Salicylate Poisoning
Blaine (Jess) Benson, Pharm.D. Director, NMPDC
Case Report
An 18 year-old female is brought to the ED by ambulance after her family witnessed a generalized seizure lasting two minutes. The patient confessed to ingesting two hundred 325 mg aspirin, eight hours prior to the seizure. The patient arrived unresponsive to verbal stimuli or pain.
Case Report Continued
Vital signs:
BP 120/50, HR 119, RR 40, T 103 F
CXR shows pulmonary edema ASA level is 140 mg%
3 hours post admission
ABGs: pH7.45, CO2 19, O2 112, Bicarb 13
Therapeutic Uses Of Salicylates
Analgesic Anti-inflammatory Antipyretic Keratolytic Rubifacient
Trends In Salicylate Poisoning
Chronic vs Acute Salicylate Poisoning
Acute Victim Young Adult Circumstances Intentional Time To Diagnosis Short Mortality 2% Morbidity 16% Chronic Elderly Accidental Long 25% 30%
Salicylate Product Strengths
Adult Aspirin
5 grain (325 mg)
Baby Aspirin
1.25 grain (81 mg)
Methylsalicylate
1 teaspoonful (100% MS) = 21 adult strength aspirin
Inherent Toxicity
Aspirin
Toxic dose = 1 grain/lbs or 150 mg/kg Minimal lethal dose = 3-4 grains/lbs or 450 mg/kg Lethal dose in children = 4 cc of 100% MS Lethal dose in adults = 6 cc of 100% MS
Methylsalicylate
Factors Influencing Salicylate Toxicity
Dose Age Of Victim Renal Function Dehydration Fever
Pharmacokinetic Parameters
Therapeutic 2 hours 70%-90% 0.15-0.2 L/kg 2-4 hours Overdose >6 hours 70%-90%* 0.35 L/kg 18-20 hours
Peak Blood Level Protein Binding Vd Half-life *Increased unbound drug
Aspirin Absorption
Solid Dosage Form
Disintegration
Solid Particles
Dissolution*
Drug In Solution Absorption
Aspirin Metabolism
Acetyl salicylic acid Salicylic acid Salicyl acyl glucuronide (5%) Salicyl phenolic glucuronide (10%) Salicyluric acid (75%) Gentisic acid (<1%)
Oxidative Phosphorylation
Cytochrome Oxidase System
Krebs Citric Acid Cycle
Pharmacology
Uncouples oxidative-phosphorylation Inhibits key dehydrogenase enzymes Interferes with carbohydrate metabolism Interferes with protein metabolism Interferes with lipid metabolism
Salicylates Effects On Carbohydrate Metabolism
Hyperglycemia
Stimulation of adrenal medulla Stimulation of adrenal cortex Increased glucose-6-phosphatase activity
Hypoglycemia
Increased glycolysis Impaired gluconeogenesis from noncarbohydrate precursors
Salicylates Effects On Protein Metabolism
Inhibits protein synthesis Accelerates protein breakdown Inhibits tubular reabsorption of amino acids
Salicylates Effects On Lipid Metabolism
Decrease lipogenesis Increased lipolysis Displaces fatty acids from plasma protein
Manifestations Of Salicylate Poisoning
Vomiting Hyperventilation (30 minutes) Metabolic acidosis (12-24 hours) Electrolytes imbalance & dehydration Hyperthermia Convulsions Death
Complications Of Salicylate Poisoning
Pulmonary edema Renal damage Hemorrhage
Assessing Salicylate Poisoning Dose
150 mg/kg 150-300 mg/kg 300-500 mg/kg No toxicity expected Mild to moderate toxicity expected Life-threatening toxicity expected
Assessing Salicylate Poisoning Clinical Evaluation
Mild (150 mg/kg) Nausea Vomiting Dizziness Moderate (150300 mg/kg) Nausea Vomiting Tinnitus Headache Confusion Hyperventilation Tachycardia Fever Severe (300500 mg/kg) Delerium Hallucinations Convulsions Coma Respiratory arrest
Assessing Salicylate Poisoning Laboratory Evaluation
Patient Status
Arterial blood gases Blood glucose Coagulation - INR Electrolytes Severe exposures
BUN, S. Cr. LFTs
Bedside Tests
Ferric chloride test Phenistix
Quantitative Test
Salicylate level (6 hours post ingestion)
Done Nomogram
Chronic Ingestion
Dose
May occur when >100 mg/kg/day ingested for two or more days
Clinical abnormalities
Severe CNS symptoms, dehydration, hyperventilation
Salicylate levels
Of no prognostic value
Management of Salicylate Poisoning
Supportive Care
Fluid/electrolyte management
Rehydrate with 0.9% saline @ 10-20 cc/hr over 1-2 hours, until urine flow is 3-6 cc/kg/hr Diuresis/alkalization with D5W with 88-132 mEq/L bicarb, plus 20-40 mEq KCl @ 2-3 cc/kg/hr. Goal: urine flow of 2-3 cc/kg/hr and urine pH of 7.5-8.0 Reduce fluid load with elderly and patients with renal or cardiac disease
Hyperthermia
Sponge bath, fans, cold water submersion
Management of Salicylate Poisoning
Preventing absorption
Ipecac Lavage Charcoal and cathartic
Management of Salicylate Poisoning
Enhancing Elimination
Forced alkaline diuresis Hemodialysis Hemoperfusion
Forced Alkaline Diuresis
pH = 6.8
pH = 7.4
pH = 8.0
HA H + + ATissue
HA H + + APlasma
HA H + + AUrine (Alkaline)
Forced Alkaline Diuresis
Indications
Salicylate level >50 mg% accompanied by symptoms and biochemical abnormalities
Utility
No studies demonstrating a decreased morbidity or mortality with this treatment
Dangers
Alkalosis, hypernatremia, fluid overload, decreased ionized Ca++ and tetany
Hemodialysis
Clearance
Hemodialysis - 80 ml/min Peritoneal dialysis - 10-30 ml/min
Indications
Absolute: renal failure, cardiac failure, hepatic compromise, pulmonary edema Relative: ASA level of 120 mg%, unresponsive acidosis; persistent severe CNS manifestations, progressive deterioration despite supportive care
Other Less Commonly Used Methods To Enhance Elimination
Exchange transfusions
49% salicylate eliminated per exchange Complications include sensitization and hypocalcemia Clearance of up to 116 ml/min Does not correct fluid and electrolyte imbalances
Hemoperfusion
