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. 2019 Dec 1;12(12):CD003006.
doi: 10.1002/14651858.CD003006.pub4.

Transient neurological symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics in adult surgical patients: a network meta-analysis

Patrice Forget  1   2 , Josip A Borovac  3 , Elizabeth M Thackeray  4 , Nathan L Pace  4
Affiliations

Transient neurological symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics in adult surgical patients: a network meta-analysis

Patrice Forget et al. Cochrane Database Syst Rev. .

Abstract

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 methods: 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.

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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Conflict of interest statement

PF: none.

JAB: none.

EMT: taught a 'safe sedation simulation' course to doctors and nurses as a consultant for Applied Medical Visualizations.

NLP: is a tenured professor (University of Utah) and has no conflicts of interest regarding the topic of this review. He has received payment for the development of educational presentations (Barash, Cullen, Toelting Clinical Anaesthesia 8th Edition) and provided consultancy (St Marks Hospital, Salt Lake City, UT; JB3 Bioscience Inc, Salt Lake City, UT; Elute, Salt Lake City, UT) on topics unrelated to the current review. He has received financial supplements to attend Cochrane meetings. He also has stocks and shares in companies who have no interests in the topic of this review (TIAA‐CREF, Fidelity, Vanguard, USAA, Morgan Stanley).

Figures

1
1
Forest plot of comparison: 1 Lidocaine versus other local anaesthetic, outcome: 1.1 Transient neurological symptoms.
2
2
Network meta‐analysis plot of interactions among included studies displayed for a random‐effects, risk ratio model, regarding the risk of transient neurological symptoms following spinal anaesthesia with lidocaine versus other local anaesthetics in adults undergoing surgery. Each node represents an individual local anaesthetic. The node size is proportional to the number of studies.
 The node colours are determined by the individual study 'Risk of bias' assessment (green: no concerns; yellow: some concerns; red: major concerns).
 The width of the edges is proportional to the inverse variance of the effect size. The edge colours reflect the average risk of bias. bupi: bupivacaine; chloro: 2‐chloroprocaine; levo: levobupivacaine; lido: lidocaine; mepi: mepivacaine; prilo: prilocaine; pro: procaine; ropi: ropivacaine.
3
3
Risk of bias (RoB) assessment among studies included in the network meta‐analysis with direct effect estimation is displayed, regarding the risk of transient neurological symptoms following spinal anaesthesia with lidocaine versus other local anaesthetics in adults undergoing surgery. Direct RoB was determined by the average RoB assigned to each particular network interaction. bupi: bupivacaine; chloro: 2‐chloroprocaine; levo: levobupivacaine; lido: lidocaine; mepi: mepivacaine; prilo: prilocaine; pro: procaine; ropi: ropivacaine.
4
4
Contributions of indirect and mixed effects in the network meta‐analysis, regarding the risk of transient neurological symptoms following spinal anaesthesia with lidocaine versus other local anaesthetics in adults undergoing surgery. bupi: bupivacaine; chloro: 2‐chloroprocaine; levo: levobupivacaine; lido: lidocaine; mepi: mepivacaine; NMA: network meta‐analysis; prilo: prilocaine; pro: procaine; ropi: ropivacaine
5
5
Analysis of imprecision among studies included in the network meta‐analysis, regarding the risk of transient neurological symptoms following spinal anaesthesia with lidocaine versus other local anaesthetics in adults undergoing surgery. bupi: bupivacaine; chloro: 2‐chloroprocaine; levo: levobupivacaine; lido: lidocaine; mepi: mepivacaine; prilo: prilocaine; pro: procaine; ropi: ropivacaine.
6
6
Heterogeneity assessment in network meta‐analysis displaying confidence and prediction intervals, regarding the risk of transient neurological symptoms following spinal anaesthesia with lidocaine versus other local anaesthetics in adults undergoing surgery. bupi: bupivacaine; chloro: 2‐chloroprocaine; levo: levobupivacaine; lido: lidocaine; mepi: mepivacaine; prilo: prilocaine; pro: procaine; ropi: ropivacaine.
7
7
Summary of risk of bias assigned to studies included in the network meta‐analysis across six domains: study limitations, imprecision, heterogeneity, incoherence, indirectness, publication bias, regarding the risk of transient neurological symptoms following spinal anaesthesia with lidocaine versus other local anaesthetics in adults undergoing surgery. Output was created with CINeMA software. bupi: bupivacaine; chloro: 2‐chloroprocaine; levo: levobupivacaine; lido: lidocaine; mepi: mepivacaine; prilo: prilocaine; pro: procaine; ropi: ropivacaine.
8
8
Study selection flow diagram corresponding to the last search update, up to November 2018.
9
9
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
10
10
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 One local anaesthetic versus a different local anaesthetic, Outcome 1 Presence of any transient neurological symptoms.
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Frisch 2018 {published data only}
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References to other published versions of this review

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