Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Zaric D, Christiansen C, Pace NL, Punjasawadwong Y
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2008, Issue 2 http://www.thecochranelibrary.com
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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TABLE OF CONTENTS ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW . . . . . . . . . . . . . . . . . . SEARCH METHODS FOR IDENTIFICATION OF STUDIES . . . . . . . . . . . . . . . . . . . METHODS OF THE REVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DESCRIPTION OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODOLOGICAL QUALITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . POTENTIAL CONFLICT OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Characteristics of included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Characteristics of excluded studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Table 01. Patients who developed TNS after intrathecal lidocaine . . . . . . . . . . . . . . . . . . ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Comparison 01. Lidocane versus other local anaesthetic . . . . . . . . . . . . . . . . . . . . . Comparison 02. Lidocaine versus other local anaesthetic (excluding mepivacaine) . . . . . . . . . . . . . INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . COVER SHEET . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . GRAPHS AND OTHER TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 01.01. Comparison 01 Lidocane versus other local anaesthetic, Outcome 01 Transient Neurologic Symptoms Analysis 02.01. Comparison 02 Lidocaine versus other local anaesthetic (excluding mepivacaine), Outcome 01 Transient Neurologic Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Zaric D, Christiansen C, Pace NL, Punjasawadwong Y
This record should be cited as: Zaric D, Christiansen C, Pace NL, Punjasawadwong Y. Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics. Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD003006. DOI: 10.1002/14651858.CD003006.pub2. This version first published online: 19 October 2005 in Issue 4, 2005. Date of most recent substantive amendment: 21 July 2005
ABSTRACT Background Spinal anaesthesia has been in use since the turn of the late nineteenth century. During the last decade there has been an increase in the number of reports implicating lidocaine as a possible cause of temporary and permanent neurologic complications after spinal anaesthesia. Follow-up of patients who received uncomplicated spinal anaesthesia revealed that some of them developed pain in the lower extremities after an initial full recovery. This painful condition that occurs in the immediate postoperative period was named “transient neurologic symptoms” (TNS). Objectives To study the frequency of TNS and neurologic complications after spinal anaesthesia with lidocaine, compared to other local anaesthetics. Search strategy We searched the Cochrane Controlled Trials Register (CENTRAL), (The Cochrane Library, Issue 1, 2005); MEDLINE (1966 to January 2005); EMBASE (1980 to week 6, 2005); LILACS (March 2005); and handsearched the reference lists of trials and review articles. Selection criteria We included all randomized and pseudo-randomized studies comparing the frequency of TNS and of neurologic complications after spinal anaesthesia with lidocaine as compared to other local anaesthetics. Data collection and analysis Two authors independently evaluated the quality of the relevant studies and extracted the data from the included studies. Main results Fifteen trials, reporting 1437 patients, 120 of whom developed transient neurologic symptoms, were included in the analysis. The use of lidocaine for spinal anaesthesia increased the risk of developing TNS. There was no evidence that this painful condition was associated with any neurologic pathology; the symptoms disappeared spontaneously by the fifth postoperative day. The relative risk (RR) for developing TNS after spinal anaesthesia with lidocaine as compared to other local anaesthetics (bupivacaine, prilocaine, procaine, levobupivacaine and ropivacaine) was 7.16 (95% confidence interval (CI) 4.02, 12.75). Authors’ conclusions The risk of developing TNS after spinal anaesthesia with lidocaine was significantly higher than when bupivacaine, prilocaine and procaine were used. The term “TNS”, which implies a positive neurologic finding, should not be used for this painful condition. One study about the impact of TNS on patient satisfaction and functional impairment demonstrated that non-TNS patients were more satisfied and had less functional impairment after surgery than TNS patients, but this did not influence their willingness to recommend spinal anaesthesia. Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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PLAIN LANGUAGE SUMMARY Lidocaine is more likely than bupivacaine, prilocaine or procaine to induce transient neurologic symptoms (TNS) when used for spinal anaesthesia. Lidocaine is the drug of choice for inducing spinal anaesthesia in ambulatory surgery because of its rapid onset of action, intense nerve blockade and short duration of action. The possible side effects of spinal anaesthesia in adults, which develop after recovery, are: backache, postdural puncture headache and transient neurologic symptoms that are characterized by slight to severe pain in the buttocks and legs. TNS symptoms develop within a few hours up to 24 hours after anaesthesia and last, in most cases, up to two days. The present review shows that lidocaine is more likely to cause transient neurologic symptoms than bupivacaine, prilocaine and procaine.
BACKGROUND August Bier performed the first spinal anaesthesia in 1898 using cocaine, which was the first known local anaesthetic (Bier 1899). Cocaine was soon replaced by another, less toxic local anaesthetic amylocaine. Other local anaesthetics were gradually introduced: procaine, dibucaine, lidocaine, tetracaine, mepivacaine, prilocaine, bupivacaine, and finally, ropivacaine and levobupivacaine. Lidocaine, procaine, tetracaine, mepivacaine, dibucaine and bupivacaine are still used for spinal anaesthesia (Axelrod 1998; Hiller 1997; Holmdahl 1998; Iselin-Chaves 1996; Masuda 1998; Tagariello 1998). The main clinical differences among these local anaesthetics are: the degree of central nervous system and cardio-vascular toxicity; the speed of onset; the intensity of motor and sensory blockade, and the duration of the surgical anaesthesia and regression phases. The choice of local anaesthetic is determined by the type and duration of surgery and by the intensity of motor blockade that is required. Regional preferences dependent upon national differences in pharmaceutical industry supply can also play an important role. The increase in day case surgery has generated a need for a local anaesthetic with a quick onset and short duration of action that allows for a speedy recovery and early discharge. So far, this profile is fulfilled only by lidocaine (Liu 1998). Intrathecally (spinally) administered local anaesthetics cause reversible blockade of nerve impulse conduction in the affected nerve roots. Experiments on animals have shown that all tested local anaesthetics have potential neurotoxic effects that are dependent on the dosage used and the duration of exposure (Li 1985). All local anaesthetics can cause permanent nerve damage, when administered in a high concentration or when applied over a long period of time. Retrospective and prospective surveys of neurological complications after spinal anaesthesia, and databases dealing with postoperative outcomes, have however shown that serious and permanent neurologic complications after spinal anaesthesia are rare incidents (Corbey 1998; Dahlgren 1995; Freedman 1998; Noble 1971; Phillips 1969; Renck 1995; Tarkkila 1991; Vandam 1955).
Reported cases of such permanent neurological deficits involve all known local anaesthetics (Auroy 1997; Green 1961; Kane 1981; Sumi 1996; Vandam 1960). From the beginning of 1990, a number of cases were published reporting cauda equina syndrome that was related to the introduction of a micro catheter-technique for continuous spinal anaesthesia with hyperbaric 5% lidocaine (the drug of choice) (Rigler 1991; Schell 1991). In 1993, a new adverse effect, “transient neurologic toxicity”, was described in patients recovering from single injection spinal anaesthesia with lidocaine (Schneider 1993). In the following years, new names for this condition appeared in the literature: “transient radicular irritation” (TRI: Hampl 1995b) and “transient neurologic symptoms” (TNS: Hampl 1998). The symptoms of TNS can appear from within a few hours up to 24 hours, after a full recovery from uneventful spinal anaesthesia. These symptoms consist of pain originating in the gluteal region and radiating to both lower extremities (Gerancher 1997; Tarkkila 1995). The intensity of pain varies from light to severe. Neurologic examination, magnetic resonance imaging and electropathological testing have showed no abnormalities in patients with TNS (Pollock 2000). In spite of this, TNS has been interpreted as a sign of possible neurotoxicity of lidocaine (Douglas 1995). These symptoms are not unique to lidocaine and are known to occur with other local anaesthetics as well (Casati 1998; Hiller 1997; Lynch 1997). The continued use of lidocaine as a spinal anaesthetic has been questioned: is it more neurotoxic than other local anaesthetics; should its use be curtailed (Drasner 1997)? The main reason for the continuing use of lidocaine for spinal anaesthesia is its short duration of action, intense blockade, quick recovery and suitability for day case surgery (Gielen 1986; McKeown 1986).
OBJECTIVES The objective of this review was to compare the frequency of transient neurologic symptoms (TNS) and neurologic complications after spinal anaesthesia with lidocaine, with the frequency of these adverse effects after other local anaesthetics in adult surgical patients. We defined neurologic complications as any sensory and
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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motor deficits lasting for longer than 48 hours after onset of spinal anaesthesia. The reason for this choice of interval is that the longest reported duration of spinal anaesthesia with bupivacaine was 48 hours.
CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW Types of studies We considered randomized controlled trials (RCTs) and pseudorandomized controlled trials, regardless of blinding, which were published in full. Types of participants We included all adult patients, including pregnant women, who received spinal anaesthesia. Follow-up period for TNS was at least 24 hours. We chose this time interval because the symptoms of TNS appear within 24 hours after spinal anaesthesia (Aouad 2001). All patients who developed TNS were to be followed until complete recovery. In case of sensory and motor deficits after spinal anaesthesia, the follow-up period should be longer than 48 hours. Types of intervention The included studies had to have at least one arm in which lidocaine (irrespective of the concentration and baricity of the solution) was used for spinal anaesthesia in preparation for surgery. The second arm consisted of any other local anaesthetic. We excluded studies dealing with meperidine as a sole intrathecal agent, or combinations of local anaesthetics and opioids. We also excluded studies in which spinal anaesthesia was combined with epidural analgesia. Types of outcome measures Dichotomous outcomes in the form of: (1) TNS; and (2) postoperative neurologic symptoms which lasted longer than 48 hours after onset of spinal anaesthesia, and which did not exist before the anaesthetic, specifically sensory deficits (numbness and pain) and/or motor deficits in the radicular distribution.
SEARCH METHODS FOR IDENTIFICATION OF STUDIES See: Cochrane Anaesthesia Group methods used in reviews. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2005); MEDLINE (1966 to January 2005); EMBASE (1980 to week 6 2005) and LILACS (March 2005). We searched MEDLINE using the following search terms: 1. explode “Lidocaine”/ all subheadings
2. explode “Anesthesia, -Spinal”/ all subheadings 3. explode “Postoperative-complications”/all subheadings 4. cauda equina syndrome 5. transitory radicular irritation 6. drug toxicity 7. exp randomised controlled trials/ 8. randomised controlled trials.pt. 9. exp random allocation/ 10. exp. double blind method/ 11. exp single blind method/ 12. exp clinical trials/ 13. clinical trial.pt. 14. controlled clinical trial.pt. 15. randomi$ 16. randomi$ near2 (assign$ or allocate$) 17. clin$ near trial$ 18. (singl$ or doubl$ or tripl$) near (blind$ or mask$) 19. or / 7-18 20. (animal not human).sh. 21. 19 not 20 We searched EMBASE (1980 to week 6 2005), LILACS (March 2005) and CENTRAL (The Cochrane Library, Issue 1, 2005) using a similar search strategy. We identified additional reports from the reference lists of retrieved trials, from review articles and from the abstracts of the European Society of Regional Anaesthesia (ESRA) meetings.
METHODS OF THE REVIEW Eligibility Two authors independently read the abstracts of all references retrieved by the electronic search and decided which studies appeared to fulfil the inclusion criteria. We obtained full text copies of the studies to be considered. We resolved disagreements by mutual consensus or by a third party. Data extraction We recorded the following information from the included studies in the table of included studies: experimental design characteristics; number of patients; demographics; country of investigation; treatment groups; concentration and volume of the local anaesthetic used; duration of follow-up period; spinal needle: size and shape. We regarded “TNS”, “sensory deficits” or “motor deficits” as three separate outcomes. Assessment of methodological quality We assessed each study that was taken into consideration for inclusion for quality on the basis of the use of randomization for allocation to treatment groups; the blinding of patients, providers, and assessors; the concealment of random allocation and the description of the withdrawals. We considered allocation concealment as adequate (“A”) if the sealed envelopes were used;
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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as uncertain (“B”) if identical blinded vials were used with no mention of sealed envelopes and not adequate (“C”) if neither was mentioned in the study. We recorded those studies that were excluded on the basis of low quality or for other reasons in the table ’Characteristics of excluded studies’ together with the reason for exclusion. Summarizing results We summarized the results using meta-analyses performed on the Cochrane Review Manager (RevMan & MetaView) software, version 4.2. We used relative risk (RR) as the metric of individual study and summary statistics with 95% confidence intervals. The initial statistical model assumed a fixed effect. We used a chi squared test to examine the included RCTs for statistical evidence of heterogeneity. We applied the random effects model in case of significant heterogeneity (p < 0.10). We planned subgroup analyses for patients placed in a special position (i.e. lithotomy) and for the use of different intrathecal needles (sharp versus pencil point, different sizes) because these factors are supposed to influence the frequency of TNS. We investigated the possibility of a publication bias using funnel plotting.
DESCRIPTION OF STUDIES See: ’Characteristics of included studies’ table. We considered 63 studies dealing with neurologic complications and spinal anaesthesia with lidocaine. Of these, we determined that 27 were not relevant, and excluded 21 for reasons cited in the ’Characteristics of excluded studies’ table (Tong 2003 is the result of this update). We included 15 RCTs in the final analysis. One of these is a newly identified RCT (Breebaart 2003). All 15 included studies satisfied the inclusion criterion comparing lidocaine as one treatment arm with different local anaesthetics in the second treatment arm. This second arm consisted of bupivacaine in seven studies (Aouad 2001; Hampl 1995b; Hampl 1998; Keld 2000; Philip 2001; Pollock 1996; Salmela 1998); prilocaine in four studies (de Weert 2000; Hampl 1998; Martinez-Bourio 1998; Salmela 1998); mepivacaine in three studies (Liguori 1998; Salazar 2001; Salmela 1998); procaine in two studies (Hodgson 2000; Le Truong 2001); ropivacaine and levobupivacaine in one study (Breebaart 2003). There were four studies (Breebaart 2003; Hampl 1998, Pollock 1996, Salmela 1998) with more than two treatment arms. In Hampl 1998 two concentrations of lidocaine were used and the results of the two lidocaine groups were pooled. In the studies of Breebaart 2003; Pollock 1996 and Salmela 1998 there were three treatment groups: two alternative local anaesthetics plus lidocaine. To avoid including the lidocaine patients twice in the comparison tables, one-half of the lidocaine patients were compared to all the patients of each of the other local anaesthetics treatment groups. In one study (Hampl 1995b), a control group with patients receiving general anaesthesia was not taken into consideration for statistical analysis.
Four studies came from the USA, three from Scandinavia, two from Switzerland, two from Spain and one each from Belgium, Canada, Lebanon and the Netherlands. Two studies (Aouad 2001; Philip 2001) differed from the rest because the participants were pregnant women. All studies investigated the frequency of TNS; one reported no events in any of the studied arms (Aouad 2001) and in six of them no events were found in the “other treatment” arm (Breebaart 2003; de Weert 2000; Hampl 1995b; Le Truong 2001; Liguori 1998; Pollock 1996). Subgroups of patients exposed to lithotomy or supine position and pencil point or sharp spinal needles were included in five RCTs (Le Truong 2001; MartinezBourio 1998; Pollock 1996; Salmela 1998; Østgaard 2000). In the rest of RCTs, the majority of patients underwent surgery in the supine position and only one kind of spinal needle (pencil point, 25G or larger) was used. All included studies investigated the incidence of TNS and none was set up to investigate sensory and motor deficits after spinal anaesthesia. The follow-up period was at least 24 hours, and all patients with TNS were followed longer than 24 hours, until recovery. The interviewer who assessed the occurrence of TNS was blinded as to which treatment group the patient belonged to in all except one RCT (de Weert 2000: blinding unclear). In six of the studies the interview was done by telephone (Breebaart 2003; Hodgson 2000; Keld 2000; Liguori 1998; Martinez-Bourio 1998; Pollock 1996) and in the remainder by direct contact with the patient, except for Le Truong 2001 (unclear).
METHODOLOGICAL QUALITY The overall quality of the included RCTs was good, (see table ’Characteristics of included studies table’). All studies were randomized. Blinding procedure was complete (patient, provider and assessor) in four studies (Hampl 1995b; Hampl 1998; Philip 2001; Pollock 1996), and blinding of patient and assessor was accomplished in eight studies (Aouad 2001; Breebaart 2003; Hodgson 2000; Keld 2000; Le Truong 2001; Liguori 1998; Martinez-Bourio 1998; Østgaard 2000). The blinding procedure was inadequate in three trials (de Weert 2000; Salazar 2001; Salmela 1998). Concealment of allocation was adequate in eight studies (Aouad 2001; Breebaart 2003; de Weert 2000; Hodgson 2000; Martinez-Bourio 1998; Pollock 1996; Salmela 1998; Østgaard 2000); uncertain in three (Hampl 1995b; Hampl 1998; Philip 2001); and not adequate in four (Keld 2000; Le Truong 2001; Liguori 1998; Salazar 2001). Outcomes were reported for dropouts by de Weert 2000; Keld 2000; Martinez-Bourio 1998; Philip 2001; Pollock 1996. Five RCTs had dropouts and failed to report outcomes (Hampl 1995b: one patient; Le Truong 2001: six patients; Liguori 1998 three patients; Salazar 2001 one patient; Østgaard 2000: one patient).
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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RESULTS See ’Comparisons and data’ for more information. Fifteen studies had a patient enrolment of 1449; outcomes were available for 1437. The overall risk of developing TNS when lidocaine was used for spinal anaesthesia was significantly higher than with all other investigated local anaesthetics (p = 0.0001) with a relative risk of 4.47 (95 % CI: 2.17, 9.20). When the studies that compared mepivacaine with lidocaine (Liguori 1998; Salazar 2001; Salmela 1998) were excluded from the analysis the heterogeneity chi-squared statistic was not significant (p = 0.83); a fixed effect model estimated the relative risk as 7.16 (4.02, 13.75). Pregnant women seem to have low frequency of TNS after spinal anaesthesia irrespective of the local anaesthetic used, but the number of participants was only 258 with three cases of TNS reported. Therefore more studies are needed to elucidate whether pregnant women are less likely to develop TNS. In the three studies that compared lidocaine with mepivacaine, the frequency of TNS was not higher for the lidocaine group, but again the number of patients was not large. It is possible that spinal anaesthesia with mepivacaine is associated with a similar frequency of TNS as with lidocaine. Bupivacaine, prilocaine and procaine, on the other hand, were associated with a lower frequency of TNS than lidocaine. Using the methods described in the British Medical Journal (BMJ) (Altman 2003), the relative risk of developing TNS after spinal anaesthesia with lidocaine compared to mepivacaine is different from the relative risk for bupivacaine versus lidocaine (z = 3.313, p = 0.002), different from prilocaine versus lidocaine (z = 2.71, p = 0.007) and different from procaine versus lidocaine (z = 2.59, p = 0.01). In seven of the included RCTs (Aouad 2001; Breebaart 2003; de Weert 2000; Hampl 1995b; Le Truong 2001; Liguori 1998; Pollock 1996) we found no events of TNS in the other treatment group; in Aouad 2001, there were no cases of TNS at all. The explanation for this lack of events may be that the patient populations differ from those in the other studies or that the number of patients is too small to encounter the event. None of the 1437 patients who received spinal anaesthesia was reported to have any permanent neurologic sensory or motor deficits. A few cases of paraesthesiae related to the spinal injection were described, but without sequelae. The total number of patients, who developed TNS after receiving spinal anaesthesia with lidocaine, was 97 of 704 patients (see table ’Patients with TNS’, Table 01). The clinical picture was typically bilateral pain in the buttocks, thighs and legs. These started within 24 hours after initiation of spinal anaesthesia and after complete recovery from spinal anaesthesia. Pain varied in intensity from mild to severe (VAS score 2 to 9.5) with most patients complaining of mild to moderate pain. Non steroidal anti-inflammatory drugs (NSAIDs) were the treatment of choice; a few patients received
opiates as well. In most patients the pain disappeared by the second day, and the maximum duration was five days, aside from one patient having symptoms for ten days. None of these patients had positive neurologic signs. Subgroup analysis We did not perform subgroup analysis based on patient position (lithotomy versus supine), or the shape and size of the spinal needle, as we could derive no systematic data from the 15 included RCTs. The majority of patients were operated on in supine position (1021 out of 1437), and pencil point needles (in most cases 25G) were used in 1018 patients. A subgroup analysis was not possible due to this lack of variability. Missing data In the trials where dropouts were reported but without mention of their outcome, we contacted the authors and completed the missing data completed when possible. In this way, we were able to reduce the number of patients who were excluded with unknown outcome. Sensitivity analysis A funnel plot of the included studies was reasonably symmetric, but that does not exclude the possibility of missing studies (unpublished data). An intention-to-treat analysis was possible for 10 of the 15 studies. Because of the small number of missing outcomes, no attempt to impute optimistic and pessimistic missing outcomes for the other five studies was made for a sensitivity analysis.
DISCUSSION The main clinical question addressed by this review is whether lidocaine used for spinal anaesthesia causes symptoms of TNS more frequently than with other local anaesthetics. The answer to this question is: yes. TNS can, however, be caused by all other investigated local anaesthetics, but the frequency associated with bupivacaine, prilocaine, procaine, ropivacaine and levobupivacaine is lower than that with lidocaine. Only one study comparing lidocaine to new local anaesthetics (ropivacaine and levobupivacaine) with 90 patients is not yet enough to conclude that the frequency of TNS with these is less than with lidocaine. Approximately one of seven patients who received spinal anaesthesia with lidocaine developed TNS. Pain in the lower back is a very common complication after spinal anaesthesia with any local anaesthetic. Its aetiology is unknown, but no connection to neurologic pathology has been suggested in the literature. Lower back pain is different from pain experienced in the buttocks and lower extremities after recovery from spinal anaesthesia, which has been characterized as “transient neurologic symptoms”, and also shows no evidence for localized nerve damage. Studies with different concentrations and doses of lidocaine
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have shown that the incidence of TNS was not dose- or concentration-dependant (Freedman 1998; Hampl 1996; Pollock 1999; Tong 2003). All forms of lidocaine have been associated with TNS: hyperbaric (Tong 2003), isobaric (Hampl 1996); as well as when diluted with cerebrospinal fluid (Pollock 1999). The cause of this painful condition is as yet unknown, and none of the speculations on its origin has been substantiated. The term “transient neurological symptoms” implies neurologic pathology. Failing identification of the pathogenesis of TNS, there should be consideration given to choosing a neutral descriptive term which does not imply a particular causation. The question is how much TNS influences patients’ satisfaction and their rehabilitation. In a recent multicentre RCT (Tong 2003), 20% of 453 patients who received spinal anaesthesia with lidocaine for short urological procedures developed TNS. TNS patients had higher pain scores, they used more analgesics postoperatively and experienced higher degrees of functional impairment during the two postoperative days than those who did not develop TNS. Satisfaction was higher in the non-TNS patients (96%) than in TNS patients (89%). However, the proportion of patients who will recommend spinal anaesthesia was the same (95%). It seems that the transitory pain and functional impairment are not of such degree that they have negative influence on the patients’ decision to receive spinal anaesthesia in the future. On the other hand, in an epidemiologic study (Freedman 1998) with 1863 patients, 30% of the 104 patients who developed TNS after intrathecal lidocaine rated their pain as severe. Permanent neurologic deficits (varying from radicular symptoms to paralysis and cauda equina) are described after both general and regional anaesthesia. Most cases are multi factorial and not related to any particular form of anaesthesia. They can often be explained by known or unknown pre-existing neurologic pathology, or as a result of incorrect positioning of patients on the operating table. As a matter of fact, the latter is described as the most frequent cause of peripheral nerve injuries, occurring in one out of 350 patients (Sawyer 2000). On the other hand, neurologic sequelae related to anaesthesia are very rare events. Their aetiology is, again, complex and difficult to elucidate. Possible causes are intrathecal hematoma due to the use of anticoagulants (especially low molecular weight heparins:Horlocker 2000); spinal cord ischaemia (Usubiaga 1975); mechanical trauma (Selander 1988) and neurotoxicity. The incidence of neurologic sequelae after spinal anaesthesia varies, depending upon whether studies are retrospective or prospective, from 1: 10000 in the older literature (Vandam 1955; Vandam 1960) to more recent reports where the highest incidence is cited as approximately one in 3000 spinal anaesthesias (Dahlgren 1995). The events are so rare that no randomized trial relating to this complication has been performed. In the patient population contained in this review, the total number of patients is only 1437 and no neurologic sequelae have been reported. These rare events
can be found in the literature as case reports, retrospective and prospective surveys, or as reports from databases for registration of postoperative complications.
AUTHORS’ CONCLUSIONS Implications for practice The relative risk of developing TNS is about seven times higher for lidocaine than for bupivacaine, prilocaine, procaine, ropivacaine and levobupivacaine. These painful symptoms disappear completely by the fifth postoperative day. The risk of TNS weighted against the benefit of rapid, short-acting anaesthesia and the patient’s view must be considered in the decision as to whether to use lidocaine for ambulatory anaesthesia. Patients should be informed about this adverse effect and its effective treatment with analgesics. Bupivacaine, prilocaine and procaine are associated with lower risks of TNS but their longer duration or lower quality of anaesthesia may limit the suitability for ambulatory surgery. There is yet not enough data to make that conclusion about ropivacaine and levobupivacaine. Implications for research In order to elucidate the frequency of TNS when mepivacaine is used for spinal anaesthesia, more RCTs are necessary. Ropivacaine and levobupivacaine are new local anaesthetics and more studies are needed to find out whether they behave like bupivacaine in this regard. Likewise more studies with pregnant women are needed to draw conclusions about the frequency of TNS in this patient population. There is still a lack of precise estimates of the incidence of rare events such as permanent neurologic deficits after regional anaesthesia. An international database for registration of serious rare events could be the solution to this problem. Regional anaesthesia societies (such as the European Society Of Regional Anaesthesia and Pain Therapy (ESRA), the American Society of Regional Anesthesia (ASRA) and the Latin American Society of Regional Anaesthesia (LASRA) ) are obvious candidates for such an important task.
POTENTIAL CONFLICT OF INTEREST None known.
ACKNOWLEDGEMENTS We would like to acknowledge and thank Dr Janet Wale for her consumer synopsis. Her efforts have greatly contributed to the editorial process of this review. We would also like to thank Helen
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Worthington (Statistical and Co-ordinating Editor Cochrane Oral Health Group) and Dr Peter Choi for reading, and commenting upon, this review.
SOURCES OF SUPPORT External sources of support • No sources of support supplied Internal sources of support • No sources of support supplied
REFERENCES
References to studies included in this review Aouad 2001 {published data only} Aouad MT, Siddik SS, Jalbout MI, Baraka AS. Does pregnancy protect against intrathecal lidocaine-induced transient neurological symptoms?. Anesthesia and Analgesia 2001;92(2):401–4. [MEDLINE: 11159240]. Breebaart 2003 {published data only} Breebaart MB, Vercauteren MP, Hoffmann VL, Adriaensen HA. Urinary bladder scanning after day-case arthroscopy under spinal anaesthesia: comparison between lidocaine, ropivacaine and levobupivacaine. British Journal of Anaesthesia 2003;90(3):309–13. [MEDLINE: 12594142]. de Weert 2000 {published and unpublished data} de Weert K, Traksel M, Gielen M, Slappendel R, Weber E, Dirksen R. The incidence of transient neurological symptoms after spinal anaesthesia with lidocaine compared to prilocaine. Anaesthesia 2000; 55(10):1020–4. [MEDLINE: 11012500]. Hampl 1995b {published data only} Hampl KF, Schneider MC, Thorin D, Ummenhofer W, Drewe J. Hyperosmolarity does not contribute to transient radicular irritation after spinal anesthesia with hyperbaric 5% lidocaine. Regional Anesthesia 1995;20(5):363–8. [MEDLINE: 8519711]. Hampl 1998 {published data only} Hampl KF, Heinzmann-Wiedmer S, Luginbuehl MC, Drasner K. Transient neurologic symptoms after spinal anesthesia. Anesthesiology 1998;88(3):629–33. [MEDLINE: 952380].
Le Truong 2001 {published and unpublished data} Le Truong HH, Girard M, Drolet P, Grenier Y, Boucher C, Bergeron L. Spinal anesthesia: a comparison of procaine and lidocaine. Canadian Journal of Anaesthesia 2001;48(5):470–3. [MEDLINE: 11394516]. Liguori 1998 {published data only} Liguori GA, Zayas VM, Chisholm MF. Transient neurologic symptoms after spinal anesthesia with mepivacaine and lidocaine. Anesthesiology 1998;88(3):619–23. [MEDLINE: 9523803]. Martinez-Bourio 1998 {published data only} Martinez-Bourio M, Arzuaga M, Quintana JM, Aguilera L, Aguirre J, Saez-Equilaz JL, et al.Incidence of transient neurologic symptoms after hyperbaric subarachnoid anesthesia with 5% lidocaine and 5% prilocaine. Anesthesiology 1998;88(3):624–8. [MEDLINE: 9523804]. Philip 2001 {published data only} Philip J, Sharma SK, Gottumukkala VNR, Perez BJ, Slaymaker EA, Wiley J. Transient neurologic symptoms after spinal anesthesia with lidocaine in obstetric patients. Anesthesia and Analgesia 2001;92(2): 405–9. [MEDLINE: 11159241]. Pollock 1996 {published data only} Pollock J, Neal JM, Stephensen CA, Wiley CE. Prospective study of the incidence of transient radicular irritation in patients undergoing spinal anesthesia. Anesthesiology 1996;84(6):1361–7. [MEDLINE: 8669677].
Hodgson 2000 {published data only} Hodgson PS, Liu SS, Barta MS, Gras TW, Pollock J, Neal JM. Procaine compared with lidocaine for incidence of transient neurologic symptoms. Regional Anesthesia and Pain Medicine 2000;25(3):218– 22. [MEDLINE: 10834773].
Salazar 2001 {published and unpublished data} Salazar F, Bogdanovich A, Adalia R, Chabas E, Gomar C. Transient neurologic symptoms after spinal anaesthesia using isobaric 2% mepivacaine and isobaric 2% lidocaine. Acta Anaesthesiologica Scandinavica 2001;45(2):240–5. [MEDLINE: 11731731].
Keld 2000 {published and unpublished data} Keld KD, Hein L, Dalgaard M, Krogh L, Rodt SÅ. The incidence of transient neurologic symptoms (TNS) after spinal anaesthesia in patients undergoing surgery in the supine position. Hyperbaric lidocaine 5% versus hyperbaric bupivacaine 0,5%. Acta Anaesthesiologica Scandinavica 2000;44(3):285–90. [MEDLINE: 10714841].
Salmela 1998 {published data only} Salmela L, Aromaa U. Transient radicular irritation after spinal anesthesia induced with hyperbaric solutions of cerebrospinal fluid-diluted lidocaine 50 mg/ml or mepivacaine 40 mg/ml or bupivacaine 5 mg/Ml. Acta Anaesthesiologica Scandinavica 1998;42(7):765– 9. [MEDLINE: 9698950].
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Østgaard 2000 {published and unpublished data} Østgaard G, Hallaråker O, Ulveseth OK, Flaatten H. A randomised study of lidocaine and prilocaine for spinal anaesthesia. Acta Anaesthesiologica Scandinavica 2000;44(4):436–40. [MEDLINE: 10757577].
References to studies excluded from this review Ben-David 2000 ∗ Ben-David B, Maryanovsky M, Gurevitch A, Lucyk C, Solosko D, Frankel R, et al.A comparison of minidose lidocaine-fentanyl and conventional-dose lidocaine spinal anesthesia. Anesthesia and Analgesia 2000;91(4):865–70. [MEDLINE: 11004039]. Bergeron 1999 ∗ Bergeron L, Girard M, Drolet P, Grenier Y, Truong HHL, Boucher C. Spinal procaine with and without epinephrine and its relation to transient radicular irritation. Canadian Journal of Anaesthesia 1999; 46(9):846–9. [MEDLINE: 10490152]. Chan 1998 ∗ Chan VW, Garcia J, Al-Kaisy A, Drasner K. A comparative study of low-dose hyperbaric spinal lidocaine 0,5% versus 5% for continuous spinal anesthesia. Regional Anesthesia and Pain Medicine 1998;23(2): 164–9. [MEDLINE: 9570605]. Frey 1998 ∗ Frey K, Holman S, Mikat-Stevens M, Vazquez J, White L, Pedicini E, et al.The recovery profile of hyperbaric spinal anesthesia with lidocaine, tetracaine and bupivacaine. Regional Anesthesia and Pain Medicine 1998;23(2):159–63. [MEDLINE: 9570604]. Gentili 1997 ∗ Gentili M, Senlis H, Houssel P, Monnier B, Bonnet F. Single-shot spinal anesthesia with small doses of bupivacaine. Regional Anesthesia 1997;22(6):511–4. [MEDLINE: 9425965]. Hampl 1995a ∗ Hampl KF, Schneider MC, Ummenhofer W, Drewe J. Transient neurological symptoms after spinal anesthesia. Anesthesia and Analgesia 1995;81(6):1148–53. [MEDLINE: 7486096]. Hampl 1996 ∗ Hampl KF, Schneider MC, Pargger H, Gut J, Drewe J, Drasner K. A similar incidence of transient neurologic symptoms after spinal anesthesia with 2% and 5% lidocaine. Anesthesia and Analgesia 1996; 83(5):1051–4. [MEDLINE: 8895284]. Henderson 1998 ∗ Henderson DJ, Faccenda KA, Morrison LM. Transient radicular irritation with intrathecal plain lignocaine. Acta Anaesthesiologica Scandinavica 1998;42(3):376–8. [MEDLINE: 9542568]. Hiller 1999 ∗ Hiller A, Karjalainen K, Balk M, Rosenberg PH. Transient neurological symptoms after spinal anaesthesia with hyperbaric 5% lidocaine or general anaesthesia. British Journal of Anaesthesia 1999;82 (4):575–9. [MEDLINE: 10472226]. Liam 1998 Liam BL, Yim CF, Chong JL. Dose response study of lidocaine 1% for spinal anaesthesia for lower limb and perineal surgery. Canadian Journal of Anaesthesia 1998;45(7):645–50. [MEDLINE: 9717596]. Loo 1999 ∗ Loo CC, Irestedt L. Cauda equina syndrome after spinal anaesthesia with hyperbaric 5% lignocaine: a review of six cases of cauda
equina syndrome reported to the Swedish Pharmaceutical Insurance 1993-1997. Acta Anaesthesiologica Scandinavica 1999;43(4):371–9. [MEDLINE: 10225068]. Markey 1997 ∗ Markey JR, Montiague R, Winnie AP. A comparative efficacy study of hyperbaric 5% lidocaine and 1,5% lidocaine for spinal anesthesia. Anesthesia and Analgesia 1997;85(5):1105–7. [MEDLINE: 9356108]. Morisaki 1998 ∗ Morisaki H, Masuda J, Kaneko S, Matsushima M, Takeda J. Transient neurologic syndrome in one thousand forty-five patients after 3% lidocaine spinal anesthesia. Anesthesia and Analgesia 1998;86(5): 1023–6. [MEDLINE: 9585290]. Murto 1999 ∗ Murto K, Lui AC, Cicutti N. Adding low dose meperidine to spinal lidocaine prolongs postoperative analgesia. Canadian Journal of Anaesthesia 1999;46(4):327–34. [MEDLINE: 10232715]. Pawlowski 2000 ∗ Pawlowski J, Sukhani R, Pappas AL, Kim KM, Lurie J, Gunnerson H, et al.The anesthetic and recovery profile of two doses (60 and 80 mg) of plain mepivacaine for ambulatory spinal anesthesia. Anesthesia and Analgesia 2000;91(3):580–4. [MEDLINE: 10960380]. Pollock 1999 ∗ Pollock JE, Liu SS, Neal JM, Stephenson CA. Dilution of spinal lidocaine does not alter the incidence of transient neurologic symptoms. Anesthesiology 1999;90(2):445–50. [MEDLINE: 9952151]. Salmela 1996 ∗ Salmela L, Aromaa U, Cozanitis DA. Leg and back pain after spinal anaesthesia involving hyperbaric 5% lignocaine. Anaesthesia 1996;51 (4):391–3. [MEDLINE: 8686832]. Sia 1998 ∗ Sia S, Pullano C. Transient radicular irritation after spinal anaesthesia with 2% isobaric mepivacaine. British Journal of Anaesthesia 1998; 81(4):622–4. [MEDLINE: 9924248]. Tong 2003 Tong D, Wong J, Chung F, Friedlander M, Bremang J, Mezei G, et al.Prospective study on incidence and functional impact of transient neurologic symptoms associated with 1% versus 5% hyperbaric lidocaine in short urologic procedures. Anesthesiology 2003;98(2):485– 94. [MEDLINE: 12552209]. Wong 1999 ∗ Wong CA, Slavenas P. The incidence of transient radicular irritation after spinal anesthesia in obstetric patients. Regional Anesthesia and Pain Medicine 1999;24(1):55–8. [MEDLINE: 9952096]. Zayas 1999 ∗ Zayas VM, Liguori GA, Chisholm MF, Susman MH, Gordon MA. Dose response relationships for isobaric spinal mepivacaine using the combined spinal epidural technique. Anesthesia and Analgesia 1999; 89(5):1167–71. [MEDLINE: 10553828].
Additional references Altman 2003 Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ 2003;236(7382):219. [MEDLINE: 12543843].
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Auroy 1997 Auroy Y, Narchi P, Messiah A, Litt L, Rouvier B, Samii K. Serious complications related to reginal anesthesia - results of a prospective survey in France. Anesthesiology 1997;87(3):479–86. [MEDLINE: 9316950]. Axelrod 1998 Axelrod EH, Alexander GD, Brown M, Schork MA. Procaine spinal anesthesia: a pilot study of the incidence of transient neurological symptoms. Journal of Clinical Anesthesia 1998;10(5):404–9. [MEDLINE: 9702622]. Bier 1899 Bier AK, von Esmarch JF. Experiments with the cocainization of the spinal cord [Versuche uber Cocainisiring des Ruckenmarkes]. Deutsche Zeitschrift fur Chirurgie 1899;51:361–9. Casati 1998 Casati A, Fanelli G, Aldegheri G, Berti M, Leoni A, Torri G. A transient neurological deficit following intrathecal injection of 1% hyperbaric bupivacaine for unilateral spinal anaesthesia. European Journal of Anaesthesiology 1998;15(1):112–3. [MEDLINE: 9522152]. Corbey 1998 Corbey MP, Bach AB. Transient radicular irritation (TRI) after spinal anaesthasia in day-case surgery. Acta Anaesthesiologica Scandinavica 1998;42(4):425–9. [MEDLINE: 9563861]. Dahlgren 1995 Dahlgren N, Tornebrandt K. Neurological complications after anaesthesia. A follow-up of 18 000 spinal and epidural anaesthetics performed over three years. Acta Anaesthesiologica Scandinavica 1995;39 (7):872–80. [MEDLINE: 8848884]. Douglas 1995 Douglas MJ. Neurotoxicity of lidocaine - does it exist?. Canadian Journal of Anaesthesia 1995;42(3):181–5. [MEDLINE: 7743565]. Drasner 1997 Drasner K. Lidocaine spinal anesthesia: a vanishing therapeutic index?. Anesthesiology 1997;87(3):469–72. [MEDLINE: 9316947]. Freedman 1998 Freedman JM, Li DK, Drasner K, Jaskela MC, Larsen B, Wi S. Transient neurologic symptoms after spinal anesthesia. Anesthesiology 1998;89(3):633–41. [MEDLINE: 9743399]. Gerancher 1997 Gerancher JC. Cauda equina syndrome following a single spinal administration of 5% hyperbaric lidocaine through a 25-gauge Whitacre needle. Anesthesiology 1997;87(3):687–9. [MEDLINE: 9316976]. Gielen 1986 Gielen MJM, Huho J, DeGrood PM, Edstrom HH. A double-blind evaluation of hyperbaric solutions of bupivacaine 0.5% and lidocaine 5% in spinal anesthesia. Regional Anesthesia 1986;11:176–181.
Holmdahl 1998 Holmdahl HM. Xylocain (Lidocaine, Lignocaine), its discovery and Gordh’s contribution to its clinical use. Acta Anaesthesiologica Scandinavica. Supplementum 1998;42(113):8–12. [MEDLINE: 9932112]. Horlocker 2000 Horlocker T, Wedel DJ. Neurological complications of spinal and epidural anesthesia. Regional Anesthesia and Pain Medicine 2000;25 (1):83–98. [MEDLINE: 10660248]. Iselin-Chaves 1996 Iselin-Chaves IA, Van Gessel EF, Donald FA, Forster A, Gamulin Z. The effects of solution concentration and epinephrine on lateral distribution of hyperbaric tetracaine spinal anesthesia. Anesthesia and Analgesia 1996;83(4):755–9. [MEDLINE: 8831316]. Kane 1981 Kane RE. Neurologic deficits following epidural or spinal anesthesia. Anesthesia and Analgesia 1981;60(3):150–61. [MEDLINE: 7011100]. Li 1985 Li DF, Bahar M, Cole G, Rosen M. Neurological toxicity of the subarachnoid infusion of bupivacaine, lignocaine or 2-chloroprocaine in the rat. British Journal of Anaesthesia 1985;57(4):424–9. [MEDLINE: 3986072]. Liu 1998 Liu SS. Drugs for spinal anesthesia: past, present and future. Regional Anesthesia and Pain Medicine 1998;23(4):344–6. [MEDLINE: 9690583]. Lynch 1997 Lynch J, zur Nieden M, Kasper SM, Radbruch L. Transient radicular irritation after spinal anesthesia with hyperbaric 4% mepivacaine. Anesthesia and Analgesia 1997;85(4):872–3. [MEDLINE: 9322473]. Masuda 1998 Masuda R, Yokoyama K, Inoue T. Spread of spinal anesthesia with 3 different hyperbaric solutions used in Japan. Masui 1998;47(12): 1444–50. [MEDLINE: 9990212]. McKeown 1986 McKeown DW, Stewart K, Littlewood DG, Wildsmith JA. Spinal anesthesia with plain solutions of lidocaine (2%) and bupivacaine (0.5%). Regional Anesthesia 1986;11:68–71. Noble 1971 Noble AB, Murray JG. A review of the complications of spinal anaesthesia with experiences in Canadian teaching hospitals from 1959 to 1969. Canadian Anaesthetists’ Society Journal 1971;18(1):5–17. [MEDLINE: 4322858].
Green 1961 Green NM. Neurological sequelae of spinal anesthesia. Anesthesiology 1961;22:682–98.
Phillips 1969 Phillips OC, Ebner H, Nelson AT, Black MH. Neurologic complications following spinal anesthesia with lidocaine: a prospective review of 10,440 cases. Anesthesiology 1969;30(3):284–9. [MEDLINE: 4305091].
Hiller 1997 Hiller A, Rosenberg PH. Transient neurological symptoms after spinal anaesthesia with 4% mepivacaine and 0.5% bupivacaine. British Journal of Anaesthesia 1997;79(3):301–5. [MEDLINE: 9389845].
Pollock 2000 Pollock JE, Burkhead D, Neal JM, Liu SS, Friedman A, Stephenson C, et al.Spinal nerve function in five volunteers experiencing transient neurologic symptoms after lidocaine subarachnoid anesthesia. Anesthesia and Analgesia 2000;90(3):658–65. [MEDLINE: 10702453].
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Renck 1995 Renck H. Neurological complications of central nerve blocks. Acta Anaesthesiologica Scandinavica 1995;39(7):859–68. [MEDLINE: 8848882]. Rigler 1991 Rigler ML, Drasner K, Krejcie TC, Yelich SJ, Scholnick FT, DeFontes J, et al.Cauda equina syndrome after continuous spinal anesthesia. Anesthesia and Analgesia 1991;72(3):275–81. [MEDLINE: 1994754]. Sawyer 2000 Sawyer RJ, Richmond MN, Hickey JD, Jarratt JA. Peripheral nerve injuries associated with anaesthesia. Anaesthesia 2000;55(10):980– 91. [MEDLINE: 11012494]. Schell 1991 Schell RM, Brauer FS, Cole DJ, Applegate RL 2nd. Persistent sacral nerve root deficits after continuous spinal anaesthesia. Canadian Journal of Anaesthesia 1991;38(7):908–11. [MEDLINE: 1742828]. Schneider 1993 Schneider M, Ettlin T, Kaufmann M, Schumacher P, Urwyler A, Hampl K, et al.Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with 5% lidocaine. Anesthesia and Analgesia 1993;76(5):1154–7. [MEDLINE: 8141862]. Selander 1988 Selander D. Nerve toxicity of local anaesthetics. In: LöfstromJB, SjöstrandU editor(s). Local anaesthesia and regional blockade. Elsevier, 1988:77–97.
Sumi 1996 Sumi M, Sakura S, Kosaka Y. Intrathecal hyperbaric 0.5% tetracaine as a possible cause of transient neurologic toxicity. Anesthesia and Analgesia 1996;82(5):1076–7. [MEDLINE: 8610872]. Tagariello 1998 Tagariello V, Bertini L. Unusually prolonged duration of spinal anesthesia following 2% mepivacaine. Regional Anesthesia and Pain Medicine 1998;23(4):424–6. [MEDLINE: 9690597]. Tarkkila 1991 Tarkkila PJ, Kaukinen S. Complications during spinal anesthesia: a prospective study. Regional Anesthesia 1991;16(2):101–6. [MEDLINE: 2043522]. Tarkkila 1995 Tarkkila P, Huhtala J, Tuominen M. Transient radicular irritation after spinal anaesthesia with hyperbaric 5% lignocaine. British Journal of Anaesthesia 1995;74(3):328–9. [MEDLINE: 7718381]. Usubiaga 1975 Usubiaga JE. Neurological complications following epidural anesthesia. International Anesthesiology Clinics 1975;13(2):1–109. Vandam 1955 Vandam LD, Dripps RD. A long-term follow-up of 10,098 spinal anesthetics II. Incidence and analysis of minor sensory neurological defects. Surgery 1955;38(3):463–9. [MEDLINE: 13246935]. Vandam 1960 Vandam LD, Dripps RD. Long-term follow-up of patients who received 10,098 spinal anesthetics. JAMA 1960;172:1483–7. [MEDLINE: 13841201]. ∗
Indicates the major publication for the study
TABLES
Characteristics of included studies Study
Aouad 2001
Methods
Randomization: yes Patient blinding: yes. Provider blinding: no. Assessor blinding: yes. Dropouts: none.
Participants
Country: Lebanon. ASA: I, II. Gender: female. Ages: 31 ± 5. Caesarean section. Surgical positioning: supine. Study patients: 200.
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Characteristics of included studies (Continued ) Interventions
Drug 1: 5% lido, hyperbaric, fixed dose (1.5ml). Drug 2: 0.75% bupi, hyperbaric, fixed dose (1.6ml). Needle: 25 G, pencil-point.
Outcomes
TNS at 1 day. Back pain
Notes
Follow-up duration : 1.3 days. Follow-up method: phone contact.
Allocation concealment
C – Inadequate
Study
Breebaart 2003
Methods
Randomization: yes Patient blinding: yes. Provider blinding: yes. Assessor blinding: unclear. Dropouts: none.
Participants
Country: Belgium ASA: I gender: male and female. Ages: 42 (20-57), 39 (18-59), 39 (19-57) Ambulatory surgery Surgical positioning: supine. Study patients: 90
Interventions
Drug 1: 2% lido, isobaric, fixed dose (3ml). Drug 2: 0.5% levo, isobaric, fixed dose (3ml), Drug 3: 0.75% ropi, isobaric, fixed dose (3ml). Needle: 27 G, pencil-point.
Outcomes
TNS at 2 day. Urinary retention.
Notes
Follow-up duration: 2 days. Follow-up method: phone contact. TNS therapy: none. TNS resolution: 1 day.
Allocation concealment
A – Adequate
Study
Hampl 1995b
Methods
Randomization: yes. Patient blinding: yes. Provider blinding: yes. Assessor blinding: yes. Dropouts: 1 outcome not reported.
Participants
Country : Switzerland. ASA: I, II. Gender: female. Ages: 19-81. Procedures: gynaecologic. Ambulatory surgery: no.
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Characteristics of included studies (Continued ) Surgical positioning: lithotomy. Study patients: 44. Interventions
Drug 1: 5% lido, hyperbaric, fixed dose (1.5 ml). Drug 2: 0.5% bupi, hyperbaric, fixed dose (1.5 ml). Needle: 25 G, pencil-point.
Outcomes
TNS at 1 day. Back pain.
Notes
Allocation concealment
Follow-up duration: 1-4 days. Follow-up method: direct contact. TNS therapy: unclear. TNS resolution: all recovered. B – Unclear
Study
Hampl 1998
Methods
Randomization: yes. Patient blinding: yes. Provider blinding: yes. Assessor blinding: yes. Dropouts: none.
Participants
Country: Switzerland. ASA: I, II. Gender: female. Ages: 39 ± 17; 39 ± 13; 36 ± 14. Procedures: gynaecologic. Ambulatory surgery: unclear. Surgical positioning: lithotomy. Study patients: 90.
Interventions
Drug 1: 2% lido, hyperbaric, fixed dose (2.5 ml). Drug 2: 2% prilo, hyperbaric, fixed dose (2.5 ml). Drug 3: 0.5% bupi, hyperbaric, fixed dose (2.5 ml). Needle: 25 G, pencil-point.
Outcomes
TNS at 1 day.
Notes
Follow-up duration: 1-5 days. Follow-up methods: direct contact. TNS therapy: unclear. TNS resolution: 2-4 days.
Allocation concealment
B – Unclear
Study
Hodgson 2000
Methods
Randomization: yes. Patient blinding: yes. Provider blinding: no. Assessor blinding: yes. Dropouts: none.
Participants
Country: USA. ASA: I, II. Gender: male, female. Ages: 49 ± 12, 49 ± 12. Procedures: arthroscopy.
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Characteristics of included studies (Continued ) Ambulatory surgery: yes. Surgical positioning: supine. Study patients: 70. Interventions
Drug 1: 5% lido, hyperbaric, fixed dose (1 ml). Drug 2: 5% pro, hyperbaric, fixed dose (2 ml). Needle: 24 & 25 G, pencil-point.
Outcomes
TNS at 1 day.
Notes
Follow-up duration: 3 days. Follow-up method: phone contact. TNS therapy: unclear. TNS resolution: 48 hours. A – Adequate
Allocation concealment Study
Keld 2000
Methods
Randomization: yes. Patient blinding: yes. Provider blinding: no. Assessor blinding: yes. Dropouts: 1 outcome reported.
Participants
Country: Denmark. ASA: I, II. Gender: male, female. Ages: 43 ± NA, 46 ± NA. Procedures: ortho, general surgery. Ambulatory surgery: unclear. Surgical positioning: supine. Study patients: 70.
Interventions
Drug 1: 5% lido, hyperbaric, fixed dose (2 ml). Drug 2: 0.5% bupi, hyperbaric, fixed dose (2.5 ml). Needle: 25 G, pencil-point.
Outcomes
TNS at 1 day. Back pain.
Notes
Allocation concealment
Follow-up duration 1-3 days. Follow-up methods: phone contact. TNS therapy: unclear. TNS resolution: 41 hours. C – Inadequate
Study
Le Truong 2001
Methods
Randomization: yes. Patient blinding: yes. Provider blinding: no. Assessor blinding: yes. Dropouts: 6 outcomes not reported.
Participants
Country: Canada. ASA: I, II. Gender: male, female. Ages: 38 ± 9, 41 ± 11.
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Characteristics of included studies (Continued ) Procedures: general surgery, gynaecologic. Ambulatory surgery: unclear. Surgical positioning: supine, lithotomy. Study patients: 66. Interventions
Drug 1: 5% lido, hyperbaric, fixed dose (2 ml). Drug 2: 10% pro, baricity unclear, fixed dose (1 ml). Needle: 27 G, pencil point.
Outcomes
TNS at 2 days.
Notes
Allocation concealment
Follow-up duration: 2 days. Follow-up method: unclear. TNS therapy: unclear. TNS resolution: unclear. C – Inadequate
Study
Liguori 1998
Methods
Randomization: yes. Patient blinding: yes. Provider blinding: no. Assessor blinding: yes. Dropouts: 3 outcomes not reported.
Participants
Country: USA. ASA: I, II, III. Gender: male, female. Ages: 18 ± 12; 42 ± 10. Procedures: arthroscopy. Ambulatory surgery: yes. Surgical positioning: supine. Study patients: 60.
Interventions
Drug 1: 2% lido, baricity unclear, fixed dose (3 ml). Drug 2: 1.5% mepi, baricity unclear, fixed dose (3 ml). Needle: 27 G, pencil-point.
Outcomes
TNS at 1-2 days.
Notes
Follow-up duration: 2-5 days. Follow-up method: phone contact. TNS therapy: NSAIDs. TNS resolution: duration 1-5 days.
Allocation concealment
C – Inadequate
Study
Martinez-Bourio 1998
Methods
Randomization: yes. Patient blinding: yes. Provider blinding: no. Assessor blinding: yes. Dropouts: 2 outcomes reported.
Participants
Country: Spain. ASA: I, II, III. Gender: male, female. Ages: 18-80.
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Characteristics of included studies (Continued ) Procedures: ortho, urologic, gynaecologic, vascular, general surgery. Ambulatory surgery: unclear. Surgical positioning: supine, prone, lithotomy. Study patients: 200. Interventions
Drug 1: 5% lido, hyperbaric, variable dose. Drug 2: 5% prilo, hyperbaric, variable dose. Needle: 25 G, pencil-point.
Outcomes
TNS at 1-2 days. Back pain.
Notes
Follow-up duration: 3-5 days. Follow-up method: direct contact, phone contact. TNS therapy: NSAIDs. TNS resolution: maximum duration 10 days.
Allocation concealment
A – Adequate
Study
Philip 2001
Methods
Randomization: yes. Patient blinding: yes. Provider blinding: yes. Assessor blinding: yes. Dropouts: 1 outcome reported.
Participants
Country: USA ASA: I. Gender: female. Ages: 27 ± 5; 25 ± 4. Procedures: postpartum tubal ligation. Ambulatory surgery: no. Surgical positioning: supine. Study patients: 58.
Interventions
Drug 1: 5% lido, hyperbaric, variable dose. Drug 2: 0.75% bupi, hyperbaric, variable dose. Needle: 25 G, pencil-point.
Outcomes
TNS at 1 day. Back pain.
Notes
Follow-up duration: 3 weeks. Follow-up method: direct contact. TNS therapy: unclear. TNS resolution: complete recovery at 2 days.
Allocation concealment
B – Unclear
Study
Pollock 1996
Methods
Randomization: yes. Patient blinding: yes. Provider blinding: yes. Assessor blinding: yes. Dropouts: 7 outcomes reported.
Participants
Country: USA. ASA: I, II.
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Characteristics of included studies (Continued ) Gender: male, female. Ages: 59 ± 17; 53 ± 12; 62 ± 14; 51 ± 13; 52 ± 16; 50 ± 16. Procedures: arthroscopy, herniorrhaphy. Ambulatory surgery: yes. Surgical positioning: supine. Study patients: 159. Interventions
Drug 1: 2%, 5% lido; hyperbaric, isobaric; fixed dose (1.2, 3.0, 1.5, 3.75 ml). Drug 2: 0.75% bupi, hyperbaric, fixed dose (1.0, 1.2 ml). Needle: 22 & 25 G, cutting & pencil-point.
Outcomes
TNS at 3 days. Back pain.
Notes
Follow-up duration: 3-14 days. Follow-up method: phone contact. TNS therapy: NSAIDs, opioids. TNS resolution: no symptoms at 14 days.
Allocation concealment
A – Adequate
Study
Salazar 2001
Methods
Randomization: yes. Patient blinding: unclear. Provider blinding: no. Assessor blinding: yes. Dropouts: 1 outcome not reported.
Participants
Country: Spain. ASA: I, II. Gender: male, female. Ages: 48 ± 16; 42 ± 16. Procedures: ortho. Ambulatory surgery: no. Surgical positioning: supine. Study patients: 81.
Interventions
Drug 1: 2% lido, isobaric, variable dose. Drug 2: 2% mepi, isobaric, variable dose. Needle: 26 & 27 G, cutting.
Outcomes
TNS at 1 day.
Notes
Follow-up duration: 1+ days. Follow-up method: direct contact. TNS therapy: NSAIDs. TNS resolution: 1 day.
Allocation concealment
C – Inadequate
Study
Salmela 1998
Methods
Randomization: yes. Patient blinding: no. Provider blinding: no. Assessor blinding: yes. Dropouts: none.
Participants
Country: Finland
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Characteristics of included studies (Continued ) ASA: I, II, III, IV. Gender: male, female. Ages: 29-91. Procedures: urologic. Ambulatory surgery: unclear. Surgical positioning: supine, lithotomy. Study patients: 90. Interventions
Drug 1: 5% lido, hyperbaric, variable dose. Drug 2: 0.5% bupi, hyperbaric, variable dose. Drug 3: 4% mepi, hyperbaric, variable dose. Needle: 25 & 27 G, cutting & pencil-point.
Outcomes
TNS at 1 day.
Notes
Follow-up duration: 1 day. Follow-up method: direct contact. TNS therapy: NSAIDs, opioids. TNS resolution: 1-2 days.
Allocation concealment
A – Adequate
Study
de Weert 2000
Methods
Randomization: yes. Patient blinding: yes. Provider blinding: unclear. Assessor blinding: unclear. Dropouts: 1 outcome reported.
Participants
Country: the Netherlands. ASA: I, II. Gender: male, female. Ages: 43 ± 14, 37 ± 11. Ambulatory surgery: unclear. Surgical positioning: supine. Study patients: 70.
Interventions
Drug 1: 2% lido, isobaric, fixed dose (4 ml). Drug 2: 2% prilo, isobaric, fixed dose (4 ml). Needle: 25 G, pencil-point.
Outcomes
TNS at 1 day.
Notes
Follow-up duration: 1-4 days. Follow-up method: direct contact, phone contact. TNS therapy: unclear. TNS resolution: 2-3 days.
Allocation concealment
A – Adequate
Study
Østgaard 2000
Methods
Randomization: yes. Patient blinding: yes. Provider blinding: unclear. Assessor blinding: yes. Dropouts: 1 outcome not reported.
Participants
Country: Norway
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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ASA: unclear. Gender: male, female. Ages: 65 ± 17; 69 ± 12. Procedures: urologic. Ambulatory surgery: unclear. Surgical positioning: supine, lithotomy. Study patients: 100. Interventions
Drug 1: 2% lido, isobaric, fixed dose (4 ml). Drug 2: 2% prilo, isobaric, fixed dose (4 ml). Needle: 25 & 26 & 27 & 29 G, cutting.
Outcomes
TNS at 1 day. Other pain.
Notes
Follow-up duration: 1 day. Follow-up method: direct contact. TNS therapy: unclear. TNS resolution: unclear. A – Adequate
Allocation concealment
ASA: American Society of Anesthesiologist Physical Status Score (I, II, III, IV). bupi: bupivacaine; levo: levobupivacaine; lido: lidocaine; mepi: mepivacaine; prilo: prilocaine; pro: procaine; ropi: ropivacaine. NA: not available. TNS: Transient Neurologic Symptoms.
Characteristics of excluded studies Study
Reason for exclusion
Ben-David 2000
Fentanyl was used together with lidocaine. No arm with another local anaesthetic.
Bergeron 1999
No lidocaine, only one arm with procaine Incidence of TNS: 1 of 62 patients, but high incidence of nausea.
Chan 1998
Continuous spinal anaesthesia with lidocaine 5% . No follow-up, no mention of TNS
Frey 1998
Volunteers - no surgery - excluded. N = 12. Cross over: lidocaine 5% (100 mg), tetracaine 1% (30 mg) and bupivacaine 0.75% (15 mg). 3 of 12 subjects had TNS - it was quite unpleasant - unable to sit and needed NSAID
Gentili 1997
No lidocaine. Bupivacaine 0.1%, 0.15% and 0.2%. Volume: 4 ml. N = 90, there were no cases of TNS.
Hampl 1995a
Nonrandomized study
Hampl 1996
Only lidocaine in two different concentrations: 5% vs. 2%. No difference in the incidence of TNS (8 of 25 vs. 10 of 25 with 2% lidocaine). Reduction in concentration did not reduce the risk of TNS.
Henderson 1998
Case history: one patient with TNS after 1% Lidocaine 40 mg. Full recovery.
Hiller 1999
Only one arm with lidocaine: second arm with general anaesthesia. Even patients who receive only general anaesthesia can develop TNS.
Liam 1998
Only lidocaine: three arms with 1% lidocaine in different volumes: 4, 6 and 8 ml - no cases of TNS.
Loo 1999
Swedish Pharmacological Insurance reported six cases of cauda equina syndrome between 1993-1997. Five cases after single spinal injection of lidocaine 5% and one case after repeated injection. Lidocaine doses was 60-100 mg. All cases sustained permanent neurological deficits. Recommendation: use plain 2% lidocaine and no more than 60 mg.
Markey 1997
1.5% lidocaine is as effective as 5% for patients undergoing hernia operation. No mention of TNS.
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Characteristics of excluded studies (Continued ) Morisaki 1998
Nonrandomized study : 4 of 1045 patients that received lidocaine 3% 45 mg (for anorectal surgery) had TNS.
Murto 1999
Intrathecal meperidine 0.3 mg/kg was added to lidocaine to prolong postoperative analgesia. No mention of TNS.
Pawlowski 2000
No lidocaine. Mepivacaine 1.5% (60 mg) and 2% (80 mg) was used in 60 patients. Follow-up 24 h: no cases of TNS.
Pollock 1999
Only lidocaine was used: three arms with 0.5%, 1% and 2% lidocaine: incidence of TNS was not concentrationdependant (20 out of 109 patients).
Salmela 1996
Only one arm with Lidocaine 5%. 13 out of 44 urological patients had signs of TNS.
Sia 1998
3 cases of TNS after spinal mepivacaine.
Tong 2003
Only lidocaine was used: two arms with 80 mg lidocaine: 1% (N = 218) and 5 % hyperbaric lidocaine (N = 235): incidence of TNS was not concentration-dependant (21% vs. 18%).
Wong 1999
Nonrandomized study
Zayas 1999
No lidocaine. Dose-response study for spinal mepivacaine 1.5%. N =25. 40, 45 and 60 mg. 5 cases of TNS out of 75 ptt. - irrespective of Mepivacaine doses.
N - numbers PTT - patients TNS -Transient neurologic symptoms Vs - versus
ADDITIONAL TABLES
Table 01. Patients who developed TNS after intrathecal lidocaine Study ID
TNS #/N (%)
Pain score (0-10)
TNS duration
Therapy
Aouad 2001
0 (0)
de Weert 2000
7/35 (20)
Day 1 mean VPS = 5.3 (range 2-8)
Maximum duration 3 days
Not described
Hampl 1995b
9/28 (32)
Not tallied
Maximum duration 4 days
Not described
Hampl 1998
9/30 (30)
Mean maximum VAS = 3.75
Maximum duration 2 days
Not described
Hodgson 2000
11/35 (31)
Mean VPS = 5
Mean duration 2 days
Not described
Keld 2000
9/35 (26)
Mean VPS = 3.5 (range 2-8)
Maximum duration 4 days
Not described
Liguori 1998
6/27 (22)
Not tallied
Maximum duration 5 days
NSAIDs
Le Truong
8/30 (27)
Not tallied
Unspecified
Not described
Martinez-Bourio 1998
4/98 (4)
Not tallied
Maximum duration 10 days
NSAIDs
Østgaard 2000
7/49 (14)
VPS range 5-9.5
Maximum duration 3 days
Not described
Philip 2001
1/30 (3)
Maximum VAS = 3
Maximum duration 2 days
Not described
Pollock 1996
16/107 (15)
Mean VPS = 6.2 (range 1-9)
Maximum duration 4 days
NSAIDs and opioids
Salazar 2001
1/40 (3)
Maximum VAS = 9-10
Maximum duration 1 day
NSAIDs
Salmela 1998
6/30 (20)
Moderate pain
Maximum duration 1 day
NSAIDs and opioids
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Table 01. Patients who developed TNS after intrathecal lidocaine (Continued ) Study ID
TNS #/N (%)
Pain score (0-10)
TNS duration
Therapy
Breebaart 2003
3/30 (10)
Not tallied
1 day
Not described
Key to abbreviations:
VPS: Verbal Pain Scale
VAS: Visual Analogue Scale
ANALYSES
Comparison 01. Lidocane versus other local anaesthetic Outcome title 01 Transient Neurologic Symptoms
No. of studies 18
No. of participants 1437
Statistical method Relative Risk (Random) 95% CI
Effect size 4.47 [2.17, 9.20]
Comparison 02. Lidocaine versus other local anaesthetic (excluding mepivacaine) Outcome title 01 Transient Neurologic Symptoms
No. of studies 15
No. of participants 1255
Statistical method Relative Risk (Fixed) 95% CI
Effect size 7.16 [4.02, 12.75]
INDEX TERMS Medical Subject Headings (MeSH) Anesthesia, Spinal [∗ adverse effects]; Anesthetics, Local [∗ adverse effects]; Leg [∗ innervation]; Lidocaine [∗ adverse effects]; Pain [∗ chemically induced]; Peripheral Nervous System Diseases [∗ chemically induced]; Randomized Controlled Trials as Topic MeSH check words Humans
COVER SHEET Title
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics
Authors
Zaric D, Christiansen C, Pace NL, Punjasawadwong Y
Contribution of author(s)
Dusanka Zaric (DZ): main writer. Yodying Punjasawadwong (YP): literature search, evaluation and construction of tables. Christian Christiansen (CC): evaluation of literature and revision of the text. Nathan Pace (NP): work on statistical problems and revision of text.
Issue protocol first published
2001/2
Review first published
2003/2
Date of most recent amendment
11 August 2005
Date of most recent SUBSTANTIVE amendment
21 July 2005
What’s New
This review was first updated in Issue 4, 2005. The literature search for this updated review resulted in the inclusion of one further randomized controlled trial (Breebart 2003).
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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The occurrence of transient neurological symptoms (TNS) after intrathecal lidocaine was compared to that after two new local anaesthetics: levobupivacaine and ropivacaine. This addition did not change the results of this review. Three new references have been added to the review: one in the Included studies tables (Breebaart 2003); one in the Excluded studies tables (Tong 2003) and one to the Additional references (Freedman 1998). Date new studies sought but none found
Information not supplied by author
Date new studies found but not yet included/excluded
Information not supplied by author
Date new studies found and included/excluded
15 March 2005
Date authors’ conclusions section amended
16 July 2005
Contact address
Dusanka Zaric M.D PhD Dept. of Anaesthesiology Frederiksberg Hospital Ndr. Fasanvej 57 Frederiksberg DENMARK E-mail:
[email protected] Tel: 45 36 18 33 12
DOI
10.1002/14651858.CD003006.pub2
Cochrane Library number
CD003006
Editorial group
Cochrane Anaesthesia Group
Editorial group code
HM-ANAESTH GRAPHS AND OTHER TABLES
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Analysis 01.01. Review:
Comparison 01 Lidocane versus other local anaesthetic, Outcome 01 Transient Neurologic Symptoms
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics
Comparison: 01 Lidocane versus other local anaesthetic Outcome: 01 Transient Neurologic Symptoms Study
Lidocaine
Other Local
Relative Risk (Random)
Weight
Relative Risk (Random)
n/N
n/N
95% CI
(%)
95% CI
01 Bupivacaine x Aouad 2001
0/100
0/100
0.0
Not estimable
Hampl 1995b
9/28
0/16
4.6
11.14 [ 0.69, 179.55 ]
Hampl 1998
4/15
0/30
4.4
17.44 [ 1.00, 304.11 ]
Keld 2000
9/35
1/35
6.8
9.00 [ 1.20, 67.31 ]
Philip 2001
1/30
2/28
5.7
0.47 [ 0.04, 4.87 ]
Pollock 1996
16/107
0/52
4.6
16.19 [ 0.99, 264.78 ]
Salmela 1998
3/15
0/30
4.3
13.56 [ 0.75, 246.76 ]
330
291
30.5
6.65 [ 2.05, 21.56 ]
Subtotal (95% CI)
Total events: 42 (Lidocaine), 3 (Other Local) Test for heterogeneity chi-square=6.30 df=5 p=0.28 I² =20.6% Test for overall effect z=3.16
p=0.002
02 Mepivacaine Liguori 1998
6/27
0/30
4.5
14.39 [ 0.85, 244.06 ]
Salazar 2001
1/40
3/40
6.1
0.33 [ 0.04, 3.07 ]
Salmela 1998
3/15
11/30
10.8
0.55 [ 0.18, 1.67 ]
82
100
21.4
1.05 [ 0.15, 7.45 ]
Subtotal (95% CI)
Total events: 10 (Lidocaine), 14 (Other Local) Test for heterogeneity chi-square=5.78 df=2 p=0.06 I² =65.4% Test for overall effect z=0.05
p=1
03 Prilocaine Hampl 1998
5/15
1/30
6.7
10.00 [ 1.28, 78.12 ]
Martinez-Bourio 1998
4/98
1/102
6.3
4.16 [ 0.47, 36.60 ]
de Weert 2000
7/35
0/35
4.5
15.00 [ 0.89, 252.96 ]
Østgaard 2000
7/49
2/50
8.8
3.57 [ 0.78, 16.35 ]
Subtotal (95% CI)
197
217
26.3
5.62 [ 2.07, 15.23 ]
Total events: 23 (Lidocaine), 4 (Other Local) Test for heterogeneity chi-square=1.21 df=3 p=0.75 I² =0.0% Test for overall effect z=3.39
p=0.0007
04 Procaine
0.1 0.2
0.5
Favours treatment
1
2
5
10
Favours control
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
(Continued . . . )
22
(. . . Study
Continued)
Lidocaine
Other Local
Relative Risk (Random)
Weight
Relative Risk (Random)
n/N
n/N
95% CI
(%)
95% CI
Hodgson 2000
11/35
2/35
9.2
5.50 [ 1.31, 23.03 ]
Le Truong 2001
8/30
0/30
4.5
17.00 [ 1.03, 281.91 ]
65
65
13.8
6.94 [ 1.94, 24.86 ]
Subtotal (95% CI)
Total events: 19 (Lidocaine), 2 (Other Local) Test for heterogeneity chi-square=0.52 df=1 p=0.47 I² =0.0% Test for overall effect z=2.98
p=0.003
05 Ropivacaine Breebaart 2003 Subtotal (95% CI)
1/15
0/30
3.9
5.81 [ 0.25, 134.73 ]
15
30
3.9
5.81 [ 0.25, 134.73 ]
2/15
0/30
4.2
9.69 [ 0.49, 189.93 ]
15
30
4.2
9.69 [ 0.49, 189.93 ]
733
100.0
4.47 [ 2.17, 9.20 ]
Total events: 1 (Lidocaine), 0 (Other Local) Test for heterogeneity: not applicable Test for overall effect z=1.10
p=0.3
06 Levobupivacine Breebaart 2003 Subtotal (95% CI)
Total events: 2 (Lidocaine), 0 (Other Local) Test for heterogeneity: not applicable Test for overall effect z=1.50 Total (95% CI)
p=0.1 704
Total events: 97 (Lidocaine), 23 (Other Local) Test for heterogeneity chi-square=28.61 df=16 p=0.03 I² =44.1% Test for overall effect z=4.07
p=0.00005
0.1 0.2
0.5
Favours treatment
1
2
5
10
Favours control
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Analysis 02.01. Review:
Comparison 02 Lidocaine versus other local anaesthetic (excluding mepivacaine), Outcome 01 Transient Neurologic Symptoms
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics
Comparison: 02 Lidocaine versus other local anaesthetic (excluding mepivacaine) Outcome: 01 Transient Neurologic Symptoms Study
Lidocaine
Other Local
Relative Risk (Fixed)
Weight
Relative Risk (Fixed)
n/N
n/N
95% CI
(%)
95% CI
01 Bupivacaine x Aouad 2001
0/100
0/100
0.0
Not estimable
Hampl 1995b
9/28
0/16
5.1
11.14 [ 0.69, 179.55 ]
Hampl 1998
4/15
0/30
2.8
17.44 [ 1.00, 304.11 ]
Keld 2000
9/35
1/35
8.1
9.00 [ 1.20, 67.31 ]
Philip 2001
1/30
2/28
16.7
0.47 [ 0.04, 4.87 ]
Pollock 1996
16/107
0/52
5.4
16.19 [ 0.99, 264.78 ]
Salmela 1998
3/15
0/30
2.8
13.56 [ 0.75, 246.76 ]
330
291
40.9
7.60 [ 3.00, 19.30 ]
Subtotal (95% CI)
Total events: 42 (Lidocaine), 3 (Other Local) Test for heterogeneity chi-square=6.30 df=5 p=0.28 I² =20.6% Test for overall effect z=4.27
p=0.00002
02 Prilocaine Hampl 1998
5/15
1/30
5.4
10.00 [ 1.28, 78.12 ]
Martinez-Bourio 1998
4/98
1/102
7.9
4.16 [ 0.47, 36.60 ]
de Weert 2000
7/35
0/35
4.0
15.00 [ 0.89, 252.96 ]
Østgaard 2000
7/49
2/50
16.0
3.57 [ 0.78, 16.35 ]
Subtotal (95% CI)
197
217
33.4
6.14 [ 2.31, 16.32 ]
Total events: 23 (Lidocaine), 4 (Other Local) Test for heterogeneity chi-square=1.21 df=3 p=0.75 I² =0.0% Test for overall effect z=3.63
p=0.0003
03 Procaine Hodgson 2000
11/35
2/35
16.2
5.50 [ 1.31, 23.03 ]
Le Truong 2001
8/30
0/30
4.0
17.00 [ 1.03, 281.91 ]
65
65
20.2
7.80 [ 2.19, 27.77 ]
2.8
5.81 [ 0.25, 134.73 ]
Subtotal (95% CI)
Total events: 19 (Lidocaine), 2 (Other Local) Test for heterogeneity chi-square=0.52 df=1 p=0.47 I² =0.0% Test for overall effect z=3.17
p=0.002
04 Ropivacaine Breebaart 2003
1/15
0/30 0.1 0.2
0.5
Favours treatment
1
2
5
10
Favours control
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
(Continued . . . )
24
(. . . Study
Subtotal (95% CI)
Continued)
Lidocaine
Other Local
Relative Risk (Fixed)
Weight
Relative Risk (Fixed)
n/N
n/N
95% CI
(%)
95% CI
15
30
2.8
5.81 [ 0.25, 134.73 ]
2/15
0/30
2.8
9.69 [ 0.49, 189.93 ]
15
30
2.8
9.69 [ 0.49, 189.93 ]
633
100.0
7.16 [ 4.02, 12.75 ]
Total events: 1 (Lidocaine), 0 (Other Local) Test for heterogeneity: not applicable Test for overall effect z=1.10
p=0.3
05 Levobupivacaine Breebaart 2003 Subtotal (95% CI)
Total events: 2 (Lidocaine), 0 (Other Local) Test for heterogeneity: not applicable Test for overall effect z=1.50 Total (95% CI)
p=0.1 622
Total events: 87 (Lidocaine), 9 (Other Local) Test for heterogeneity chi-square=8.20 df=13 p=0.83 I² =0.0% Test for overall effect z=6.69
p<0.00001
0.1 0.2
0.5
Favours treatment
1
2
5
10
Favours control
Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics (Review) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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