Circulation 36,825 • Volume 18, No. 3 • Fall 2003

More Research on TRI is Needed

Julia E. Pollock, MD; Terese T. Horlocker, MD

To the Editor

We appreciate the comments of Dr. Lambert and the opportunity to reply. Specifically because of concerns such as those expressed by Dr. Lambert, in November 2001, the American Society of Regional Anesthesia and Pain Medicine (ASRAPM) conducted a conference on the toxicity of local anesthetics, and the proceedings of this conference have subsequently been published in three issues of the journal Regional Anesthesia and Pain Medicine.1-3 Participants in this conference included international researchers with expertise in the neurotoxicity of lidocaine.

When the initial reports of transient neurologic symptoms (TNS)4 were published, many of the researchers and clinicians at this conference expressed the same views as Dr. Lambert. Given the fact that reports of TNS followed previously published data on cauda equina syndrome (CES) after continuous spinal catheters5 (which was known to result from local anesthetic neurotoxicity), it seemed perfectly logical to conclude that if CES was caused by a large dose of a neurotoxic agent, then TNS was caused by a smaller dose, and perhaps TNS simply represented the more benign end of the neurotoxicity spectrum.

The discussion and published reports from the local anesthetic conference address this idea and provide an excellent summary of the currently available objective evidence on TNS, CES, and the toxicity of local anesthetics-particularly lidocaine. There are two points from this conference that we would like to emphasize.

  1. The factors that increase the incidence of CES are not the same factors which increase the incidence of TNS. For example, the incidence of CES is increased by increasing doses of local anesthetics, by increasing concentrations of local anesthetics, by the addition of glucose to the solution, and by the addition of vasoconstrictors.6 None of these factors appear to increase the incidence of TNS in prospective, randomized studies. The factors which increase the incidence of TNS include the use of lidocaine spinal anesthesia, surgical position (with lithotomy position having the highest incidence) and perhaps ambulatory surgery status.7 (Outpatients had a higher risk of TNS in the large epidemiological study conducted by Freedman,8 but have not been shown to have a higher incidence in smaller, randomized, controlled trials.9)
  2. The drugs which exhibit the most neurotoxicity in the laboratory (lidocaine, tetracaine, and prilocaine) are not necessarily the ones with the highest incidence of TNS in surgical patients. For example, prilocaine is at least as neurotoxic as lidocaine in lab studies,10 but has been shown in randomized, prospective clinical trials to cause no TNS.11,12

Obviously these factors alone do not prove that TNS is not caused by direct neurotoxicity of lidocaine; however, they do at least suggest that the mechanisms for the development of CES and TNS may be very different.

Finally, we totally agree with Dr. Lambert that an alternative agent for outpatient surgical anesthesia is desperately needed. Despite Dr. Lambert’s suggestion, most of the currently available spinal anesthetics are really not ideal for outpatients. We recently have completed a review of our use of spinal bupivacaine for outpatients at Virginia Mason Medical Center. We have actually made suggestions to restrict the use of bupivacaine based on patient complaints of very long discharge time and a high incidence of urinary retention (personal communication, JM Neal, MD). Procaine is a drug that has been studied carefully and is associated with an incidence of TNS of 6%, a high incidence of block failures versus lidocaine (17% vs. 3%) and a higher incidence of nausea (17% vs. 3%) than lidocaine. Average hospital discharge times were 29 minutes longer with 100 mg procaine versus 50 mg lidocaine.13 Ropivacaine has been shown to be an ineffective drug for spinal anesthesia.14 Chloroprocaine with no preservatives is a drug that shows excellent promise for outpatient spinal anesthesia, and indeed numerous studies are underway evaluating its characteristics and potential side effects.15 Clearly additional studies are in order.

In conclusion, we applaud Dr. Lambert’s concern for patient safety, and we completely agree that anesthesiologists should try to avoid anything that causes patient discomfort. We do not believe that single dose spinal anesthesia with lidocaine should be prohibited but that techniques should be used to reduce the incidence of TNS.6 Indeed, one of us has had a spinal anesthetic with lidocaine within the past year. However, despite what we or other clinicians may feel about the use of lidocaine, it is only through continued research and ongoing dialogue, as was presented at the recent local anesthetic toxicity conference, that we will begin to learn the answers to these perplexing questions.

Julia E. Pollock, MD Seattle, WA

Terese T. Horlocker, MD Rochester, MN


1. Regional Anesthesia and Pain Medicine 2002;27: 543-586.

2. Groban L. Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model. Reg Anesth Pain Med 2003;28:3-11.

3. Neal JM. Effects of epinephrine in local anesthetics on the central and peripheral nervous systems: Neurotoxicity and neural blood flow. Reg Anesth Pain Med 2003;28:124-34.

4. Schneider M, Ettlin T, Kaufmann M, et al. Transient Neurologic Toxicity after hyperbaric subarachnoid anesthesia with 5% lidocaine. Anesth Analg 1993;76:1154-7.

5. Rigler M, Drasner K, Krejcie T, et al. Cauda equina syndrome after continuous spinal anesthesia. Anesth Analg 1991;72:275-81.

6. Drasner K. Local anesthetic neurotoxicity: clinical injury and strategies that may minimize risk. Reg Anes Pain Med 2002;27:576-80.

7. Pollock JE. Transient neurologic symptoms: etiology, risk factors and management. Reg Anes Pain Med 2002;27:581-586.

8. Freedman J, Li D, Drasner K, et al. Risk Factors for transient neurologic symptoms after spinal anesthesia. Anesthesiology 1998;89:633-641.

9. Lindh A, Andersson AS, Westman L. Is transient lumbar pain after spinal anaesthesia with lidocaine influenced by early mobilisation? Acta Anaesthesiol Scand 2001;45:290-293.

10. Kishimoto T, Bollen A, Drasner K. Comparative spinal neurotoxicity of prilocaine and lidocaine. Anesthesiology 2002;97: 1250-3.

11. Hampl K, Heinzmann-Wiedmer RA, Luginbuehl I, et al. Transient neurologic symptoms after spinal anesthesia. Anesthesiology 1998;88:629-33.

12. de Weert K, Traksel M, Gielen M, et al. The incidence of transient neurologic symptoms after spinal anaesthesia with lidocaine compared to prilocaine. Anaesthesia 2000;55:1003-24.

13. Hodgson P, Liu S, Batra M, et al. Procaine compared with lidocaine for incidence of transient neurologic symptoms. Reg Anesth Pain Med 2000;25:218-22.

14. McDonald S, Liu S, Kopacz D. Hyperbaric spinal ropivacaine a comparison to bupivacaine in volunteers. Anesthesiology 1999;90:971-7.

15. Smith K, Kopacz D, Mcdonald S. Spinal chloroprocaine. Anesth Analg 2003;96:S285.