Prolonged coma due to amitriptyline overdose and genetic polymorphism: a case report.

BACKGROUND: Reduced consciousness has a wide variety of possible causes, not infrequently being toxic in nature. An intoxication might be obvious, but in this paper an unexpected case with a tricyclic antidepressant is presented. CASE PRESENTATION: A 76-year-old caucasian female was found unconscious. Primary diagnostic evaluation, including a negative drugs of abuse test, did not give direction to any clear cause. Yet an intraventricular conductive disorder with widening of the QRS complex and electroencephalogram abnormalities did suggest a possible drug effect. Heteroanamnestic information led to the suspicion of an amitriptyline intoxication, which was confirmed by further laboratory analysis. The patient remained comatose for several days. High concentrations of amitriptyline indicated a large overdose of amitriptyline and, in combination with a cytochrome P450 2D6 poor metabolizer status, could explain the long persistence of her comatose state. CONCLUSION: We present a tricyclic antidepressant intoxication, where the patient is thought to have taken a large amount of amitriptyline at once, which, in combination with a cytochrome P450 2D6 poor metabolizer status, led to an unusual long persistence of her coma.

Use of CytoSorb in cases of acute amitriptyline intoxication.

WHAT IS KNOWN AND OBJECTIVE: Intoxications with the tricyclic antidepressant amitriptyline frequently occur in the clinical setting and require immediate treatment. Although various poisonings can be counteracted with specific remedies, treatment options for amitriptyline intoxication remain sparse. Besides conventional approaches, a new haemoadsorption device might represent an opportunity for therapeutic detoxification. CASE SUMMARY: We report on two patients who were admitted as an emergency case with suspected amitriptyline overdose. Due to potentially life-threatening intoxication, the decision was made to initiate continuous renal replacement therapy (CRRT) together with CytoSorb haemoadsorption. As a result, drug-level measurements showed fast and efficient reduction of amitriptyline levels in the blood (case 1 from 186 µg/l to 54.7 µg/l, case 2 from 844 µg/l to 290 µg/l) and helped to stabilize a critical situation. WHAT IS NEW AND CONCLUSION: We were able to quickly and efficiently reduce amitriptyline to non-toxic serum levels and to stabilize a critical situation using the CytoSorb adsorber. Therefore, in the absence of other proven beneficial treatment regimen, the use of CytoSorb haemoadsorption could represent a potential treatment modality for severe amitriptyline intoxication.

Successful Outcome Following Intravenous Lipid Emulsion Rescue Therapy in a Patient with Cardiac Arrest Due to Amitriptyline Overdose.

BACKGROUND The management of patients with tricyclic antidepressant drug overdose can be a challenge for the emergency department physician. Tricyclic antidepressants block alpha-adrenergic receptors and the anticholinergic effects may lead to cardiotoxicity, resulting in arrhythmias and hypotension that can lead to patient mortality. This report is of a case of a 28-year-old woman who presented with cardiac arrest due to amitriptyline overdose and who responded to intravenous lipid emulsion (ILE) therapy. CASE REPORT A 28-year-old woman was admitted to the emergency department with amitriptyline overdose. She suffered a cardiac arrest followed by cardiovascular and neurological complications. Hypotension and lack of a pulse did not respond to treatment with high-dose sodium, but she stabilized following treatment with ILE. The prompt response from the emergency team guaranteed rapid intervention that may have influenced the successful results. CONCLUSIONS Despite the frequency and severity of poisoning with tricyclic antidepressants, there is little consensus among physicians regarding patient management. This case showed the successful use of ILE as rescue therapy in a patient in cardiac arrest following amitriptyline overdose. However, the successful outcome obtained in this case is not a recommendation for the use of ILE as a first-line treatment for the management of patients with tricyclic antidepressant drug overdose. Controlled clinical studies are required to evaluate the safety and efficacy of ILE in the management of tricyclic antidepressant drug overdose.

Childhood Drug and Non-Drug Poisoning in Nigeria: An Economic Appraisal.

BACKGROUND: The dearth of information on the economic cost of childhood poisoning in sub-Saharan Africa necessitated this study. OBJECTIVE: This study has investigated the prevalence of childhood drug and non-drug poisoning, treatment modalities and economic costs in Nigeria. METHOD: A retrospective study of childhood drug and non-drug poisoning cases from January 2007 to June 2014 in the University of Port Harcourt Teaching Hospital (UPTH), Port Harcourt, Nigeria was carried out. Medical records were analysed for demographic and aetiological characteristics of poisoned children (0-14 years of age), as well as fiscal impact of poisoning cases. FINDINGS: Of the 100 poisoned patients, 46% were male and 54% female, with female/male ratio of 1.17:1. Most of the children were under five years of age. Paracetamol, amitriptyline, chlorpromazine, ferrous sulphate, kerosene, organophosphates, carbon monoxide, snake bite, alcohol and rodenticides were involved in the poisoning. The average cost of poison management per patient was about $168, which is high given the economic status of Nigeria. CONCLUSION: Childhood poisoning is still a significant cause of morbidity among children in Nigeria and accounts for an appreciable amount of health spending, therefore preventive strategies should be considered.

Amitriptyline accumulation in tissues after coated activated charcoal hemoperfusion-a randomized controlled animal poisoning model.

Amitriptyline poisoning (AT) is a common poisoning, and AT possess the ability to promote life-threatening complications by its main action on the central nervous and cardiovascular systems. The pharmacokinetic properties might be altered at toxic levels compared to therapeutic levels. The effect of coated activated charcoal hemoperfusion (CAC-HP) on the accumulation of AT and its active metabolite nortriptyline (NT) in various tissues was studied in a non-blinded randomized controlled animal trial including 14 female Danish Land Race piglets. All piglets were poisoned with amitriptyline 7.5 mg/kg infused in 20 min, followed by orally instilled activated charcoal at 30 min after infusion cessation. The intervention group received 4 h of CAC-HP followed by a 1-h redistribution phase. At study cessation, the piglets were euthanized, and within 20 min, vitreous fluid, liver tissue, ventricle and septum of the heart, diaphragm and lipoic and brain tissues were collected. AT and NT tissue concentrations were quantified by UHPLC-MS/MS. A 4-h treatment with CAC-HP did not affect the tissue accumulation of AT in the selected organs when tested by Mann-Whitney U test (p values between 0.44 and 0.73). For NT concentrations, p values were between 0.13 and 1.00. Although not significant, an interesting finding was that data showed a tendency of increased tissue accumulation of AT and NT in the CAC-HP group compared with the control group. Coated activated charcoal hemoperfusion does not significantly alter the tissue concentration of AT and NT in the AT-poisoned piglet.

Dexamethasone changes the pharmacokinetics of amitriptyline and reduces its accumulation in rat brain: The roles of P-gp and cyp3a2.

The wide spread use of central nervous system (CNS) drugs has caused thousands of deaths in clinical practice while there are few antidotes or effective treatments to decrease their accumulation in CNS. In this study, we used amitriptyline (AMI) and dexamethasone (DEX) as the corresponding poisoning and pre-protecting drugs, respectively, to study whether DEX has the potential to reduce AMI accumulation in brain. By measuring the pharmacokinetic data of AMI and its main metabolite nortriptyline (NOR), we found that DEX possibly accelerated the metabolism and elimination of AMI with minimal effects on the concentrations of NOR in blood. Nevertheless, the results indicated that DEX reduced the brain/plasma concentration ratio of AMI and NOR, even if the plasma concentration of NOR had an upward trend. Western blot results showed the overexpression of cyp3a2 and P-gp in rat liver and brain capillaries tissues. We propose that cyp3a2 and P-gp could be upregulated in the liver and blood-brain barrier (BBB) when using DEX. Further experiments suggest that DEX may serve as the ligand of PXR to induce P-gp expression.

Advanced Electrocardiogram Analysis in the Amitriptyline-poisoned Pig Treated with Activated Charcoal Haemoperfusion.

Coated activated charcoal haemoperfusion (CAC-HP) does not reduce the plasma concentration in amitriptyline (AT)-poisoned pigs. The aim of this non-blinded, randomized, controlled animal trial was to determine if CAC-HP reduces the pathological ECG changes caused by AT poisoning. Fourteen female Danish Landrace pigs (mean weight 27.7 kg, range 20-35 kg (CAC-HP) and 24.4 kg, range 18-30 kg (control group, CG), n = 7 in each group) were included. After randomization, the pigs were anaesthetized and intravenously poisoned with AT. The intervention group underwent 4 hr of CAC-HP plus standard care (oral activated charcoal). Intervention was compared to standard care alone. From each pig, a 12-lead ECG and haemodynamic variables were obtained at baseline, at full AT loading dose, before and during CAC-HP. Baseline ECG variables (RR, PR, QRS, QTc, QTp, QTe, TpTe and TpTe/QT) for lead II, v2 and v5 were not significantly different (F = 0.035-0.297, p-values 0.421-0.919). Differences within groups over time and between groups were tested by anova repeated measures. For all variables, the time-plus-group level of significance revealed a p-value > 0.05. Severe cardiovascular arrhythmias occurred in both groups with 3 in the CAC-HP group versus 1 incident with premature death in the CG. The attenuating effect of CAC-HP to orally instilled activated charcoal alone on AT-induced ECG alterations did not differ significantly. We conclude that the use of modern CAC-HP as an adjunctive treatment modality in AT-poisoned pigs is inadequate.

[Successful lipid rescue therapy in a case of severe amitriptyline/quetiapine intoxication]. / Erfolgreiche "Lipidrescuetherapie" bei Amitriptylin-Quetiapin-Mischintoxikation in mehrfach letaler Dosis.

A 25-year-old patient was admitted urgently due to mixed amitriptyline/quetiapine intoxication at a potentially lethal dose. Alongside severe anticholinergic toxidrome, she presented with antiadrenergic and quinidin-like cardiotoxic findings, including ventricular tachycardia. In the present case, arrhythmia and circulatory shock responded neither to alkalization and elevated sodium levels after infusion of sodium bicarbonate, nor to any other established therapies. Following the lipid rescue paradigm, bolus infusion of a 20% lipid emulsion led to rapid stabilization and continued reversal of all intoxication features.

Unusual complications from amitriptyline intoxication.

Althoughtricyclic antidepressants(TCAs) are frequently prescribed to patients with depression, these drugs can also be misused. A 21-year-old comatose patient was referred to our hospital presenting with ventricular tachycardia. Despite initial treatment including intravascular lipid emulsion, ventricular fibrillation occurred soon after arrival. Venoarterial extracorporeal membrane oxygenation and therapeutic hypothermia were administered. Refractory arrhythmia disappeared on the next day. A high concentration of amitriptyline was identified in his blood samples on arrival. Mechanical bowel obstruction followed after abdominal compartment syndrome caused by anticholinergic effects, and refractory seizure occurred due to TCA intoxication. Although seizure was brought under control with anticonvulsant agents, his Glasgow Coma Scale did not recover to the full score. MRI presented irreversible damage to the bilateral frontal lobe and insula. Amitriptyline has the potential to cause unusual serious complications, such as abdominal compartment syndrome, irreversible central nervous system disability and lethal arrhythmia.

Amitriptyline-induced ventricular tachycardia: a case report.

BACKGROUND: In Bangladesh, each emergency physician faces amitriptyline overdose nearly a day. An acute cardiovascular complication, one of the worst complications is mainly responsible for the mortality in tricyclic overdose. Recently, we managed ventricular tachycardia in a young female presented with an impaired consciousness 10 h after intentionally ingesting 2500 mg amitriptyline. Here, we report it, discuss how the electrocardiography is vital to acknowledge and predict it and its' complications and also the recent update of the management of it. CASE PRESENTATION: A young married Bangladeshi-Bengali girl, 25-year-old, having a history of disharmony with her husband, came with an impaired consciousness after intentionally ingesting 2500 mg amitriptyline about 10 h before arrival. There was blood pressure 140/80 mmHg, heart rate 140 beats-per-min, temperature 103 °F, Glasgow coma scale 10/15, wide complex tachycardia with QRS duration of 178 ms in electrocardiography, blood pH 7.36. Initially, treated with 100 ml 8.4% sodium bicarbonate. After that, QRS duration came to 100 ms in electrocardiography within 10 min of infusion. To maintain the pH 7.50-7.55 over the next 24 h, the infusion of 8.4% sodium bicarbonate consisting of 125 ml dissolved in 375 ml normal saline was started and titrated according to the arterial blood gas analysis. Hence, a total dose of 600 mmol sodium bicarbonate was given over next 24 h. In addition to this, gave a 500 ml intravenous lipid emulsion over 2 h after 24 h of admission as she did not regain her consciousness completely. Afterward, she became conscious, though, in electrocardiography, ST/T wave abnormality persisted. So that, we tapered sodium bicarbonate infusion slowly and stopped it later. At the time of discharge, she was by heart rate 124/min, QRS duration 90 ms in electrocardiogram along with other normal vital signs. CONCLUSION: Diagnosis of amitriptyline-induced ventricular tachycardia is difficult when there is no history of an overdose obtained. Nevertheless, it should be performed in the clinical background and classic electrocardiographic changes and wise utilization of sodium bicarbonate, intravenous lipid emulsion, and anti-arrhythmic drugs may save a life.

Dramatic resuscitation with Intralipid in an epinephrine unresponsive cardiac arrest following overdose of amitriptyline and propranolol.

Amitriptyline and propranolol are life threatening in overdose. The efficacy of intravenous lipid emulsion (ILE) in tricyclic antidepressant and propranolol overdose is unclear. We report a dramatic response to ILE following pulseless electrical activity arrest due to mixed amitriptyline and propranolol overdose.

Activated Charcoal Haemoperfusion in the Treatment of Experimental Amitriptyline Poisoning in Pigs - The Effect on Amitriptyline Plasma Concentration and Haemodynamic Parameters.

Coated activated charcoal haemoperfusion (CAC-HP) is a well-known treatment modality. Case reports have revealed conflicting results about the efficacy of CAC-HP in the treatment of amitriptyline (AT) poisoning, and no randomized clinical trials have been identified in the literature. This study aimed at quantifying the efficacy of modern CAC-HP as an adjunctive treatment of AT intoxication compared with standard care alone. Fourteen female Danish landrace pigs were randomized to either standard care or standard care plus 4 hr of CAC-HP. The pigs were anaesthetized, and vital parameters were continuously recorded. Amitriptyline infusion (7.5 mg/kg) was completed in 20 min. Thirty minutes after AT infusion, activated charcoal was instilled orally in both groups. In the intervention group, CAC-HP was initiated 60 min. after AT infusion. Blood and urine samples were collected as were vital parameters at specific time intervals. The protocol was approved by the Danish Experimental Animal Expectorate and complied with the NIH guide for care and use of laboratory animals. Data were managed according to the ARRIVE guidelines. No statistical significant differences between intervention and control groups were found when analysing for differences in AT levels in plasma at any time-point. Furthermore, significant differences between the control and intervention groups in regard to vital parameters could not be found either. In our animal model, the addition of CAC-HP did not improve the clearance of AT compared with standard treatment alone. We suggest that the effect of modern CAC-HP as a treatment modality in AT-poisoned human patients may be inadequate.

Serum alkalinisation is the cornerstone of treatment for amitriptyline poisoning.

A 28-year-old woman was admitted in a comatose state following ingestion of 5 g of amitriptyline. On arrival, there was intermittent seizure activity and a broad complex tachycardia on the ECG. Immediate resuscitation included 8 mg lorazepam, 2 L crystalloid fluid, 100 mL 8.4% sodium bicarbonate, 2 g of magnesium sulphate and lipid emulsion infusion. Despite this, the broad complex tachycardia persisted with haemodynamic instability. The case was discussed with the National Poisons Information Service, which advised further 8.4% sodium bicarbonate to achieve serum alkalinisation. Following this, the QRS duration reduced and haemodynamic stability was achieved. Serum alkalinisation continued in the intensive treatment unit before the patient was successfully extubated on day 5 and discharged on day 7 with no neurological sequelae. To our knowledge, this case is the largest recorded overdose of amitriptyline to have survived to discharge. The importance of serum alkalinisation in the management of tricyclic antidepressant poisoning is highlighted.

Survival after severe amitriptyline poisoning with prolonged ventricular tachycardia and cardiac arrest.

BACKGROUND: Tricyclic antidepressants (TCA) are becoming one of the most frequently used substances in self poisoning. Significant morbidity and mortality associated with TCA overdose are often related to and refractory hypotension. We report the first case of survival after severe amitriptyline poisoning, leading to prolonged cardiac arrest and ventricular tachycardia (VT), resuscitated with 3 h of uninterrupted cardiac massage and Direct current (DC) shocks. CASE PRESENTATION: A 25 year old girl presented with severe amitriptyline poisoning causing pulseless VT and prolonged cardiac arrest. After 3 h of uninterrupted external cardiac massage, together with nine DC shocks and intra venous bicarbonate injections the rhythm reverted to a nodal tachycardia, initial 2D echocardiogram showed left ventricular dysfunction, which recovered to normal after 2 weeks and the patient had a complete recovery subsequently. CONCLUSION: Our case highlights the importance of continued resuscitation in patients presenting with TCA poisoning and resistant arrhythmia, especially in young and otherwise healthy patients.