Alkalinization is an important therapeutic strategy in the management of tricyclic antidepressant toxicity and salicylate toxicity. Systemic alkalinization can be achieved by administering intravenous sodium bicarbonate and by hyperventilation.

Intravenous sodium bicarbonate increases the serum pH and alters the ionization status of the xenobiotic. This can result in multiple effects.

Reduced receptor binding
Many toxic effects, such as TCA-induced cardiotoxicity (QRS widening, arrhythmias), result from receptor binding by the ionized form of the drug. Alkalinization shifts weak bases like amitriptyline (pKa 8.5) toward their unionized form, reducing their ability to bind to the fast Na⁺ channels, improving cardiac conduction.

Alteration of lipid solubility and compartment redistribution
Alkalinization increases the ionized fraction of weak acids like salicylate (pKa 3.0), decreasing lipid solubility and trapping the drug within the vascular space, preventing CNS distribution.

Reduced free plasma concentration via protein binding
A more alkaline environment may increase drug-protein binding, reducing its free (active) fraction. For example, amitriptyline protein binding increases in an alkaline environment, reducing its free (unbound) fraction by up to 20-42% ^[1].

This is generally only feasible in patients who are mechanically ventilated but can be used to assist systemic alkalinization ^[2]. When combined with sodium bicarbonate administration, there is a risk of inducing profound alkalemia. Thus, serum pH should be closely monitored to avoid complications associated with excessive alkalinization.

Video: Why all the bicarb? Pitfalls of overtreatment - A/Prof Katherine Isoardi - TAPNA ASM 2023

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