Introduction

Local anaesthesia systemic toxicity (LAST) is a rare but potentially life-threatening adverse reaction associated with the administration of local anaesthesia [1]. The incidence of LAST is low; however, there are difficulties in accurately estimating it due to misdiagnosis. It is estimated that events are reported in 2 to 2.8 per 10,000 peripheral nerve blocks [2]. Other sources state that the incidence is estimated at 1 to 500 peripheral nerve blocks and can occur in up to 4 per 10,000 epidural procedures [3, 4]. LAST occurs when the concentration of local anaesthetics in the blood reaches the toxic range. This can occur as a result of direct arterial or intravenous administration, as well as gradual absorption from extravascular tissue [5]. The two most common complications of this rare syndrome include cardiovascular and central nervous system disorders.

A comprehensive diagnostic work-up is necessary because the clinical manifestations of allergic reactions and LAST may overlap, making differential diagnosis challenging. In this report, we discuss the case of a pregnant patient who developed LAST in the postpartum period, which could have resembled a drug hypersensitivity reaction. We also describe the proposed diagnostic work-up.

Case report

A 37-year-old, non-atopic, otherwise healthy patient was admitted to the Department of Gynaecology at 41 weeks’ gestation for her first delivery (2020). Labor proceeded by spontaneous vaginal delivery. Due to incomplete placental separation, the patient was anesthetised using combined spinal–epidural anaesthesia. Ten millilitres of 1% lignocaine was administered through the epidural catheter, and 100 mg of propofol was given intravenously under continuous cardiopulmonary monitoring. The procedure and perineal repair were completed without complications. Following the procedure, the patient was transferred from the delivery bed to a transport trolley, and the epidural catheter was removed. At this time, progressive symptoms consistent with LAST were observed. Initially, within the first 5 minutes, the patient reported a metallic taste, agitation, and decreased blood pressure, followed by tachycardia, profound weakness, tachypnoea, and generalised muscle tremors. The patient was re-monitored. Oxygen therapy was initiated, and she received 150 mg of hydrocortisone, 10 mg of ephedrine, a 100-ml bolus of 20% Intralipid, followed by a 200-ml continuous infusion, as well as additional intravenous fluids (500 ml Gelaspan and 500 ml Sterofundin). After approximately 30 minutes, the patient’s overall condition improved and her subjective symptoms resolved.

After the incident, the patient subsequently received articaine administered by a dentist without any adverse reactions. She also underwent two surgical procedures under general anaesthesia. The first, in 2022, involved the removal of lower-limb varicose veins and was performed with fentanyl and propofol, without any signs of hypersensitivity. In September 2023, functional endoscopic sinus surgery was performed with administration of fentanyl, midazolam, cisatracurium, propofol, dexamethasone, ondansetron (Ondansetron), etamsylate, and remifentanil, again without any hypersensitivity symptoms.

Prior to her second delivery, the patient was evaluated by an allergist to determine whether local anaesthesia could be safely administered. The clinical presentation of her previous reaction during local anaesthesia for incomplete placental separation was consistent with either LAST or a hypersensitivity reaction (Table 1). Therefore, lignocaine could not be used for her subsequent delivery, creating an absolute indication to identify a safe alternative local anaesthetic.

Following multidisciplinary consultation with the anaesthesiology team, it was determined that, given the benefit–risk balance in pregnancy, tolerance to bupivacaine should be assessed. Bupivacaine was considered necessary as a potential agent for regional anaesthesia in the event of a caesarean section, thereby avoiding general anaesthesia, which carries increased risk for both mother and foetus. After obtaining the patient’s written consent, skin prick and intradermal tests with bupivacaine were performed, both yielding negative results. Subsequently, a subcutaneous provocation test with bupivacaine up to a total dose of 2 ml was carried out, with no hypersensitivity symptoms observed.

Discussion

In the described patient some symptoms of adverse reaction to lignocaine could have been perceived as drug hypersensitivity symptoms, but not as typical features of LAST, such as blood pressure drop and breathing difficulties, which prompted us to perform an allergological work-up during pregnancy and to find a safe alternative local anaesthetic. According to the European Academy of Allergy and Clinical Immunology (EAACI) and the European Network of Drug Allergy (ENDA) guidelines, a drug provocation test (DPT) may be performed during pregnancy only when the expected therapeutic benefit of the suspected drug clearly outweighs the potential risks – for example, in cases of relevant infections such as syphilis in a patient with suspected penicillin allergy, or when evaluating suspected local anaesthetic hypersensitivity prior to planned spinal anaesthesia for a possible caesarean section [6]. The guidelines of the Drug Hypersensitivity Section of the Polish Society of Allergology are consistent with European recommendations. Allergological diagnostics is permitted only in situations of absolute necessity, following a thorough assessment of the risk–benefit ratio. Pregnancy constitutes a relative contraindication to performing skin prick tests and intradermal tests with drugs [7].

Local anaesthetics (LA) are widely used across multiple medical and surgical specialties, primarily for pain control. LAST is a rare but serious complication of regional anaesthesia, with contemporary reported mortality rates ranging from 4.3% to 10% [8]. The main risk factors include the administered dose and volume of the LA, extremes of age (infants and the elderly), low body mass, and underlying cardiovascular, hepatic, renal, or metabolic disorders, as well as concomitant treatment with β-blockers, digoxin, calcium channel blockers, or cytochrome P450 inhibitors [8, 9]. Pregnancy is an additional factor that may precipitate or exacerbate LAST [9, 10].

Physiological changes during pregnancy alter the pharmacokinetics of many drugs, including local anaesthetics. Increased cardiac output and blood volume enhance perfusion at the injection site, thereby accelerating systemic absorption of the anaesthetic agent [10–12]. These physiological adaptations, combined with reduced epidural space secondary to foetal compression, promote venous engorgement in the epidural compartment, increasing the risk of inadvertent intravascular injection during neuraxial procedures [10–12]. In our patient, the most probable mechanism leading to LAST was rapid absorption from the highly vascularised epidural space during the postpartum period.

LAST in pregnant women may become more frequent, given the increasing use of local anaesthesia for both labour analgesia and surgical procedures during pregnancy. Furthermore, factors such as advanced maternal age, obesity, and comorbidities including cardiovascular disease may contribute to heightened susceptibility to LAST [13, 14]. The onset of LAST symptoms is typically very rapid. Following a single LA injection, symptoms generally begin within 50 s or up to 5 minutes [15]. In our patient, the first symptoms appeared within 5 minutes, subsequently intensifying as additional manifestations developed. The classic presentation of LAST involves a progressive, “biphasic” sequence of central nervous system (CNS) and then cardiovascular system (CVS) involvement. Initial subthreshold symptoms – such as agitation, auditory disturbances, and a metallic taste – may precede more severe CNS toxicity, including seizures or CNS depression (drowsiness, coma, and respiratory arrest). This is followed by cardiovascular excitation (tachycardia, ventricular arrhythmias, and hypertension), which may progress to cardiovascular depression (bradycardia, conduction block, asystole, and myocardial depression). Notably, cardiovascular collapse associated with LAST is often refractory to standard resuscitative measures [9, 15].

In a study by Tsuji et al. involving pregnant patients, all but 1 case demonstrated neurological toxicity, with seizures being the most commonly reported symptom (n = 11). Eleven patients exhibited cardiovascular toxicity, most frequently tachycardia (n = 6) and hypertension (n = 5) [14], findings consistent with the symptoms observed in our patient. In another study, De Valle et al. retrospectively compared LAST in pregnant and non-pregnant individuals. Both groups demonstrated the typical pattern of CNS and cardiovascular excitation followed by depression. However, pregnant patients exhibited a higher prevalence of cardiovascular depression, particularly hypotension [12].

The main treatments for LAST include advanced life support measures, airway stabilisation, seizure control, and intravenous administration of a 20% lipid emulsion [8, 16]. According to current guidelines, treatment begins with an initial intravenous bolus administered for 2–3 minutes, followed by a continuous infusion lasting 15–20 minutes, with dosing adjusted to body weight [2, 16]. In cases of refractory cardiovascular instability, additional bolus doses may be repeated every 5 minutes. The introduction of lipid emulsion therapy has significantly improved the management of LAST. Based on a review of published cases, Tsuji et al. demonstrated the safety and efficacy of lipid emulsion in pregnant patients, supporting its use as a key therapeutic intervention [14]. Our patient likewise received lipid emulsion therapy with a favourable clinical response.

Conclusions

With the rising number of caesarean deliveries and the increased use of local anaesthesia during vaginal childbirth, the management and treatment of LAST in pregnant women is becoming an increasingly important clinical concern. The presentation of LAST may resemble that of hypersensitivity reactions, and in select cases, an allergological evaluation may be required during pregnancy to ensure safe anaesthetic management.