 mg/kg per hour, based on the severity of clinical symptoms.

Desferoxamine - iron complex is renally excreted. If oliguria or anuria develop, peritoneal dialysis or haemodialysis may become necessary to remove desferroxamine.

Because of the kinetics of iron absorption and the possibility of lung toxicity with administration of desferoxamine, consultation with a medical toxicologist and/or regional poison control center is recommended.

When To Stop Desferoxamine? There is no specific guidelines about duration

of desferoxamine treatment but Recommendations have used resolution of clinical symptoms and normalization of lab investigations as the end point for stopping therapy. This may lead to prolonged treatment with increase the risk of lung toxicity.

So , decision to stop desferoxamine therapy should be made according to clinical toxicologist and/or regional PCC, guided by the patient's clinical status.

Urgent stop of desferoxamine: Desferoxamine should be stopped urgently if

pulmonary toxicity appears , and should be used with caution if indications persist  >24 hours.

Pitfalls In Management 0f Acute Iron Toxicity

Inadequate hydration of the patient. Failure to recognize patients in the latent phase. Excessive reliance on the SIC, TIBC, or abdominal

radiograph in diagnosis and management decisions.

Inadequate  desferoxamine  dose. Inappropriate discontinuation of  desferroxamine. Prolonged use of desferroxamine (more than 24

hours)

Discussion of first Clinical Sinario

Mistakes of first Pediatrician

He didn’t pay attention to the most important 2 words in the history:

Sudden onset – Blood tinged vomitus He didn’t think about toxicological cause. He had to put In mind that the mother may deny

child ingestion for fear of medico legal or social responsibilities.

Thank you