Resistance to local anaesthetics administered via epidural, intrathecal and pudendal injections

Summary

A primigravida presented to our institution in established labour. Her past medical history included joint hypermobility, postural orthostatic tachycardia syndrome, Raynaud's syndrome, fibromyalgia and gastroparesis. Two technically uneventful lumbar epidurals with bupivacaine and fentanyl provided no analgesia. The spinal element of a planned combined spinal and epidural was also ineffective, so alternative analgesia was offered. While this was being prepared, the obstetric team recommended an instrumental delivery. An attempted pudendal nerve block with lidocaine had no effect, and general anaesthesia was therefore provided for a lower segment caesarean delivery. We believe this is the first report of local anaesthetic resistance via three distinct routes of administration in a single patient. Resistance to local anaesthetics is unusual and is more common in patients with hypermobility spectrum disorders. This case demonstrates the unique experience of a patient with a hypermobility condition who had failed epidural, spinal and pudendal local anaesthetic. We suggest that patients with a hypermobility condition should be specifically assessed for local anaesthetic resistance as part of anaesthetic pre‐assessment, to enable early planning.

Introduction

Local anaesthetic (LA) resistance is a rare phenomenon, but one which may be under reported. The occurrence of LA resistance via three different routes of administration in the same patient has not been previously documented. We report a case of local anaesthetic resistance in an obstetric patient with a past medical history of joint hypermobility, fibromyalgia and postural orthostatic tachycardia syndrome (POTS).

Report

A 31‐year‐old primigravida presented to the labour ward. Her past medical history included POTS, Raynaud's syndrome, fibromyalgia, joint hypermobility and gastroparesis. Her only regular medication was fludrocortisone. The patient presented following spontaneous rupture of membranes, one day after their estimated due date. On examination by the obstetric team, the patient's cervix was 7 cm dilated. Due to her POTS diagnosis, a plan was made for intravenous steroids, labour epidural analgesia and limitation of the active second stage of labour to 1 h.

Following assessment and consent, the patient received a lumbar epidural which was technically uneventful. However, the patient remained uncomfortable and there was no demonstrable sensory block after three 10 ml boluses of low‐dose mix (bupivacaine 0.1% and 2mcg.ml⁻¹ fentanyl). A second anaesthetist reviewed the patient and performed a repeat epidural with the patient's consent. Although the second epidural catheter insertion was also uneventful, three further 10 ml boluses of low‐dose mix led to no improvement in the patient's pain and produced no motor or sensory block.

Following senior anaesthetic review, alternative analgesia options were discussed, and a plan made to perform combined spinal and epidural (CSE) analgesia. For the spinal component, we administered 4 ml low‐dose mix from a new bag and observed aspiration of cerebrospinal fluid prior, during and after injection. However, there was no reduction of the patient's pain and there were no sensory or motor changes. Ten minutes after the spinal injection the patient was still able to straight leg raise with no weakness and could stand unsupported. Considering the three failed neuraxial procedures, a decision was made to abandon the epidural component of the CSE.

Further discussion with the patient at this stage revealed that local anaesthetic for previous dental procedures had ‘not worked’. A remifentanil patient‐controlled analgesia (PCA) pump was prepared, but prior to commencing it, a decision for an urgent trial of instrumental delivery in theatre was made due to non‐reassuring fetal status. A pudendal block with 20 ml 1% lidocaine was attempted, but this was not effective, and an instrumental delivery was not possible due to the lack of analgesia. The patient underwent uneventful general anaesthesia for a lower segment caesarean delivery.

At the end of surgery, we considered abdominal wall blocks, but given the failure of other regional techniques, we decided against any further LA‐based analgesia. Instead, we provided multimodal analgesia with paracetamol, non‐steroidal anti‐inflammatory medications, ketamine, clonidine and a morphine PCA. Despite this, satisfactory postoperative analgesia remained challenging to achieve. The patient was fully debriefed about the events of their labour, delivery and postoperative period both as an inpatient and six weeks postnatally in the anaesthetic follow up clinic.

Discussion

This case demonstrates resistance to LA via three different routes of administration – epidural, intrathecal and pudendal nerve block, using two different LA agents. Local anaesthetic resistance occurs when an appropriate dose of LA administered via an appropriate route fails to provide the required or expected effect [1]. It has been reported to occur more frequently in patients with Ehlers–Danlos syndrome (EDS) [2]. As many as 88% of patients with EDS report LA resistance as being either complete, partial or rapidly waning in effect [3]. According to the 2017 nomenclature, terms such as joint hypermobility syndrome (JHS), Ehlers–Danlos syndrome hypermobility type (EDS‐HT) and Ehlers–Danlos type 3 (ED‐III) are considered outdated. Hypermobility spectrum disorder (HSD) is the recommended term, which includes a spectrum of disorders from asymptomatic joint hypermobility (JH) to hypermobile Ehlers–Danlos syndrome (hEDS) [4]. The patient in this case was diagnosed with hypermobility and comorbidities which may suggest the presence of a HSD, such as POTS and gastroparesis. Nevertheless, there was no evidence of formal assessment or diagnosis of HSD in this case.

The mechanism of LA resistance in patients with HSD is not clear. A potential explanation may be increased microvascular permeability, leading to an altered pharmacokinetic effect of LA due to more rapid dispersal through fragile connective tissue [1]. Neuraxial structural variations or anomalies, such as dural ectasiae or Tarlov cysts, can impair the expected spread of LA, leading to unpredictable effects [5, 6].

There are numerous reports of patients living with HSD who experienced LA resistance, most commonly during dental surgery [3]. Several case reports exist of obstetric patients with HSD who had varying effects of neuraxial LA administration [5, 7, 8]. Wloch and colleagues report a case of a patient with EDS who underwent an elective caesarean delivery with an intrathecal catheter, which was only partially effective and required multiple top ups [5]. Glynn and Yentis report a patient with classic EDS who had an epidural for labour which produced an insufficiently dense block and required frequent top ups [7]. However, patients with EDS have also received neuraxial anaesthesia without displaying features of LA resistance [8].

Sood et al. describe a case where caesarean delivery was undertaken because of failed LA infiltration and attempt at episiotomy in a patient with previous LA resistance [2]. In our case, a similar decision was made after being unable to provide adequate analgesia for a trial of instrumental delivery. This clearly demonstrates the significant role LA resistance can play in obstetric outcomes, especially achieving certain modes of birth. It is our opinion that patients with HSD who report previous LA resistance should be carefully counselled about failure of neuraxial and infiltrative analgesia or anaesthesia and how this may affect obstetric outcomes.

Proceeding to general anaesthesia and caesarean birth is associated with a number of risks in patients with HSD. Airway management may be more challenging for patients with EDS, with higher rates of cervical spine instability and temporomandibular joint dysfunction, although these issues were not present in this case [2]. Obstetric considerations following failed instrumental delivery include caesarean deliveries being technically difficult, due in part to an impacted fetal head [9]. Additionally, second‐stage caesarean births potentially carry increased risks compared to first‐stage caesarean deliveries, including higher rates of intra‐operative trauma [10]. Local anaesthetic resistance can greatly affect the mode of delivery, with associated challenges.

This case demonstrates the unique experience of a patient with a hypermobility condition who has had failed epidural and spinal analgesia, in addition to an unsuccessful pudendal block. Such a case has not previously been described, with most previous work describing one or two routes of LA administration. The rates of LA resistance in HSD/hEDS are not defined, with current literature mainly consisting of case reports; this is an area that warrants further research. Clinically, an early plan should be made for any patient who describes previous failure of local anaesthesia and patient concerns over the effectiveness of local anaesthesia should be recognised. LA resistance affects not only patient experience of labour but can significantly impact on obstetric outcomes, such as labour progression and mode of birth. Patients with HSD/hEDS should be specifically assessed for LA resistance as part of their antenatal care, and any medical or surgical clerking.