Salicylates poisoning

By: Dr. Maisa NABULSI

Friday, January 3, 2025

Salicylates
• Objectives
• Discuss the toxicological effects of salicylate overdose
• Identify key management issues
• Discuss the limitations of the Done nomogram and
how to avoid pitfalls of management
Salicylate Overdose
• Therapeutic doses
• Pediatric 10-20 mg/kg
• Adults 650-1000 mg q 4-6 hrs
• Produce a serum level of 5-10 mg/dL
• Potential Toxic Acute dose > 150 mg/kg
• Serious toxicity: 300-500 mg/kg
• Chronic toxicity: >100 mg/kg/day
Salicylate Overdose
• Peak levels
• Therapeutic Tmax– 1-2 hours
• Vd = 10 L
• half-life= 6 h but may increase up to 20 h(depending
on dose).
• Reason for delay ? contraction of the pylorus or combination
of drugs that delay gastric emptying (opioids and
anticholinergics)
• Liquids absorbed in 1 hr
Case 1: ASA
• A 24-year-old male presented to the ED with
nausea, vomiting, tinnitus, and tachypnea after
ingesting 100 aspirin tablets. His 4-hour salicylate
level was 78 mg/dL; Chem-8 revealed Na 143, Cl
105, K 4.2, HCO3 17; pH 7.38, pO2 107, and pCO2 27
on room air. He was initially treated with
reasonable volume and admitted to the ward.
Case 1: ASA
• Orders for sodium bicarbonate were given to
alkalinize the urine, but this was ineffective in
raising urine pH. Approximately 6 hours later the
attending was notified that the patient had
become confused.
• He was transferred to the ICU where he was
sedated and intubated.
Case 1: ASA

• Approximately 20
minutes after
intubation, the
patient rapidly
deteriorated and
died.
Salicylate Overdose:
Pathophysiology
• ASA is hydrolyzed to salicylic acid
• Responsible for therapeutic and toxic effects
• Direct stimulation of respiratory center
• Medulla
• Uncouples oxidative phosphorylation
• Increase in O2 consumption and CO2 production
• Increase respiration
• Respiratory alkalosis
Salicylate Overdose:
Pathophysiology
• Renal excretion of bicarb, Na and K
• Metabolic acidosis
• Inhibition of mitochondrial respiration
• Increase pyruvate and lactic acid
• Metabolic acidosis
• Disruption of Krebs cycle metabolism and
glycolysis
• Hyperglycemia, ketonemia
Salicylate Overdose:
Pathophysiology
• Dehydration
• Hyperpnea
• Diaphoresis
• Vomiting
• Fever (increased muscle metabolism)
• Vasoconstriction of auditory microvasculature
• Enhance insulin secretion => hypoglycemia
• Decrease peripheral glucose utilization =>
hyperglycemia
Salicylate Overdose:
Pathophysiology
• Increase permeability of pulmonary vasculature
• Increase the production of leukotrienes
• Stimulate medullary chemoreceptor trigger zone
• Hematologic effects
Salicylate Overdose: Clinical
Presentation
• ASPIRIN Mnemonic
• Altered mental status (lethargy – coma)
• Sweating/diaphoresis
• Pulmonary edema
• Increased vital signs (HTN, inc RR, inc T, tachycardia)
• Ringing in the ears
• Irritable
• Nausea and vomiting
Laboratory Reference Ranges in
Healthy Adults
The values listed below are generalizations. Each laboratory has specific reference ranges.

• Ammonia: 15-50 µmol/L • Phosphate: 0.8-1.5 mmol/L

• Ceruloplasmin: 15-60 mg/dL • Potassium: 3.5-5 mmol/L
• Chloride: 95-105 mmol/L • Pyruvate: 300-900 µg/dL
• Copper: 70-150 µg/dL • Sodium: 135-145 mmol/L
• Creatinine: 0.8-1.3 mg/dL • Total calcium: 2-2.6 mmol/L (8.5-
10.2 mg/dL)
• Blood urea nitrogen: 8-21 mg/dL
• Total iron-binding capacity: 45-
• Ferritin: 12-300 ng/mL (men), 12- 85 µmol/L
150 ng/mL (women)
• Glucose: 65-110 mg/dL • Total serum iron: 65-180 µg/dL
(men), 30-170 µg/dL (women)
• Inorganic phosphorous: 1-1.5 • Transferrin: 200-350 mg/dL
mmol/L
• Urea: 1.2-3 mmol/L
• Ionized calcium: 1.03-1.23
mmol/L • Uric acid: 0.18-0.48 mmol/L
• Magnesium: 1.5-2 mEq/L • Zinc: 70-100 µmol/L

Source: medscape
• Hemoglobin: 13-17 g/dL (men), 12-15 • Neutrophils: 2-8 x 10^9/L
g/dL (women)
• Lymphocytes: 1-4 x 10^9/L
• Hematocrit 40%-52% (men), 36%-47%
• Monocytes: 0.2-0.8 x 10^9/L
• Glycosylated hemoglobin 4%-6%
• Eosinophils: < 0.5 x 10^9/L
• Mean corpuscular volume (MCV):
80-100 fL • Platelets: 150-400 x 10^9/L
• Red blood cell distribution width • Prothrombin time: 11-14 sec
(RDW): 11.5%-14.5% • International normalized ratio
• Mean corpuscular hemoglobin (INR): 0.9-1.2
(MCH): 0.4-0.5 fmol/cell • Activated partial thromboplastin
• Mean corpuscular hemoglobin time (aPTT): 20-40 sec
concentration (MCHC): 30-35 g/dL • Fibrinogen: 1.8-4 g/L
• Reticulocytes 0.5%-1.5% • Bleeding time: 2-9 min
• White blood cells (WBC) 4-10 x
10^9/L
• Triglycerides: 50-150 • pH: 7.35-7.45
mg/dL • H+: 36-44 nmol/L
• Total cholesterol: 3-5.5 • Partial pressure of
mmol/L oxygen (pO2): 75-100
• High-density lipoprotein mm Hg
(HDL): 40-80 mg/dL • Oxygen saturation: 96%-
• Low-density lipoprotein 100%
(LDL): 85-125 mg/dL • Partial pressure of
carbon dioxide (pCO2):
35-45 mm Hg
• Bicarbonate (HCO3): 18-
22 mmol/L
Salicylate Overdose: Clinical
Presentation
• Early
• Nausea, vomiting, diaphoresis, tinnitus, deafness
• Level 25-30 mg/dL
• Hyperventilation
• Later
• Hypotension, oliguria, acidemia, cerebral edema,
delirium, seizure, coma
Clinical Presentation
Features Acute Chronic
Age Young adult Older adult/infants

Etiology Overdose RX misuse

Co-ingestions Frequent Rare

Mental status Normal Altered

Presentation Early Late

Mortality Low w/ Rx High

Serum levels 40 to >120 30 to >80

Salicylate Overdose: Laboratory
studies
• Salicylate level
• Peak 4-6 hr
• EC and SR preparations late rise
• Every 2-4 hours until clearly decreasing
• Then q 4-6 until <30 mg/dL
• Always confirm units!
• Mg/dL vs. mg/L
Laboratory studies

• Severity of ingestion
• Serum levels
• Acid-base status
• Acuteness of ingestion
• Mental status
Treatment
• Gastric lavage / WBI
• Activated charcoal - MDAC
• Hydration and electrolyte replacement
• Correct hypokalemia aggressively
• Urine alkalinization
• Increase salicylate excretion
• 1-2 mEq/kg NaHCO3 bolus IV
• Then 150 mL in 850 ml D5W run 1.5-2 times maintenance
• Caution in elderly and chronic
• Monitor UO
Treatment
• Dialysis
• Serum levels > 100 in acute
• Levels > 60 in chronic
• Pulmonary edema
• Renal failure
• CHF
• Poor response to standard Rx
ASA Pearls
• Enteric Coated aspirin
• Can cause delayed symptom onset
• Don't wait for clinical deterioration.
• Alert you nephrology team early and call the poison
center even earlier.
• Serial salicylate levels are imperative.
ASA Pearls
• One teaspoon of methyl salicylate contains 7,000 mg
of salicylate which is equivalent to approximately 21
regular strength aspirin tablets!
• The presence of fever is a poor prognostic sign in
adults!
• Cerebrospinal fluid salicylate levels correlate with
symptoms better than blood levels
ASA Pearls
• Start potassium supplementation early (in the
absence of renal insufficiency) because
hypokalemia makes urinary alkalization
impossible!
• Multiple-dose activated charcoal and
alkalinization are currently the most popular
methods of treatment.
ASA Pearls
• Be aggressive. Dialyze early if signs of toxicity
are evident.
ASA Pearls
• ASA and elderly
• Impaired renal function
• Decreased elimination
• Impaired hepatic function
• The risk of salicylate nephrotoxicity is increased with
age,
• Upper gastrointestinal bleed is associated with
increased mortality in older age groups.
Case 2
• Case #2: A 40-year-old man developed fever and diaphoresis and
ingested an unknown amount of aspirin and acetaminophen as therapy.
The following morning he was transported to an ED complaining of
hearing loss, dizziness, and nausea. He had diaphoresis and tachypnea.
His arterial blood gas showed pH, 7.39; pCO², 16mmHg; PO², 120 mm
Hg; and bicarbonate, 10mEq/L. Serum electrolytes revealed an anion gap
of 22mEq/L; bicarbonate, 17 mEq/L; and creatinine, 1.3 mg/dl. Shortly
after admission he became unresponsive and required intubation. CT
scan of the head was negative. He had a single seizure that was
effectively treated with diazepam and phenytoin. The diagnosis was
unclear until his serum salicylate level returned at 98.8 mg/dL. The
poison center was contacted 5 hours after admission. Preparation for
hemodialysis was begun but the patient expired 7 hours after admission
before hemodialysis was initiated.
•
PEARL:
Don't wait for clinical deterioration. Alert you nephrology
team early and call the poison center even earlier.