Occurrence of transient neurological symptoms following spinal anaesthesia with lidocaine versus other local anaesthetics in adults undergoing surgery

Review question

We aimed to determine if transient neurological symptoms (TNS) occur more frequently after recovery from spinal anaesthesia with lidocaine than with other local anaesthetics in adults. The symptoms are mild to severe pain in the buttocks and legs that can last for days. We also looked for longer-lasting sensory or motor disturbances caused by nerve damage by local anaesthetics, known as neurological complications.

Background

Mild pain in the lower back is a common complaint following spinal anaesthesia (where a local anaesthetic is injected into the spinal column rather than using general anaesthetic into the whole body). People may also experience headache and low blood pressure. TNS symptoms are different. They appear within a few hours up to 24 hours after spinal anaesthesia and may last up to two to five days.

Lidocaine (a local anaesthetic) continues to be used for spinal anaesthesia because of its unique short duration of action, intense blockade, quick recovery, and suitability for day-case surgery, but alternatives are needed.

This review was originally published in 2005 and previously updated in 2009.

Study characteristics

We included all randomized trials and quasi-randomized trials comparing the frequency of TNS and neurological complications after spinal anaesthesia with lidocaine compared to other local anaesthetic agents. Randomized trials compare two or more treatments where the treatments are allocated to participants in a random manner that cannot be predicted by the study organizers. Quasi-randomized studies are similar but are not truly random, but carry a greater likelihood that the study organizer can predict which treatment the participants receive (e.g. based on date of birth or the order in which people were recruited).

The evidence is current to 25 November 2018.

Key results

We included 24 trials reporting on 2226 participants, 239 of whom developed TNS. There was no evidence TNS was associated with any specific neurological disease and symptoms disappeared spontaneously by the fifth postoperative day. The risk of developing TNS with lidocaine for spinal anaesthesia was increased compared to bupivacaine, prilocaine, or procaine; and similar compared to 2-chloroprocaine and mepivacaine.

Specifically, when alternative local anaesthetics were compared directly to lidocaine, the risk of developing TNS was reduced by between 82% and 90% when bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine were used rather than lidocaine. There were no clear differences in TNS between lidocaine and 2-chloroprocaine or mepivacaine. In the case of 2-chloroprocaine, TNS occurred in only one study and the results varied greatly for the small number of participants. Painful symptoms stopped by the fifth postoperative day in all participants. Among pregnant women undergoing surgery, only 3/310 women developed TNS; no conclusions could be drawn on whether symptoms were more likely with lidocaine.

The authors also used the statistical method of network meta-analysis to compare the various local anaesthetics. This analysis similarly showed that the risk of TNS was lower for bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine, while 2-chloroprocaine and mepivacaine did not differ in risk of TNS compared to lidocaine. 

Quality of the evidence

Due to the very low- to moderate-quality of evidence among currently available studies, future research efforts in this field are needed to assess alternatives to lidocaine that can provide high-quality anaesthesia without TNS development.

Conclusion

Lidocaine has been the drug of choice for inducing spinal anaesthesia in ambulatory surgery (or day surgery) because of its rapid onset of action, intense nerve blockade, and short duration of action. The present review shows that lidocaine is more likely to cause TNS than bupivacaine, prilocaine, and procaine. However, these drugs produce longer local anaesthetic effects and therefore are not desirable for ambulatory patients.

Our results suggest that 2-chloroprocaine might be a viable alternative to lidocaine for day surgery of short duration and obstetric procedures since this local anaesthetic has a rapid onset of action, is quickly metabolized, and has low toxicity. However, this conclusion is based on only two studies and low-quality evidence.

Authors' conclusions: 

Results from both NMA and pair-wise meta-analysis indicate that the risk of developing TNS after spinal anaesthesia is lower when bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine are used compared to lidocaine. The use of 2-chloroprocaine and mepivacaine had a similar risk to lidocaine in terms of TNS development after spinal anaesthesia.

Patients should be informed of TNS as a possible adverse effect of local anaesthesia with lidocaine and the choice of anaesthetic agent should be based on the specific clinical context and parameters such as the expected duration of the procedure and the quality of anaesthesia.

Due to the very low- to moderate-quality evidence (GRADE), future research efforts in this field are required to assess alternatives to lidocaine that would be able to provide high-quality anaesthesia without TNS development. The two studies awaiting classification and one ongoing study may alter the conclusions of the review once assessed.

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Background: 

Spinal anaesthesia has been implicated as one of the possible causes of neurological complications following surgical procedures. This painful condition, occurring during the immediate postoperative period, is termed transient neurological symptoms (TNS) and is typically observed after the use of spinal lidocaine. Alternatives to lidocaine that can provide high-quality anaesthesia without TNS development are needed. This review was originally published in 2005, and last updated in 2009.

Objectives: 

To determine the frequency of TNS after spinal anaesthesia with lidocaine and compare it with other types of local anaesthetics by performing a meta-analysis for all pair-wise comparisons, and conducting network meta-analysis (NMA) to rank interventions.

Search strategy: 

We searched CENTRAL, MEDLINE, Elsevier Embase, and LILACS on 25 November 2018. We searched clinical trial registries and handsearched the reference lists of trials and review articles.

Selection criteria: 

We included randomized and quasi-randomized controlled trials comparing the frequency of TNS after spinal anaesthesia with lidocaine to other local anaesthetics. Studies had to have two or more arms that used distinct local anaesthetics (irrespective of the concentration and baricity of the solution) for spinal anaesthesia in preparation for surgery.

We included adults who received spinal anaesthesia and considered all pregnant participants as a subgroup. The follow-up period for TNS was at least 24 hours.

Data collection and analysis: 

Four review authors independently assessed studies for inclusion. Three review authors independently evaluated the quality of the relevant studies and extracted the data from the included studies. We performed meta-analysis for all pair-wise comparisons of local anaesthetics, as well as NMA.

We used an inverse variance weighting for summary statistics and a random-effects model as we expected methodological and clinical heterogeneity across the included studies resulting in varying effect sizes between studies of pair-wise comparisons. The NMA used all included studies based on a graph theoretical approach within a frequentist framework. Finally, we ranked the competing treatments by P scores.

Main results: 

The analysis included 24 trials reporting on 2226 participants of whom 239 developed TNS. Two studies are awaiting classification and one is ongoing. Included studies mostly had unclear to high risk of bias.

The NMA included 24 studies and eight different local anaesthetics; the number of pair-wise comparisons was 32 and the number of different pair-wise comparisons was 11. This analysis showed that, compared to lidocaine, the risk ratio (RR) of TNS was lower for bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine with RRs in the range of 0.10 to 0.23 while 2-chloroprocaine and mepivacaine did not differ in terms of RR of TNS development compared to lidocaine.

Pair-wise meta-analysis showed that compared with lidocaine, most local anaesthetics were associated with a reduced risk of TNS development (except 2-chloroprocaine and mepivacaine) (bupivacaine: RR 0.16, 95% confidence interval (CI) 0.09 to 0.28; 12 studies; moderate-quality evidence; 2-chloroprocaine: RR 0.09, 95% CI 0.01 to 1.51; 2 studies; low-quality evidence; levobupivacaine: RR 0.13, 95% CI 0.02 to 0.69; 2 studies; low-quality evidence; mepivacaine: RR 1.01, 95% CI 0.18 to 5.82; 4 studies; very low-quality evidence; prilocaine: RR 0.18, 95% CI 0.07 to 0.49; 4 studies; moderate-quality evidence; procaine: RR 0.14, 95% CI 0.04 to 0.52; 2 studies; moderate-quality evidence; ropivacaine: RR 0.10, 95% CI 0.01 to 0.78; 2 studies; low-quality evidence).

We were unable to perform any of our planned subgroup analyses due to the low number of TNS events.

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