Regarding the efficacy of ESIs in the treatment of lumbar radiculopathies, we have three main sources of information: clinical experience, Cochrane systematic reviews, and systematic reviews using methods adapted from the U.S. Preventive Services Task Force (U.S.P.S.T.F.).
Most interventional pain physicians strongly believe that ESIs are effective in the treatment of patients with sciatica. This belief, based on judgments and opinions of experts, is reinforced by the observation that ESIs have been widely used for over half a century and are still a current therapeutic tool used internationally in many specialized centers. It is therefore difficult to conceive that the absence of efficacy could have been missed over the years by so many practitioners. However, traditional clinical experience can be misleading. It is well known in other domains of medicine that the opinions of clinicians and conclusions of experts can be biased, inducing the continuation of useless, costly and possibly harmful therapies [3
]. A scientific approach is clearly needed.
The other principal sources of information are provided by the two types of evidence-based systematic reviews: the Cochrane reviews and the reviews emanating from the U.S. Evidence-based Pratice Centers. The two types of reviews have adopted a different strategy in analyzing RCTs. They also differ in the methods used to assess the quality of each individual study. Variations of methodology are also detected in each of the two types. This is particularly noticeable in the Cochrane reviews. For example, concerning the methodologic quality assessment, Luijsterburg et al. [44
] used a Delphi list and Staal et al. [64
] the criteria recommended by the Cochrane Back Review Group. The three principal systematic reviews separating techniques and pathologies used similar methodologic criteria adapted from Koes et al. [39
] to evaluate the quality of the RCTs. Concerning the analysis of evidence, variations are also observed between the two types of review: the Cochrane reviews usually summarize evidence according to a rating system with five levels of evidence (best evidence synthesis), whereas Henschke et al. [32
] used a different grading quality of evidence as recommended by Guyatt and Osman; the non-Cochrane systematic reviews used a system adapted from the U.S. Preventive Services Task Force with five levels of evidence ranging from level I–III, with three subcategories of evidence in level II.
The inconclusive results of the Cochrane reviews have cast doubt on the therapeutic role that ESIs had for over 50 years in the treatment of sciatica. One can question the reasons for the absence of meaningful conclusions generated by the high-quality Cochrane systematic reviews, creating a difficult situation of uncertainty. The impossibility to conclude for or against effectiveness of ESIs has a multifactorial origin mainly related to the low quality of the RCTs.
The sample sizes of most of the primary RCTs were small, lowering their capacity to detect discrete but relevant differences. A strong heterogeneity exists between studies with respect to the type and dosage of the steroid, the fluid volume injected, the number of injections and their intervals. Symptom duration before treatment, not always mentioned in the RCTs, is another confounding variable: mechanisms of pain in acute, subacute or chronic situations are not similar. The nature of the controls varies between studies: it can be epidural injections of saline or anesthesic. In some RCTs, the effect of ESIs is compared with no treatment or with other treatments. As discussed below, inconsistency between trials may depend on the type of control used.
Other factors may also explain why beneficial effects could have been missed. Most primary RCTs were performed without X-ray guidance, with a risk of incorrect position of the needle. The importance of X-ray guidance has recently been emphasized by Barham and Hilton [5
], who showed in a series of 137 patients treated by caudal ESIs that the miss rate without radioscopic control was 26%. The miss rate is lower in non-obese patients treated blindly by the interlaminar route [55
]. The outcome criteria variable between studies can also be misleading. As suggested by Nelemans [51
], the use of visual analog scales to measure the pain relief may miss small but true effects especially if the dichotomized results (improved/not improved) are used.
Efficacy may vary according to the pathology. In a 2008 updated Cochrane review on injection therapy for subacute and chronic low-back pain, Staal et al. [64
] stated that “one of the main problems when studying the effects of injection therapy was the lack of diagnostic criteria for determining the injection site”. In the case of radicular pain caused by discal herniation or lumbar canal stenosis, the diagnostic is known and the site of injections can be determined accordingly. Moreover, the natural evolution of radiculopathies related to discal herniation, radiculitis and stenosis is not the same. Interlaminar, caudal and transforaminal routes may have different efficacy rates. For example, Koes et al. [39
] reviewed systematically 12 RCTs of lumbar ESIs combining five caudal and seven interlaminar injections. As pointed out by Boswell et al. [8
], four of the five caudal were positive, while only two of the seven interlaminar were positive.
Taken together, these observations may explain why high-quality scientific assessment of efficacy of ESIs combining different techniques and diseases may produce inconclusive results. Systematic reviews including in a same overall evaluation such a heterogenous group of patients carries a risk of dilution of efficacy of the treatment method. A part of this risk is eluded when evidence is evaluated after separating the different techniques and pathologies, which also generates a better clinical relevance. It is recognized, however, that in the latter reviews, the other confounding factors discussed above were not eluded, thus illustrating the difficulty in synthesizing the evidence in this topic. As indicated above, the variations of methodology in quality assessment and analysis of evidence between reviews add to the difficultly.
The authors of systematic reviews adapted from the U.S.P.S.T.F. used a different methodological approach and reported more conclusive results. A short-term benefit of ESIs has been shown in patients with discal herniation and radiculitis by reviews analyzing the data separately: according to imaging [19
] or according to the routes of administration [13
]. The duration of this effect is not clarified in all studies; approximately 6 weeks have been proposed by some authors [1
]. The magnitude of the effect is considered as moderate by Chou et al. [19
], who have noted inconsistency between studies. In a higher quality trial, Carette et al. [16
] found that during the first 6 weeks of the trial, patients reported less leg pain than those receiving the placebo consisting of 1 ml of saline compared with 80 mg of methyl prednisolone acetate in 8 ml of saline. To evaluate the magnitude of the benefit, Carette et al., calculated the effect size and found 0.50 for the radicular pain. This value is considered as moderate (small effect 0.20, large effect 0.80), which is consistent with the conclusions of Chou et al. Few studies have evaluated the long-term effect, which is more difficult to assess owing to the natural evolution of a discal herniation, depending in part on its size and location. Some RCTs using the caudal or foraminal routes [48
] have reported long-term benefits, but it is not clear whether this effect is related or not to repeat injections. Additional ESIs may prolong the analgesic effect. This is an important goal in the management of nerve root pain to prevent peripheral and central sensitization and the risk of chronicity [11
Concerning the therapeutic value of ESIs in managing radiculopathies related to spinal stenosis, the literature is sparse and controversial [28
]. However, ESIs are commonly and increasingly used, owing to the aging of the general population. In the survey by Friedly et al. [27
] in the U.S. Medicare population, spinal stenosis accounted for 23% of all ESIs. After reviewing the data of the literature, it is clear that the level of scientific evidence of efficacy of ESIs in spinal stenosis is yet to be determined. It relies now on observational studies and on one RCT [47
The effect due to the intervention must be distinguished from the placebo effect related to the influence of the patient’s expectation of the injection. The strength of evidence depends on the controls used. Systematic reviews emanating from U.S. Evidence-based Centers have disclosed a short-term benefit of ESIs. Most of them have compared epidural steroid injections as the intervention with various controls. The placebo controls presented on Tables , and consist of epidural saline or local anesthetic injections, and of non-epidural controls, i.e., local intramuscular, ligamentous structures, painful trigger-point injections of saline, anesthetic or steroid. Chou et al. [19
] have noted that trials using a sham soft-tissue placebo injection as controls reported short-term benefits more consistently than studies with epidural placebo injections. However in the Carette et al.’s trial already cited, the steroid was compared with a small quantity of epidural saline (1 ml), which excluded the possibility of a washout effect of saline, suggested by some authors [67
]. The use of a local anesthetic as epidural placebo control may create a difficult issue, as an equivalent positive effect between steroid and lidocaine has been detected in studies using a local anesthetic as a control [47
]. The effect of lidocaine, persisting a few weeks and outlasting the normal duration of a local anesthetic, is unexpected and difficult to understand. This finding, however, must be seriously considered in future studies. In addition, the use of an epidural anesthetic carries the risk of a subdural anesthesia in case of dural puncture during the injection and of accidental intravenous injections possibly followed by convulsions and arrhythmias. Chou et al. [19
] have suggested that trials comparing epidural saline or anesthetic injection versus non-epidural placebo injection would be helpful to clarify the efficacy of non-steroid epidural injections. This recommendation is particularly important since the epidural steroid injected as an intervention is often diluted in saline or in anesthetic [4
In future X-ray guided RCTs, in addition to the many pertinent recommendations for research made by the Cochrane reviewers, an appropriate choice of the intervention of interest, i.e., epidural steroid injection and of the control will be of primary importance. The injected steroid must have a sufficient volume to correctly fill the epidural space, the diluent being a neutral ineffective fluid. For safety reasons, the steroid chosen must have the least tendency to coalesce [70
]. The only way to clearly distinguish the efficacy of the procedure from a simple placebo effect is through the use of a sham ineffective control, such as a local intramuscular ineffective injection, simulating an epidural injection on a blinded randomized patient. In the course of this review, it was noted that many other aspects of this complex area must be clarified, confirmed and strengthened by additional research.