- levels
<10 mg/kg - don’t worry
< 20 mg/kg and asymptomatic
> 30 mg/kg = worry
> 60 mg/kg = life threatening
- serum
normal 80 - 180 mcg/dL ( 14 - 32 mMol/L )
action level > 500 mcg/dL ( > 90 mMol/L ) values less may require intervention
based on clinical state
- iron pills are 1 mg/kg for the average adult
- chewable are 15 mg = 1 mg/kg for 1 year old
- early GI Sx - n,v, pain, d
usually by 30 - 120 min
if none, then than not significant od
Pathophysiology
- multisystem toxin ( GI, liver, CVS, CNS )
- free Fe is responsible - vasodilation, negative ionotrope - hypotension
- GI Sx results from direct local toxicity, , vomiting is the hallmark of Fe toxicity
corrosion - mucosal congestion, venous thrombosis, infarction, ulceration, hemorrhage
n,v, abdo pain, d, GI bleed
perforation, peritonitis
- Fe liver deposition causes cellular injury, avid hepatocyte free iron uptake during first pass metabolism, hepatocellular transferrin receptor avidly binds transferrin, free iron released into cell within 15 minutes- free radicals, LPS, electron transport disruption, lactic acidosis
hyperbilirubinemia, increased aminotransferases, coagulopathy
- CVS
decreased MAP, CO, HR all decrease ( in absence of hypovolemia )
- Neuro
secondary to hypoperfusion, acidosis, hepatic compromise, coagulopathy
poor prognosis with coma
- multifactorial acidosis
lactate due to hypotension
proton transfer ( Fe++ - Fe+++
oxidative phosphorylation
liver
lipid peroxidation
- multifactorial hypotension ( fluid loss, vd, neg ionotrope )
1) direct caustic effects to GI tract- n,v, GI bleed
2) uncouples ox phosphorylation - electron sink
3) free radicals - lipid peroxidation
4) coagulopathy
Stages
- timing is variable
1) GI Sx < 6 hr
2) latent ( 6 - 24 hrs ) - just stop vomiting ( and treated with fluids )
serum iron is being unloaded to intracellular sites
3) Systemic toxicity - shock, acidosis, lethargy, coma, coagulopathy, hepatocellular
CV collapse, bleeding, acidosis
metabolic dysfn, CV collapse, hepatic, renal, neurologic failure
4) delayed hepatic and renal ( 7 to 10n days )- unusual
5)late complications - pyloric outlet obstruction ( 2 - 8 weeks ), intestinal obstruction
late obstructions, strictures
Dx by UGI series and Ba enema
Laboratory
WBC > 15,000
glucose > 150
metabolic acidosis
- predict Fe > 300, not toxicity
- helpful if elevated but poor NPV
- due to stress and catecholamine release
- AXR - helpful if positive but not equivalent to toxicity
negative withn chewables and liquids
- levels ( take too long, base Rx on clinical Sx only )
0 - 100 = normal
>350 - 500 = GI Sx, potentially serious
500 - 1000 = systemic toxicity
> 1000 associated with fatality
- TIBC
not helpful, will be falsely elevated in the iron poisoned patient
- DCT
Treatment
- ABC
- usual Rx for UGI bleed ( large bore iv, fluids, Xmatch, lavage )
- fluids +++ tank up ( vd, v, d )
- no Ipecac - already vomiting, interefere with marker for toxicity
- no charcoal - no binding, only for mixed od
- lavage - large pills in child who has already vomited
- WBI - pos AXR plus sick
history of large ingestion
mainstay for large GI burdens
- DEF - treat until aSx and urine is back to normal color
binds Fe+++ - ferrioxime excreted in urine as colored complex
100 mg binds 9.53 mg elemental Fe
goal is 15 mg/kg/hr - start at 5 and titrate up
rate related hypotension - tank up
obtain baseline urine - follow color change - continue until clear
complications - hypoT, anaphylaxis, local im pain, eye toxicity,
- no benefit from NaHCO3 lavage
- Fe levels not helpful in acute management, take too long
- exchange transfusion - but no evidence for increased survival
dependant upon initiation before cellular entry of iron
Critical Therapeutic Decisions
- lack of absorption by charcoal, large size limits lavage
- patients who have already vomited should not be made to vomit with Ipecac
- patients who present within 1 hour without vomiting may benefit from lavage as adult pills do not fit up lavage tubes, however nausea and vomiting will simulate phase 1 toxicity and complicate the decision making process
- charcoal is not efficaceous and accumulates in mucosal erosions, making endoscopy less successful
- phosphate lavage - limited production od ferrous phosphate, can cause hypocalcemia, hyperphosphatemia
- bicarbonate solutions do not effectively complex
- efficacy of oral DEF debatable , may increase ferroxiamine absorption
- when lavage is complete or following emesis, an AXR should be taken
- if pills persist in GI tract then WBI should be initiated ( 2L/hr in adults, 500 ml/hr in kids)
- endoscopy if large GI bleed
Determination of Significant Ingestion
1) Quantity Ingested
- any child suspected of ingesting > 20 mg/kg of elemental iron, and who has not spontaneously vomited, may be given syrup of ipecac at home, and brought to hospital
- FeSO4 is 20 % elemental ( 325 mg = 65 mg )
- levels
<10 mg/kg - don’t worry
< 20 mg/kg and asymptomatic
> 30 mg/kg = worry
> 60 mg/kg = life threatening
2) Clinical Symptoms
- initial GI Sx may be local, but similar symptoms may also result from systemic toxicity
- if GI Sx do not develop within 6 hours, it is unlikely that severe systemic symptoms will result
- hypotension, hypoperfusion, hypo0tonia, letargy = immediate chelation therapy
3) Serum iron levels
- draw immediately and repeat in 4 to 6 hours
- levels ( take too long, base Rx on clinical Sx only )
0 - 100 = normal
>300 - 500 = GI Sx, potentially serious
500 - 1000 = systemic toxicity
> 1000 associated with fatality
DFO intereferes with standard assays
4) TIBC
- adding iron to pooled serum results in artifactual rise in TIBC
- varies greatly between labs
- may elevate and remain above serum Fe but severe toxicity still can result
- measured TIBC is unreliable
5) Abdominal Radiograph
- can be used to determine the efficacy of GI decontaimination
- potential for false negative ( chewables, liquids, dissolved )
6) WBC and glucose
- not sensitive or specific enough
Deferoxamime
- a specific iron-binding ligand used as a chelating agent in iron poisoning
- greater affinity consytanrt for iron than other metals
- avidly chelates free inorganic iron
- does not remove iron from transferrin, Hgb, or cytochrome-bound iron
- 100 mg binds only 9 mg of elemental iron
- mild to moderate toxicity resolves with supportive care alone
- increases renal excretion of iron as FO