Experimental tricyclic antidepressant toxicity: a randomized, controlled comparison of hypertonic saline solution, sodium bicarbonate, and hyperventilation.
OBJECTIVE
We sought to compare the effects of hypertonic sodium chloride solution (HTS), sodium bicarbonate solution, and hyperventilation (HV) on severe tricyclic antidepressant (TCA) toxicity in a swine model.


METHODS
Twenty-four mixed-breed, domestic swine of either sex were given an intravenous infusion of nortriptyline (NT) until development of both a QRS duration longer than 120 ms and a systolic blood pressure (SBP) less than or equal to 50 mm Hg. Animals were randomly assigned to 1 of 4 groups. On reaching toxicity, the control group received 10 mL/kg of 5% dextrose in water (D5W); the HTS group received 10 mL/kg of 7.5% NaCl solution (15 mEq Na+/kg); the NaHCO3 group received 3 mEq/kg of 8.4% sodium bicarbonate solution followed by enough D5W solution to equal 10 mL/kg of total volume; and the HV group was mechanically hyperventilated to maintain arterial pH between 7.50 and 7.60 and given 10 mL/kg of D5W.


RESULTS
The mean SBP 10 minutes after treatment was 54+/-18 mm Hg in the control group, 134+/-21 mm Hg in the HTS group, 85+/-19 mm Hg in the NaHCO3 group, and 60+/-12 mm Hg in the HV group (P<.05). Mean QRS duration 10 minutes after treatment was 144+/-38 ms in the control group, 80+/-14 ms in the HTS group, 105+/-38 ms in the NaHCO3 group, and 125+/-46 ms in the HV group (P<.05).


CONCLUSIONS
In this model of TCA, toxicity HTS was more effective than sodium bicarbonate. Hyperventilation had little effect. Sodium loading may be the most important factor in reversing TCA toxicity.
McCabe
J L
JL
Department of Emergency Medicine, University of Pittsburgh School of Medicine, PA, USA.
Cobaugh
D J
DJ
Menegazzi
J J
JJ
Fata
J
J
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D002021:Buffers; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005440:Fluid Therapy; D005947:Glucose / Q000008:administration & dosage / Q000627:therapeutic use; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008297:Male; D009661:Nortriptyline / Q000009:adverse effects*; D011897:Random Allocation; D012121:Respiration, Artificial / Q000379:methods; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000627:therapeutic use*; D012964:Sodium / Q000097:blood / Q000627:therapeutic use; D017693:Sodium Bicarbonate / Q000008:administration & dosage / Q000627:therapeutic use*; D013552:Swine; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000188:drug therapy
D000929:Antidepressive Agents, Tricyclic; D002021:Buffers; D012462:Saline Solution, Hypertonic; D017693:Sodium Bicarbonate; D012964:Sodium; D009661:Nortriptyline; D005947:Glucose