Table 3. Agents Used for Gastrointestinal Decontamination in Children.
Pathophysiology The absorption of iron is normally very tightly controlled by the GI system. However, in overdose, local damage to the GI mucosa allows unregulated absorption, which leads to potentially toxic serum levels. Much of the pathophysiology of iron poisoning is a result of metabolic acidosis and its effect on multiple organ systems. Toxicity manifests as local and systemic effects. Typically, iron poisoning is described in 5 sequential phases. No consensus has been reached regarding the number of phases and the times assigned to those phases. Patients may not always demonstrate all of the phases. Phase 1 Phase 1, initial toxicity, predominantly manifests as GI effects. This phase begins during the first 6 hours postingestion and is associated with hemorrhagic vomiting, diarrhea, and abdominal pain. This is predominantly due to direct local corrosive effects of iron on the gastric and intestinal mucosa. Early hypovolemia may result from GI bleeding, diarrhea, and third spacing due to inflammation. This can contribute to tissue hypoperfusion and metabolic acidosis. Convulsions, shock, and coma may complicate this phase if the circulatory blood volume is sufficiently compromised. In these cases, the patient progresses directly to phase 3, possibly within several hours. Phase 2 Phase 2 is known as the latent phase and typically occurs 4-12 hours postingestion. It is usually associated with an improvement in symptoms, especially when supportive care is provided during phase 1. During this time, iron is absorbed by various tissues, and systemic acidosis increases. Clinically, the patient may appear to improve, especially to nonmedical personnel, because the vomiting that occurs in phase 1 subsides. However, laboratory analysis demonstrates progressive metabolic acidosis and, potentially, the beginning of other end-organ dysfunction (ie, elevation of transaminase levels). Phase 3 Phase 3 typically begins within 12-24 hours postingestion, although it may occur within a few hours following a massive ingestion. Following absorption, ferrous iron is converted to ferric iron, and an unbuffered hydrogen ion is liberated. Iron is concentrated intracellularly in mitochondria and disrupts oxidative phosphorylation, resulting in free radical formation and lipid peroxidation. This exacerbates metabolic acidosis and contributes to cell death and tissue injury at the organ level. Phase 3 consists of marked systemic toxicity caused by this mitochondrial damage and hepatocellular injury. GI fluid losses lead to hypovolemic shock and acidosis. Cardiovascular symptoms include decreased heart rate, decreased myocardial activity, decreased cardiac output, and increased pulmonary vascular resistance. The decrease in cardiac output may be related to a decrease in myocardial contractility exacerbated by the acidosis and hypovolemia. Free radicals from the iron absorption may induce damage and play a role in the impaired cardiac function. The systemic iron poisoning in phase 3 is associated with a positive anion gap metabolic acidosis. The following explanations for the acidosis have been proposed: Conversion of free plasma iron to ferric hydroxide is accompanied by a rise in hydrogen ion concentration. Free radical damage to mitochondrial membranes prevents normal cellular respiration and electron transport, with the subsequent development of lactic acidosis. Hypovolemia and hypoperfusion contribute to acidosis. Cardiogenic shock contributes to hypoperfusion. A coagulopathy is observed and may be due to 2 different mechanisms. Free iron may exhibit a direct inhibitory effect on the formation of thrombin and thrombin&apos;s effect on fibrinogen in vitro. This may result in a coagulopathy. Later, reduced levels of clotting factors may be secondary to hepatic failure. Phase 4 Phase 4 may occur 2-3 days postingestion. Iron is absorbed by Kupffer cells and hepatocytes, exceeding the storage capacity of ferritin and causing oxidative damage. Pathologic changes include cloudy swelling, periportal hepatic necrosis, and elevated transaminase levels. This may result in hepatic failure. Phase 5 Phase 5 occurs 2-6 weeks postingestion and is characterized by late scarring of the GI tract, which causes pyloric obstruction or hepatic cirrhosis.
pecac-induced emesis is not recommended. This is especially true in iron ingestion. GI distress is an early finding in iron poisoning and is present in all potentially serious ingestions. Ipecac-induced vomiting may cloud the clinical picture. Gastric lavage is not recommended because iron tablets are relatively large and become sticky in gastric fluid, making lavage unlikely to be of benefit. Whole bowel irrigation has been used to speed the passage of undissolved iron tablets through the GI tract. A polyethylene glycol electrolyte solution (eg, GoLYTELY) may be administered orally or nasogastrically at a rate of 250-500 mL/h for toddlers and preschoolers and 2 L/h for adolescents. Continue irrigation until the repeat radiographic findings are negative or rectal effluent is clear. Deferoxamine is the iron-chelating agent of choice. Deferoxamine binds absorbed iron, and the iron-deferoxamine complex is excreted in the urine. Deferoxamine does not bind iron in hemoglobin, myoglobin, or other iron-carrying proteins. Base the indications for using deferoxamine on both clinical and laboratory parameters. Indications for treatment include shock, altered mental status, persistent GI symptoms, metabolic acidosis, pills visible on radiographs, serum iron level greater than 500 µg/dL, or estimated dose greater than 60 mg/kg of elemental iron. Initiate chelation if a serum iron level is not available and symptoms are present. The administration of deferoxamine may be intramuscular or intravenous. The intramuscular route is not recommended because it is painful and less iron is excreted compared with the intravenous route. The intravenous route is administered as a continuous infusion. The standard dose is 15 mg/kg/h, with an initial dose administered for 6 hours. No clear end point of therapy is noted; however, indications for cessation include significant resolution of shock and acidosis. Deferoxamine, administered 6-12 hours, has been suggested for moderate toxicity. For severe toxicity, administer deferoxamine for 24 hours. Because these end points are arbitrary, observe the patient for the recurrence of toxicity 2-3 hours after the deferoxamine has been stopped. Adverse effects from deferoxamine are unusual. Pulmonary toxicity (ie, acute respiratory distress syndrome [ARDS], tachypnea) has been described, especially if patients are treated with deferoxamine for more than 24 hours. Rate-related hypotension can occur. Therefore, monitor the patient while titrating the infusion rate upward to a final rate of 15 mg/kg/h.
Pathophysiology Therapeutic oral doses of acetaminophen are rapidly absorbed by the GI tract, with body serum levels peaking at 0.5-2 hours postingestion. Therapeutic levels are 10-20 mcg/mL (66-132 mcmol/L). Serum peak levels occur after an overdose within 4 hours postingestion for an immediate-release preparation. Co-ingestion with drugs that delay gastric emptying (such as opiates, anticholinergic agents) or ingestion of an APAP extended-release formulation may increase the peak serum level to more than 4 hours postingestion. The elimination half-life of acetaminophen is estimated to be 2-4 hours.Metabolism of acetaminophen is primarily hepatic. The liver metabolizes more than 90% of an acetaminophen dosage to sulfate and glucuronide conjugates, which are water soluble and are then eliminated in the urine. Sulfation is the primary metabolic pathway in children aged 12 years and younger. Glucuronidation predominates in adolescents and adults. Two percent of an acetaminophen dose is excreted unchanged by the kidneys. The remaining acetaminophen is metabolized by the hepatic cytochrome P450 (CYP450) system to form a reactive, highly toxic metabolite known as N -acetyl-p-benzoquinone imine (NAPQI). Glutathione binds NAPQI, enabling the excretion of nontoxic mercapturate conjugates in the urine.Therapeutic doses of acetaminophen do not cause hepatic injury; however because hepatic glutathione stores are depleted (by 70-80%) in an acetaminophen overdose, NAPQI cannot be detoxified and covalently binds to the lipid bilayer of hepatocytes, causing hepatic centrilobular necrosis. Necrosis primarily occurs in this hepatic region due to the greater production of NAPQI by these cells. Glutathione stores to enable metabolism of this toxic metabolite are replaced by sulfhydryl compounds from the diet (eg, fruits and vegetables) or from drugs, such as the antidote, NAC. Age, diet, liver disease, and medical conditions (eg, malnutrition due to prolonged fasting, gastroenteritis, chronic alcoholism, or HIV disease) affect glutathione stores in the body. Ethanol and drugs such as isoniazid (INH), rifampin, phenytoin, phenobarbital, barbiturates, carbamazepine, trimethoprim-sulfamethoxazole, and zidovudine induce CYP2E1 enzymes (part of the CYP450 system). Activation of the cytochrome system increases the production of NAPQI and, therefore, can increase the risk of hepatocellular injury in patients who ingest these agents. Herbal supplements may also play a role in amplifying the risk for acetaminophen-induced hepatic injury.
Symptoms seen in stage 1 reappear along with signs of hepatic failure with jaundice, hypoglycemia, bleeding (coagulopathies), encephalopathy, and/or sepsis. Renal failure and cardiomyopathy may also occur. Severe toxicity is evident on Lactic acidosis, prolonged PT or (INR), markedly elevated ALT and AST (&gt;10,000 IU/L), elevated bilirubin level of more than 4 mg/dL (primarily indirect) and hyperammonemia. Hepatic centrilobular necrosis is diagnosed on liver biopsy. 4% of those progress to fulminant hepatic failure. ATN is evident with proteinuria, hematuria and granular casts on urinalysis. Acute renal failure occurs in 25% of patients with significant hepatotoxicity and in &gt; 50% of those with hepatic failure.
Pathophysiology After ingestion, acetylsalicylic acid is rapidly converted to salicylic acid, its active moiety. Salicylic acid is readily absorbed in the stomach and small bowel. At therapeutic doses, salicylic acid is metabolized by the liver and eliminated in 2-3 hours. Salicylate poisoning is manifested clinically by disturbances of several organ systems, including the CNS and the cardiovascular, pulmonary, hepatic, renal, and metabolic systems. Salicylates directly or indirectly affect most organ systems in the body by uncoupling oxidative phosphorylation, inhibiting Krebs cycle enzymes, and inhibiting amino acid synthesis. Acid-base status Salicylates stimulate the respiratory center, leading to hyperventilation and respiratory alkalosis. Salicylates also interfere with the Krebs cycle, limit production of ATP, and increase lactate production, leading to ketosis and a wide anion-gap metabolic acidosis. Adult patients with acute poisoning usually present with a mixed respiratory alkalosis and metabolic acidosis. However, respiratory alkalosis may be transient in children such that metabolic acidosis may occur early in the course. Patients with mixed acid-base disturbances have been found to have normal anion-gap metabolic acidosis; therefore, normal anion-gap acidosis does not exclude salicylate.Salicylates are weak acids that may produce metabolic acidosis through various mechanisms. In toxic concentrations, salicylates interfere with energy production by uncoupling oxidative phosphorylation and may produce renal insufficiency that causes accumulation of phosphoric and sulfuric acids. The metabolism of fatty acids is likewise increased in patients with salicylate toxicity, generating ketone body formation. These processes all contribute to the development of an elevated anion gap metabolic acidosis in patients with salicylate poisoning. Respiratory system effects Salicylates cause both direct and indirect stimulation of respiration. A salicylate level of 35 mg/dL or higher causes increases in both rate (tachypnea) and depth (hyperpnea) of respiration. Salicylate poisoning may rarely cause noncardiogenic pulmonary edema (NCPE) and acute lung injury in pediatric patients. It is more common in elderly patients with chronic salicylate toxicity. Although the exact etiology is not known, it causes severe hypoxia, necessitating treatment with high concentrations of oxygen. It also makes adequate hydration and sufficient administration of sodium bicarbonate difficult. Pulmonary edema has extremely high mortality in both children and adults; if present, hemodialysis should be considered as soon as possible. Glucose metabolism Increased cellular metabolic activity due to uncoupling of oxidative phosphorylation may produce clinicalhypoglycemia, although the serum glucose levels may sometimes be within the normal range. As intracellular glucose is depleted, the salicylate may produce discordance between levels of plasma and cerebrospinal fluid (CSF) glucose and symptoms of CNS hypoglycemia (eg, altered mental status) may occur even when blood glucose levels are within the reference range. Fluid and electrolyte effects Salicylate poisoning may result in dehydration because of increased GI tract losses (vomiting) and insensible fluid losses (hyperpnea and hyperthermia). All patients with serious poisoning are more than 5-10% dehydrated. Renal clearance of salicylate is decreased by dehydration. Hypokalemia and hypocalcemia can occur as a result of primary respiratory alkalosis. CNS effects Salicylates are neurotoxic; this initially manifests as tinnitus. Significant ingestion can lead to hearing loss at serum levels of 30-45 mg/dL or higher. CNS toxicity is related to the amount of drug bound to CNS tissue. It is more common with chronic than acute toxicity. Acidosis worsens CNS toxicity by increasing the amount of salicylate that crosses the blood brain barrier and increases CNS tissue levels. Other signs and symptoms of CNS toxicity include nausea, vomiting, hyperpnea, and lethargy. Severe toxicity can progress to disorientation, seizures, cerebral edema, hyperthermia, coma, cardiorespiratory depression, and, eventually, death. GI tract effects Nausea and vomiting are the most common toxic effects. This can be caused by CNS toxicity or by direct damage to the gastric mucosa. Salicylates can disrupt the mucosal barrier and occasionally cause GI bleeding. Pylorospasm, decreased GI tract motility and bezoar formation can occur with large doses. These slow elimination and cause greater amounts of salicylates to be absorbed from the GI tract. Hepatic effects Hepatitis can occur in children ingesting doses at or above 30.9 mg/dL.3 Reye syndrome is another form of pediatric salicylate-induced hepatic disease characterized by nausea, vomiting, hypoglycemia, elevated levels of liver enzymes and ammonia, fatty infiltration of the liver, increased intracranial pressure, and coma. Hematologic effects Hypoprothrombinemia and platelet dysfunction are the most common effects. Bleeding may also be promoted either by inhibition of vitamin K–dependent enzymes or by the formation of thromboxane A2. Musculoskeletal effects Rhabdomyolysis can occur because of dissipation of heat and energy resulting from oxidative phosphorylation uncoupling.
Centers for Disease Control and Prevention (CDC
Oral ingestion of a large amount of acetylsalicylate, given for treatment of ear pain, has resulted in severe metabolic derangements and death. Brain histopathology revealed sparse grey matter changes and acute white matter damage.6
Bedside ferric chloride testing: Historically, qualitative determination for the presence of salicylates was rapidly performed in the emergency department by adding a few drops of 10% ferric chloride (FeCl3) to 1 mL of urine. If salicylates are present, the solution changes to a brown/purple color. Positive results with the urine ferric chloride test only indicate that a salicylate is present; however, even very small amounts of a salicylate, such as a single ingested aspirin tablet can give a positive test result. Most emergency departments no longer perform this test and instead obtain a plasma salicylate level because these results are rapidly available from almost all hospital laboratories. Other laboratory studiesSerum electrolytes and renal function studies (BUN and creatinine levels): These should be done initially, and electrolyte levels (especially potassium) should be obtained every 2-4 hours, when the patient is being alkalinized. Serum glucose level Serum acetaminophen levels: These should always be obtained in any unknown overdose Liver function tests Coagulation studies (prothrombin time and activated partial thromboplastin time) Urinalysis Repeat testing: Repeated blood gases and serum salicylate levels should be done every 2 hours, until the acid-base status is improving, levels are falling, and the patient is clinically improving.
Treatment Medical Care Principles of treatment include stabilizing the ABCs as necessary, limiting absorption, enhancing elimination, correcting metabolic abnormalities, and providing supportive care. No specific antidote is available for salicylates. Although determination of serial serum salicylate concentrations offers valuable information regarding the effectiveness of the treatment implemented, assessment of these levels alone is not a substitute for clinical evaluation of the patient. When considering treatment options, the final decision should be individualized according to the clinical status of the patient and should not depend only on a particular salicylate level.Optimal management of a salicylate poisoning depends on whether the exposure is acute or chronic. Gastric lavage and activated charcoal are useful for acute ingestions but not in cases of chronic salicylism. Patients with chronic rather than acute ingestions of salicylates are more likely to develop toxicity, especially of the CNS, and require intensive care. Salicylate poisoning has been shown to cause metabolic derangements with significant inhibition of Krebs cycle enzymes.8 It also uncouples oxidative phosphorylation. Because of impaired glucose homeostasis, CNS glucose supply is sometimes lowered, which results in hypoglycorrhachia and delirium, even when serum glucose concentration is normal. Glucose boluses in euglycemic patients with salicylate induced delirium have sometimes caused a prompt improvement in mental status and therefore should be given to any patient with a salicylate overdose, who has a change in mental status, despite a serum glucose level within the reference range. Triage care: In one study, authors reviewed US poison center data for 2004 and determined that over 40,000 exposures to salicylate-containing products occurred.9 They published guidelines on triage care of these patients which are divided as follows: Immediate emergency department referral by local poison control centers Patients who state ingestion or in whom a large administration is suspected should immediately be referred to the emergency department. Typical symptoms of salicylate toxicity warrant referral to the emergency department for evaluation. Further triage care Determine the dose, time of ingestion, presence of symptoms, history of other medical conditions, and presence of co-ingestants in patients without evidence of self-harm. Do not induce vomiting for salicylate ingestion. Activated charcoal for acute ingestions of a toxic dose can be given if no contraindications are observed. Asymptomatic dermal exposures to methyl salicylate or salicylic acid: The skin should be thoroughly washed with soap and water and the patient can be observed at home. Ocular exposure of methyl salicylate or salicylic acid: The eye or eyes should be irrigated with room-temperature tap water for 15 minutes. If pain, decreased visual acuity, or persistent irritation is reported after irrigation, referral to an ophthalmologist is recommended. Poison centers should monitor the onset of symptoms at periodic intervals for approximately 12-24 hours after ingestion. An evidence-based consensus guideline to assist poison center personnel in the appropriate out-of-hospital triage and initial out-of-hospital management of patients with a suspected exposure to salicylates is also available from Department of Health and Human Services.10 Emergency department management ABCs: As with all significant overdoses the airway, breathing and circulation should be evaluated and stabilized as necessary. Dehydration and concomitant electrolyte abnormalities must be immediately corrected. GI tract decontamination Initial treatment should include the use of oral activated charcoal, especially if the patient presents within one hour of ingestion. Some authorities recommend performing gastric lavage in all symptomatic patients regardless of time of ingestion. Activated charcoal can limit further gut absorption by binding to the available salicylates. The recommended initial dose of activated charcoal is 1 g/kg of body weight to a maximum of 50 g in children and 1-2 g/kg to a maximum of 100 g in adults. Use of cathartics is not routinely indicated with activated charcoal; however, many clinicians administer the first dose of activated charcoal with sorbitol. Sorbitol should not be used in young children. Repeated doses of charcoal may enhance salicylate elimination and may shorten the serum half-life.11 Most experts strongly recommend this for patients with a serious ingestion. Repeated doses of charcoal can remove salicylates from the circulation into the GI tract. Repeated doses of activated charcoal can assist in treating bezoars with ongoing absorption of salicylates, which should be suspected when salicylate levels continue to rise or fail to decrease, despite appropriate management. The passage of stool with charcoal and the resolution of clinical manifestations may be the reasonable criteria for discontinuing multiple doses of activated charcoal. Whole bowel irrigation (WBI) with polyethylene glycol has been compared with single-dose activated charcoal in salicylate absorption in volunteer subjects 4 hours after ingesting enteric-coated aspirin.12 WBI was more effective in reducing absorption. When enteric-coated aspirin has been ingested or when salicylate levels do not decrease despite treatment with charcoal, WBI should probably be used in addition to charcoal therapy. Urinary alkalization Renal excretion of salicylic acid depends on urinary pH. Increasing the urine pH to 7.5 prevents reabsorption of salicylic acid from the urine.13 Because acidosis facilitates transfer of salicylate into tissues, especially in the brain, it must be aggressively treated by raising blood pH higher than brain pH, thereby shifting the equilibrium from the tissues to the plasma. Concomitant alkalinization of blood and urine keeps salicylates away from brain tissue and in the blood, in addition to enhancing urinary excretion. When the urine pH increases to 8 from 5, renal clearance of salicylate increases 10-20 times. Raising the urinary pH level from 6.1 to 8.1 results in a more than 18-fold increase in renal clearance by preventing nonionic tubular back-diffusion, which decreases the half-life of salicylates from 20-24 hours to less than 8 hours. Because aspirin is a weak acid, it ionizes when exposed to a basic environment, such as alkaline urine. Ions are poorly reabsorbed in the tubules and are excreted more readily. This phenomenon is called ion trapping and also works well for overdoses of other weak acids, such as phenobarbital. Hypokalemia and dehydration limit the effectiveness of urine alkalization. Hypokalemia prevents excretion of alkaline urine by promoting distal tubular potassium reabsorption in exchange for hydrogen ions. Symptomatic patients typically have low serum potassium concentrations or serum potassium concentrations low in the reference range. Treatment with sodium bicarbonate alone may produce further intracellular shift of potassium ions, which further impairs the ability to excrete alkaline urine. Repletion of potassium is often necessary, even when serum potassium levels are in the low reference range (eg, &lt;4.5 mEq/L). Urinary alkalization should be continued at least until serum salicylate levels decrease into the therapeutic range (&lt;30 mg/dL). Although acetazolamide results in the formation of a bicarbonate-rich alkaline urine, it unfortunately also causes metabolic acidosis that can worsen toxicity and, therefore, should not be used. Hemodialysis Indications for hemodialysis include a serum level greater than 120 mg/dL (acutely) or greater than 100 mg/dL (6 h postingestion), refractory acidosis, coma or seizures, noncardiogenic pulmonary edema, volume overload, and renal failure. In chronic overdose, hemodialysis may be required for a symptomatic patient with a serum salicylate level greater than 60 mg/dL. Although hemoperfusion has a slightly higher rate of drug clearance than hemodialysis, dialysis is recommended because of its ability both to correct for fluid and electrolyte disorders and to remove salicylates. Peritoneal dialysis is only 10-25% as efficient as hemoperfusion or hemodialysis and is not even as efficient as renal excretion. Consultations No specific antidote for salicylate poisoning is available; therefore, therapy is focused on immediate resuscitation, correction of volume depletion and metabolic derangements, GI tract decontamination, and reduction of the body&apos;s salicylate burden by alkalinzation of the urine and by hemodialysis in life threatening cases. Early consultation with a medical toxicologist is prudent to assist in guiding management. Also, consultation with a nephrologist is indicated in serious overdoses to arrange for hemodialysis, if it becomes necessary. Patients with intentional ingestions should have psychiatric consultation prior to discharge in the emergency department or on the ward.
Pediatrics drug poisoning
Dina F. El Wahaidi
Dr. Mostafa El KahLout .
POISONING IN CHILDREN
Definition of Poisoning:
Exposure to a chemical or other agent that adversely
affects functioning of an organism.
Circumstances of Exposure can be intentional, accidental,
environmental, medicinal or recreational.
Routes of exposure can be ingestion, injection, inhalation
or cutaneous exposure.
“All substances are poisons...the right dose separates poison from a
US Poison Centers receive 1.5 million calls a
year regarding pediatric ingestions.
79% of these calls involve children younger
than age six.
56% of pediatric exposures are from products
around the house including medicines, cleaning
agents, pesticides, plants and cosmetics.
99% of ingestions by children under 6 are
Approximately 40% of ingestions
reported to the poison center by
adolescents are intentional.
Approximately 56% of adolescent
ingestions are by females.
Major four toxidromes are:
Opiates/Sedatives- Hypnotics/ Alcohol
What toxic agent/medications were found near the
What medications are in the home?
What approximate amount of the “toxic” agent was
How much was available before the ingestion?
How much remained after the ingestion?
When did the ingestion occur ?
Were there any characteristic odors at the scene of the
Was the patient alert on discovery?
Has the patient remained alert since the ingestion?
How has the patient behaved since the ingestion?
Does the patient have a history of substance abuse?
ABC’S OF TOXICOLOGY:
Resuscitation medications if needed
chemistry, coagulation, blood gases, drug levels
Expose / Examine
Full vitals / Foley / Monitoring
Give specific antidotes / treatment
– Flush eyes with saline
– Remove contaminated clothing
– Brush off
– Irrigate skin
– Activated charcoal:
May Prevent /delay absorption of some drugs/toxins
Almost always indicated Only in the 1st
– Naso/oro-gastric Lavage
– Bowel Irrigation:
Awake alert patient
500 cc NS Children / 2000cc adults
Orally / Nasogastric tube
ABC’S OF TOXICOLOGY:
The most common
cause of death in
Classically taught as
having five clinical
Toxic doses occur at 10-20mg/Kg of
Prenatal vitamins typically contain about
65 mg of elemental iron.
Children's vitamins contain about 10-18
mg of elemental iron.
THE FIVE STAGES :
Stage 1 ( first 6 hrs )
Nausea, vomiting, abdominal pain and diarrhea.
Stage 2 ( 6- 12 hrs )
This is the latent phase often between 4-12hours as the
patient resolves GI symptoms.
Stage 3 ( 12 - 24 hrs )
Shock stage involving multiple organs including
coagulopathy, poor cardiac output, Hypovolemia,
lethargy and seizures.
Stage 4 (2-3 days)
Continuing of hepatic failure and ongoing oxidative
damage by the iron in the reticuloendothelial system.
Stage 5 ( 2 -6 weeks )
Gastric outlet obstruction secondary to scarring & Liver
Other Problems to Be Considered
It is a clinical diagnosis
Little is known about the absorption rate of iron
in an overdose or the timing of peak serum iron
Serum levels Of :
Mild - Less than 300 µg/dL
Moderate - 300-500 µg/dL
Severe - More than 500 µg/dL
TIBC has no utility in the acute
Detailed history and physical including
a rectal exam for frank blood.
Aggressive fluid resuscitation and intravenous
Whole bowel irrigation and KUB to
Look for pills.
Laboratory analysis for CBC,
chemistry, and iron levels (peak around 4 hours)
Will often require repeat levels with
a repeat chemistry
- shock, altered mental status,
persistent GI symptoms,
metabolic acidosis, pills
visible on radiographs, serum
iron level greater than 500
µg/dL, or estimated dose
greater than 60 mg/kg of
- if a serum iron level is not
available and symptoms are
If the patient is in shock, remember to at
least type and screen (if not cross match)
Deferoxamine was derived from
Ferrioxamin :This complex imparts a
reddish, vin rosé, color to the urine
Hypotension and allergic reactions are
ARDS is a known complication and usually
limit its use to 24 hours or less.
Acetaminophen is the most widely used analgesic-
antipyretic medication taken by people in the
United States and the world.
or paracetamol, is also known by its chemical
name, N -acetyl-p -aminophenol (APAP)
In Great Britain, acetaminophen toxicity is cited
as the most common etiology of hepatic
failure requiring liver transplantation
Patients with acetaminophen-
induced hepatotoxicity present in 4
clinical stages :
Stage I 0-24 hrs
Neurologic, respiratory, and cardiac symptoms
are rare in stage 1. If CNS involvement and/or
severe metabolic acidosis (elevated anion gap)
are present, consider co-ingestants
Nausea, vomiting, malaise and diaphoresis.
Normal bilirubin Transaminases and PT but
may elevate after 12 hrs Post Ingestion
Stage 2 (24-72 h )
Stage 1 symptoms become less evident or resolve.
pain and tenderness in the right upper quadrant.
(hepatomegaly) can be present. Some patients may
Serum studies reveal elevated ALT and AST levels,
(PT), and bilirubin values.
RF may also be present and indicate nephrotoxicity
Stage 3 (72-120 h)
Stage 3 develops 3-5 days after ingestion
Severe toxicity is evident on sera laboratory studies.
Lactic acidosis, prolonged PT or (INR), markedly
elevated ALT and AST (>10,000 IU/L )
Death is most common during stage 3, with
multiorgan failure as the primary cause
Stage 4 (5-14 d)
This stage can last as long as 21 days.
Patients either have a complete recovery or they
the period to normalization may take several
weeks. Hepatic histiologic can take as long as 3
months to resolve.
DOES NOT cause chronic hepatic dysfunction
Stage 1 : non specific (Pallor, diaphoresis, &
Stage 2 : RUQ Tenderness, tachycardia &
Stage 3 : hepatic injury (abdominal pain, jaundice,
and GI bleeding ) Encephalopathy and cerebral
Stage 4 : resolve or death occurs.
Remember the Dose
Aceta = 4 gday for adults
= 80mgKgday for #
Aceta =352-650mg every 4-6hrs for adults
=10-15mgKg every 4-6 hrs for #
Not more than 5 doses
Not more than 2.6g Per Day
# = Children < 12 Years Or < 50 Kg
Hepatitis A , B Or C
EBV or Varicella
Measurement of acetaminophen serum
Any serum sample drawn 4 hours or
longer after a single ingestion may be
plotted on (Rumack-Matthew nomogram)
to estimate the risk of hepatotoxicity
Measurement of hepatic (ALT) and (AST)
hepatic injury is defined by elevation of
the plasma transaminases more than 1000
1) Consider decontamination with activated charcoal in
any patient who presents within 4 hours of ingestion.
Consider gastric lavage if ingestion occurred within 1
hour of evaluation
2) Oral N-acetylcysteine (Mucomys)
3) Intravenous (IV) NAC (Acetadote)
INDICATIONs : altered mental status, GI bleeding and/or
obstruction or a history of caustic ingestion, potential fetal toxicity
from maternal toxicity, or an inability to tolerate oral
SE : flushing, pruritus, and a rash (15%)
Bronchospasm and hypotension (<2% of patients)
Probable toxicity should be treated with:
N-acetylcysteine bolus 140 mg/kg
Then 70 mg/kg Q 4 hrs for 17 doses.
Assess hepatic function:
Continue other support
One teaspoon of 98% methyl salicylate
contains 7000 mg of salicylate, the
equivalent of nearly 90 baby aspirin and
more than 4 times the potentially toxic
dose for a child who weighs 10 kg !
consider salicylate poisoning when topical
herbal medicinal oil is involved
acetylsalicylic acid is rapidly converted to
salicylic acid, its active moiety
salicylic acid is metabolized by the liver and
eliminated in 2-3 hours
Salicylate poisoning is manifested clinically by
disturbances of several organ systems
Salicylates directly or indirectly affect most
organ systems in the body by uncoupling
oxidative phosphorylation, inhibiting Krebs
cycle enzymes, and inhibiting amino acid
synthesis but lipid metabolism is stimulated
GI tract & Hepatic effects : Nausea and vomiting.
Hepatitis at or above 30.9 mg/d & Rey syndrome
CNS effects : tinnitus, hearing loss at serum levels of
30-45 mg/dl, seizures, cerebral edema, hyperthermia, coma,
Acid-base status :normal anion-gap acidosis does not
Respiratory system effects 35 mg/dL
Fluid and electrolyte effects : 5-10 %dehydration,
Hypokalemia and hypocalcemia ( due to Resp. Alka. )
Hematologic effects Hypoprothrombinemia and platelet
Musculoskeletal effects Rhabdomyolysis
Reye syndrome is characterized by acute
noninflammatory encephalopathy and hepatic failure
of unknown etiology , typically occurs after a viral
illness, partic. an (URTI), influenza, Varicella or GE & it
is associated with the use of aspirin during the illness .
Diagnostic criteria from the (CDC) :
1) Acute noninflammatory encephalopathy with an altered
level of consciousness
2) Hepatic dysfunction with a liver biopsy showing fatty
metamorphosis or a more than 3-fold increase in (ALT),
(AST), and/or ammonia levels
3) No other explanation for cerebral edema or hepatic
4) CSF with WBCs (usually lymphocytes) (8 X 109
5) Brain biopsy with cerebral edema without inflammation
CLINICAL AND LABORATORY
Phase 1 : hyperventilation respiratory alkalosis
and compensatory alkaluria. Both K & NaHCO3 are
excreted in the urine. may last as long as 12 hours
phase 2 : paradoxic aciduria occurs when sufficient
potassium has been lost from the kidneys. may begin
within hours & may last 12-24 hours
Phase 3 : includes dehydration, hypokalemia, and
progressive metabolic acidosis. This phase may begin
4-6 hours after ingestion in a young infant or 24 hours
or more after ingestion in an adolescent or adult.
When possible take :
Type of salicylate
Approximate time of ingestion
Possibility of long-term ingestion
Presence of other medical conditions (eg, cardiac,
The presence of tinnitus is a clue for salicylate
ingestion. Tachypnea, tachycardia, and elevated
temperature can be detected by evaluating vital
Bedside ferric chloride testing (No longer)
ABG: the most common abnormality is a mixed acid-
Salicylate concentration: Therapeutic range of salicylate
is 15-30 mg/Dl
the peak serum concentration may not occur for 4-6
hours . A 6-hour salicylate level higher than 100 mg/dL
is considered potentially lethal and is an indication for
the Done nomogram is regarded as not very useful and
is seldom used by clinicians
Others . Repeat every 2 hrs till stabilization !
MORBIDITY OF AN ACUTE, SINGLE
less than 150 mg/kg - ranges from no toxicity to
From 150-300 mg/kg - Mild-to-moderate
From 301-500 mg/kg - Serious toxicity
Greater than 500 mg/kg - Potentially lethal
Gastric lavage and activated charcoal are useful for acute
ingestions but not in chronic salicylism.
ABCs & lactated Ringer or isotonic Na Cl solution for
volume expansion at 10-20 cc/kg/h until a 1-1.5-cc/kg/h
urine flow is established
GI tract decontamination :initial dose of activated charcoal
is 1 g/kg of body weight to a maximum of 50 g in children
and 1-2 g/kg to a maximum of 100 g in adults . If enteric-
coated aspirin has been ingested or salicylate levels do not
decrease despite charcoal, WBI should probably be used in
addition to charcoal
Urinary alkalization the U pH to 7.5-8 .Ion trapping :
ions are poorly reabsorbed in the tubules and are excreted
more readily. Correct hypokalemia and dehydration
1. serum level greater than 120 mg/dL (acutely) or
greater than 100 mg/dL (6 h postingestion)
2. refractory acidosis,
3. coma or seizures,
4. noncardiogenic pulmonary edema,
5. volume overload
6. renal failure.
In chronic overdose, for a symptomatic patient
with a serum salicylate level greater than 60
Peritoneal dialysis is only 10-25% as efficient as