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Controlled human studies are only possible when looking at surrogate endpoints such as ECG
changes or myocardial depression and suggest a similar ranking of effect (Scott et al, 1989
Level II; Knudsen et al, 1997 Level II; Bardsley et al, 1998 Level II; Mather & Chang, 2001 Level II), with
bupivacaine being the most toxic and levobupivacaine being less toxic and similar to
ropivacaine (Stewart et al, 2003 Level II).
Successful resuscitation from a massive overdose is of greater relevance in clinical practice.
A canine study investigating resuscitation and survival following local anaesthetic‐induced
circulatory collapse showed survival rates of 50%, 70% and 90% with bupivacaine,
levobupivacaine and ropivacaine respectively (Groban & Dolinski, 2001).
Case reports of accidental toxic overdose with ropivacaine and bupivacaine suggest that
outcomes are more favourable and resuscitation more straightforward (in particular requiring
less cardiovascular [CV] support) with ropivacaine (Pham‐Dang et al, 2000; Chazalon et al, 2003;
Huet et al, 2003; Klein et al, 2003; Soltesz et al, 2003; Khoo & Corbett, 2006; Kimura et al, 2007).
Total plasma levels of local anaesthetic tend to rise during the first 48 hours of postoperative
infusion, although free levels remain relatively low (Emanuelsson et al, 1995; Scott et al, 1997).
Thus, in published studies, toxicity due to systemic absorption from epidural or perineural
infusions has not been a problem. However, the risk of accidental absolute overdose with
postoperative infusions suggests that the less toxic agents should be used in preference and
that the doses administered should be the minimum needed for efficacy.
There is basic scientific evidence and several case reports to support the use of IV lipid
emulsion therapy for systemic local anaesthetic toxicity resulting in CV collapse (Felice &
Schumann, 2008 Level IV). Animal experimental data (Weinberg et al, 2003; Weinberg et al, 1998)
have been supported by a few case reports of successful resuscitation following bupivacaine CHAPTER 5
(Rosenblatt et al, 2006), ropivacaine (Litz et al, 2006), levobupivacaine (Foxall et al, 2007),
mepivacaine/prilocaine (Litz et al, 2008) and mepivacaine/bupivacaine (Warren et al, 2008)
toxicity. The mechanism of action of the lipid emulsion may be due to partitioning of local
anaesthetic within the emulsion itself (Weinberg, 2006) or mitochondrial substrate
enhancement in the myocardium (Weinberg et al, 2000). Uncertainties relating to dosage,
efficacy and side effects still remain and therefore it is recommended that lipid emulsion only
be administered after advanced cardiac life support has commenced, including adrenaline
administration, and convulsions controlled (Corman & Skledar, 2007 Level IV). Guidelines have
been established to facilitate management of local anaesthetic toxicity, which now include
reference to lipid emulsion therapy (AAGBI, 2007). It should be noted that local anaesthetic
toxicity might recur following successful initial resuscitation, suggesting a need for continued
intensive observation if a large dose of local anaesthetic has been administered (Marwick
et al, 2009).

Key messages
1. Lignocaine is more likely to cause transient neurologic symptoms than bupivacaine,
prilocaine and procaine (N) (Level I [Cochrane Review]).
2. The quality of epidural analgesia with local anaesthetics is improved with the addition of
opioids (U) (Level 1).
3. Ultrasound guidance reduces the risk of vascular puncture during the performance of
regional blockade (N) (Level I).
4. Continuous perineural infusions of lignocaine (lidocaine) result in less effective analgesia
and more motor block than long‐acting local anaesthetic agents (U) (Level II).

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