Describe the factors that increase the risk of systemic toxicity of the amide local anaesthetics.
The amide group oflocal anaesthetics consist of lignocaine, prilocaine, ropivacaine and bupivacaine. The systemic toxicity primarily relates to toxic plasma levels and the factors that influence this. The main factors expected can be categorized under drug factors (including kinetics), patient factors, site of injection and external factors. Many candidates omitted important details such as pKA, lipid solubility and addition of vasoconstrictors. For example, absorption is affected by drug pKA, (thecloser to physiological pH themore rapid the absorption), use of vasoconstrictors and the drugs own vasoactive properties, site of injection (intercostal>epidural>brachial plexus>subcutaneous infiltration). Distribution is dependent on physicochemical properties of the amide. The rate of metabolism, mechanism of action (bupivacaine, in comparison to lignocaine has stronger binding to inactivated
resting sodium channels and a slower rate of dissociation) and external factors (e.g. systemic acidosis) are other factors that should have been mentioned, and expanded upon with relevant detail.
Drug factors:
Patient factors:
Finucane, Brendan T. Complications of regional anesthesia. New York: Springer, 2007.
Scott, D. B. "Toxic effects of local anaesthetic agents on the central nervous system." BJA: British Journal of Anaesthesia 58.7 (1986): 732-735.
Shibata, Masatoshi, et al. "Tetraphasic actions of local anesthetics on central nervous system electrical activities in cats." Regional Anesthesia and Pain Medicine 19.4 (1994): 255-263.
Ladd, Leigh A., et al. "Effects of CNS site-directed carotid arterial infusions of bupivacaine, levobupivacaine, and ropivacaine in sheep." The Journal of the American Society of Anesthesiologists 97.2 (2002): 418-428.
Blair, M. R. "Cardiovascular pharmacology of local anaesthetics." BJA: British Journal of Anaesthesia 47 (1975): 247-252.
Newton, D. J., et al. "Mechanisms influencing the vasoactive effects of lidocaine in human skin." Anaesthesia 62.2 (2007): 146-150.
Christie, Linsey E., John Picard, and Guy L. Weinberg. "Local anaesthetic systemic toxicity." Bja Education 15.3 (2015): 136-142.
Mauch, J., et al. "Electrocardiographic changes during continuous intravenous application of bupivacaine in neonatal pigs." British journal of anaesthesia 105.4 (2010): 437-441.
Nancarrow, C., et al. "The influence of acidosis on the distribution of lidocaine and bupivacaine into the myocardium and brain of the sheep." Anesthesia and analgesia 66.10 (1987): 925-935.
Avery, Pamela, et al. "The influence of serum potassium on the cerebral and cardiac toxicity of bupivacaine and lidocaine." Anesthesiology 61.2 (1984): 134-138.
Dillane, Derek, and Brendan T. Finucane. "Local anesthetic systemic toxicity." Canadian Journal of Anesthesia/Journal canadien d'anesthésie 57.4 (2010): 368-380.
Garg, Divya, Shikha Soni, and Rakesh Karnawat. "Local Anesthetic Systemic Toxicity." Topics in Local Anesthetics. IntechOpen, 2020.
Naguib, Mohamed, et al. "Adverse effects and drug interactions associated with local and regional anaesthesia." Drug safety 18.4 (1998): 221-250.