Lidocaine is an amide local anaesthetic agent. Much of the special chemistry features of local anaesthetic agents are class effects and so discussed together.
Protein binding: 70% - alpha1-acid glycoprotein pKa: 7.9 - 25% ionised at pH 7.4
These physical characteristics provide lidocaine with a fast onset but relatively short duration.
As well as its more traditional use as a local anaesthetic, there has been some interest in lidocaine as a general analgesic adjunct. This is because of the recognised problems with both perioperative pain itself (e.g. distress, risk of chronic pain, complications) and the notable limitations of opioids (including the risk of hyperalgesia).
It has analgesic (including anti-hyperalgesic) and anti-inflammatory effects. Some of these do arise from its classical ‘local anaesthetic’ effect of sodium channel blockade and inhibition of nerve impulse transmission. However, the effects of these when lidocaine is given parenterally is more than just inhibition of neuronal transmission. Analgesia:
Na+, NMDA and G-protein coupled receptor inhibition
Inhibition of spontaneous impulses from damaged nerves
Attenuation of neurogenic inflammation (by neuronal blockade)
Direct anti-inflammatory effect
Inhibits granulocyte migration
Reduces cytokine production
The overall result is there is a reduction in the peripheral and central sensitisation mechanisms that can contribute to hyperalgesia.
The therapeutic window is quoted as being 2.5-3.5 mcg/ml. Toxicity can occur at levels over 5 mcg/ml.
Lidocaine obeys a multicompartmental model. However, the plasma levels will be affected by protein binding and ionisation, and so the patient’s acid-base status and available proteins will have an impact and may lead to significant variability.
As such, the effective dose is not fully established and may vary between patients. A general guide to the regimes used in recent studies has been:
Bolus dose - 1-2mg/kg (or 100mg) - slow IV bolus
Infusion - 0.5-3mg/kg/h (1 to 2 being the most used)
These regimes achieved plasma concentrations of 2-5 mcg/ml
A steady state will generally be achieved after 4-8 hours of infusion.
Lidocaine is metabolized in the liver to active metabolites. Altered hepatic blood flow can therefore impact on its clearance. The metabolites are:
Monoethylglycinexylidide (MEGX)- similar convulsant and antiarrhythmic potency
Glycinexylidide (GX)- notably less activity
MEGX undergoes further metabolism into GX. GX undergoes renal metabolism and excretion.
This metabolism is rapid and relatively context insensitive (at least in most clinical application of infusion studied so far). There is clearly an impact on this from hepatic and renal dysfunction.
The evidence base for IV lidocaine is still relatively small. The postulated benefits are that by decreasing sensitisation of the nociceptive pathways, both directly and as an anti-inflammatory, then acute pain will be reduced. There may also be an reduced risk of the development of chronic pain. As with other adjuvant analgesia options, the reduced opioid requirements may then be able to result in other benefits.
Postulated benefits with some evidence include:
Decreased pain intensity (static and dynamic)
Reduced opioid requirements
Reduced persistent pain after breast surgery
Improved gut function post-op
Some of the benefit may be prolonged after the initial treatment, suggesting that the prevention of sensitisation may be a part of its effect. However, greater effects may be demonstrated with more prolonged infusions (24 hours) suggesting benefit from a more prolonged anti-inflammatory effect.
Whilst there has been little evidence of harm arising, the majority of the studies have not been designed or powered to assess for this, so caution is still warranted.
This occurs in the classical pattern of local anaesthetics, with CNS features occurring first, followed by cardiac toxicity. This starts to occur at plasma levels of 5-6 mcg/ml. There is classically a progression with increasing plasma levels:
Depression of conscious level
CVS toxicity is rarer in the awake patient due to the relatively low cardiac toxicity of lidocaine (at least compared to bupivacaine) and so occurring after CNS symptoms at plasma levels >10 mcg/ml. These may include: