In this issue Hampl et al.  report the first prospective investigation of transient radicular symptoms after spinal anesthesia. Their data suggest that radicular pain and/or dysesthesia may be more common when spinal anesthesia is performed with hyperbaric lidocaine than with hyperbaric bupivacaine. In this study, patients received either 5% lidocaine in 7.5% glucose or 0.5% bupivacaine in 8.5% glucose. Standardized data were collected on the third postoperative day by a blinded quality assurance nurse. Neurologic symptoms were defined as "pain and/or dysesthesia in the buttocks, thighs, or lower limbs occurring after recovery from the anesthetic." These symptoms occurred in 44/120 patients (37%) receiving lidocaine and 1/150 patients (0.7%) receiving bupivacaine. Furthermore, symptoms in the one patient receiving bupivacaine appeared to be due to positioning during the procedure. The authors conclude that this difference in incidence suggests "that symptoms were the result of a specific drug effect."
This study provides new information regarding the role of several factors in the genesis of radicular symptoms. For example, the lithotomy position may predispose patients to development of radicular symptoms. This concept is supported by previous case reports in which radicular symptoms predominantly occurred in patients having surgery in lithotomy position [2-4] and by cadaveric dissection suggesting that the lithotomy position stretches the nerve roots in the cauda equina . Stretching of the nerves may reduce blood flow and increase vulnerability to local anesthetics. Indeed 44/120 patients receiving lidocaine for surgery performed in the lithotomy position had radicular symptoms. However, only 1/93 patients receiving bupivacaine for surgery performed in the lithotomy position had similar symptoms. Therefore, these data suggest that lithotomy position alone is insufficient to cause these symptoms. Prolonged duration of surgery may also cause postoperative back pain and increase the risk of radicular symptoms. However, duration of surgery was significantly longer for patients receiving bupivacaine and yet the incidence of radicular symptoms was less frequent. Hyperosmolarity and hyperbaricity of the 5% lidocaine solution have also been proposed as potential causes of these radicular symptoms . However, the bupivacaine solution contained 8.5% glucose and was both hyperbaric and hyperosmolar. Similarly, data obtained in rats suggest that addition of glucose does not increase neurotoxicity observed with 5% lidocaine . Thus, information presented in this report suggests that the syndrome is not caused solely by the lithotomy position or addition of glucose to the anesthetic solution, and that the syndrome may be uniquely associated with the use of lidocaine for spinal anesthesia.
Although this study provides more convincing evidence than the previous case reports [2-4], it fails to clearly identify lidocaine as the cause for the transient radicular syndrome due to limitations in study design which are identified by the authors. The most important limitation is lack of randomization which is critically important in clinical studies such as this to reduce the potential for biased distribution of the treatments to different patient populations. The investigators' decision to select lidocaine or bupivacaine based on expected duration of operation undoubtedly contributed to the observed differences between groups in surgical procedures and positioning for those procedures. These factors have previously been suggested to affect the incidence of postoperative back pain . Equally important is the possibility that the drug selection technique introduced a biased distribution of unrecognized risk factors. For example, the drug selection technique may have produced differences in gender distribution between the groups. Although gender is not currently considered to be a risk factor, it may be important as 5/6 cases previously reported occurred in females [2-4]. The importance of this factor cannot be assessed in this study, since gender was not reported. The possibility that other risk factors were nonrandomly distributed between the two groups raises serious questions about the ability to extrapolate these results to the general surgical population. The authors recognize these potential deficiencies and suggest that randomized, prospective trials need to be performed before conclusive recommendations can be made.
Another concern relates to the authors' suggestion that the radicular symptoms result from specific lidocaine neurotoxicity. Although the bilateral distribution and radicular nature of symptoms may be consistent with mild neurotoxicity, none of the patients demonstrated objective signs of neurologic deficit. Also seemingly inconsistent with the concept of direct lidocaine neurotoxicity is the long duration between exposure to lidocaine and onset of symptoms--as long as 20 h after surgery in previous patients reported by this group . Times to onset of symptoms were not reported in this study. Finally, it is unlikely that these symptoms resulted from spinal cord ischemia since intrathecal administration of lidocaine increases  while bupivacaine decreases  spinal cord blood flow. Thus, although repeatedly defined as neurologic symptoms, no evidence is provided to support a neurologic origin for the pain and/or dysesthesia observed in these patients.
A final concern is the lack of quantitative measures for severity of pain and/or dysesthesias. The clinical importance of these symptoms would be quite different if the median visual analog scale score was 10/10 as opposed to 1/10. The clinical importance of this syndrome is difficult to assess since neither intensity of pain nor necessity for analgesic therapy are reported in the manuscript. However, only 2/4 patients in the previous cases reported by these authors received analgesic therapy, so pain may not be a clinically relevant component of this syndrome. A more important concern is whether the radicular symptoms caused functional impairment. Although not reported, this possibility seems unlikely. If lidocaine spinal anesthesia caused functional impairment in 37% of patients, I suspect it would not have taken 40 yr for the first report to be published. Since all patients had complete recovery, and the severity of morbidity was not reported, it is impossible to determine whether this "syndrome" is associated with significant postoperative morbidity.
Although it is possible to identify potential weaknesses in study design or to raise questions regarding the clinical significance of the radicular pains and/or dysesthesias, the observed differences in incidence of these symptoms is disconcerting. Adding to this concern are the results of a recently completed, but as yet unpublished, randomized, prospective, controlled trial (personal communication, J. E. Pollock) which essentially confirm the findings of Hampl et al. The incidence of transient radicular back pain in this study was 8/51 after 5% hyperbaric lidocaine, 8/51 after isobaric 2% lidocaine, and 0/50 after 0.75% hyperbaric bupivacaine. Furthermore, preliminary data from the same group suggest that this phenomenon may occur with similar frequency when 30-40 mg of hypobaric lidocaine (0.5% concentration) is used for brief operations performed in the horizontal jacknife position . These data provide additional support for the concept that lidocaine may be uniquely associated with this syndrome.
Why was this side effect of lidocaine only recently recognized? Lidocaine was first used for spinal anesthesia in 1948. After a 1969 report found no major central nervous system sequelae associated with 10,440 spinal anesthetics, lidocaine's safety seemed firmly established. Subsequent experience in millions of patients served to reinforce this impression of safety. However, the recent distinction between radicular symptoms and a localized backache has been critical for appreciation of this phenomenon . Back pain is a common postoperative complaint reported by approximately 20% of patients in many studies. The incidence of back pain is similar after surgery performed under a variety of anesthetic techniques including general anesthesia with or without muscle relaxation, spinal anesthesia, or epidural anesthesia . Thus, the consensus opinion has been that back pain is more influenced by patient position and duration of surgery than by anesthetic technique. Of note, Hampl et al.'s study is consistent with these reports in that approximately 25% of patients receiving lidocaine or bupivacaine experienced localized back pain at the site of injection. In contrast to the equivalent incidence of localized back pain, radicular symptoms into the buttocks or legs were experienced only in patients receiving lidocaine. Another possible explanation for recognition of this syndrome is the recent association of lidocaine, microcatheters, and cauda equina syndrome. These case reports may have heightened awareness of the potential for neurotoxicity. Studies in animals which demonstrated the potential for lidocaine to cause neurotoxicity further increased this awareness . Thus, the delayed recognition of this phenomenon may be due to the high underlying rate of nonspecific back pain, a heightened awareness of the potential for local anesthetic induced neurotoxicity, and/or recognition of a distinct pattern of symptoms.
Still unclear is whether concerns regarding lidocaine are well founded or represent an overreaction to a minor side effect. Astra USA has taken a proactive approach to this controversy by revising the prescribing information for lidocaine. A "Dear Doctor" letter mailed to anesthesiologists on June 8, 1995, acknowledges the recent reports of transient radicular symptoms, highlights changes in the package insert, and makes the following recommendations: 1) dilution of the 5% lidocaine with an equal volume of cerebrospinal fluid or preservative-free saline; 2) a maximum dose of 100 mg; 3) removal and replacement of the needle if inadequate spread of anesthesia requires an additional dose; and 4) use of a spinal needle of sufficient gauge to ensure adequate withdrawal of cerebrospinal fluid through the needle prior to and after anesthetic administration. Implementation of these recommendations, which are based on data from animal toxicity studies and physiologic models of the spinal canal, may reduce the risk of permanent neurologic damage. Whether these recommendations will reduce the incidence of transient radicular symptoms after lidocaine spinal anesthesia remains to be established.
Should we alter clinical practice based on these findings? Keep in mind that severe radicular back pain which results in functional impairment appears to be relatively uncommon. Furthermore, objective evidence of neurotoxicity has not been observed in any patient with these radicular symptoms, and the possibility that this phenomenon is caused by some other related factor or factors has not been excluded. Even if transient radicular symptoms are ultimately proven to be caused by lidocaine, this symptom complex appears to produce relatively minor morbidity. In contrast, single injection hyperbaric lidocaine spinal anesthesia has a long, extensive history of safe use with a low rate of serious sequelae. On this basis, I plan to continue to use hyperbaric lidocaine for spinal anesthesia.
Nevertheless, caution is warranted while awaiting results from definitive prospective studies. Until these data are available, it may be prudent to substitute bupivacaine for lidocaine when performing operations where lidocaine with epinephrine would normally be used. Bupivacaine is clearly less likely than lidocaine to produce permanent neurologic deficit in a variety of animal models [11,12]. It may be particularly prudent to substitute bupivacaine for lidocaine in situations where spinal nerve roots will be stretched or there is potential for pooling of the local anesthetic around sacral nerve roots (e.g., operations performed in lithotomy position or "saddle blocks" performed in the sitting position). Clinical experience suggests that an appropriate dose ratio for lidocaine:bupivacaine is 8-9:1 when using hyperbaric formulations of each drug. Although higher than the typical 4:1 ratio quoted for peripheral blockade, this clinical impression is supported by potency ratios identified in animals . When used in this dose ratio, duration of anesthesia after bupivacaine is similar to that for the comparable dose of lidocaine with epinephrine. If a shorter duration of anesthesia is desired, plain hyperbaric lidocaine will have a shorter duration than hyperbaric bupivacaine . In this situation, it may be reasonable to administer a more dilute concentration of lidocaine, since permanent neurologic toxicity in animals increases with increasing concentration . This can be accomplished by using the commercially available 1.5% hyperbaric solution , diluting the 5% hyperbaric solution with cerebrospinal fluid, or use of the preservative-free epidural solutions . However, choice of lidocaine solution will alter the characteristics of the resultant spinal anesthesia. For example, hyperbaric 1.5% lidocaine solution appears to produce motor and sensory block of shorter duration than the 5% hyperbaric or 1.5% isobaric solutions [15,17]. Similarly, the isobaric lidocaine solutions may result in lower peak sensory block levels . Although administration of dilute concentrations of lidocaine is an innocuous and reasonable suggestion and reduces the severity of neurologic injury in controlled animal experiments, alteration of lidocaine concentration within the above ranges may not alter the incidence of the transient radicular syndrome observed in humans. It is quite possible that this syndrome is produced through a different mechanism than that responsible for permanent neurologic injury. For, as discussed previously, lowering the concentration of lidocaine to 0.5% may not be sufficient to reduce the incidence of radicular symptoms .
Currently there are no data to support the selection of an alternative, short-acting local anesthetic. Although procaine is approved for subarachnoid administration, preliminary data suggest that it may be associated with a similar phenomenon . No comparable data are available in the English language literature regarding the use of mepivacaine, prilocaine, or 2-chloroprocaine, and none of these drugs is approved for subarachnoid administration in the United States. Until definitive data are available which support the safety of an alternative short-acting local anesthetic, I would not recommend substituting one of these drugs for lidocaine.
There is no question that lidocaine's stellar reputation has been tarnished. A previous editorial in this journal suggested that lidocaine should be "used with due respect--if at all--in anesthetic procedures where product pooling, nerve stretching, or both could compromise neural viability" . In contrast, I do not believe available data indicate that there is a significant risk of permanent damage to our patients after a single injection lidocaine spinal anesthesia. The report by Hampl et al. in this issue raises serious questions that deserve further study in well designed, randomized, prospective protocols. Ongoing laboratory investigations may also provide insight into mechanisms for these effects. These concerns should promote investigations aimed at identifying an alternative shortacting local anesthetic or alternative formulations for lidocaine. However, it will be a long time before we have a replacement that can duplicate the safety record of lidocaine. Until a short-acting alternative has been identified, and its safety confirmed, I plan to continue to use lidocaine when indicated for spinal anesthesia.
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