Lidocaine
Last updated 17th Dec 2018 - Tom Heaton
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.
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.
IV Lidocaine
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).
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).
Pharmacodynamics
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:
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.
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
- Inhibits granulocyte migration
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.
Pharmacokinetics
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:
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:
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.
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)
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
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.
Clinical
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:
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.
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.
Toxicity
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:
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:
Risk factors for toxicity include:
This starts to occur at plasma levels of 5-6 mcg/ml.
There is classically a progression with increasing plasma levels:
- Numb tongue
- Metallic taste
- Lightheadedness
- Tinnitus
- Visual disturbance
- Muscle twitching
- Depression of conscious level
- Seizures
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:
- Negative inotropy
- Conduction abnormalities
- Blood pressure disturbances
Risk factors for toxicity include:
- Organ dysfunction
- Cardiac
- Hepatic
- Renal
- Cardiac
- Sedation /anaesthesia
- Metabolic disturbance
- Acidosis
- Hypoxia
- Acidosis
Links & References
- Ramaswamy, S. et al. Non-opioid-based adjuvant analgesia in perioperative care. CEACCP. 2013. 13(5): 152-157. https://academic.oup.com/bjaed/article/13/5/152/273387
- Eipe, N. et al. Intravenous lidocaine for acute pain: an evidence-based clinical update. 2016. 16(9):292-298. https://academic.oup.com/bjaed/article/16/9/292/1743710
- Peck, T. Hill, S. Williams, M. Pharmacology for anaesthesia and intensive care (3rd ed). Cambridge University Press. 2008.
