poisoning

1. poisoning Selected Compounds Commonly Involved in Pediatric Poisonings

2. Acetaminophen • it can be unintentionally ingested by young children, taken in an intentional overdose by adolescents and adults, or inappropriately dosed in all ages. • Pathophysiology • Acetaminophen toxicity results from the formation of a highly reactive intermediate metabolite, N-acetyl-p-benzoquinoneimine (NAPQI).

3. which is then immediately conjugated with glutathione to form a nontoxic mercapturic acid conjugate. The single acute toxic dose of acetaminophen is generally considered to be >200 mg/kg in children and >7.5-10 g in adolescents and adults. Clinical and Laboratory Manifestations: The fowllowing are the 4 stages of the clinical course of acetaminophen toxicity

4. Stage I….. • 0.5-24 hr onset after ingestion • Anorexia, nausea, vomiting, malaise, pallor, diaphoresis  • Labs typically normal, except for acetaminophen level • Stage II ……24-48 hr • Resolution of earlier symptoms; right upper quadrant abdominal pain and ; elevated bilirubin, prothrombin time, and hepatic enzymes; oliguria

5. Stage III……..72-96 hr • Peak liver function abnormalities; fulminant hepatic failure; multisystem organ failure and potential death. • stage IV……4 days-2 wk   • Resolution of liver function abnormalities   • Clinical recovery precedes histologic recovery Acetaminophen levels obtained <4 hr after ingestion are difficult to interpret and cannot be used to estimate the potential for toxicity

6. Assessment of the patient who presents with an unknown time of ingestion or a history of chronic supratherapeutic >90 mg/kg ingestion is more complicated. • Treatment • Initial treatment should focus on the ABCs and consideration of decontamination with activated charcoal in patients who present within 1-2 hr of ingestion. • The antidote for acetaminophen poisoning is NAC, which works primarily via replenishing hepatic glutathione stores.

7. NAC is continued for at least 21-24 hr and until the patient is clinically well, with improving transaminases, normalizing synthetic function, and acetaminophen level <10 microg/mL. Patients who develop hepatic failure in spite of NAC therapy may be candidates for liver transplantation • Transaminases, synthetic function, and renal function should be followed daily while the patient is being treated with NAC. • Side effects:anaphylaxis,mild increase in INR.

9. 1. Prophylactic: By definition, these patients have a normal aspartate aminotransferase (AST). If the APAP level is known and the ingestion is within 24 hr of the level being drawn, then treatment.Any patient with a serum APAP level in the possible or probable hepatotoxicity range per the nomogram should be treated with N-acetylcysteine (NAC)..

10. 2. Hepatic Injury: These patients are exhibiting evidence of hepatocellular necrosis,. Any patient in this category requires therapy with NAC (IV or oral). • 3. Acute Liver Failure: patients should be referred for consideration of liver transplant. • 4. Repeated Supratherapeutic Ingestion: In the asymptomatic patient, if the AST is normal and the APAP is <10 μg/mL, then no therapy is indicated. elevated AST puts the patient in the “hepatic injury” category described above.

11. N-acetylcysteine (NAC) • Prevents binding of NAPQI to hepatocytes • Reduces NAPQI • Conjugates NAPQI • Increases sulfation metabolism***

12. NAC • Smells like rotten eggs • Oral formulation may need to be given via NGT • Dilute with juice • Use metoclopramide or ondansetron if not tolerated due to vomiting

13. Salicylates • The incidence of salicylate poisoning in young children has declined dramatically . • Pathophysiology Salicylates lead to toxicity by direct stimulation of the respiratory center, uncoupling of oxidative phosphorylation, inhibition of the tricarboxylic acid cycle, and stimulation of glycolysis and gluconeogenesis.

14. The acute toxic dose of salicylates is generally considered to be >150 mg/kg, Therapeutic salicylate levels are 10-20 mg/dL, and levels >30 mg/dL warrant treatment.

15. Clinical and Laboratory Manifestations • Salicylate ingestions are classified as acute or chronic. • Early signs of acute salicylism include nausea, vomiting, diaphoresis, and tinnitus. • Chronic salicylism can have a more insidiouspresentation. • BGA,LFT,ELECTROLYTE,B.G,SALICYLATE LEVEL,ACETAMINOPHEN LEVEL, Serum and urine pH ,CXR.

16. Treatment • For the patient who presents soon after an acute ingestion, initial treatment should include gastric decontamination with activated charcoal. • Initial therapy focuses on aggressive volume resuscitation and prompt initiation of sodium bicarbonate therapy in the symptomatic patient, even before obtaining serum salicylate levels. • The primary mode of therapy for salicylate toxicity is urinary alkalinization.

17. Alkalinization is achieved by administration of a sodium bicarbonate infusion at approximately 1.5 times maintenance fluid rates. The goals of therapy include a urine pH of 7.5-8, a serum pH of 7.45-7.55. • In cases of severe toxicity, dialysis may be required

18. Digoxin • Digoxin is a cardiac glycoside extracted from the leaves of Digitalis lanata • Therapeutically, digoxin is used in the management of heart failure and some supraventriculartachydysrhythmias. • Acute overdose can occur in the setting of dosing errors (especially in younger children), unintentional or intentional medication ingestion.

19. Chronic toxicity can result from alteration of the digoxin dose, alteration in digoxin clearance due to renal impairment, or drug interactions. • Pathophysiology Digoxin blocks the Na+, K+-ATPase pump, leading to intracellular loss of K+ and gain of Na+ and Ca2 rise in ca improve intropysubsequent increase in atrial,nodal and ventricular ectopy. Digoxin also affects nodal conduction, leading to slowed conduction through the AV node.

20. Digoxin has a very narrow therapeutic index. Therapeutic plasma digoxin concentrations are 0.5-2.0 ng/mL; a level of >2 ng/mL is considered toxic . • Medications known to increase serum digoxin concentrations include the macrolides,spironolactone • Clinical and Laboratory Manifestations • Nausea and vomiting are common initial symptoms of acute digoxin toxicity, manifesting within 6 hr of overdose.

21. Cardiovascular manifestations include bradycardia, heart block, and a wide variety of dysrhythmias. CNS manifestations consist of lethargy, confusion. Chronic toxicity is more insidious and manifests with GI symptoms, altered mental status, and visual disturbances. • Investigations:should include an ECG, serum digoxin level, serum potassium, and kidney function tests. The serum digoxin level should be assessed at least 6 hr after ingestion.

22. Treatment • good general supportive care and gastric decontamination with activated charcoal if the ingestion was recent. • An antidote for digoxin, digoxin-specific Fab antibody fragments (Digibind or Digifab) . • Fab fragments bind free digoxin in both the intravascular and the interstitial spaces to form a pharmacologically inactive complex that is subsequently renally eliminated. • Indications for Fab…….

23. If Digibind or Digifab are not readily available, phenytoin or lidocaine may be beneficial in managing ventricular irritability. Atropine is potentially useful in managing symptomatic bradycardia. • Consultation with a cardiologist. Cholinesterase-Inhibiting Insecticides The most commonly used insecticides are organophosphates and carbamates; both are inhibitors of cholinesterase enzymes (acetylcholinesterase,pseudocholinesteras, and erythrocyte acetylcholinesterase).

24. Pathophysiology • Organophosphates and carbamates produce toxicity by binding to and inhibiting acetylcholinesterase, preventing the degradation of acetylcholine and resulting in its accumulation at nerve synapses. Clinical and Laboratory Manifestations Clinical manifestations of toxicity relate to the accumulation of acetylcholine at peripheral nicotinic and muscarinic synapses and in the CNS.

25. symptoms of cholinergic excess at muscarinic receptors is DUMBBELS, which stands for diarrhea/defecation, urination, miosis, bronchorrhea/bronchospasm, bradycardia, emesis, lacrimation, and salivation. Nicotinic signs and symptoms include muscle weakness, fasciculations, tremors, hypoventilation (diaphragm paralysis), hypertension, tachycardia, and dysrhythmias. Severe manifestations include coma, seizures, shock, arrhythmias and resp. failure.

26. Diagnosis is based primarily on history and physical exam findings. Red blood cell cholinesterase and pseudocholinesterase concentrations. Treatment • Basic decontamination should be performed, including washing all exposed skin with soap and water and immediately removing all exposed clothing. • Administering activated charcoal after ingestion of insecticides is controversial, • Basic supportive care

27. Two antidotes are useful in treating cholinesterase inhibitor poisoning: atropine and pralidoxime. • Even with treatment, some patients develop a delayed polyneuropathy and a range of chronic neuropsychiatric symptoms. Hydrocarbons • Hydrocarbons include a wide array of chemical substances found in thousands of commercial products

28. Pathophysiology • The most important manifestation of hydrocarbon toxicity is aspiration pneumonitis via inactivation of the type II pneumocytes and resulting surfactant deficiency . • . Compounds with low viscosity, such as mineral spirits, naphtha, kerosene, gasoline, and lamp oil, spread rapidly across surfaces and cover large areas of the lungs when aspirated.

29. Only small quantities (<1 mL) of low-viscosity hydrocarbons need be aspirated to produce significant injury. • Pneumonitis does not result from dermal absorption of hydrocarbons or from ingestion in the absence of aspiration. • A number of volatile hydrocarbons, including toluene, propellants, refrigerants, and volatile nitrites, are commonly abused by inhalation. ), can sensitize the myocardium to the effects of endogenous catecholamines.

30. Clinical and Laboratory Manifestations • Transient, mild CNS depression • Aspiration is characterized by coughing, which usually is the first clinical finding. • Chest radiographs may initially be normal, but they often show abnormalities within 6 hr of exposure in patients who have aspirated. . Pneumatoceles can appear on the chest radiograph 2-3 wk after. • Respiratory symptoms. can remain mild or progress rapidly to (ARDS) .

31. Fever and leukocytosis. Treatment • Emesis and lavage are contraindicated given the risk of aspiration. • Activated charcoal is not useful because it does not bind the common hydrocarbons and can also induce vomiting. • respiratory treatment is supportive, Neither corticosteroids nor prophylactic antibiotics have shown any clear benefit . • Patients with dysrhythmias should be treated with β-blockers (usually esmolol)