TOXICOLOGY
COMPLICATIONS
■ Liver failure →
■ Metabolic acidosis
■ Hepatorenal syndrome
■ Coagulopathy
■ Infection
■ Cerebral edema
■ Hypoglycemia
■ Indications for liver transplantation include pH < 7.3 after resuscita-
tion, INR > 7, Creatinine > 3.4, grade 3 or 4 encephalopathy.A 33-year-old female presents to the ED with complaint of N/V and back
pain. The back pain has been ongoing since she lifted some heavy boxes
2 days earlier and was severe enough that she took a “handful” of aspirin
4 hours earlier to treat the symptoms. On examination she is tachypnic, but oth-
erwise alert and hemodynamically stable. ABG reveals a pH of 7.51, PCO 2 of 13.9,
PO 2 of 110 mmHg. Serum HCO 3 – = 12 mEq/L. What is the goal of initial therapy
in this patient?
Therapy with sodium bicarbonate boluses, and then drip should be initiated
with a goal of urinary alkalinization to a pH of 7.5—8.0. Alkalinization keeps sali-
cylate in the nonionized form, which increases renal clearance and decreases
CNS uptake of salicylate.SalicylatesSalicylates are found in a variety of over-the-counter preparations such as
analgesics (eg, Bayer aspirin), cold medicines, antidiarrheal agents (bismuth
subsalicylate in Pepto Bismol), and topical dermatological products for warts
(methyl salicylate), and as combination products in decongestants, antihista-
mines, and narcotic medications.Salicylic acid is a weak acid that at normal serum pH is mostly ionized, therefore
will not cross the blood-brain barrier or the renal tubules (for reabsorption). As the
blood becomes more acidemic, a more nonionized form develops, allowing sali-
cylate to enter the brain and be reabsorbed by the kidneys (decreasing renal excre-
tion). Treatment is logically geared toward keeping salicylate in the ionized form.Chronic excessive use of salicylates (chronic ingestion) is seen primarily in
the elderly and is associated with a higher clinical toxicity for a given serum
salicylate level.MECHANISM/TOXICITY
■ Direct stimulation of respiratory center→hyperventilation and respira-
tory alkalosis.
■ Stimulation of chemoreceptor trigger zone→vomiting.
■ Uncoupling of oxidative phosphorylation→anaerobic metabolism, lac-
tate production anion-gap acidosis and hyperthermia.
■ Increased fatty acid metabolism→metabolic acidosis (ketones).
■ Platelets permanently lose their ability to aggregate at therapeutic aspirin
doses. Bleeding is rare in overdose.
■ Ototoxicity→tinnitus and hearing loss correlate with salicylate level.Chronic salicylate ingestion is
associated with higher toxicity
for a given salicylate level.