This study was a prospective evaluation of the effectiveness of percutaneous adhesiolysis with targeted delivery of injectate in 70 patients suffering from lumbar central stenosis with a 2-year follow-up. The results showed a successful primary outcome measure with a significant reduction of pain and improvement in function in 71% of the patients at the end of 2 years. The results were similar to the previous evaluation of a randomized trial 32
in which 76% of patients in the adhesiolysis group showed over 50% pain relief and functional improvement. The average procedures for 2 years were 5.7 ± 2.73. The average relief over a period of 2 years was 71.1 ± 37.4 weeks over a period of 104 weeks. The results of this observational study illustrate that percutaneous adhesiolysis with targeted delivery of injectate is superior to either caudal or lumbar interlaminar epidural injections in central spinal stenosis, specifically in those who have failed to respond to fluoroscopically directed caudal or lumbar epidural injections 24,25,28,29
This study may be criticized for the lack of a control group and inclusion of less than 100 patients in an observational study. In conducting this study, however, specifically with the randomized phase, we faced multiple issues with recruitment, continuation in the study without unblinding despite the lack of pain relief and long-term follow-up. Consequently, the consideration of central spinal stenosis after a failure to respond to fluoroscopically directed epidural injections is a difficult management issue. We consider that 70 patients in the observational phase with a 2-year follow-up is appropriate. The number of patients who withdrew or were not available for follow-up at the end of 2 years was less than 30%, which is acceptable based on Cochrane review criteria for randomized trials 64
. On the issue of placebo control, the difficulties are insurmountable when utilizing interventional techniques in the United States. These difficulties contributed to our failure to complete the study as expected. Damen et al 65
reviewed the issue of terminating clinical trials due to an insufficient number of subjects. They noted that the research question is unlikely to be answered reliably if the requisite number of subjects is not met, and that the continued participation of the study participants at inadequate levels may expose patients to unnecessary risks and burdens. The results of this study 65
showed that a considerable proportion of studies (41 of 107) were terminated due to failure to recruit a sufficient number of subjects. Furthermore, the authors found that investigator-initiated studies have significantly more problems when recruiting the requisite number of subjects than studies initiated by pharmaceutical companies. This may be due to the remuneration offered in pharmaceutical studies when compared with investigator-initiated studies. Our experience has been to the contrary when recruiting required subjects. Of the 16 studies performed by these investigators, this was the first study for which the required number of patients was not recruited. The major issue has been placebo control groups, for which patients are difficult to recruit. Consequently, active-control groups facilitate easier recruitment and also short-term follow-up will facilitate the recruitment. In addition, Damen et al 65
found that 40% of study results were published with the inclusion of the correct number of subjects, compared with 32% of studies where the requisite number of subjects was not obtained. Nevertheless, protocol violations were reported only twice. Consequently, in this evaluation, all information has been provided so that the study may be assessed appropriately. The study was converted into an observational study as to avoid having to subject patients to enrollment and subsequent withdrawal.
An observational study is defined as an etiologic or effectiveness study 66
. Even though in the paradigm of evidence-based medicine (EBM) randomized trials have been considered as the highest quality of evidence, EBM by no means is limited to randomized trials only. The World Health Organization (WHO) defines clinical trials as, “any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes 67
.” Thus, to improve the effectiveness and safety of patient care, there is a growing emphasis on evidence-based interventional pain management and the incorporation of high quality evidence into clinical practice including observational studies. Furthermore, the majority of studies in interventional pain management are observational and treatments, including surgery, are more likely to be based on observational studies than are those in internal medicine, which are based on randomized controlled trials. The basis for randomized trials arises from the evidence that many surgical and medical interventions recommended that were based on observational studies have later been demonstrated to be ineffective or even harmful 68-72
. However, contradictory evidence has been demonstrated for randomized control trials also 49,73
. The evidence from observational studies has been shown to be viable in multiple reviews. The poor quality of reporting in observational intervention studies was reported as a potential factor for confounding bias in 98% of studies 74
. In a 2005 publication, Hartz et al 75
assessed observational studies of medical treatments and concluded that reporting was often inadequate for use in comparing the study designs or allowing for any other meaningful interpretation of the results. However, the concept that the assignment of subjects randomly to either experimental or control groups is a perfect science also has been questioned. In contrast to Hartz et al's assessment in 2005 75
, Benson and Hartz 76
in a 2000 publication comparing observational studies and randomized controlled trials found little evidence that estimates of treatment effects in observational studies reported after 1984, were either consistently larger than or qualitatively different from those obtained in randomized controlled trials. Furthermore, Hartz et al 77
, in a 2003 publication assessing observational studies of chemonucleolysis, concluded that the results suggested that a review of several comparable observational studies may help evaluate treatment, identify patient types most likely to benefit from a given treatment, and provide information about study features that can improve the design of subsequent observational studies or even randomized controlled trials. However, they caution that the potential of comparative observational studies has not been realized because of concurrent inadequacies in their design, analysis, and reporting. Concato et al 78
in a 2000 publication evaluating published articles in 5 major medical journals from 1991 to 1995, concluded that the results of well-designed observational studies do not systematically overestimate the magnitude of the effects of treatment as compared with those of randomized controlled trials on the same topic. In fact, Shrier et al 79
in 2007, found that the advantages of including both observational studies and randomized trials in a meta-analysis could outweigh the disadvantages in many situations and that observational studies should not be excluded a priori. In addition, an assessment of the methodological quality of observational studies has been described extensively 24-27,49,80
. Thus, observational studies are important in assessing the effectiveness of interventions.
The mechanism of neural blockade has been described to be complex with alternation or interruption of nociceptive input, the reflex mechanism of afferent fibers, self-sustaining activity of the neurons, and the pattern of central neuronal activities 81
. Among the multiple drugs utilized in this procedure, corticosteroids have been shown to reduce inflammation by inhibiting the synthesis of a number of pro-inflammatory mediators 82-84
. Local anesthetics also have shown to provide short to long-term symptomatic relief based on various mechanisms including suppression of nociceptive discharge, blockade of the sympathetic reflex arch, block of axonal transport of nerve fibers, and anti-inflammatory effects 85-90
. In addition, local anesthetics and steroids also provided similar relief when they were injected individually in experimental settings 91,92
and also in multiple clinical settings 26,28,29,32,43,54-63,81
. Finally, hypertonic sodium chloride solution has been shown to provide neurolysis and analgesia by various mechanisms 43,46
. While the results in this study are shown to improve patients after they have failed conservative modalities including fluoroscopically directed epidural injections, the role of percutaneous adhesiolysis in foraminal stenosis without central spinal stenosis is not known. The results of this evaluation are only limited to central spinal stenosis without surgical interventions. It is interesting to evaluate the role of each component of percutaneous adhesiolysis in reference to adhesiolysis, injection of local anesthetic, injection of steroids, and injection of hypertonic sodium chloride solution.
Overall, the results of this observational study of 70 patients with a long-term follow-up of 2 years show that percutaneous adhesiolysis may be an effective modality in patients failing to respond to fluoroscopically directed epidural injections and also other conservative modalities of treatment.