Naguib M, Magboul M M, Samarkandi A H, Attia M
Department of Anaesthesia, Faculty of Medicine at King Khalid University Hospital, Riyadh, Saudi Arabia.
Drug Saf. 1998 Apr;18(4):221-50. doi: 10.2165/00002018-199818040-00001.
Systemic and localised adverse effects of local anaesthetic drugs usually occur because of excessive dosage, rapid absorption or inadvertent intravascular injection. Small children are more prone than adults to methaemoglobinaemia, and the combination of sulfonamides and prilocaine, even when correctly administered, should be avoided in this age group. The incidence of true allergy to local anaesthetics is rare. All local anaesthetics can cause CNS toxicity and cardiovascular toxicity if their plasma concentrations are increased by accidental intravenous injection or an absolute overdose. Excitation of the CNS may be manifested by numbness of the tongue and perioral area, and restlessness, which may progress to seizures, respiratory failure and coma. Bupivacaine is the local anaesthetic most frequently associated with seizures. Treatment of CNS toxicity includes maintaining adequate ventilation and oxygenation, and controlling seizures with the administration of thiopental sodium or benzodiazepines. Cardiovascular toxicity generally begins after signs of CNS toxicity have occurred. Bupivacaine and etidocaine appear to be more cardiotoxic than most other commonly used local anaesthetics. Sudden onset of profound bradycardia and asystole during neuraxial blockade is of great concern and the mechanism(s) remains largely unknown. Treatment of cardiovascular toxicity depends on the severity of effects. Cardiac arrest caused by local anaesthetics should be treated with cardiopulmonary resuscitation procedures, but bupivacaine-induced dysrhythmias may be refractory to treatment. Many recent reports of permanent neurological complications involved patients who had received continuous spinal anaesthesia through a microcatheter. Injection of local anaesthetic through microcatheters and possibly small-gauge spinal needles results in poor CSF mixing and accumulation of high concentrations of local anaesthetic in the areas of the lumbosacral nerve roots. In contrast to bupivacaine, the hyperbaric lidocaine (lignocaine) formulation carries a substantial risk of neurotoxicity when given intrathecally. Drugs altering plasma cholinesterase activity have the potential to decrease hydrolysis of ester-type local anaesthetics. Drugs inhibiting hepatic microsomal enzymes, such as cimetidine, may allow the accumulation of unexpectedly high (possibly toxic) blood concentrations of lidocaine. Reduction of hepatic blood flow by drugs or hypotension will decrease the hepatic clearance of amide local anaesthetics. Special caution must be exercised in patients taking digoxin, calcium antagonists and/or beta-blockers.
局部麻醉药的全身和局部不良反应通常是由于剂量过大、吸收过快或意外血管内注射所致。小儿比成人更易发生高铁血红蛋白血症，即使正确给药，该年龄组也应避免磺胺类药物与丙胺卡因合用。对局部麻醉药真正过敏的发生率很低。如果通过意外静脉注射或绝对过量导致局部麻醉药血浆浓度升高，所有局部麻醉药都可引起中枢神经系统毒性和心血管毒性。中枢神经系统兴奋的表现可能为舌部和口周区域麻木、烦躁不安，进而可能发展为惊厥、呼吸衰竭和昏迷。布比卡因是最常与惊厥相关的局部麻醉药。中枢神经系统毒性的治疗包括维持充分的通气和氧合，并用硫喷妥钠或苯二氮䓬类药物控制惊厥。心血管毒性一般在中枢神经系统毒性症状出现后开始。布比卡因和依替卡因似乎比大多数其他常用局部麻醉药的心脏毒性更大。在神经轴阻滞期间突然发生严重心动过缓和心搏停止令人高度关注，其机制在很大程度上仍不清楚。心血管毒性的治疗取决于效应的严重程度。局部麻醉药引起的心脏骤停应采用心肺复苏程序治疗，但布比卡因引起的心律失常可能难以治疗。最近许多关于永久性神经并发症的报告涉及通过微导管接受连续脊麻的患者。通过微导管以及可能的细规格脊麻针注射局部麻醉药会导致脑脊液混合不良以及高浓度局部麻醉药在腰骶神经根区域积聚。与布比卡因不同，鞘内给予高压利多卡因制剂具有相当大的神经毒性风险。改变血浆胆碱酯酶活性的药物有可能减少酯类局部麻醉药的水解。抑制肝微粒体酶的药物，如西咪替丁，可能使利多卡因的血药浓度意外升高（可能达到中毒水平）。药物或低血压导致肝血流减少会降低酰胺类局部麻醉药的肝清除率。服用地高辛、钙拮抗剂和/或β受体阻滞剂的患者必须格外小心。
