Salicylate overdose(Salicylism)

Dr.Malathe Noralla

PGY1-Internal medicine

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.

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.

Therapeutic Uses Of Salicylates

Analgesics

Anti inflammatorys

Antipyretics

Keratolytics

Antiplatelets.

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

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

Chronic vs Acute SalicylatePoisoning Acute Chronic

Victim Young Adult Elderly

Circumstances Intentional Accidental

Time To Diagnosis Short Long

Mortality 2% 25%

Morbidity 16% 30%

Factors Influencing SalicylateToxicity

Dose

Age Of Victim

Renal Function

Dehydration

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

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).

Pathophysiology of salicylate toxicity. Metabolic disturbance.

Respiratory system disturbance.

CNS disturbance.

CVS disturbance.

GIT disturbance.

Hematological disturbance.

Musculoskeletal system disturbance.

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)

Respiratory system Disturbance

Tchypnea & hyperpnea.

None cardiogenic pulmonary edema.

Acute lung injury.

Hypoxia.

CNS Disturbance

Tinnitus (>30mg/dl).

Hearing loss (serum level 35-40mg/dl).

Tremors.

Seizures.

Confusion.

Encephalopathy.

Coma & Death.

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

GIT Disturbance Nausea & Vomiting.

Abdominal pain.

Bleeding.

Intestinal perforation.

Pancreatitis.

Hepatitis.

Pylorospasm, decreased GI tract motility, and bezoar formation can occur with large doses.

Hematological Disturbance

Hypoprothrombinemia

Platelet dysfunction

 Inhibition of vitamin K–dependent enzymes

Inhibition of thromboxane A2

Musculoskeletal Disturbance

Rhabdomyolysis

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

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 Respiratory arrest

Hyperventilation

Tachycardia

Fever

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

Urinalysis:

- PH.

- ketones.

- Glucose.

- 10% ferric chloride test (100% sensitive, 71%specific)

Blood glucose:

- Hypoglycemia

- Normal

- Hyperglycemia

Urea & Electrolytes:

- Hypokalemia.

- Hyponatremia.

- Urea: elevated.

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.

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.

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.

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%

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

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