Lignocaine as an intravenous analgesic

Case history

A 56-year-old male with a background of atrial fibrillation (AF), chronic obstructive pulmonary disease (COPD), current smoking status and chronic opioid use secondary to a previous back injury, underwent an emergency laparotomy for a bowel perforation. Due to recent use of anticoagulants and the urgent nature of the procedure, regional anaesthesia was contraindicated. Given the patient’s opioid tolerance, comorbidities and the extensive surgical insult, postoperative analgesia was anticipated to be challenging, increasing the patient’s risk of postoperative pulmonary complications.

How can lignocaine be used intravenously as an adjunctive analgesic for those with complex pain needs and what are the common complications to avoid?

Discussion

Lignocaine is an amide-type local anaesthetic with broad clinical utility. It is widely used for multiple purposes including:

• local, regional and intravenous (IV) analgesia;

• as an adjunct in multimodal analgesic regimes to reduce opioid requirements and mitigate opioid side effects;

• enhancement of general anaesthesia by decreasing anaesthetic agent requirements;

• treatment of arrhythmias as a class Ib anti-arrhythmic agent.

Evidence for use of lignocaine in chronic post-surgical pain (CPSP), preventative analgesia and acute pain

CPSP affects approximately 20–30% of patients following surgery with risk varying amongst individuals [1]. Risk factors for CPSP development can be broadly grouped into preoperative, intraoperative and postoperative contributors. Preoperatively, higher-risk individuals include those with persistent moderate-severe pain for greater than 1 month, a history of ineffective pain control, recurrent surgeries, psychological or genetic vulnerability and demographic factors such as younger age and female sex [1]. Intraoperative contributors are primarily influenced by surgical technique and the risk of nerve damage whilst postoperative factors include ongoing severe pain, exposure to radiation or neurotoxic chemotherapy treatment and ongoing psychological vulnerability [1]. Evidence suggests that agents such as IV lignocaine, gabapentinoids, ketamine and possibly dexmedetomidine may reduce the incidence of CPSP for up to 6 months [2]. Specifically, IV lignocaine has been shown to decrease CPSP following breast cancer surgery at 3 months compared with systemic analgesia alone [1].

Lignocaine also demonstrates a role in preventative analgesia due to its prolonged clinical effect that extends up to 8.5 hours beyond the infusion period [3]. Its ability to attenuate acute postoperative pain has been supported by numerous randomised controlled trials. However, variability in study protocols, including dosing, infusion rates, duration and the analgesic regimen of control groups, necessitates a more critical assessment of the evidence [4]. A detailed summary of the available evidence is provided by Dunn et al. (2017) [3].

In addition to analgesia, perioperative lignocaine infusions have been associated with secondary benefits including reduced nausea, shorter duration of an ileus, decreased opioid requirements and reduced length of hospital stay [3].

Mechanism of action

Lignocaine exerts its primary action by reversibly blocking the conduction of central and peripheral nerve impulses by inhibiting voltage-gated sodium channels on nerve cell membranes [5]. This maintains the channels in an inactive state, preventing sodium influx into the cell membrane, depolarisation and subsequent propagation of an action potential. Thus, it results in the interruption of nociceptive nerve transmission [5]. Beyond its anti-nociceptive properties, lignocaine also exhibits anti-hyperalgesic and anti-inflammatory properties. Its multimodal mechanism is reflective of its action on multiple receptor sites beyond the sodium channel, including muscarinic receptors, NMDA receptors, serotonin receptors, Toll-like receptors and more [4]. These additional properties prove beneficial in contributing to systemic analgesia in complex perioperative pain scenarios.

Pharmacology

Lignocaine has a rapid onset of action, typically within 5 to 10 minutes, with an intermediate duration of action ranging from 60 to 120 minutes [5]. Approximately 60–80% of lignocaine is protein bound, primarily to alpha-1-glycoprotein. It undergoes hepatic metabolism by oxidative N-dealkylation, predominantly mediated by the cytochrome P450 enzyme CYP3A4 [6]. Its metabolites are rapidly metabolised within the liver and are renally excreted with an elimination half-life ranging from 90 to 120 minutes in healthy individuals [6]. Metabolism and excretion of lignocaine may be impaired in patients with cardiac, hepatic and renal dysfunction, increasing the risk of metabolite accumulation and systemic toxicity [6].

Method of use

After conducting a pain assessment to determine whether the patient would benefit from IV lignocaine as an adjunct analgesic, clinicians must first review any contraindications, potential drug interactions and any concurrent use of local anaesthetic techniques. Absolute contraindications include patient refusal, known or suspected allergy to lignocaine or amide-type local anaesthetics, significant cardiac conduction abnormalities (e.g. complete heart block, severe myocardial depression) and weight under 40 kg [4]. Dose reductions may be required in high-risk groups including elderly, pregnant or paediatric patients, low body weight, heart failure, hepatic or renal impairment, acidaemia or hypoxaemia and hypoalbuminaemia or plasma protein depletion. However, patient selection criteria may also be guided by local institutional protocols.

If alternative local anaesthetic techniques have been used, such as regional anaesthesia, peripheral nerve blocks or local infiltration, a minimum interval of 4 hours should be observed prior to initiating IV lignocaine. No delay is required following spinal or intrathecal opioid use, whilst any topical lignocaine plasters must be removed beforehand [4]. These safety recommendations align with the Association of Anaesthetists of Great Britain and Ireland (AAGBI) 2021 consensus statement to promote safe clinical practice and avoidance of local anaesthetic toxicity [4]. The treating doctor must determine the appropriate dosage and administration based on clinical assessment and monitoring for effectiveness and potential side effects. In this context, lignocaine is most often administered as an IV bolus followed by an infusion in accordance with local institutional policy/guidelines.

IV lignocaine is administered as a 1% solution (10 mg/ml) without adrenaline. Dosing is based on the patient’s ideal body weight (IBW) unless their actual weight is lower. Doctors must determine the appropriate dosage and administration based on clinical assessment and monitoring for effectiveness and potential side effects. Intraoperative administration should ideally be completed prior to skin incision [4]. In patients at higher risk of toxicity, this bolus dose must be reduced, infused over a longer duration or omitted altogether.

Dose adjustments should only be made after 8 hours, once steady state is reached. The maximum duration of the infusion is 24 hours [4]. This may vary among institutions, but hospital-based policies should define settings, personnel and protocols for safe administration.

Adverse events

Local anaesthetic systemic toxicity (LAST) is influenced by several factors, including the total dose administered (adjusted for weight and comorbidities), infusion rate and duration. In healthy patients, lignocaine exhibits linear and predictable pharmacokinetics with an elimination phase up to 12 hours [4]. To minimise toxicity, if the infusion is necessary beyond 24 hours, the rate should be reduced in accordance with local prescribing policy.

LAST comprises neurological and cardiovascular symptoms, which correlate with rising plasma lignocaine concentrations [7]. CNS toxicity progresses through two distinct phases; an initial excitatory phase marked by perioral tingling or numbness, tinnitus, slurred speech and twitching, followed by the development of an inhibitory phase with higher plasma lignocaine concentrations characterised by confusion, CNS depression, coma and ultimately respiratory depression and arrest [7, 8]. At higher plasma lignocaine concentrations, cardiovascular toxicity develops characterised by myocardial depression and progressing to cardiac arrhythmias (sinus bradycardia, conduction blocks, ventricular tachyarrhythmias) and ultimately ventricular arrest [7, 8].

Whilst not all complications may be directly attributed to LAST, a high degree of clinical suspicion is necessary when lignocaine infusions are used. This is particularly critical in sedated or intubated patients, in which classical symptoms may be masked or go unreported by the patient, further reinforcing the need for ongoing clinical vigilance [7]. Signs of muscle twitching, arrhythmia and hypotension should raise suspicions of toxicity in such patients and be acted upon immediately.

Management of LAST

All clinical staff must be familiar with the signs, symptoms and management of LAST, as well as the location of intralipid treatment therapy. For a comprehensive guideline on the recognition and treatment, refer to the AAGBI management guidelines (Fig. 1) [8].

Figure 1.

AAGBI Safety Guideline for the management of LAST.

Source: Association of Anaesthetists [8].

Declarations and conflicts of interest