Case Study: Successful use of plasma exchange in a case of multiple drug overdose in Bangladesh

Abstract

Tricyclic antidepressant (TCA) and sedative overdose remains one of the most common forms of poisoning particularly in the setting of suicidal attempts. Standard of treatment in TCA poisoning is supportive with the administration of sodium bicarbonate infusion. However, in refractory cases there is increasing evidence of lipid emulsion and extracorporeal therapy such as therapeutic plasma exchange (TPE). Here we report a 26-year-old patient who ingested multiple drugs, predominantly tricyclic antidepressant and was successfully managed with additional lipid emulsion and plasma exchange when she was not responding to supportive care alone.

Background

Acute poisoning is one of the major medical emergencies globally with significant mortality and morbidity. Exposure of poison varies in different geographic regions. In Bangladesh poisoning is responsible for 200,000 deaths annually and more than one million illness episodes are reported from poisoning. Compared to the developed countries where death from poisoning is not even one percent, Bangladesh recorded a mortality rate of eight to 10 percent due to acute poisoning.¹ According to American Association of Poison Control Center, serious outcomes from exposure to anti-depressants (5.61%) were increasing rapidly over the past 10 years than sedatives (4.73%).² A retrospective study documented that Organo Phosphate Compound was the most common cause of poisoning in Bangladesh, and poisoning from sedative overdose was roughly 13%.³

TCA is used in the treatment of depression, enuresis, obsessive compulsive disorder, attention deficit hyperactivity, chronic pain, and migraine. Patients with suicidal ideation seek TCAs with or without sedatives as a way of attempting suicide.4 Symptoms usually appear within 4 hours of an overdose. The most common clinical features are dry mouth, blurred vision, dilated pupils, sinus tachycardia, pyramidal neurological signs, and drowsiness. In severe poisoning, there may be coma, convulsions, respiratory depression, hypotension, and a wide range of electrocardiographic (ECG) abnormalities. The most frequent findings on the ECG are prolongation of the PR and QT intervals,5 QRS>100 msec indicates severe poisoning.

Case Presentation

A 26-year-old lady got admitted to ICU of Square hospital with altered mental status around eight hours after deliberate ingestion of multiple drugs which included- 100 tablets of imipramine (TCA), 40 tablets of alprazolam, and 10 tablets of bromazepam. She had generalized anxiety disorder, but otherwise was healthy before this admission. On examination, her Glasgow coma scale (GCS) was E1V1 M2 = 4, pupil- pinpoint but reacting, and planter reflex was bilaterally extensor. Her blood pressure (BP) was 90/ 50 mmHg, pulse 100/min, respiratory rate 19/min, and SpO2 94% in Room air. Investigations revealed the following:

ECG showed long QRS 112 msec and prolong QT interval of 0.48 which were signs of cardiotoxicity. [Fig-1]

Arterial Blood Gas (ABS) showed metabolic acidosis with pH 7.32, PaCO2 46, PaO2 199, and HCO3 23 mmHg. Toxic screening showed urinary Benzodiazepine level > 800 ng/ml (high above normal range).

Evidently, she was a case of benzodiazepine and tricyclic anti-depressant overdose which is a dire emergency with high fatality rates. Her management started immediately as ABCDE approach. She needed and was started with intubation & ventilation to protect airway in unconscious state along with other supportive care. A bolus dose of 7.5% sodium bicarbonate (150 mEq) was administered as mainstay of treatment and a maintenance dose (50 mEq/h) was ordered. However, after few hours of sodi-bi-carb infusion, there was metabolic alkalosis (pH 7.53 in ABG) [Fig-2] and prolong QRS still persisted > 100 msec which could have led to ventricular arrythmia. There was clear indication to start on adjunctive therapy such as lipid emulsion therapy and plasma exchange as it had become a refractory case. Because TCA is lipophilic with large volume distribution (Vd) and highly protein bound which could be eliminated by intra venous lipid emulsion and plasmapheresis, 10% lipid emulsion IV 500 ml bolus over 1 hour was given, followed by another 500 ml over 2 hours. Two sessions of Therapeutic Plasma exchange (TPE) [Fig-3] with Fresh frozen plasma (5 Liter) over 2 hours were given on 2 consecutive days.

Techniques

TPE was carried out daily using intermittent type of cell separator (Haemonetics MCS+, Haemonetics Corporation, Massachusetts, USA) [Fig-3] via a double lumen hemodialysis femoral catheter. Hemodynamic parameters were monitored throughout the procedure. Estimated plasma volume (EPV) was calculated according to the Kaplan formula, EPV = {(0.065 x bwt in kg) x (1− Ht)} where bwt signifies body weight and Ht is Hematocrit. In each session, about 1.0 calculated plasma volumes were exchanged. Acid citrate dextrose (ACD-A Haemonetics) was used as anticoagulant and to prevent citrate toxicity a 10% calcium gluconate was given during the procedure according to serum calcium levels and the amount of ACD solution used.^6,7

Outcome: She became conscious after 2 sessions of TPE. Her Vitals became stable, and she was weaned off ventilator. Her follow up ECG became normal. (QRS < 100 ms). [Fig-4] She was kept under observation in cabin for few days with psychiatric consultation. Finally, she was discharged home after 10 days of hospitalization in stable condition.

Discussion

Our patient showed classic manifestations of severe TCA and sedative poisoning with signs of cardio and neuro toxicity. These features are induced by TCA ingestion in toxic dose which block cardiac fast sodium channels and antagonize the central and peripheral muscarinic acetylcholine receptors, peripheral alpha-adrenergic receptors, histamine H1 receptors, and central nervous system GABA A receptors. Her resuscitation started immediately from the emergency room of the hospital including gastric lavage with activated charcoal and airway protection, oxygenation, fluid etc. It was followed by supportive treatment in ICU. Sodium bicarbonate, the cornerstone treatment, induces an alkalosis and provides a sodium load which improves cardiac conduction. However, severe toxicity and clinical instability of some patients despite the standard sodium bicarbonate infusion necessitates the trial of other adjunctive therapies such as lipid emulsion and therapeutic plasma exchange, as with our patient. This procedure is basically an exchange technique which is carried out by using apharesis machine. Patient’s blood is passed through the machine, which simultaneously filters plasma, reinfuses red blood cells along with replacement of equivalent amount of fluid such as plasma or albumin into the patient. This procedure is commonly known as therapeutic plasma exchange (TPE). Lowering plasma levels as much as 63% have been reported after plasmapheresis for TCA poisoning.⁶ Due to lack of enough evidence, use of plasma exchange in TCA poisoning is not a recommended option as per guideline by The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup. However, several case reports have suggested good outcomes following the use of TPE in critical cases nonresponsive to standard treatment. As in our case, refractory to recommended treatment, lipid emulsion and TPE was deployed as a rescue therapy to save a life. As there is no specific antidote to TCA, extracorporeal treatment could be a potential option as adjunctive therapy in critical cases.^8–10