Placement of catheter for prolonged anesthetic infusion.High-volume blocks, with doses approaching the maximal safe dose range (see table below).Mitochondrial diseases, carnitine deficiency.Pregnancy (hyperdynamic circulation may accelerate systemic absorption following nerve blocks reduced concentration of alpha-1 acid glycoprotein leads to higher free drug levels).Low muscle mass (e.g., older age, cachexia).Renal dysfunction: Uremia and acidosis may increase free drug levels, exacerbating toxicity. Cardiac dysfunction: Reduced cardiac reserve function may render LAST more dangerous (e.g., patients with severe chronic systolic heart failure or underlying conduction disease).Clearance rate is most relevant if the agent is slowly absorbed, administered in multiple doses, or provided as a continuous infusion. Hepatic dysfunction: Most anesthetics are hepatically cleared.
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