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5.1.3 Local anaesthetic toxicity

Direct toxicity
Lignocaine (5%) infused via lumbar subarachnoid microcatheters has been associated with
case reports of cauda equina syndrome (Rigler et al, 1991 Level IV; Schell et al, 1991 Level IV). This
suggested that high local concentrations of lignocaine were potentially neurotoxic and led to
the technique falling into disfavour.
Transient Neurological Symptoms (TNS) is a clinical syndrome associated with spinal
anaesthesia. Patients experience pain or muscle spasms in the buttocks or lower limbs
following initial recovery from the spinal anaesthetic. The onset of symptoms is usually within
24 hours of the procedure and it fully resolves spontaneously within a few days. A meta‐
analysis was performed of all randomised and pseudo‐randomised (Level II and Level III‐1)
studies comparing the frequency of TNS and neurological complications after spinal
anaesthesia with lignocaine to other local anaesthetics; the overall incidence was 14.2%
following lignocaine and the relative risk (RR) for developing TNS after spinal anaesthesia with
lignocaine compared with other local anaesthetics (bupivacaine, prilocaine, procaine,
levobupivacaine, ropivacaine and 2‐chloroprocaine) was 7.31 (95% CI 4.16 to 12.86); there was
no association with baricity or lignocaine concentration in the individual studies that
compared these factors (Zaric et al, 2009 Level I).
Systemic toxicity
There are consistent laboratory data showing that the S‐enantiomers of the long‐acting amide
CHAPTER 5 local anaesthetics exhibit less central nervous system (CNS) or cardiac toxicity than the R‐
enantiomers or the racemic mixtures for doses resulting in equivalent sensory nerve
conduction block. It is difficult to define relative toxicities for these agents because it depends
on the parameters measured.
There is a lack of scientific data available to determine the safe dose of local anaesthetic.
However the upper limit of a safe dose should take into account patient weight, age and
comorbidities. There is a pharmacokinetic rationale to support fractional dosing by
incremental injection of local anaesthetic. There are case reports of systemic local anaesthetic
toxicity occurring using ultrasound guidance, although a meta‐analysis found a significantly
decreased risk of vascular puncture using ultrasound (RR 0.16; 95% CI 0.05 to 0.47) (Abrahams
et al, 2008 Level I).
In blinded human volunteer studies, CNS symptoms were detected at IV doses and plasma
levels that were 25% higher for ropivacaine compared with bupivacaine (Scott et al, 1989
Level II) and 16% higher for levobupivacaine than bupivacaine (Bardsley et al, 1998 Level II).
Although these data show that CNS toxicity might occur less frequently or be less severe with
the S‐enantiomers, all local anaesthetics are toxic. A rapid IV bolus of any of these agents may
overwhelm any of the more subtle differences found at lower plasma concentrations.
Severe myocardial depression and refractory ventricular fibrillation have been described as
the hallmark of accidental IV administration of moderately large doses of bupivacaine. This has
been attributed to the slow dissociation of bupivacaine from the myocardial sodium channel,
which is less marked with levobupivacaine and ropivacaine (Mather & Chang, 2001; Mather et al,
2005). Animal studies confirm that higher systemic doses of ropivacaine and levobupivacaine
are required to induce ventricular arrhythmias, circulatory collapse or asystole (Ohmura et al,
2001), with the ranking of toxicity risk being bupivacaine > levobupivacaine > ropivacaine
(Groban & Dolinski, 2001).

124 Acute Pain Management: Scientific Evidence