Efficacy and mechanism of action of sodium bicarbonate in the treatment of desipramine toxicity in rats

Alkalinization of the blood by administration of sodium bicarbonate or hyperventilation is widely recommended for treatment of cardiac toxicity due to tricyclic antidepressant overdose, yet its efficacy and mechanism of action are poorly defined. We studied the effects and possible mechanism of action of 1 M NaHCO₃ of desipramine (DMI) toxicity in anesthetized, paralyzed rats. Administration of DMI (45 mg/kg i.p.) produced a mean increase in QRS duration of 142% and a mean decrease in mean arterial pressure of 46%. Treatments were administered i.v. 35 min after DMI and their effects were assessed 10 min later. NaHCO₃ (1 M) at doses of 3 and 6 mEq/kg decreased mean QRS duration 15 ± 5 and 24 ± 6%, respectively (mean ± S.D.) and was superior to no treatment (P < .01). NaCl (1 M) was as effective as NaHCO₃ in decreasing QRS duration, as was 1 M NaHCO₃ supplemented with 48 mM KCl. Respiratory alkalosis and 10% mannitol did not decrease QRS duration. NaHCO₃ NaCl and NaHCO₃/KCl all produced comparable increases in mean arterial blood pressure. Respiratory alkalosis and mannitol did not increase mean arterial pressure, but did prevent the decline seen in control animals. Acidosis produced by ventilation with 10% CO₂ exacerbated QRS prolongation due to DMI. In acidotic animals, NaHCO₃ and NaCl were equally effective in reversing QRS prolongation and hypotension. Correction of respiratory acidosis by discontinuation of inhaled CO₂ did not improve QRS duration or mean arterial pressure. The beneficial effects of treatments on QRS prolongation correlated with increases in plasma sodium concentration but not with changes in plasma potassium or DMI concentrations, arterial pH or the degree of intravascular volume expansion. We conclude that (1) 1 M NaHCO₃ can partially reverse the cardiovascular toxicity of DMI in both normal pH and acidotic animals, (2) the beneficial effects of NaHCO₃ on QRS prolongation may be due to increasing the plasma sodium concentration, (3) acidosis exacerbates DMI toxicity but correction of acidosis or increasing blood pH above normal were not effective therapies and (4) the beneficial effect of NaHCO₃ on blood pressure may be due to factors in addition to increasing plasma sodium concentration, such as intravascular volume expansion.