title: Management of the cardiovascular complications of tricyclic antidepressant poisoning : role of sodium bicarbonate.
abstract: Experimental studies suggest that both alkalinisation and sodium loading are effective in reducing cardiotoxicity independently. Species and experimental differences may explain why sodium bicarbonate appears to work by sodium loading in some studies and by a pH change in others. In the only case series, the administration of intravenous sodium bicarbonate to achieve a systemic pH of 7.5-7.55 reduced QRS prolongation, reversed hypotension (although colloid was also given) and improved mental status in patients with moderate to severe tricyclic antidepressant poisoning. This clinical study supports the use of sodium bicarbonate in the management of the cardiovascular complications of tricyclic antidepressant poisoning. However, the clinical indications and dosing recommendations remain to be clarified. Hypotension should be managed initially by administration of colloid or crystalloid solutions, guided by central venous pressure monitoring. Based on experimental and clinical studies, sodium bicarbonate should then be administered. If hypotension persists despite adequate filling pressure and sodium bicarbonate administration, inotropic support should be initiated. In a non-randomised controlled trial in rats, epinephrine resulted in a higher survival rate and was superior to norepinephrine both when the drugs were used alone or when epinephrine was used in combination with sodium bicarbonate. Sodium bicarbonate alone resulted in a modest increase in survival rate but this increased markedly when sodium bicarbonate was used with epinephrine or norepinephrine. Clinical studies suggest benefit from norepinephrine and dopamine; in an uncontrolled study the former appeared more effective. Glucagon has also been of benefit. Experimental studies suggest extracorporeal circulation membrane oxygenation is also of potential value. The immediate treatment of arrhythmias involves correcting hypoxia, electrolyte abnormalities, hypotension and acidosis. Administration of sodium bicarbonate may resolve arrhythmias even in the absence of acidosis and, only if this therapy fails, should conventional antiarrhythmic drugs be used. The class 1b agent phenytoin may reverse conduction defects and may be used for resistant ventricular tachycardia. There is also limited evidence for benefit from magnesium infusion. However, class 1a and 1c antiarrhythmic drugs should be avoided since they worsen sodium channel blockade, further slow conduction velocity and depress contractility. Class II agents (beta-blockers) may also precipitate hypotension and cardiac arrest.
authors.affiliation: National Poisons Information Service (Birmingham Centre), City Hospital, Birmingham, UK.
authors.forename: Sally M
authors.initials: SM
authors.lastname: Bradberry
authors.forename: H K Ruben
authors.initials: HK
authors.lastname: Thanacoody
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Watt
authors.forename: Simon H L
authors.initials: SH
authors.lastname: Thomas
authors.forename: J Allister
authors.initials: JA
authors.lastname: Vale
mesh_terms: D000472:Alkalosis, Respiratory / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000506:poisoning*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D011041:Poisoning / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017693:Sodium Bicarbonate / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000889:Anti-Arrhythmia Agents; D000929:Antidepressive Agents, Tricyclic; D017693:Sodium Bicarbonate