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Salicylate overdose 2

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  • 1. Salicylate overdose (Salicylism) Dr.Malathe Noralla PGY1-Internal medicine
  • 2. Objectives:  Introduction.  Therapeutic uses of salicylates & product strength.  Inherent toxicity.  Chronic vs Acute.  Factors influencing toxicity.  Assessing poisoning dose.  Pharmacokinetics .  Pathophysiology of toxicity.  Diagnosis & Clinical presentation.  Treatment.  Prognosis.
  • 3. Introduction Intentional salicylate overdose usually occurs predominantly in adolescents & young adults. Overdoses in children are usually accidental & in the elderly they occur as therapeutic misadventures. The severity of aspirin overdose is often underestimated by ER personnel because of lack of familiarity. This is an important problem because delay in treatment of severe intoxication is associated increased mortality in severe cases. With good management mortality rates are low but even at best about 5% of severely toxic patients die, usually from cardiovascular & central nervous system complications.
  • 4. Therapeutic Uses Of Salicylates  Analgesics  Anti inflammatorys  Antipyretics  Keratolytics  Antiplatelets.
  • 5. Salicylate Product Strengths  Adult Aspirin (300mg, 325 mg)  Baby Aspirin (81 mg)  Bismuth subsalicylate 1 ml is equivalent to 8.77 mg of salicylic acid. 60 ml is equivalent to a therapeutic dose (650 mg) of aspirin.  Methylsalicylate 1 teaspoonful (100% MS) = 21 adult strength aspirin
  • 6. Inherent Toxicity  Aspirin Toxic dose = 150 mg/kg Minimal lethal dose = 450 mg/kg  Methylsalicylate Lethal dose in children = 4 cc of 100% MS Lethal dose in adults = 6 cc of 100% MS
  • 7. Chronic vs Acute Salicylate Poisoning Acute Chronic  Victim Young Adult Elderly  Circumstances Intentional Accidental  Time To Diagnosis Short Long  Mortality 2% 25%  Morbidity 16% 30%
  • 8. Factors Influencing Salicylate Toxicity  Dose  Age Of Victim  Renal Function  Dehydration
  • 9. Assessing Salicylate Poisoning Dose  150 mg/kg No toxicity expected  150-300 mg/kg Mild to moderate toxicity expected  300-500 mg/kg Life-threatening toxicity expected
  • 10. PHARMACOKINETICS  Absorbed rapidly by passive diffusion.  90 % Binds to albumin .  Has a very short half-life (30 min).  Metabolized by the liver. (hepatic conjugation with glycin or glucuronic acid).  Excreted in the urine (PH dependent).
  • 11. Pathophysiology of salicylate toxicity.  Metabolic disturbance.  Respiratory system disturbance.  CNS disturbance.  CVS disturbance.  GIT disturbance.  Hematological disturbance.  Musculoskeletal system disturbance.
  • 12. Metabolic Disturbance  Hyperthermia.  Acid-base disturbances (respiratory alkalosis, metabolic acidosis)  Dehydration  Electrolyte imbalance (hypokalemia, hyponatremia)  Altered glucose levels (elevated, normal, or low; CNS glucose concetrations may be low despite normal or even high blood glucose concentrations)
  • 13. Respiratory system Disturbance  Tchypnea & hyperpnea.  None cardiogenic pulmonary edema.  Acute lung injury.  Hypoxia.
  • 14. CNS Disturbance  Tinnitus (>30mg/dl).  Hearing loss (serum level 35-40mg/dl).  Tremors.  Seizures.  Confusion.  Encephalopathy.  Coma & Death.
  • 15. CVS Disturbance  Tachycardia  Hypotension  Dysrhythmias - Eg, ventricular tachycardia, ventricular fibrillation, multiple premature ventricular contractions  Asystole - With severe intoxication  Electrocardiogram (ECG) abnormalities - Eg, U waves, flattened T waves, QT prolongation; may reflect hypokalemia
  • 16. GIT Disturbance  Nausea & Vomiting.  Abdominal pain.  Bleeding.  Intestinal perforation.  Pancreatitis.  Hepatitis.  Pylorospasm, decreased GI tract motility, and bezoar formation can occur with large doses.
  • 17. Hematological Disturbance  Hypoprothrombinemia  Platelet dysfunction   Inhibition of vitamin K–dependent enzymes Inhibition of thromboxane A2
  • 18. Musculoskeletal Disturbance  Rhabdomyolysis
  • 19. Diagnosis  History :  Amount  Approximate time of ingestion  Possibility of long-term ingestion  Potential co-ingestants  Presence of other medical conditions (eg, cardiac, renal diseases)  Physical examination:  Vital signs.  CVS  Chest  Abdomen  CNS
  • 20. Assessing Salicylate Poisoning from Clinical Evaluation Mild (150mg/kg) Moderate (150-300 mg/kg) Severe (300-500 mg/kg) Nausea Nausea Delerium Vomiting Vomiting Hallucinations Dizziness Tinnitus Convulsions Headache Coma Confusion Hyperventilation Tachycardia Fever Respiratory arrest
  • 21.  Laboratory markers:  Serum salicylate: - Low serum levels early after acute ingestion do not preclude toxicity . - Levels should be obtained every 2 hours until a decrease is noted on two consecutive measurements. - Acute ingestions of non–enteric-coated aspirin should result in peak serum levels by 6 hours after ingestion. A delayed increase may be seen in patients with a salicylate pharmacobezoar, patients who have ingested enteric-coated or sustained-released products (due to delayed absorption), and patients with worsening acidosis. - Acute toxicity, levels ranging from 31 to 100 mg/dL - Chronic toxicity, toxic levels may be as low as 30 to 40 mg/dL
  • 22.  Urinalysis: - PH. - ketones. - Glucose. - 10% ferric chloride test (100% sensitive, 71%specific)  Blood glucose: - Hypoglycemia - Normal - Hyperglycemia  Urea & Electrolytes: - Hypokalemia. - Hyponatremia. - Urea: elevated.
  • 23.  Creatinine: - Elevated.  ABG  CXR  ECG  Abdominal imaging: - Suspicion of aspirin concretion & pharmacobezoar. - US, CT, Endoscopy.  Hepatic, hematologic, and coagulation profiles - Obtain for patients with clinical evidence of moderate to severe toxicity.
  • 24. Treatment  Fluid resuscitation : - Correction of dehydration with 0.9% sodium chloride or lactated Ringer solution, 10 to 20 mL/kg/h over 1 to 2 hours until a good urine flow is established of at least 2 to 3 mL/kg/h  GI decontamination: - Gastric lavage in the first hr (warmed NS 38C,protect airway) - Activated charcoal in the first 4 hr, 1-2g/kg (maximum 100g) - Whole-bowel irrigation (WBI) with polyethylene glycol(enteric coated or slow release formulas, 2 L/h (20 mL/kg/h until the rectal effluent is clear)  Urinary alkalinization with sodium bicarbonate: - Moderate to sever toxicity. - 1 to 2 mEq/kg of sodium bicarbonate IV bolus, then infusion of DW5% with 100 to 150 mEq of sodium bicarbonate and 20 to 40 mEq of potassium chloride in each liter at a rate of 1.5 to 2.5 mL/kg/h. - Goal urine output is 2 to 3 mL/kg/h.
  • 25.  Hemodialysis: - Management of patients with salicylate poisoning and a serum salicylate level >100 mg/dL after acute ingestion or >40 mg/dL after chronic ingestion, altered mental status, renal failure, pulmonary edema, progressive clinical deterioration, refractory acidosis, or failure to respond to more conservative therapy.
  • 26. Prognosis  The prognosis in patients with acute salicylate poisoning is very good: the mortality rate is 1%, and the morbidity rate is 16%  The prognosis is worse in patients with chronic salicylate poisoning: the mortality rate is 25%, and the morbidity rate is 30%
  • 27. Refrences  The American Association of Poison Control Centers ,Chyka PA, Erdman AR, Christianson G, et al. Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management . Clin Toxicol (Phila). 2007;45:95-131  The American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists ,Vale JA, Kulig K; American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Position paper: gastric lavage . J Toxicol Clin Toxicol. 2004;42:933-43 Position paper: whole bowel irrigation . J Toxicol Clin Toxicol. 2004;42:843-54 Proudfoot AT, Krenzelok EP, Vale JA. Position paper on urine alkalinization . J Toxicol Clin Toxicol. 2004;42:1-26  Supplement to Emergency Medicine Reports, January 17, 2011: “Aspirin Overdose.” Author: Marc S. Lampell, MD, Associate Professor, Pediatric Emergency Medicine, University of Rochester, NY.Emergency Medicine Reports’ “Rapid Access Guidelines.” Copyright © 2011 AHC Media, a division of Thompson Media Group LLC, Atlanta, GA. Editors: Sandra M. Schneider, MD, FACEP, and J. Stephan Stapczynski, MD. Executive Editor: Russ Underwood. Specialty Editor: Shelly Morrow Mark. F
  • 28.  Williams GD, Kirk EP, Wilson CJ, Meadows CA, Chan BS. Salicylate intoxication from teething gel in infancy. Med J Aust. Feb 7 2011;194(3):146-8. [Medline].  Davis JE. Are one or two dangerous? Methyl salicylate exposure in toddlers. J Emerg Med. Jan 2007;32(1):63-9. [Medline].  Lewis TV, Badillo R, Schaeffer S, Hagemann TM, McGoodwin L. Salicylate toxicity associated with administration of Percy medicine in an infant. Pharmacotherapy. Mar 2006;26(3):403-9. [Medline].  Hamdan JA, Manasra K, Ahmed M. Salicylate-induced hepatitis in rheumatic fever. Am J Dis Child. May 1985;139(5):453-5. [Medline].  Herres J, Ryan D, Salzman M. Delayed salicylate toxicity with undetectable initial levels after large-dose aspirin ingestion. Am J Emerg Med. Nov 2009;27(9):1173.e1-3. [Medline].  Waasdorp Hurtado CE, Kramer RE. Salicylic acid ingestion leading to esophageal stricture. Pediatr Emerg Care. Feb 2010;26(2):1468. [Medline].  Haslinger V, Dietz W, Bartsch M, Simma B. Salicylate intoxication with symptoms of septicaemia in a 17-month-old girl. Klin Padiatr. Dec 2011;223(7):436-7. [Medline].  Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics. Jun 1975;55(6):871-6. [Medline].  Pearlman BL, Gambhir R. Salicylate intoxication: a clinical review. Postgrad Med. Jul 2009;121(4):162-8.[Medline].  Kuzak N, Brubacher JR, Kennedy JR. Reversal of salicylate-induced euglycemic delirium with dextrose. Clin Toxicol (Phila). Jun-Aug 2007;45(5):526-9. [Medline].  Rauschka H, Aboul-Enein F, Bauer J, Nobis H, Lassmann H, Schmidbauer M. Acute cerebral white matter damage in lethal salicylate intoxication. Neurotoxicology. Jan 2007;28(1):33-7. [Medline].  [Guideline] Chyka PA, Erdman AR, Christianson G, Wax PM, Booze LL, Manoguerra AS, et al. Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2007;45(2):95-131. [Medline].  Kirshenbaum LA, Mathews SC, Sitar DS, Tenenbein M. Does multiple-dose charcoal therapy enhance salicylate excretion?. Arch Intern Med. Jun 1990;150(6):1281-3. [Medline].  Kirshenbaum LA, Mathews SC, Sitar DS, Tenenbein M. Whole-bowel irrigation versus activated charcoal in sorbitol for the ingestion of modified-release pharmaceuticals. Clin Pharmacol Ther. Sep 1989;46(3):264-71.[Medline].  Proudfoot AT, Krenzelok EP, Brent J, Vale JA. Does urine alkalinization increase salicylate elimination? If so, why?. Toxicol Rev. 2003;22(3):129-36. [Medline].  Ong GY. A simple modified bicarbonate regimen for urine alkalinization in moderate pediatric salicylate poisoning in the emergency department. Pediatr Emerg Care. Apr 2011;27(4):306-8. [Medline].  Chyka PA, Erdman AR, Christianson G, et al. Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2007;45(2):95-131. [Medline]