Letters to the Editor:

Transient Radicular Irritation Remains a Danger

More Research on TRI is Needed

Transient Radicular Irritation Remains a Danger

To the Editor:

I write because I believe many patients are still receiving spinal anesthesia that is associated with transient radicular irritation (TRI, also known as transient neurologic syndrome or TNS). Dr. Marcus Schneider first described TRI in 1993.1 TRI is a constellation of low back, buttock, and lower extremity pain that occurs usually within 24 hours of spinal anesthesia and persists for as long as 4 to 5 days. Lidocaine and mepivacaine are more likely to cause TRI than other anesthetics. Bupivacaine and prilocaine rarely cause TRI, and procaine and tetracaine are intermediate in causing this disorder.2

Some anesthesiologists believe that lidocaine-induced TRI is possibly benign because it is poorly understood and because of its transience,3,4 and they argue that lidocaine's "long safety record" and the "lack of a suitable short duration substitute" is a reason to continue using lidocaine for spinal anesthesia.5,6 This is not a reasonable argument to continue a practice that is harmful to patients.

The true cause of TRI remains unknown. I have argued that TRI is likely toxicity that is clinically undetectable after the symptoms of TRI resolve.7 Others have argued that it is not toxicity.3,5 We may never know if TRI is due to local anesthetic toxicity because studies of toxicity involving patients are unethical and because we do not have an animal model that adequately duplicates TRI. Nonetheless, it is my opinion that anesthesiologists should avoid local anesthetics in spinal anesthesia that:

  1. Cause pain that can last from 2 to 5 days.
  2. Cause pain that is often worse than the pain associated with the operation for which the spinal was used.
  3. Cause pain that can rate as high as a 6 on a 10-point VAS.
  4. Cause patients to visit the emergency room out of fear that something is wrong.
  5. Sometimes result in CT or MRI scans to rule out serious neurologic injury.2

Anesthesiologists should prevent and treat pain, not cause it. We may not know what TRI is, but we know how to avoid it. It can be avoided by using drugs that do not cause it. Procaine and bupivacaine are two approved local anesthetics that can substitute for lidocaine.8,9 Procaine has been downplayed because of a perceived poor quality of anesthesia and high incidence of nausea and vomiting.9 It is argued that bupivacaine results in a prolonged motor block that is unacceptable in this day of "fast-tracking" anesthesia in outpatients.10 On the other hand, is it reasonable to continue to use lidocaine to save an hour of PACU time, only to have some patients returning to the emergency room for the reasons outlined above?

Chloroprocaine is a drug that has recently been tested in volunteers.11 If it is similar to procaine, it may cause less TRI than lidocaine, and it may have a duration that would make it useful for outpatient anesthesia. Similarly, ropivacaine should be evaluated both in terms of toxicity and its TRI potential. Unlike bupivacaine, it produces less motor block and could have a recovery profile that would also make it useful for outpatient operations.

Eight years ago, one anesthesiologist wrote in the APSF Newsletter that lidocaine was safe and that it was used in 500,000 to 1,000,000 spinal anesthetics annually.5 Just this year, others argued, "Since spinal lidocaine has been used previously for approximately 50 million spinal anesthetics, it seems hard to imagine that the use of lidocaine should be limited or abandoned."12 Because of the reports of cauda equina syndrome and TRI owing to lidocaine spinal anesthesia, lidocaine is probably used much less frequently today. Nonetheless, even if it is used only one-tenth as often today, then 50,000 to 100,000 lidocaine spinal anesthetics are still being given. That means that as few as 2,500 or as many as 10,000 patients are suffering from TRI after the lowest risk operations (operations performed in the supine position =5% incidence of TRI).

Those numbers rise to 17,500 to 70,000 for patients having lower extremity arthroscopy or operations performed in the lithotomy position (35% incidence of TRI). Even if it does not result in permanent injury, we should eliminate the pain and suffering caused by TRI. In keeping with the APSF mission, that no patient shall be harmed by [or suffer from] anesthesia, we can eliminate TRI simply by not using the local anesthetics that cause it.

Donald H. Lambert, PhD, MD Boston, MA

References

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

2. Pollock JE. Transient neurologic symptoms: etiology, risk factors, and management. Reg Anesth Pain Med 2002;27:581-6.

3. Moore D, Thompson G. Commentary: neurotoxicity of local anesthethics—an issue or a scapegoat? Reg Anesth Pain Med 1998;23:605-10.

4. Neal J, Pollock J. Can scapegoats stand on shifting sands? Reg Anesth Pain Med 1998;23:533-7.

5. Blitt C. Safety of 5% lidocaine heavily defended. APSF Newsletter 1995;10:24.

6. Pollock JE. TNS: Is it clear that lidocaine is the culprit (reply). Reg Anesth Pain Med 2003;28:151-2.

7. Lambert DH. Continuous spinal anesthesia redux. Anesthesiology 2003;98:797-8.

8. Lambert DH. Limiting transient radicular irritation. Reg Anesth Pain Med 2001;26:177-8.

9. Hodgson PS, Liu SS, Batra MS, et al. Procaine compared with lidocaine for incidence of transient neurologic symptoms. Reg Anesth Pain Med 2000;25:218-22.

10. Pollock JE, Neal JM, Stephenson CA, et al. Prospective study of the incidence of transient radicular irritation in patients undergoing spinal anesthesia. Anesthesiology 1996;84:1361-7.

11. Smith KN, Kopacz DJ, McDonald SB. Spinal chloroprocaine. Anesth Analg 2003;96:S285.

12. Pollock JE, Alley E. Virginia Mason Medical Center's promotion of outpatient lidocaine spinal anesthesia questioned (reply). Anesth Analg 2003;96:1237-8.


Roanoke, VA

More Research on TRI is Needed

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

References

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.