Iron Poisoning in Pediatrics: Pathophysiology, Clinical Manifestations, and Treatment

Continue on selected drug poisoning Iron lead

Iron Historically, iron was a common cause of childhood poisoning deaths. The severity of an exposure is related to the amount of elemental iron ingested. Ferrous sulfate contains 20% elemental iron, ferrous gluconate 12%, and ferrous fumarate 33%.

Pathophysiology Iron is directly corrosive to the GI mucosa, leading to hematemesis, melena, ulceration, infarction, and potential perforation. Early iron-induced hypotension is due to massive volume losses, increased permeability of capillary membranes, and venodilation mediated by free iron. Iron accumulates in tissues, including the Kupffercells of the liver and myocardial cells, leading to hepatotoxicity, coagulopathy, and cardiac dysfunction

Pediatric patients who ingest >40 mg/kg of elemental iron should be referred to medical care for evaluation, though moderate to severe toxicity is typically seen with ingestions of >60 mg/kg. Clinical and Laboratory Manifestations: Iron toxicity is classically described in 4, often overlapping, stages The initial stage, 30 min to 6 hr after ingestion, consists of profuse vomiting and diarrhea (often bloody), abdominal pain, and significant volume losses leading to potential hypovolemic shock.

The second stage, 6 to 24 hrafter ingestion, is the quiescent phase, as GI symptoms typically resolve. careful clinical exam can reveal subtle signs of hypoperfusion, including tachycardia, pallor, and fatigue

During the third stage, occurring 12 to 24 hr after ingestion, patients develop multisystem organ failure, shock, hepatic and cardiac dysfunction. the fourth stage (4 to 6 wk after ingestion) is marked by formation of strictures and signs of GI obstruction. Symptomatic patients and patients with a large exposure by history should have serum iron levels drawn 4-6 hr after ingestion. Other lab. Invstigations . blood gas, complete blood count, serum glucose level, liver function tests, and coagulation parameters An abdominal x-ray might reveal the presence of iron tablets.

Treatment Close clinical monitoring, combined with aggressive supportive and symptomatic care, is essential to the management of iron poisoning. Activated charcoal does not adsorb iron, and WBI remains the decontamination strategy of choice. Deferoxamine, a specific chelatorof iron, is the antidote for moderate to severe iron intoxication. Indications for deferoxamine treatment include a serum iron concentration of >500 mg/dL or moderate to severe symptoms of toxicity, regardless of serum iron concentration.

Deferoxamine is preferably given via continuous IV infusion at a rate of 15 mg/kg/hr. Hypotension is a common side effect of deferoxamine infusion. Prolonged deferoxamine infusion (>24 hr) has been associated with pulmonary toxicity (acute respiratory distress syndrome) and Yersinia sepsis. The deferoxamine-iron complex can color the urine reddish ( vin ros? ), though this is an unreliable indicator of iron excretion, therapy is typically continued until clinical symptoms resolve.

Lead Poisoning Lead is a metal that exists in four isotopic forms. Clinically, it is purely a toxicant; no organism has an essential function that is lead-dependent.. The blood lead level (BLL) is the gold standard for determining health effects. BLL of 5 microg/dL ???or greater regarded as a level of concern for public health purposes.

Sources of Exposure Several hundred products contain lead, including batteries, cable sheathing, cosmetics, mineral supplements, plastics, toys,lead-based paint. As paint deteriorates, it chalks, flakes, and turns to dust .The dust can coat all surfaces, including children's hands. All of these forms of lead can be ingested.

SOURCES OF LEAD Paint chips Dust Soil Parent's or older child's occupational exposure (painting) Home remedies, including antiperspirants Stored battery casings (or living near a battery smelter) Lead-based gasoline Lead-based cosmetics (kohl) Imported foods in lead-containing cans Imported toys Home renovations Antique toys or furniture

Metabolism The nonnutritive hand-to-mouth activity of young children is the most common pathway by which lead enters the body. In nearly all cases, lead is ingested. After absorption, lead is disseminated throughout the body. Most retained lead accumulates in bone, where it may reside for years. It circulates bound to erythrocytes; about 97% in blood is bound on or in the red blood cells.

Lead has multiple effects in cells It binds to enzymes, particularly those with available sulfhydryl groups, changing the contour and diminishing function. The heme pathway, present in all cells, has three enzymes susceptible to lead inhibitory effects. The last enzyme in this pathway, ferrochelatase, enables protoporphyrin to chelate iron, thus forming heme. Protoporphyrin is readily measurable in red blood cells. Levels of protoporphyrin higher than 35 microg/dLare abnormal and are consistent with lead poisoning, iron deficiency, or recent inflammatory disease.

A second mechanism of lead toxicity works via its competition with calcium. Many calcium-binding proteins have a higher affinity for lead than for calcium. a third mechanism prevents the development of the normal tertiary brain structure. Clinical Effects The BLL is the best-studied measure of the lead burden in children.

Hearing and height are inversely related to BLLs in children;. Children with higher BLLs are slightly shorter than those with lower levels; for every 10 microg increase in the BLL, the children are 1 cm shorter. Chronic lead exposure also may delay puberty. there is agreement that BLLs are inversely related to cognitive test scores. Because the BLLs from early childhood are predictors of the cognitive test results performed years later, this finding implies that the effects of lead can be permanent.

The effect of in utero lead exposure is less clear maternal blood lead levels between 0 and 10microg/dL even as early as the first trimester were associated with about a 6- point drop in cognitive test score results when the children were tested up to age 10 yr. Behavior also is adversely affected by lead exposure. Hyperactivity is noted in young school-aged children with histories of lead poisoning or with concurrent elevations in BLL.

Clinical Symptoms Gastrointestinal Tract and Central Nervous System GI symptoms of lead poisoning include anorexia, abdominal pain, vomiting, and constipation, often occurring and recurring over a period of weeks. CNS symptoms are related to worsening cerebral edema and increased intracranial pressure. Headaches, change in mentation, lethargy, papilledema, seizures, and coma leading to death are rarely seen at levels lower than 100 microg/dL but have been reported in children with a BLL as low as 70 microg/dL.

At high levels (>100 microg/dL), renal tubular dysfunction is observed. Lead may induce a reversible Fanconi syndrome. at high BLLs, red blood cell survival is shortened, possibly contributing to a hemolytic anemia, although most cases of anemia in lead-poisoned children are due to other factors, such as iron deficiency and hemoglobinopathies. Older patients may develop a peripheral neuropathy.

Diagnosis Screening It is estimated that 99% of lead-poisoned children are identified by screening procedures rather than through clinical recognition of lead-related symptoms In general, it is advisable to screen high-risk children, including those with the following characteristics: 1.Having a sibling or playmate with an elevated lead level 2.Living with an adult whose job or hobby involves lead 3.Living near an industry that is likely to release lead (e.g., smelting plant, battery-recycling plant 4. the child is a recent immigrant from a country that still permits use of leaded gasoline 5.or the child has pica or developmental delay

NOT RECOMMENDED AT ANY BLOOD LEAD CONCENTRATION Searching for gingival lead lines Evaluation of renal function (except during chelation with CaNa2EDTA [ethylenediaminetetraaceticacid]) Testing of hair, teeth, or fingernails for lead Radiographic imaging of long bones X-ray fluorescence of long bones

Other Tools for Assessment BLL determinations remain the gold standard for evaluating children. Experimentally, the method of x-ray fluorescence (XRF) allows direct and noninvasive assessment of bone lead stores. the lead mobilization test. Lead in hair also is measurable but has problems of contamination and interpretability. Radiographs of long bones may show dense bands at the metaphyses.

For children with acute symptoms,, a kidneys-ureters-bladder (KUB) radiograph may reveal radiopaque flecks in the intestinal tract, a finding that is consistent with recent ingestion of lead-containing plaster or paint chips. An elevated EP value that cannot be attributed to iron deficiency or recent inflammatory illness is both an indicator of lead effect and a useful means of assessing the success of the treatment.

Treatment Once lead is in bone, it is released only slowly and is difficult to remove even with chelating agents. Because the cognitive/behavioral effects of lead may be irreversible, the main effort in treating lead poisoning is to prevent it from occurring and to prevent further ingestion by already-poisoned children. (1) identification and elimination of environmental sources of lead exposure, (2) behavioral modification to reduce nonnutritive hand-to-mouth activity, and (3) dietary counseling to ensure sufficient intake of the essential elements calcium and iron.

(4)For the small minority of children with more severe lead poisoning, drug treatment is available that enhances lead excretion. Parental efforts at reducing the hand-to-mouth activity of the affected child are necessary to reduce the risk of lead ingestion, handwashing is best limited to the period immediately before nutritive hand-to- mouth activity occurs. Because there is competition between lead and essential minerals, it is reasonable to promote a healthy diet that is sufficient in calcium and iron. In general, for children 1 yr of age and up a calcium intake of about 1 g per day is sufficient

Iron requirements also vary with age, ranging from 6 mg/day for infants to 12 mg/day for adolescents. Drug treatment to remove lead is lifesaving for children with lead encephalopathy. In nonencephalopathic children, it prevents symptom progression and further toxicity. Four drugs are available : 1. 2,3-dimercaptosuccinic acid (DMSA [succimer]) 2. CaNa2EDTA (versenate) 3. penicillamine 4. British antilewisite (BAL [dimercaprol]), DMSA and penicillaminecan be given orally, whereas CaNa2EDTA and BAL can be administered only parenterally .

Chelation is not indicated. <25 g/dL 25-45 g/dL Chelation is not routinely indicated because no evidence exists that chelation prevents or reverses neurotoxicity. Some patients may benefit from (oral) chelation (e.g., succimer), especially if elevated levels persist despite aggressive environmental intervention and abatement 45-70 g/dL Chelation is indicated with either succimeror CaNa2EDTA (if no clinical symptoms suggestive of encephalopathy are present [e.g., headache, persistent vomiting]). If symptoms of encephalopathy are seen, chelation With dimercaprol and CaNa2EDTA are indicated. Before chelation, an abdominal radiograph scan should be taken to evaluate for the possible removable of enteral lead. >70 g/dL Inpatient chelation therapy with dimercaprol and CaNa2EDTA is indicated.

NAME SYNONYM DOSE TOXICITY 350 mg/m2body surface area/dose (not 10 mg/kg) q8h, PO for 5 days, then q12h for 14 days Gastrointestinal distress, rashes; elevated LFTs, depressed white blood cell count Chemet, 2,3- dimercaptosuccinic acid (DMSA) Succimer Proteinuria, pyuria, rising blood urea nitrogen/creatinine all rare Hypercalcemia if too rapid an infusion Tissue inflammation if infusion infiltrates 1,000-1,500 mg/m2 body surface area/d; IV infusion continuous or intermittent; IM divided q6h or q12h for 5 days CaNa2EDTA (calcium disodium edetate), versenate Edetate

GI distress, altered mentation; elevated LFTs, hemolysis if glucose-6-phosphate dehydrogenase deficiency; no concomitant iron treatment 300-500 mg/m2body surface area/ day; IM only divided q4h for 3-5 days. Only for BLL 70 ?g/dL British antilewisite (BAL) Dimercaprol, British antilewisite Rashes, fever; blood dyscrasias, elevated LFTs, proteinuria Allergic cross- reactivity with penicillin 10 mg/kg/d for 2 wk increasing to 25- 40 mg/kg/d; oral, divided q12h. For 12-20 wk D-Pen Penicillamine

All of the drugs are effective in reducing BLLs when given in sufficient doses and for the prescribed time. These drugs also may increase lead absorption from the gut and should be administered to children in lead-free environments. None of these agents removes all lead from the body. Within days to weeks after completion of a course of therapy the BLL rises, even in the absence of new lead ingestion. The source of this rebound in the BLL is believed to be bone. With successful intervention, BLLs decline, with the greatest fall in BLL occurring in the first 2 mo after therapy is initiated. Subsequently the rate of change in BLL declines slowly so that by 6-12 mo after identification, the BLL of the average child with moderate lead poisoning (BLL >20 microg/dL) will be 50% lower.

Early screening remains the best way of avoiding and therefore obviating the need for the treatment of lead poisoning.