This chapter tries to address Section K2(ii) of the 2017 CICM Primary Syllabus, which expects the exam candidate to demonstrate an "understanding of the pharmacology of local anaesthetic drugs, including their toxicity". Lignocaine on its own appears to be the only drug to be asked about in any great detail, even though intensivists do often manage and initiate various other local anaesthetics as infusions and nerve blocks. Question 1 from the first paper of 2019 and Question 17 from the first paper of 2014 both incorporated lignocaine in some way. Fortunately, the subjects of local anaesthetic mechanism of action and local anaesthetic toxicity have all been explored elsewhere, making this page much shorter than it could have been.
Class Class Ib antiarrhythmic Chemistry Aminoamide Routes of administration IV, inhaled, subcutaneous Absorption Oral bioavailability = 35% Solubility pKa = 7.9; about 25% is not ionised at pH 7.4 Distribution VOD= 0.9L/kg; 70% protein-bound Target receptor Nav1.5 subunit of the fast voltage-gated sodium channels Metabolism Hepatic metabolism (90-95%) Elimination Minimally renally excreted; half-life 10-20 minutes following IV bolus, closer to 45-90 minutes with subcutaneous infiltration Time course of action Duration of action is similar to half-life Mechanism of action Regional anaesthesia, by differential block (pain and temperature finres are blocked earlist). With higher doses, also motor block. In toxicity, CNS effects (visual disturbances, perioral mumbness, delirium,seizures, coma) and cardiovascular side effects (initially tachycardia and hypertension followed by bradycardia, negative inotropy, vasodilation and arrhythmias) Does not prolong the QRS, and actually shortens the QT. Clinical effects Antiarrhythmic effect, analgesic and local anaesthetic effects. Lowers seizure threshold, causes CNS excitation. Does not prolong the QRS, and actually shortens the QT. Single best reference for further information Weinberg et al (2015)
Lignocaine is an aminoamide local anaesthetic. It is also variably referred to as Xylocaine, a registered trademark of Astra which became popularised in the same way as Novacaine (the trade name of procaine). It also helped that, in 1947 when it entered the market, lignocaine was still known only as LL-30. According to a fascinating historical account by Holmdahl et al (1998), the "xylo" came from xylidine, which was one of the raw precursor chemicals used in the synthesis. Lignocaine, as adrenaline, is a carryover of a British formulary name which has propagated to the former colonies, and lidocaine is the "recommended international non-proprietary name" which enjoys international use.
The other amide anaesthetics are prilocain, bupivacaine, mepivacaine and ropivacaine. This subclass all share the property of having a longer duration of action than the ester anaesthetics (eg. tetracaine and procaine), partly because of their hepatic metabolism.
Administration and dosing: Lignocaine can be administered as a local anaesthetic (in which case it is injected into, or slather over, or sprayed upon, the direct surface which is meant to be anaesthetised). It can also be given as an infusion for its antiarrhtyhmic effect. It can also be given as an infusion to produce a systemic local anaesthetic effect, which has been demonstrated as an effective analgesic choice in various forms of major surgery (Eipe et al, 2016). In case one might be wondering, the dose required for analgesia and the dose required for the antiarrhtyhmic effect is basically the same, 1-2mg/kg/hr. A loading dose bolus of 1-2mg/kg is usually required in both scenarios. For subcutaneous infiltration, the dose is obviously going to depend significantly on the intended use, and on whether or not there is vasoconstrictor involved. Borrowing from the author's local guidelines, which seem representative of other such guidelines, the maximum dose for regional use is no more than 4mg/kg, or 8mg/kg if using adrenaline.
Absorption from mucosa is excellent, to the point where care must be taken with atomisers which can deliver concentrated lignocaine to mucosal surfaces. A 10% lignocaine spray can overdose a smaller person in just a few sprays (0.1ml per pump = 10mg lignocaine). Absorption from the GI tract is also excellent, and bioavailability is 35%, which has mainly toxicological implications (as no enteric preparation is available, and one would only really encounter this in toxicological situations where a child has accidentally ingested lignocaine gel).
Distribution: The volume of distribution for most local anaesthetics is relatively modest, and lignocaine is no exception (0.9L/kg).
Protein binding: Lignocaine is about 70% protein bound; its duration of action is therefore somewhat shorter than the duration of action of drugs like bupivacaine and ropivacaine, which have over 90% protein-bound.
pKa and solubility: The pKa of lignocaine is generally quoted as 7.8. At normal body fluid pH, 25% of the drug is present in an unionised lipid-soluble form, which means its onset of action is reasonably quick. Compare to drugs with slower onset, such as bupivacaine which has a pKa 8.1 and only has 15% of its molecules unionised at a pH of 7.4.
Metabolism is hepatic, by the CYP450 system (specifically, 3A4). Drugs which act as competing substrates, activators or inhibitors for this enzyme are numerous, and theoretically, all of them could interfere with the metabolism of lignocaine
Elimination half-life is about 90 minutes, but the duration of action is more variable and depends on regional phenomena (eg. blood flow to the anaesthetised area).
As a local anaesthetic:
As an antiarrhythmic: