Anaes · Local anaesthetic pharmacology
Local anaesthetic pharmacology
Also known as Local anaesthetics · Lidocaine · Bupivacaine · Ropivacaine · LAST · Lipid rescue
Local anaesthetics reversibly block nerve conduction at the voltage-gated sodium channel (textbook framework; exact doses per local formulary). The ASRA LAST checklist 2020 version was created per user feedback, simulation studies and medical-knowledge advances (Neal 2021). Lipid resuscitation combines scavenging (lipid shuttle, redistribution to storage/detox/excretion) with nonscavenging effects (postconditioning via prosurvival kinases, cardiotonic/vasoconstrictive, perfusion); direct channel-current and mitochondrial mass-effect mechanisms have diminished for lack of evidence (Fettiplace & Weinberg 2018). Bupivacaine is an amide-type agent for epidural, spinal, caudal, peripheral and infiltration use with prolonged sensory/motor blockade (McAllister StatPearls 2026). The IPSIS LAST protocol covers seizures, arrhythmias and cardiovascular collapse with rapid identification, lipid emulsion, airway, seizure control and modified ACLS (Meral 2026). Elderly patients carry disproportionate toxicity risk from comorbidities and decreased muscle mass, with inadvertent overdosing in over-65 case reports (Waldinger 2020).
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- Bupivacaine is uniquely cardiotoxic: its tight binding to the cardiac sodium channel produces refractory ventricular arrhythmias and an arrest that resists standard ACLS — the reason lipid emulsion must be given early and the reason ropivacaine and levobupivacaine were developed.
- Every dose must be calculated in mg per kg before drawing up — the safe dose of lidocaine with adrenaline (7 mg/kg) is very different from the plain dose (3 mg/kg), and a miscalculation is the commonest cause of LAST.
- The earliest sign of rising plasma local-anaesthetic concentration is CNS excitation: perioral tingling, tinnitus, a metallic taste, agitation — recognise it, stop the injection, and prepare for seizures.
- Lipid emulsion 20 per cent should be given immediately for any LAST-induced arrhythmia or arrest: 1.5 mL/kg bolus, then an infusion — do not wait for standard ACLS to fail.
- Local anaesthetics are less effective in infected or ischaemic tissue because the acidic environment ionises the drug, preventing it from crossing the nerve membrane — 'you cannot anaesthetise pus'.
Meet the patient
A 70-year-old man is having an epidural for a total knee replacement. Halfway through injecting he tells you his lips are tingling and he feels strange, and the monitor throws up a run of multifocal ventricular ectopics. That is the opening chord of local-anaesthetic systemic toxicity — excessive systemic absorption or intravascular injection causing seizures, arrhythmias and cardiovascular collapse — stop the injection, call for help, secure the airway, control seizures and give lipid emulsion early with modified ACLS per protocol.[4][1]
Two questions decide every local-anaesthetic stem: did you calculate the weight-based dose before drawing up the syringe per local formulary? and is lipid emulsion available per the local LAST protocol? Hold those two and the whole topic organises itself around them. Elderly patients carry disproportionate risk from comorbidities and decreased muscle mass, with inadvertent overdosing reported in over-65 case reports.[5]
References5ShowHide
- [1]Neal JM, Neal EJ, Weinberg GL. American Society of Regional Anesthesia and Pain Medicine Local Anesthetic Systemic Toxicity checklist: 2020 version Reg Anesth Pain Med, 2021.PMID 33148630
- [2]Fettiplace MR, Weinberg G. The Mechanisms Underlying Lipid Resuscitation Therapy Reg Anesth Pain Med, 2018.PMID 29356774
- [3]McAllister RK, Patel P. Bupivacaine StatPearls, 2026.PMID 30422478
- [4]Meral RM, Nagpal AS, Wasserman R. International Pain and Spine Intervention Society Emergency Protocols: Local Anesthetic Systemic Toxicity (LAST) Interv Pain Med, 2026.PMID 42325878
- [5]Waldinger R, Weinberg G, Gitman M. Local Anesthetic Toxicity in the Geriatric Population Drugs Aging, 2020.PMID 31598909