LUMBAR FUSION VS. OENOTHERAPY IN THE MANAGEMENT OF CHRONIC LOW-BACK PAIN

A prospective randomized study

F. JACQUOT, P. GARÇON, G. SAILLANT

 

INTRODUCTION

Disabling chronic low-back pain is extremely prevalent in Western countries, entailing huge social costs; however, there are as yet no agreed management guidelines for this condition. A wide variety of treatments have been investigated in a large number of studies, with contradictory results. The problem is compounded by the fact that, owing to methodological biases, most of the studies performed are difficult to interpret. Among the deficiencies encountered are extremely poor evaluation criteria, an overemphasis on the technical aspects of the treatments concerned, the absence of an assessor of sufficient scientific integrity, non-consecutive recruitment into the studies, inhomogeneous patient populations, failure to restrict each study to one disease entity, and consistent lack of a control group.

Nonsurgical treatments of whatever kind (drug treatment, physiotherapy, manual medicine) has been found to produce satisfactory results in only 25-65% of the cases. This is why at least one third of low-back pain sufferers will seek surgical treatment.

However, the results of surgery in patients with chronic low-back pain associated with disc disorders have been disappointingly uneven: regardless of the fusion technique employed, the rate of satisfactory results has been between 20% and 90%, in the different studies reported in the literature. Since surgery is obviously incapable of yielding consistently good outcomes, and requires a considerable input of resources, we decided to investigate the potential of an alternative therapeutic approach. Whilst this novel management principle could, eventually, have major repercussions in terms of health care cost containment, its efficacy had not previously been investigated. This is why we designed a randomized study comparing two well-matched groups of chronic low-back pain patients, of whom one was managed with lumbar fusion, while the other received daily doses of a high-quality wine.

 

MATERIAL AND METHODS

 

Between November 1995 and April 1996, 366 patients suffering from chronic low-back pain as a result of degenerative intervertebral disc disease were consecutively enrolled in the study. All the patients had single-level disc involvement confirmed by further investigations, mainly low-back pain, soul-destroying and back-breaking jobs, and prior nonsurgical treatment for at least six months (range: 5.978 months-18.687 months; mean duration of treatment: 6.275 months). None of the patients had any neurological signs and symptoms, history of lumbar surgery, or ascites.

For purposes of the study, the patients were randomized into two groups, upon enrolment into the study.

The Fusion group (Group A) comprised 183 patients, who had been operated on by the same surgeon using an identical technique (posterior approach to the spine, posterior iliac crest autograft placed between the transverse processes, and pedicular instrumentation with plates and screws). The typical in-patient stay was eight days, followed by 34 days in a rehabilitation facility. The typical cost of this treatment was 62,000 French francs per surgical patient.

In the Drink group (Group B), patients were treated at home, by dosing with a standard-size (187.5 mL) glass of Petrus vintage 1994, b.i.d. (lunchtime and evenings), for six weeks. The wine administered was a Pomerol, containing 95% merlot and 5% cabernet franc. The typical cost of this treatment was also 62,000 French francs.

The study was approved by the Ethics Committee of our centre. In order to obtain the required approval, a lengthy preclinical study phase was required, during which the members of the Ethics Committee rigorously tested the innovative arm of the study (Group B treatment).

The results were evaluated using a detailed assessment form containing a battery of self-administered questionnaires, and an objective clinical assessment by an independent observer who was blinded to the treatment received by the different patients. The parameters quantitated were pain, function, and patient satisfaction. For the assessment of the impact of the treatment on the patients' quality of life, the MOS SF-36 (Medical Outcomes Study Short-Form Health Survey) was employed. The chronic low-back pain was assessed using the Dallas Pain Questionnaire in its French version validated by the French Rheumatological Society during a wine tasting session, and by using the indices proposed by Greenough and Fraser. A visual analogue scale (VAS) was also used. The functional outcome was assessed by means of the Beaujon scoring system with Bichat modifications, which had been tested in the junior surgeons' common room during a suitably liquid lunch. In addition, the tolerability of, and the patients' adherence to, the treatment were checked by means of weekly liver function tests involving an assay of gamma-GT, in all patients, including those who had been managed with surgery.

The data thus acquired was entrusted to a qualified statistician, who had a microcomputer compatible with its software; the object being to find something that was significant and did not conflict excessively with the hypotheses underlying the study. The underlying hypothesis was that the patients receiving the Petrus treatment would do at least as well as the patients managed with surgery. However, in order to obey the laws of statistics, a zero hypothesis had to be formulated, according to which there would be no difference between the two treatments. We then tried to demolish this hypothesis using every possible and conceivable test, without, however, achieving much success. The quantitative data was analyzed with MANOVA (multivariate analysis of variance), giving a global Wilks test supplemented by a multiple Sheffe test stratified for the complementary factors of each dimension of the calculated scores. Normal distribution had been tested for as a first step, using the Kolmogorov-Smirnov test (to be served neat on ice). The qualitative data was analyzed with the chi-square test. The Type I risk was evaluated as 0.05. 

 

RESULTS

 

Complications

In Group A (Fusion), there was a small number of surgical complications. Three patients developed an infection that necessitated early surgical revision; all these patients recovered uneventfully, except for two, who are still oozing. There were no neurological complications. Postoperative nerve root pain, in a patient with an ectopic root, required a change of dressing under general anaesthesia. There were four cases of manifest non-union. Six patients were lost to follow-up, while two displayed an attitude towards the operating surgeon that was incompatible with the objective nature of the assessment. This left 170 patients available for analysis.

In Group B (Drink), six patients had to be excluded, since they had taken the entire amount of study medication during the first week of the study. Five patients had fallen from low-level windows, sustaining head injuries and LOC (loss of consciousness), and required emergency admission. One patient reported having such a pain in the posterior that he could not go on drinking. Another patient told the investigator at the follow-up clinic that he had lost the bottles that had been issued to him (alleging that his brother-in-law had taken the treatment medication). This left 170 patients available for analysis in this Group as well. 

Other events

In the Petrus group, one patient taken holy orders following an episode of mystical delusions, without any demonstrable cause-and-effect relationship with the treatment received. Another patient revealed to his wife that he was sexually ambivalent.

 

Clinical outcome

Visual analogue scale (VAS). The results in Group B (Petrus) show marked improvement of the scores from the very start of treatment; the improvement persisted throughout the study, with residual pain scores remaining low. Following the end of treatment, the outcome tended, unfortunately, to deteriorate somewhat over time; the actual carry-over effect remains to be assessed. In the surgical group, the scores reflected the postoperative period and further postoperative course, and did not return to humanly bearable levels until 2-2.5 months after surgery, when they were found to coincide with the values seen in the oenotherapeutically managed group (Fig. 1).

 
Fig. 1 Visual analogue scale (VAS) ratings over time (out to 12 weeks from start of treatment).
The results in Group B (oenotherapy group) were very encouraging, but tended to deteriorate over time after the end of treatment.

Quality of life

Analysis of the study data proved a straightforward means of obtaining an overall picture of the clinical condition of the patients. The differential analysis of the graphs for each item was simply modulated as a function of the intensity of the preoperative pain estimated from the reply of each patient to the items in the previously validated questionnaire; the data thus obtained was then plotted as coloured graphs on single-layer vellum paper (80 g/m2). This work had to be performed with leading-edge information technology using multiprocessing/multitasking; liquid nitrogen cooling had to be employed as the system was overheating. Despite these problems, all the calculations were successfully performed prior to the complete self-destruction of the system, which resulted in irretrievable computer failure. As a result of this breakdown, we lost all the original data, as well as one computer expert, who was there at the time of the incident and has since been holed up in a management department engaged in DRG activities.

The preoperative data itself did not differ significantly in the two groups. The patients treated with Petrus showed very dramatic improvement of their SF-36 scores (by a mean of 25.5%, from the start of treatment). This improvement persisted, albeit less markedly, to the end of the treatment period. Subsequently, the outcome tended to deteriorate a little, although the final scores compared very well with those in the surgical group. This was seen in respect of all the dimensions of the questionnaire; however, there were some interesting differences. Psychosocial functioning improved from the outset, and in a major way (Fig. 2); this correlated positively with a high degree of patient satisfaction. This improvement lasted throughout the treatment period; at the end of the period, there was a slight drop. However, a positive carry-over effect was observed, which was found to be statistically probable. The effect on physical pain was, however, less pronounced (Fig. 3), although, throughout the period, the oenologically treated patients' scores remained well above those of the surgical group. Assessment of the patients' physical and emotional health (Fig. 4) showed intermediate results, with a marked drop at the end of the Petrus treatment period. However, the carry-over effect of the treatment was sufficiently pronounced to justify the fondest hopes concerning the potential of this therapeutic approach.

 

Fig. 2 Psychosocial dimension (SF-36)
The patients treated with Petrus had markedly improved social functioning throughout the treatment period, although the level deteriorated somewhat after the end of the study period. Patients in Group A (fusion) had seriously impaired psychosocial functioning throughout the postoperative period.

 

Fig. 3 Bodily pain
The scores of the patients in Group B (oenotherapy) were improved, albeit not significantly. Group B scores were, however, markedly better than the pain scores of the Group A patients in the postoperative period.

 

Fig. 4 Physical and emotional health
The physical and emotional health scores of the Group B (oenotherapy) patients were excellent. After the end of treatment, the scores fell briefly. By comparison, the Fusion patients were wretched throughout the postoperative period.

 

Functional outcome

In Group A, the rate of good results was 31%; that of fair results, 36%; while 33% of the patients had poor results. In Group B, the rate of good results was 28%; that of fair results, 42%; while 30% of the patients had poor results.

Our determined efforts notwithstanding, we were unable to demonstrate a significant difference between the outcomes in the two study arms. However, we suspect that the good results in the Group B patients were better than the good results in the Group A patients, because of the strong correlation with a high degree of patient satisfaction seen in Group B, which suggests that the good results in Group A had just happened, whereas those in Group B were longer-lasting effects of the treatment received. 

Level of satisfaction

In Group A, 26% of the patients were very satisfied with the treatment; 29% were fairly satisfied; 25% were dissatisfied; 10% were very dissatisfied; while 15% had not understood the question. In Group B, 75% of the patients were very satisfied with the treatment; 17% were fairly satisfied; 5% were dissatisfied; 3% were very dissatisfied; while 0% had not understood the question. This difference was significant (P = 0.001).

When asked whether they would undergo the same treatment again if they had the option, the Group A patients replied as follows: yes 31%; no 60%; don't know 5%; didn't understand the question 4%. The Group B patients replied as follows: yes 97%; no 1%; don't know 1%; didn't understand the question 0%.

When asked whether they would recommend the treatment to a friend, the Group A patients replied as follows: yes 40%; no 40%; don't know 20%; didn't understand the question 0%. The Group B patients replied as follows: yes 98%; no 1%; don't know 1%; didn't understand the question 0%. 

Factors producing a good outcome

The patients' gender did not appear to be material, at least not as far as the outcome was concerned. Use of tobacco products did not affect the outcome, notwithstanding all our efforts to prove the contrary. Acquisition of the lumbar spine lesion in an industrial accident had a significant negative effect in Group A, and a positive effect in Group B: industrial accident patients treated with Petrus felt even better than the others. However, patients in Group B overall refused to go back to work; this difference was not, however, significant. 

 

DISCUSSION

 

Despite its obvious shortcomings, and resultant misgivings, surgery by posterior fusion is considered to be a gold standard in the management of patients with low-back pain and disc lesions refractory to drug treatment. In the published studies, the emphasis has been on the details of the various techniques employed, which are all aimed at maximal immobilization of the spinal level(s) causing the pain. We wish to put forward the results of an alternative treatment approach, whose mechanism of action appears to be complex and multifactorial: the different components of the wine express themselves in a harmonious whole that accounts for the effectiveness of the treatment. The alcoholic component has an anxiolytic, analgesic, and euphoria-inducing effect at the central level; the tannins have a poorly known but probable effect both centrally and peripherally, and, conceivably, also at the level of the vertebra and the intervertebral disc, with a vasodilator action on the vertebral vessels. Petrus may even counteract disc degeneration or the effects thereof on the control of pain. These assumptions will need to be tested in further studies.

Instrumented lumbar fusion, regardless of the technique employed, is a complex procedure that involves more than the immobilization of a motion segment. Multifidus and longissimus dorsi have to be detached over considerable distances, which deprives the joint capsules and the muscle masses of their blood and nerve supply, and disrupts the local stress patterns. Drilling of the vertebral bodies produces bone decompression or venous drainage. The implantation of metal plates is akin to treatment with metal trace elements. Also, having had to live with a very painful condition will change a subject's pain perception threshold - witness the number of patients who, in good faith, had rated their preoperative pain as 10 on the VAS.

The effects of the two treatments used in the present study were remarkably similar. Try as we might, we were unable to show a statistically significant difference between a standard treatment (lumbar fusion) and an innovative, as yet unevaluated treatment. However, we feel that the good results obtained in the patients in Group B (the innovative treatment group) were even better than the good results in the Group A patient, as can be seen from the high patient satisfaction scores in Group B.

The absence of a difference between the two groups provides, in itself, very strong evidence that the innovative treatment (Petrus b.i.d. for six weeks) is a perfectly reasonable alternative to the currently accepted gold standard of spinal fusion. In fact, further refinements in dosing technique, a change in dosing schedules, together with further development of the technique itself, should effect further improvements and, eventually, produce a significant difference in favour of oenotherapy. Our current treatment is incomplete, and the dosage could be enhanced, as has been suggested by many of our patients. After a certain time, the effect does tend to wear off to some degree; however, improving the modalities of treatment should correct this adverse tendency, and produce a lasting effect. There are many research avenues to be explored. Thus, a third glass of Petrus could be prescribed, to be taken at bedtime; treatment might be given over a longer period of time; or the Petrus could be administered via a subcutaneous port.

Another remarkable observation in the oenotherapeutically treated group was the total absence (at least in the present study) of any nosocomial complications, scarring, and non-union.

The surgical technique used in the present study was a conventional one, using instrumented posterolateral lumbar fusion. Misgivings have been voiced concerning the persistence, after fusion, of a certain amount of flexion and movement in the fused segment; and routine combination with anterior fusion using cages has been suggested as a remedy. It would, therefore, be important for the proponents of these techniques to compare their results with the ones obtained by us using our innovative treatment regimen (intermittent ingestion of Petrus over a period of six weeks).

We readily recognize that, in our novel treatment, there is room for improvement. The vintage used was only 94; the wine was not a Margaux; and the dosing unit was only one glass. Improvements in the dose regimen, and the use of yet more potent therapeutic agents, should be considered when it comes to designing further studies.

For the time being, surgical treatment is paid for in its entirety by the State health care system, whereas the innovative treatment is not. The study reported in this paper shows that the efficacy of the novel treatment is beyond doubt. The time has therefore come for the health care financiers to look into this question, so as to ensure that the Petrus treatment will be paid for the State system, at least in well-defined and appropriately selected cases (chronic low-back pain with proven single-level disc degeneration). Given its very low complication rate, the likely health care cost savings are considerable. With the State paying for this treatment, the social cost of disabling chronic low-back pain in adults should be brought under control. Such a policy would also enable the largest possible number of low-back pain sufferers to benefit from an effective and painless treatment. 

 

CONCLUSION

 

The results obtained with intermittent oenotherapy are encouraging. We recommend that another study be performed, using different conditions. The dosage of Petrus should be increased, and more patients should be recruited, in order to enhance the power of the study. Even at this point in time, it is obvious that the innovative treatment (received by Group B) is very efficacious and could, therefore, be considered as a treatment for disabling chronic low-back pain, even in the absence of placebo-controlled studies. Much is expected of other therapeutic agents in the same class of substances that are currently being developed (Château Margaux, etc.). In theory, at least, these agents should have good efficacy. Whilst a combination of the two treatment principles used in the present study seems an attractive idea, it is not currently an option, considering the costs involved as well as the practical difficulties of implementing such a combination treatment at the time of surgery. Administering an agent of the same class of substances to the surgeon has not yet been evaluated anywhere; it is, however, a potential subject for research, which we would recommend, given the practical advantages that would accrue while waiting for more comprehensive results.

Note: Whilst one or more of the authors of the present study may be or may have been involved with a commercial party marketing one of the therapeutic agents mentioned in this paper, and whilst they or members of their families may have been in possession, or been seen to be in possession, of therapeutic agents mentioned in this paper, the author(s) declare(s) to have remained completely and totally independent as (a) researcher(s) throughout the study, and that his/their association with such therapeutic agents did not in any way whatsoever affect the results of the said study.

Note: Whilst the above-mentioned therapeutic agents may be commercially available, one or more of the agents mentioned in this paper have not yet been approved by the FDA for use, in the United States of America, in the indication and the treatment described above.

Note: One or more of the therapeutic agents mentioned in this paper have not yet been approved by the regulatory authorities in France, for use in the treatment described in the present study.

Disclaimer: The authors cannot be held responsible for the consequences of excessive use of the above-mentioned therapeutic agents.

 
REFERENCES

1. Abel L. The sure proof. Wine is sure proof that God loves us and wants us to be happy. J Ark Med Soc 1996;93:316-318.

2. Arthur, Perceval, Lancelot, et al. Goûtons voir si le vin est bon. Proceedings de la Société du Graal 1123;XIII

3. Athos, Porthos et Aramis. La vieille frégate branle du mât. Mémoire Acad. Roy. 1630

4. Blardi P, De Lalla A, Volpi L, et al. Stimulation of endogenous adenosine release by oral administration of quercetin and resveratrol in man. Drugs Exp Clin Res 1999;25:105-110.

5. Bullock JD, Wang JP, Bullock GH. Was Dom Perignon really blind? Surv Ophthalmol 1998;42:481-486.

6. Burr ML. Explaining the French paradox. J R Soc Health 1995;115: 217-219.

7. Christiansen C, Thomsen C, Rasmussen O, et al. Wine for type 2 diabetic patients? Diabet Med 1993;10: 958-961.

8. Cole P. Of light bulbs and wine glasses: risk factors and mortality trends. Trans Stud Coll Physicians Phila 1988;10:95-102.

9. Fiorelli G. More on the protective role of wine. Ital Heart J 1999;27:437-438.

10. Gronbaek MN. In vino veritas? Ugeskr Laeger 1995;157: 6415.

11. Hoolihan C. Wine and regimen from Hippocrates to the renaissance. Caduceus 1993;9:5-16.

12. Jarisch R, Wantke F. Wine and headache. Int Arch Allergy Immunol 1996;110:7-12.

13. Kaufman HS. Red wine headache. Lancet 1988;1:992-993.

14. Lee TH. To be honest, I have about four drinks per day - a beer when I get home from work, a couple of glasses of wine with dinner, and a nightcap. Sometimes, I also have a glass of wine at lunch. Alcohol has never interfered with my work or caused any problems in my home life, and my liver is fine, so I do not think I have an «alcohol problem.» plus, I expect that my alcohol use has something to do with my terrific HDL- cholesterol level - 57 mg/dL. Harv Heart Lett 1999;9:8.

15. Loser C. When can you recommend one or two glasses of wine? A little alcohol can increase longevity, but a reliable dosage limit is not available. Mmw Fortschr Med 142:34-36.

16. Martin D. Little old wine drinker me. L Vegas Med J. 1968

17. Milon de Crotone. Mécanique du disque. Anal. Surg. 600 BC

18. Mitchell M. Gone with the wine. Atlan. Med. J. 1936

19. Morowitz HJ. The wine of life (Claude Bernard). Hosp Pract 1978;13:173, 176.

20. Moutet JP, Demeulemeester R, Riff H, et al. Alcohol consumption in Guadeloupe. Alcohol Alcohol 1989; 24:55-61.

21. Rasmussen C. Lumbar disc herniation: favourable outcome associated with intake of wine. Eur Spine J 1998;7:24-28.

22. Ritterband DR. Disease management: old wine in new bottles? J Health Manag 1969;45:255-266.

23. Rimbeaud A. Le bateau ivre. in Les illuminations 1871

24. Trethewie ER. Wines and headaches. Med J Aust 1979;1:94.

25. Van HJ, David JR. Alcohol tolerance and alcohol utilisation in Drosophilia: partial independence of two adaptive traits. Heredity 1980;44:229-235.

26. Villon F. Tant va la cruche à l'eau...in Ballade des proverbes. 1460

Traîtrise Orthopédique - Maîtrise Orthopédique n° 100 - January, 2001