Clinical Course, Therapy, Outcome and Analytical Data in Amitriptyline and Combined Amitriptyline/Chlordiazepoxide Overdose

Abstract

<jats:p> A total of 103 cases of amitriptyline (AT) overdose (group 1) and 81 cases of overdose with a fixed combination of AT and chlordiazepoxide (CDE) (group 2), treated at our Intensive Care Unit or reported to our Poison Information Center between 1985-1990, were evaluated with respect to clinical course, symptoms and outcome, as well as efficacy of therapy. The mean amount of AT was considerably higher in group 1 compared to group 2 (13 mg kg<jats:sup>-1</jats:sup> vs 7.7 mg kg<jats:sup>-1</jats:sup> ). The most frequent symptoms in both groups were impaired consciousness, anticholinergic symptoms, seizures, arrhythmia and hypotension. Respiratory insufficiency necessitated respirator therapy in 63 of the patients. Two patients in group 1 and one patient in group 2 did not survive. </jats:p><jats:p> Therapy included primary detoxification by gastric lavage and repeated administration of activated charcoal. In four of eight patients with cardiac conduction disturbances, hypertonic sodium bicarbonate led to a significant reduction in QRS duration and AV interval. Physostigmine was effective in eight of 14 patients with pronounced anticholinergic symptoms. No effect was observed in the other six patients. Haemoperfusion, which was performed in five patients, led to rapid improvement of coma after initiation of therapy in four patients. The clinical efficacy of haemoperfusion in AT overdose despite the high volume of distribution of AT deserves further investigation. </jats:p><jats:p> The rather high average overdose of AT implies that large package sizes of AT were available to the patients. A major step towards prevention of serious AT overdose would be the prescription of package sizes containing a total amount of less than 500 mg AT. </jats:p><jats:p> Different analytical methods (enzyme immunoassay, fluorescence polarization immunoassay, and gas chromatography/mass spectrometry) for rapid detection of AT and its metabolites in plasma and urine were evaluated. Commercially available immunoassays like EMIT and ADX were highly reliable and sensitive in the detection of AT overdose. Five previously unknown metabolites or derivatives of AT could be detected in cases of AT overdose with the aid of a gas chromatography/mass spectrometry screening procedure. </jats:p>

Part 12: Cardiac Arrest in Special Situations

“…107 Although there is no human evidence in cocaine poisoning, extrapolation from evidence in the treatment of wide-complex tachycardia caused by other class Ic agents (flecainide) and tricyclic antidepressants suggests that administration of hypertonic sodium bicarbonate may be beneficial. 334 A typical treatment strategy used for these other sodium channel blockers involves administration of 1 mL/kg of sodium bicarbonate solution (8.4%, 1 mEq/mL) IV as a bolus, repeated as needed until hemodynamic stability is restored and QRS duration is Յ120 ms. [335][336][337][338][339][340][341][342] Current evidence neither supports nor refutes a role for lidocaine in the management of wide-complex tachycardia caused by cocaine.…”

“…Sodium bicarbonate boluses of 1 mL/kg may be administered as needed to achieve hemodynamic stability (adequate mean arterial blood pressure and perfusion) and QRS narrowing (Class IIb, LOE C). [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.…”

Part 8: Advanced Life Support

“…627 Diazepam improved seizure control and survival in 1 animal study (LOE 5). 627 The use of physostigmine for tricyclic-induced anticholinergic symptoms was not supported by the current literature given the conflicting associations suggested by several case series (LOE 4 613 ; LOE 5 608,629,630 ). Limited animal research demonstrates a benefit for IV lipid infusions in models of tricyclic toxicity (LOE 5).…”

Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management

“…There were a number of articles in which the recognition of the amitriptyline ingestion was retrospective, so there was uncertainty about the actual amount ingested. Among these were five level 2b articles (16,53,(59)(60)(61), a single level 3b article (62), and five level 4 articles (6,48,(63)(64)(65). Also, there were over 50 level 4 or 6 articles in which detailed information was presented concerning 65 cases (see Table 5).…”

“…In a level 2b review of 184 patients admitted to an ICU after amitriptyline overdose, four of eight patients treated with bicarbonate had improvements in cardiac conduction (60). A level 2b, retrospective cohort analysis compared the outcomes of 91 patients with TCA overdose who received bicarbonate with those of 24 patients who did not.…”