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 on 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 less than .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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000142:Acidosis, Respiratory / Q000188:drug therapy; D000818:Animals; D001639:Bicarbonates / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003891:Desipramine / Q000633:toxicity*; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects; D007022:Hypotension / Q000188:drug therapy; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D011188:Potassium / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000097:blood; D017693:Sodium Bicarbonate; D012965:Sodium Chloride / Q000627:therapeutic use; D013997:Time Factors
D001639:Bicarbonates; D008353:Mannitol; D012965:Sodium Chloride; D017693:Sodium Bicarbonate; D012964:Sodium; D011188:Potassium; D003891:Desipramine