Iron and Lithium

By : Ahmed Al Jabri20/12/2010

Facts

• The most common iron exposures >> form of pediatric multivitamin formulation . • These are minimally toxic .

• Life-threatening toxicity is associated with ingestion of adult preparation,

esp. by children .

Facts

• Iron tablets in MoH : Ferrous sulphate : 1. They are usually 156 mg , 2. The elemental iron is usually 20% ,

• But, always check with the pharmacist .

How to calculate the total elemental iron ingested ?

How to calculate the total elemental iron ingested ?

# of tabs X mg X % of elemental iron

Facts

• What is the normal serum iron level in micg/dl ?

Facts

• What is the normal serum iron level in micg/dl ?

50 to 150 micg/dl

Toxicity of iron by amount ingested and Peak serum levels ?

• Severe iron toxicity is anticipated with which amount ingested ( In MG/KG ) ?

• Severe or lethal iron tox. Is given with Peak serum level of ............... ( in micrg/dl ) ?

Toxicity of iron by amount ingested and Peak serum levels ?

• Severe iron toxicity is anticipated with which amount ingested ?

> 60 MG/KG

• Severe or lethal iron tox. Is given with Peak serum level of > 500 micrg/dl?

Facts

• TIBC ? • Indicates the ability of serum proteins-

including transferrin-to bind iron . • Normal range ?

Facts

• TIBC ? • Indicates the ability of serum proteins-

including transferrin-to bind iron . • Normal range ? • 300 to 400 micrg/dl • Crude measure , never used to assess the

severity of iron ingestion

Pathophysiology ?

• 2 main toxic effects : 1.causes direct caustic injury to the GI mucosa

2.impairs cellular metabolism, primarily of the heart, liver, and central nervous system (CNS)

BY WHICH MECHANISM ?

Pathophysiology ? • 2 main toxic effects : 1. causes direct caustic injury to the GI mucosa

2. impairs cellular metabolism, primarily of the heart, liver, and central nervous system (CNS)

BY WHICH MECHANISM ? uncoupling of oxidative phosphorylation >> free

radicals >> cell injuries mainly in brain , liver and heart .

All the following can be found in iron overdose except ?

1. Abd. pain 2. Vomiting3. Bloody diarrhea 4. Hypertension 5. Tachycardia6. Anion gap metabolic acidosis7. Hyperglycemia 8. leukocytosis

All the following can be found in iron overdose except ?

1. Abd. pain 2. Vomiting3. Bloody diarrhea 4. Hypertension 5. Tachycardia6. Anion gap metabolic acidosis7. Hyperglycemia 8. leukocytosis

How would hypotension develops in Iron toxicity?

How would hypotension develops in Iron toxicity?

Iron increases capillary permeability and induces both arteriolar and venodilation

Clinical effects in 5 phases

• Phase 1 >>>>>> R1 • Phase 2 >>>>>> R2 • Phase 3 >>>>>> R3 • Phase 4 >>>>>> R4 • Phase 5 >>>>>> R5

Phase 1

• After 80 min of ingestion • Main S/S :1.VOMITNG >> >90% of symptomatic pts , 2.DIARRHEA ( CAN BE BLOODY )

Phase 2

• Usually last less 24 hrs , CAN EXTEND to 2 days

• It the the recovery phase .

• Most pts recover after this point

Phase 3• ( serum iron level can be normal ( redistribution)• Recurrence of GI symptoms , with : • Severe lethargy or even coma, • Anion gap met. Acidosis, • Leukocytosis , • Coagulopathy • Renal failiure , • Cardiovascular collapse ,• Elevated liver enzymes, • Increased bilirubin , blood sugar .

Phase 4

• Occur 2 to 5 days after ingestion ,

• Fulminant hepatic failure ,

• Dose dependent .

• Pts can have significant GI bleeds .

Phase 5

• Occurs 4 to 6 weeks after ingestion

• Represent consequences of healing the injured GI mucosa :

• Gastric outlet obstruction >>> 2nd to corrosive effects of iron .

All of the following statements are true regarding the phases of iron poisoning except?

1. Phase II (6-24 hours post ingestion): the calm before the storm: symptoms may improve transiently before the appearance of multisystem toxicity. Patients will appear normal.

2. Phase I (first few hours): bowel edema and hemorrhagic gastroenteritis, with abdominal pain, vomiting, diarrhea, hematemesis, hypovolemic shock, and metabolic acidosis.

3. Phase IV (days to weeks post-ingestion): acute hepatic failure with jaundice, hepatic coma, elevated transaminase and ammonia levels, hypoglycemia and coagulation defects.

4. Phase V (weeks to months post-ingestion): pyloric or proximal bowel scarring may develop, sometimes with obstruction.

5. Phase III (begins about 24 hours following ingestion): lethargy or coma, gastrointestinal bleeding, cardiac failure, metabolic acidosis, renal failure, shock, and leukocytosis. Serum iron levels may be normal.

All of the following statements are true regarding the phases of iron poisoning except?

1. Phase II (6-24 hours post ingestion): the calm before the storm: symptoms MAY improve transiently before the appearance of multisystem toxicity. Patients will appear normal.

2. Phase I (first few hours): bowel edema and hemorrhagic gastroenteritis, with abdominal pain, vomiting, diarrhea, hematemesis, hypovolemic shock, and metabolic acidosis.

3. Phase IV (days to weeks post-ingestion): acute hepatic failure with jaundice, hepatic coma, elevated transaminase and ammonia levels, hypoglycemia and coagulation defects.

4. Phase V (weeks to months post-ingestion): pyloric or proximal bowel scarring may develop, sometimes with obstruction.

5. Phase III (begins about 24 hours following ingestion): lethargy or coma, gastrointestinal bleeding, cardiac failure, metabolic acidosis, renal failure, shock, and leukocytosis. Serum iron levels may be normal.

Ix and Mx

WHOLE BOWEL IRRIGATION ?

• With polyethylene glycol solution . • Either oral or through NGT , • 20 TO 40 ML/KG/HR FOR CHILDREN,

• 1.5 to 2 L/hr for adults .

• When to stop PEG-ELS ? Is it safe in Pregnancy ?

When to stop PEG-ELS ?Any side effects ?

until the rectal effluent is clear and there is no radiographic evidence of pill fragments

What are the side effects and the contraindications for PEG-ELS ?

What are the side effects and the contraindications for PEG-ELS ?

• SE : Nausea, vomiting, abd cramping and bloating .

• C.I. : 1.Bowel obstruction ,2.Perforation , 3. Ileus .

Management : Antidot

• Deferoxamine . • Chlates iron to form water-soluble compound

ferrioxamine >>>> renally excreted

• What would be the urine colour ?

Management : Antidot

• Deferoxamine . • Chlates iron to form water-soluble compound

ferrioxamine >>>> renally excreted

• What would be the urine colour ? • Red or Orange ( vin rose )

Deferoxamine:

• Indications ? • Dose ? • Route ? • For how long ? • One important SE ? How can this SE avoided ?• CI ? • WHAT special consideration in pregnant

lady ?

Indications for Rx with Deferoxamine ?

1. Ingestion of greater than 60 mg/kg of elemental iron

2. Peak SIC greater than 500 mcg/dL3. Persistent serious symptoms such as vomiting,

diarrhea, and/or altered mental status4. Systemic symptoms, including subtle symptoms that

can be seen in the latent phase, such as tachycardia, poor perfusion, tachypnea, and/or hypotension

5. Significant number of radiopaque pills on a plain radiograph of the abdomen

Deferoxamine

• IV infusion of 15/mg/kg/hr for up to 24 hrs , • Max. IV infusion is 35mg/kg/hr .• Hypotension >> can be avoided by reducing

the initial rate of IVI , and slowly increasing it to the desired rate .

• In pregnant lady : use the pre-pregnancy weight to calculate the iv infusion

Facts :

• Hemodialysis and hemoperfusion are not effective in removing iron due to its large volume of distribution .

• Excahnge transfusions are recommended for severly symptomatic patients with SIC > 1000 micrg/dl

When it is safe to send the patient home ?

When it is safe to send the patient home ?

1. asymptomatic patient who has ingested less than 20 mg/kg of elemental and he remains asymptomatic after 6 hours of observation

When it is safe to send the patient home ?

1. ............2. If peak levels are less than 300 µg/dL, are not

rising, and the patient is asymptomatic during 6 hours of observation

When it is safe to send the patient home ?

1. ...........2. ...........3. In RURAL hospitals : if the serum glucose and

WBC are normal, there are no signs or symptoms of toxicity during the 6-hour postingestion period, and the abdominal radiographs do not show pills in the gastrointestinal tract

LITHIUM

All of the following are appropriate measures for the management of a lithium overdose EXCEPT:

1. activated charcoal and sodium polystyrene sulfonate (Kayexalate) may lower blood levels.

2. IV saline to promote renal lithium excretion and support blood pressure.

3. Whole bowel irrigation may be beneficial in cases of sustained lithium preparation ingestion.

4. hemodialysis in cases of elevated lithium levels and renal failure, confusion, ataxia, seizures, coma

All of the following are appropriate measures for the management of a lithium overdose EXCEPT:

1. activated charcoal and sodium polystyrene sulfonate (Kayexalate) may lower blood levels.

2. IV saline to promote renal lithium excretion and support blood pressure.

3. Whole bowel irrigation may be beneficial in cases of sustained lithium preparation ingestion.

4. hemodialysis in cases of elevated lithium levels and renal failure, confusion, ataxia, seizures, coma

All of the following factors can contribute to the development of lithium toxicity EXCEPT:

1. Volume depletion due to use of diuretics, febrile illnesses, gastrointestinal losses, and other states which may cause sodium depletion

2. Diabetes 3. Renal insufficiency and impaired renal

perfusion, such as seen in cases of congestive heart failure

4. Concomitant use of nonsteroidal inflammatory drugs or ACE inhibitors

All of the following factors can contribute to the development of lithium toxicity EXCEPT:

1. Volume depletion due to use of diuretics, febrile illnesses, gastrointestinal losses, and other states which may cause sodium depletion

2. Diabetes 3. Renal insufficiency and impaired renal

perfusion, such as seen in cases of congestive heart failure

4. Concomitant use of nonsteroidal inflammatory drugs or ACE inhibitors

s/s of lithium tox. Include all of the following except ?

• GI symptoms : nausea and vomting , • Bradycardia and QT prlongation , • Leukocytosis , • Hyperthyroidism , • Clonus , confusion , seizures • Fever

s/s of lithium tox. Include all of the following except ?

• GI symptoms : nausea and vomting , • Bradycardia and QT prlongation , • Leukocytosis , • Hyperthyroidism , • Clonus , confusion , seizures • Fever

5 drugs ( by group that can increase lithium toxicity ?

5 drugs ( by group that can increase lithium toxicity ?

• NSAID,• DIURETICS , • ACE inhibitors, • Serotonin agonists ( MAO inhibitors , selective

serotonin reuptake inhibitors ) • Antiepileptic : phenytoin, • Antibiotics :metronidazole, and spectinomycin

The therapeutic lithium level is __ mEq/L; toxicity is common with levels above __ mEq/L.?

• 0.2-0.6; 1.0

• 0.6-1.2; 2.0

• 1.0-2.0; 4.0

The therapeutic lithium level is __ mEq/L; toxicity is common with levels above __ mEq/L.?

• 0.2-0.6; 1.0

• 0.6-1.2; 2.0

• 1.0-2.0; 4.0

HD in lithium tox

• Should be considered in pts with severe s/s of neurotoxicity , renal insufficiency or CHF ,

• Serum level > 4.o mEq/L in case of acute tox.or• Serum level > 2.o mEq/L in case of chronic tox.

THANKS for YOUR attention