Effects of Epinephrine and Norepinephrine on Hemodynamic Parameters and Arrhythmias During a Continuous Infusion of Amitriptyline in Rats

Abstract

Epinephrine and norepinephrine were evaluated in treatment of hemodynamic compromise in amitriptyline intoxication. One hundred and one male Wistar rats were monitored hemodynamically during amitriptyline intoxication and given one of three infusion rates (0.1, 0.5 or 5.0 mg/kg/min) of either epinephrine or norepinephrine. Sixteen rats served as controls and received only glucose after intoxication. Amitriptyline intoxication lowered mean arterial pressure, heart rate, left ventricular max dP/dt, and increased left ventricular end-diastolic pressure. All doses of norepinephrine and the two higher doses of epinephrine increased mean arterial blood pressure and left ventricular max dP/dt. Heart rate increased with both drugs, more with epinephrine, but not beyond pre-intoxicated levels at any dose. Left ventricular end-diastolic pressure was unaltered by both drugs. Malignant arrhythmias appeared in 7% of all animals, whereas a progressive decline of cardiac contractility caused cardiac arrest in 36% of all animals. This suggests that myocardial depression is the aspect most likely to cause death. At intermediate doses epinephrine resulted in significantly fewer arrhythmias and lower mortality compared to norepinephrine. We conclude that epinephrine and norepinephrine each appeared effective in reversing amitriptyline-induced hemodynamic alterations. Epinephrine had fewer arrhythmogenic properties than norepinephrine and may be preferable to norepinephrine.

Part 12: Cardiac Arrest in Special Situations

“…[335][336][337][338][339][340][341][342] Serum sodium levels and pH should be monitored, and severe hypernatremia (sodium Ͼ155 mEq/L) and alkalemia (pH Ͼ7.55) should be avoided. A number of vasopressors and inotropes have been associated with improvement in the treatment of tricyclic-induced hypotension, ie, epinephrine, 239,344,345 norepinephrine, [345][346][347][348] dopamine, 348 -350 and dobutamine. 349 …”

Guidelines in Emergency Medicine Network (GEMNet): guideline for the management of tricyclic antidepressant overdose

“…Norepinephrine + sodium bicarbonate treatment > survival rate than norepinephrine alone (p<0.01)

Animal study hence extrapolation to humans may be difficult.

Not blinded.

Raw data unavailable in some measurements

ArrhythmiasEpinephrine-treated rats had a longer time to onset of arrhythmias than norepinephrine-treated rats (21.5 vs 11.6 min) (p<0.05). Epinephrine + sodium bicarbonate-treated rats had the longest time in sinus rhythmQRS durationEpinephrine treatment associated with shorter QRS interval than norepinephrine treatment (p<0.05)Knudsen and Abrahamsson, 199390101 male Wistar rats poisoned with amitriptylinegiven 0.1, 0.5 or 5.0 mg/kg/min epinephrine or norepinephrine.Control group received glucose infusionNon-randomised, animal controlled intervention trialMean arterial pressure (MAP)All doses of norepinephrine and two higher doses of epinephrine increased MAP. Norepinephrine > epinephrine at low and intermediate doses

Animal study: difficult to apply data to humans.

Experiment not blinded.

Raw data absent from study.

No significant difference between treatment according to Fisher exact test

Mortality at 75 min (%)Control group=75%; norepinephrine=45%; epinephrine=27%.…”

Hypotones Kreislaufversagen und metabolische Azidose nach suizidaler Mischintoxikation mit Trimipramin und Quetiapin

“…Zusätzlich können komplexe Herzrhythmusstörungen durch Blockade muskarinartiger Acetylcholinrezeptoren und durch Blockade des Reuptakes von Noradrenalin im präsynaptischen Neuron resultieren [1,2,15,16,18,21,22].Lebensgefährliche Rhythmusstörungen kön-nen mit einer Verlängerung des QRSKomplexes im EKG assoziiert sein [2].Ein Quinidin-ähnlicher Effekt (myokardiale Depression) führt zu Bradyarrhythmien bis hin zur Asystolie, zu einer Reduktion der myokardialen Kontraktilität und zu einer unspezifischen Verminderung der myokardialen Konduktivität [18,21].Eine α-adrenerge Blockade an postsynaptischen sympathischen Neuronen verursacht eine Vasodilation mit konsekutiver Hypotension [12,21].…”

“…Dabei können Dopamin oder Dobutamin sowie Norepinephrin oder Epinephrin genutzt werden. Tierexperimentelle Untersuchungen gaben Hinweise darauf, dass die Wirkung von Dopamin bei Intoxikationen mit TCA reduziert sein kann [22] und deshalb Norepinephrin oder Epinephrin bevorzugt werden sollten [12].…”

“…Die Verwendung von Antiarrhythmika der Klasse Ia ist bei allen TCA-bedingten Herzrhythmusstörungen obsolet, da diese, ähnlich wie die TCA selbst, zu einer Verlängerung des Aktionspotenzials füh-ren und so die TCA-bedingte Kardiotoxizität [12] durch eine Verlängerung des Aktionspotenzials (Natriumkanalhemmung) noch weiter verstärken können [14,18,21]. Entsprechend sind sie bei Herzrhythmusstörungen im Zusammenhang mit einer Intoxikation durch TCA absolut kontraindiziert.…”