EM Toxicology 10 - Iron

Question 1

Symptomatology of iron toxicity

Answer 1

GI toxicity (vomiting, abd pain, mucosal ulceration and bleeding)
Multifactorial acidosis
Hepatotoxicity
Coagulopathy (inhibition of thrombin formation and the effect of thrombin on fibrinogen)
Myocardial and vascular dysfunction

Question 2

toxic levels of iron

Answer 2

moderate toxicity: 20 to 60 mg/kg of elemental iron
severe toxicity: >60 mg/kg of elemental iron

Question 3

ferrous sulfate has how many elemental iron?

Answer 3

20%
therefore a 325-mg tablet contains 65 of elemental iron
and approx 20 tablets would be expected to produce moderate toxicity after an acute ingestion in an average-size (65-kg) adult

Question 4

stage 1 of iron toxicity

Answer 4

vomiting, abdominal pain, diarrhea

vomiting is the clinical sign most consistently associated with acute iron toxicity

the absence of GI symptoms within 6 hours of ingestion essentially excludes a significant iron ingestion

Question 5

stage 2 of iron toxicity

Answer 5

“the latent stage”

6- to 24- hour interval following ingestion

in severe poisonings, the latent stage is marked by ongoing clinical illness and progressive systemic deterioration secondary to volume loss and worsening metabolic acidosis

Question 6

stage 3 of iron toxicity

Answer 6

shock and lactic acidosis
iron-induced coagulopathy may worsen bleeding and hypovolemia
- biphasic; initial coagulopathy appears to be reversible with chelation therapy
- subsequent coagulopathy is due to iron-induced hepatic injury

Question 7

stage 4 of iron toxicity

Answer 7

“the hepatic stage”
develops 2-5 days following ingestion
manifests as elevation of aminotransferase levels and may progress to acute fulminant hepatic failure

Question 8

stage 5 of iron toxicity

Answer 8

refers to delayed sequelae, including gastric outlet obstruction secondary to the corrosive effects of iron on the pyloric mucosa

rare and occur 4-6 weeks after ingestion

Question 9

remarks on iron toxicity

Answer 9

iron toxicity is largely a clinical diagnosis

patients who develop GI effects that resolve and who continue to look well clinically and have near normal laboratory findings will not develop significant systemic toxicity

Question 10

what are the MUDPILES

Answer 10

Methanol
Uremia
DKA
P**ropylene glycol, **Paraldehyde
*Iron, Isoniazid
Lactic acidosis
Ethanol, Ethylene glycol
Salicilates

Question 11

remarks on imaging in iron toxicity

Answer 11

standard ferrous sulfate tablets and reduced iron are radioopaque and frequently visible on routine radiographs, and this may help guide GI decontamination when present

absence of radioopaque material on radiographs does not exclude iron ingestion

Question 12

remarks on treatment of iron toxicity

Answer 12

signs and symptoms consistent with iron poisoning should guide treatment, rather than serum iron concentrations alone

patients who vomit once or twice from the gastric irritant effects of iron but are are otherwise asymptomatic, hemodynamically stable, and without metabolic acidosis can also be observed and may require no specific treatment

chelation therapy is with deferoxamine

antiemetics such as metoclopramide or ondansetron should be used for repetitive vomiting

coagulopathy whould be traeted with parenteral Vitamin K1 and/or FFP, as indicated

Question 13

GI decontamination in iron toxicity

Answer 13

whole-bowel irrigation with a polyethylene glycol solution may be effective in patietns with large iron gestions

administration of 250-500 mL/hour in children or 2 L/hour in adults by NGT may clear the GI tract of iron pills before absorption can occur

Question 14

remarks on deferoxamine

Answer 14

derived from Streptomyces pilosus

Upon binding iron, it forms the complex ferrioxamine, which is renally excreted

although deferoxamine binds only a small amount of iron (9 mg of elemental iron for each 100 mg of deferoxamine) and thus chelates only a small fraction of the total amount of iron ingested, this generally proves clinically effective in restoring cellular function

Question 15

indications of deferoxamine

Answer 15

systemic/progressive toxicity
persistent emesis
metabolic acidosis
serum iron level predictive of moderate to severe toxicity
mod: 300-500 mcg/dL
(54-90 mcmol/L)
sev: >500 mcg/dL
(>90 mcmol/L)

Question 16

administration of deferoxamine

Answer 16

initial adult dose of 1000 mg (children 50mg/kg) IV
begin infusion slowly, starting at 5 mg/kg per hour to avoid producing a rate-related hypotension
hypotension is not a contraindication to IV deferoxamine

the infusion rate can be titrated to 15 mg/kg per hour as tolerated

the recommended amount od deferoxamine for an acute iron overdose is a total of 360 mg/kg or 6 grams in adult during the first 24 hours
- typically ordered as 500 mg infusions over 4-8 hours after the initial 1000-mg dose (?)

Question 17

complications of deferoxamine therapy

Answer 17

renal insufficiency or failure
pulmonary toxicity

occurs when larger that recommended amounts are given or when administered longer than 24 hours

Question 18

as ferrioxamine is excreted, the urine color changes to what is classically called

Answer 18

vin rose
but is more typically a brown or rusty hue

the disappearance of the “vin rose” color suggests there is no more free iron available to be complexed with deferoxamine and excreted

Question 19

most important factor guiding the decision to terminate deferoxamine therapy

Answer 19

clinical recovery of the patient is the most imptorant factor guiding the decision to terminate deferoxamine therapy
because measured iron levels are articifically depressed by the presence of deferoxamine and urine color change can be unreliable

continue deferoxamine therapy in patients who continue to exhibit severe iron toxicity after 24 hours of treatment, using a decreased rate to avoid associated risks mentioned (renal/pulmonary)

Question 20

other therapies is iron toxicity

Answer 20

hemodialysis and hemofiltration may be necessary to remove the deferoxamine-iron complex in patients with renal failure

severe iron poisoning can be treated with exchange transfusion in addition to deferoxamine therapy

liver transplantation

Question 21

who can be discharged?

Answer 21

1) patients who have not ingested a potentially toxic amount of iron
2) who remain asymptomatic (other than transient vomiting from the gastric irritant effects of iron)
3) and who have normal findings on PE and laboratory evaluation
4) for a period of 4-6 hours

Question 22

when to take serum iron

Answer 22

4-6 hours post-ingestion