A Simple Technique to Reduce Preservative/Excipient Related Neurotoxicity of Intrathecal (Spinal) Drugs

This is the authors' abstract. We don't add key points for this paper.

Munir et al. suggest a method for the dilution of the vehicle used to suspend depo type steroids as a technique to reduce the potential for neurotoxicity. I presume their advice pertains to the intentional intrathecal injection of drugs, such as methylprednisolone acetate (Depomedrol) or triamcinolone diacetate (Aristocort Intralesional), because there is almost no evidence that the epidural injection of these preparations poses a significant risk. This brings up several questions. 1. What are the indications, if any, for the intrathecal injection of depo steroids? Most neurologists have given up the practice of intrathecal steroid injections for advanced multiple sclerosis because of the perceived risk of arachnoiditis. For patients with lumbar radiculopathy, there is no evidence that the intrathecal route is any more effective than epidural administration (1). 2. Is there, indeed, a real risk of neurologic dysfunction after the intrathecal injection of the commercial preparations used for epidural steroid injections? The evidence that intrathecal steroids produce adhesive arachnoiditis is meager, consisting mainly of case reports involving multiple injections in patients with severe neurologic dysfunction associated with multiple sclerosis (2). I am aware of only one case report of arachnoiditis after intrathecal steroid injection therapy for sciatica (3). That patient’s symptoms resolved after surgical discectomy. There have been several case reports of aseptic meningitis after epidural steroids administration, but symptoms have been transient in all reported cases, and there has been no evidence of permanent sequelae (2). 3. If intrathecal steroid injections do predispose to arachnoiditis, is the vehicle the offending agent? The steroid suspensions we use for epidural injection contain 3% polyethylene glycol. Benzon et al. (4) showed that concentrations of this agent up to 10% had no effect on desheathed nerve preparations, and concentrations as high as 40% produced only transient slowing of conduction. Early studies that were held out as examples of the potential neurotoxic effect of polyethylene glycol actually assessed the effects of propylene glycol, in 80% concentrations (2). It may be the case that there is indeed some risk of arachnoiditis after intrathecal steroid injections, but that the offending agent is the steroid itself. In that case, resuspension of the insoluble steroid in saline would provide no added safety and might actually enhance the potential for problems by promoting clumping and maldistribution of the solid material. If polyethylene glycol or benzyl alcohol are potentially neurotoxic, there is no evidence that the 43% reduction in their concentration achieved by using the authors’ technique will reduce the potential for serious sequelae. My final concern is a medicolegal one. If there is sufficient concern about the use of these preparations to prompt us to dilute the vehicle with saline, we should probably not be using them at all. I am convinced that there is substantial evidence for the safety of epidural injections of these drugs. I am not as convinced that intrathecal use is entirely safe, and we have no evidence that dilution of the vehicle with normal saline improves its safety when administered intrathecally. Stephen E.