2015A04 A surgeon wishes to use topical local anaesthetic in the nose before surgery in a 30 year old 70kg man.
He normally uses topical cocaine 5% plus lignocaine 2% with adrenaline 1:100,000 injection.
What volumes of these drugs can be used safely?
What are the potential toxic effects of cocaine and how does lignocaine and adrenaline affect these?

List:

· Numbers table

· Purpose

· Localised toxicity

· CNS toxicity

· CVS toxicity

· Final answer

Numbers:

	Concentration presented	Toxic plasma concentration	Toxic subcutaneous dose
Cocaine	5% = 50mg/mL	0.5mcg/mL	2mg/kg = 140mg = ~3mL
Lignocaine	2% = 20mg/mL	5mcg/mL	7mg/kg w adr = 490mg = ~25mL
Adrenaline	1:100k = 10mcg/mL	?	?

Purpose:

	Mechanism of action	Function
Cocaine	Inhibit VdNaC Monoamine reuptake Norad : dopamine : serotonin 5:3:2	Local anaesthetic Vasoconstriction
Lignocaine	Inhibit VDNaC	Local anaesthetic
Adrenaline	α₁ agonist	Vasoconstriction

Localised toxicity:

Cocaine	· Septal necrosis possible even with single use
Lignocaine	· Rare
Adrenaline	· Necrosis if large amount of drug

CNS toxicity:

LAST

· Cause: inhibition of neuronal VDNaC

· Initial excitation (block inhibitory interneurons): paraesthesia, peri-oral tingling, vertigo, tinnitus, inattention, slurred speech, muscle twitching, seizure

· Then inhibition: coma, apnoea

Cocaine (non-LAST)

· Cause: dopamine and serotonin reuptake inhibition

· Euphoria, delirium, seizure

CVS toxicity:

LAST

· Inhibit VDNaC;, also VDKC and VDCC at higher concentration

· ECG “pulled apart” (long Q, wide QRS), tachyarrhythmia, VF arrest

· First phase: ↑HR, ↑mAP

· Second phase: myocardial depression, ↓mAP

· Terminal phase: vasodilatation, arrhythmia, arrest

Cocaine (non-LAST)

· NRI, ↑ICF Ca²⁺

· Tachyarrhythmia, ↑mAP, coronary vasospasm, ischaemia, arrest

Adrenaline

· ↑ICF Ca²⁺ -> tachyarrhythmia, ischaemia, stroke, arrest

Considerations:

Drugs

· Cocaine’s vasoconstriction = protective (↓absorption rate -> ↓peak plasma concentration)

· Cocaine’s LA activity = ? additive ? synergistic for toxicity

· Overall impact unclear

Patient

· PK: nasal mucosa is highly vascular -> ↑↑absorption rate

· PD: patient’s youth and health confer resistance to CVS and CNS toxicity

Answer:

How much

· Cocaine – 1mL

· Lignocaine 2% with Adr 1:100k – 5mL

(I have no idea. Suggestions for a definitive answer are welcome)

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