S1E2: TCA overdose

Written By Mohammed Hamza

Welcome back to TheCase.Report! We’re delighted to have you with us for the June 2020 edition.
This month, it’s all about Tox!
For our case this month, Barry, Hugh, and Mohammed will take us through a challenging scenario.

Long story short, myocardial tickles are no laughing matter!



Approach to the undifferentiated poisoning patient

Epidemiology

  • 1% of ED visits in the states (although this data is about 20 years old)

  • Poisons information centre annual reports provide interesting information:

  • (https://www.poisons.ie/docs/2018%20Annual%20Report_Final%20version.pdf)

  • 16000 different agents they were asked about, most of which were drugs but also:

    • Fabric detergents, bleach, dishwasher products, but also essential oils (serious potential for CNS toxicity) and agrochemicals.

  • 84% of enquiries involved accidental poisonings or therapeutic errors. 13% were intentional overdoses or recreational abuse. 

  • Overall mortality in Ireland well below European average, but that’s likely very variable throughout the country.

Top medicinal culprits in Ireland:

topmedculprits.png

Systematic approach

It’s important to have a structured approach that you will apply every time, no matter what the presumed agent is. This will keep you and the patient out of trouble! Here’s a generalised overview of how we’d approach it:

  • Primary Survey

  • History

  • Exam/Secondary survey

Primary Survey:

  • To include vitals, gcs, and pupils, skin temperature and moisture, cardiac monitoring and an ECG, glucose* and a VBG

  • IV access x2

  • Always send a paracetamol level in patients with low GCS and presumed poisoning

  • Tox screen may/may not be helpful (TCA assay on Tox screen has cross reactivity with multiple other agents incl. Carbamazepine and quetiapine)

  • Have a look (carefully) through bag/pockets etc for notes or… paraphernalia

  • Core temp (catheter/rectal/oesophageal)

* Important to give thiamine if correcting hypoglycaemia, many may be thiamine deficient and a Wernicke’s encephalopathy may develop. Not much evidence for this in the acute setting, but what have we got to lose?

History:

  • May be unreliable (low GCS/uncooperative/psychiatric illness)  

  • Collateral may be vital (family/friends/bystanders/prehospital/gardai) or past records

  • Look up and print out information about most likely toxins 

  • Toxbase available in most hospitals, but contact poisons information centre if not/in doubt (24 hr phone line for healthcare professionals https://www.poisons.ie/Contact-Us)

Physical exam:

  • Reevaluate ABCs periodically while looking for signs of physiologic excitation/depression

  • This is where it’d be useful to know your toxidromes… Which we obviously do really really well.

  • But when I forget I refresh my memory over here.

  • Kloss & Bruce’s Toxicology in a Box is also a very good resource, and pretty colourful and entertaining to boot!

Management:

So that’s the general overview… but what about the specifics for TCAs?

Tricyclic Antidepressants (TCAs)

  • Amitriptyline

  • Clomipramine (Anafranil)

  • Imipramine

  • Nortriptyline

Pharmacology

  • Rapidly absorbed – max plasma levels @ 2-8hrs

  • Severe Toxicity usually manifests within 2 hours

  • Can be delayed due to delayed gastric emptying (AntiCh effects)

  • Lipophilic (large vol. of distribution)

  • Acidaemia complicates overdose  increases amount of free drug due to effects on glycoprotein binding

  • Metabolism: mainly by liver (CYP2D6) many phase 1 metabolites are still  pharmacologically active and may persist 12-24 hours

  • Half Life 7-58 hours (Dependant on agent)

  • Excretion: 70% renal, ~30% via biliary system (thus enterohepatic circulation may delay final elimination)

Mechanism of toxicity

  • Blockade of Na fast channels (Cardiac)

  • Antagonism of central and peripheral AcetylCh receptors

  • Antagonism of α1 adrenergic receptors

  • Antagonism of H1 receptors

  • Antagonism of GABA –a receptors

Clinical features

  • Important to note Tricyclic involved (different T1/2)

  • Course is unpredictable: may deteriorate rapidly due to variation in absorption

  • Physical findings:

    • CNS:

      • Sedation, Confusion, delirium, hallucinations

    • Cardiac

      • Conduction delays, arrhythmias and hypotension

    • Anticholinergic toxicity

      • hyperthermia, flushing, dilated pupils

CNS features

  • Sedation Due to antihistaminic effects

  • Delirium due to anticholinergic effects

  • Seizures likely due to effect on GABA-A receptors

Cardiac features

  • Sinus Tachycardia

    • due to antiCh effects and compensatory to hypotension.

  • Hypotension

    • Decreased contractility from reduced Ca influx

    • Peripheral vasodilation - blockade of α1 adrenergic receptors

    • TCA Mortality mainly due to refractory hypotension

  • Conduction abnormalities

    • Fast Na channels in His Purkinje system and myocardium

    • Decreasing conduction velocity and increased duration of repolarisation

    • VT / VF occur in ~4% of TCA ODs

  • Cardiac Toxicity

    • QRS >100ms is a sign of potential cardiac toxicity

    • Trial of therapy with sodium Bicarbonate

  • Other ECG findings

    • prolonged PR and QT 

    • Intraventricular conduction delay i.e. BBB (may contribute to hypotension)

  • In one study 26% of those with QRS> 100ms had seizures those with QRS >160 had 50% chance of ventricular arrhythmia

Investigations

  • ECG

    • Should be performed hourly IF ASYMPTOMATIC

    • Examples here.

  • FBC

  • U+E

    • If NaHCO3 will need to monitor electrolytes closely 

  • Blood Sugar

  • LFTs

    • if abnormal may lead to longer T1/2 of TCA

  • VBG

  • Coag

  • Temperature


Caution RE: Urine tox testing

  • Urine tox i.e. qualitative immunoassays

  • They only note use NOT OVERUSE

  • Multiple drugs cross react giving false positives, including: carbamazepine and quetiapine

Management

  • Initial – ABCs – securing Airway if required

    • If for intubation avoid drugs likely to worsen hypotension

  • Decrease Absorption

    • Activated charcoal if normal GCS and if <2 hours

  • Agitation

    • Benzodiazepines - 1mg lorazepam

    • Titrated slowly ~Q10mins (may lead to profound sedation)

  • Hypotension

    • Boluses of Crystalloids 250mls

    • May require vasopressors (noradrenaline / phenylephrine prefered)

  • Cardiac Toxicity

    • Sodium bicarbonate (100mls 8.4%) 

    • (official dose 1-2mEq/Kg) may be repeated after 5 mins

  • Anticholinergic toxicity – 

    • May go into urinary retention

    • AVOID physostigmine  precipitates cardiac arrest in setting of TCA overdose

Sodium Bicarbonate

  • Initial dose 1-2mEq/Kg*

  • If QRS narrows n response to bolus  Infusion

  • Infusion Dose: 150mEq NaHCO3 in 1L of dextrose 5%

    • infuse at 250mls/Hr (if in children rate of infusion is at twice maintenance fluid rate

  • Goal pH: 7.5 – 7.55 

  • If QRS stabilises goal is to reduce infusion rate by 25% over 4 hours

  • If QRS fails to narrow (in absence of an alt diagnosis) sodium bicarbonate should still be started

  • If the patient is intubated the pH may be maintained via hyperventilation

*Very good point from Dr. Hennessy regarding dosing of bicarb. The 8.4% solution that we’ll most commonly see is 1 mmol/ml (or 1mEq/ml), which will help a lot in calculating doses!

Severe haemodynamic instability/peri-arrest

  • Lipid emulsion 20% – 1-1.5mg/Kg over 1 minute.

    • Should be discussed with medical toxicologist

    • May be repeated in cardiac arrest (max 8mls / Kg)

  • External pacing – if junctional bradycardia

Drugs to avoid

  • Flumazenil

  • Physostigmine

  • With the exception of Lidocaine and Magnesium there are concerns around all antiarrhythmics 1A and 1C are contraindicated (inhibit rapid Na channels) Amiodarone (Class III) is potentially dangerous (potential QT prolongation)

  • Anticonvulsants - Phenytoin should also be avoided (Class 1B antiarrhythmic) benzodiazepines/ Barbiturates should be used in preference

Move on.gif

You know what lady, I couldn't agree more...

The Papers

For our second segment this month, Andy joined Barry and Mohammed to chat through a couple of important recent papers in toxicology. Have a read of them and see what you think:

Very interesting discussion around two papers which have some relevance to Irish EM, particularly in Dublin.

Some things that came up in the discussion:

Join the discussion on twitter @TheCaseReport and let us know your thoughts on the papers!

The Interview

For our last segment, we were delighted to have Dr. Kiran Santlal come on the show to chat to us about Chemsex.

Dr. Santlal has worked in the HSE National Drug Treatment Centre, since 2014, and helped to develop the HSE Club Drugs Clinic Ireland in 2014.

We spoke in depth about what Chemsex is, common drugs used, recognising and managing acute intoxication and withdrawals, issues around detoxing and support services available.

If you want a quick primer on G (GHB/GBL), the drugs.ie GHB campaign webpage is a great resource, and contains links to the G campaign fact sheet, G pocket card (has helpful info for layperson and for emergency services) and a list of organisations and resources.

Some other important resources discussed:

Mohammed Hamza
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