S1E2: TCA overdose | Toxicology papers | Chemsex
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:
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:
If you identify the culprit, you gotta know the fix, and very importantly where to get it!
Our own national antidotes document is in the process of being updated, will be published on poisons.ie when it is, but this will do nicely in the meantime.
Have a look at these and figure out where everything is kept in your department, where the antidotes press is for example.
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
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:
Take home naloxone has been available in Ireland since 2015, some more background available here.
Andy recalled a useful paper on the topic of medical chart reviews and their reliability, which was central to the methodology of one of the papers.
Note: Gilbert and Lowenstein, not Gilbert and Sullivan, although the latter pairing have some notable publications of their own.
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:
Club Drugs Clinic Ireland
Contactable by calling NDTC at 016488600, and asking for Dr. Kiran Santlal, in the G Clinic (more known abbreviation), or Dr.Santlal’s direct line is 01 6488649
Graham Ryall – who provides a lot of support, for anyone referred to him.
085 1337536
Page last updated:
08/06/2020