Salicylates

April 26, 2019

• Hidden in many drugs and products: mouthwash, oil of wintergreen, headache/cold medicine, antacids, wart remover
• Analgesic, anti-inflammatory and antipyretic through inhibition of COX
• PGe2 → ↑ cAMP → triggers hypothalamus to elevate temp set point → ↑heat generation and ↓heat loss (antipyretic)
• May directly inhibit neutrophils (anti-inflammatory)
• uncoupling of oxidative phosphorylation (neuroglycopenia)

Toxic Dose:

150–300 mg/kg mild to moderate toxic reactions, 300–500 mg/kg serious reactions
>500 mg/kg potentially lethal
Ingestion of greater than a lick or taste of oil of wintergreen (98% methyl salicylate) by children <6 y and more than 4 mL by patients > 6 y could cause systemic toxicity

Clinical Picture:

Buzzwords:
mild to moderate: tinnitus, hearing loss, tachypnea, hyperpyrexia, diaphoresis
Severe: AMS, Sz, ALI, AKI, arrhythmias, Shock

Acute: younger, SI, markedly elevated serum levels, easily recognized hence more readily treated, hence less mortality
Chronic: older, iatrogenic vs therapeutic misadventures, moderate serum level elevation, easily missed, hence higher mortality.
Acid-base
HAGMA, Resp Alk (hypervent), Metabolic alk (if ↑ vomiting), Resp acidosis (ALI)

Serum Concentrations:

Therapeutic: 10-30mg/dL, Toxicity: >40-50mg/dL
Rapidly absorbed forms- measurable levels in 30 minutes
Peak occurs ~6hr after absorption (up to 60hr if EC or ER)
consider obtaining >1 value in any suspected salicylate exposure
Definitely obtain more than one if 1st level is >15 mg/dl
Repeat q3-4h until trending down or undetectable

Management:

Airway:
do not intubate! (try your best not to since any more compromise in respiratory functions may prove deadly, consider HCO3 peri-intubation)

Breathing:
may need high vent requirements (ALI)

Cardiovascular:
Resuscitate using NS then use dextrose containing fluids (neuroglycopenia)

Decontamination:
AC (charcoal can be used in acute overdose)
WBI (with EC or ER preparations)

Specific treatment:
HCO3 : 1-2 mEq/kg bolus followed by 150 mEq (3 amps) in 1L D5W until serum pH around 7.5, urine pH 8.0
(Alkalinization: increase pH of both serum and urine to shift towards charged state to prevent neurotoxicity and enhance elimination through the urine.)
DON’T FORGET TO REPLETE K+ (for HCO3 to work)

Enhanced elimination:
MDAC
HD indications:
Organ system failure (Renal, CHF, ALI, Hepatic+ coagulopathy)
Severe/persistent (lvl >100mg/dL, Persistent CNS changes, progressive decline in VS, severe acid-base changes despite treatment)

Clinical Bottom Line:

Hidden in many drugs and products, may be clinically challenging to detect in chronic overdose, therefore have a low index of suspicion.
Obtain more than one serum level
Be wary of intubation, hypoglycemia, hypokalemia during alkalinization, and the indications of HD.