Sciatica: Treatment with Intradiscal and Intraforaminal Injections of Steroid and Oxygen-Ozone versus Steroid Only

Sciatica: Treatment with Intradiscal and Intraforaminal Injections of Steroid and Oxygen-Ozone versus Steroid Only

Ozone Injections for Sciatica and disc Herniations

Abstract

Purpose: To prospectively compare the clinical effectiveness of intraforaminal and intradiscal injections of a mixture of a steroid, a local anesthetic, and oxygen-ozone (O2-O3) (chemodiscolysis) versus intraforaminal and intradiscal injections of a steroid and an anesthetic in the management of radicular pain related to acute lumbar disk herniation.

Materials and Methods: Medical Ethical Committee approval and informed consent were obtained. One hundred fifty-nine patients (86 men, 73 women; age range, 18–71 years) were included and were randomly assigned to two groups. Seventy-seven patients (group A) underwent intradiscal and intraforaminal injections of a steroid and an anesthetic, and 82 patients (group B) underwent the same treatment with the addition of an O2-O3 mixture. Procedures were performed with computed tomographic guidance. An Oswestry Low Back Pain Disability Questionnaire was administered before treatment and at intervals, the last at 6-month follow-up. Patients and clinicians were blinded as to which treatment was performed. Results were compared with the χ2 test.

Results: After 6 months, treatment was successful in 36 (47%) patients in group A and in 61 (74%) patients in group B. The difference was significant (P < .01).

Conclusion: Intraforaminal and intradiscal injections of a steroid, an anesthetic, and O2-O3 are more effective at 6 months than injections of only a steroid and an anesthetic in the same sites.

Low back pain and sciatica are said to affect most of the population at least once during a lifetime (1). Nevertheless, the natural history of lumbar disk herniation is favorable: Improvement of symptoms is the norm, and most episodes resolve spontaneously or after conservative therapy (2,3). The natural history of lumbar disk herniation has been elucidated by means of serial imaging studies, which showed spontaneous clinical and anatomic resolution in 67%–76% of patients after 1 year (4–8). Therefore, an invasive approach is reserved for patients failing to respond to conservative treatment.

Surgery is less invasive than it was in the past because of new microsurgical techniques. However, its success rate is not optimal: Pain resolution is present in no more than 80%–85% of patients (9), and a failed back surgery syndrome develops in 10%–40% of patients (10).

In the past decades, many new minimally invasive image-guided interventional techniques have been developed to reduce the need for surgery and to improve the quality of life of patients requiring systemic drugs (11–13). Yet, few of these treatments have been tested in controlled randomized studies.

A recently proposed treatment for lumbar disk herniation is chemodiscolysis by means of percutaneous intradiscal oxygen-ozone (O2-O3) injection. The effectiveness of this treatment has been tested in large clinical studies, findings of which have shown a positive outcome in 70%–80% of patients (14–18). Findings of a randomized controlled study (19) to assess the effectiveness of intraforaminal injection of O2-O3 versus steroids have been recently published, with O2-O3injection being more effective than steroids.

The purpose of our study was to prospectively compare the clinical effectiveness of intraforaminal and intradiscal injections of a mixture of a steroid, a local anesthetic, and O2-O3 (chemodiscolysis) versus intraforaminal and intradiscal injections of a steroid and an anesthetic in the management of radicular pain related to acute lumbar disk herniation.

Previous SectionNext Section

MATERIALS AND METHODS

Patients

The study protocol was approved by the Medical Ethical Committee of our institution. We obtained informed consent from all patients. From March 2004 to April 2005 (14 months), we treated 159 patients (86 men, 73 women; age range, 18–71 years) with lumbar disk herniation (L3-4, 23 patients; L4-5, 61 patients; L5-S1, 75 patients) and radicular pain. The mean duration of radicular pain at the time of treatment was 15 weeks. Preliminary clinical evaluation was performed by two experienced neurosurgeons (R.G., 25 years experience; A.R., 10 years experience). Moreover, all patients underwent computed tomography (CT) or magnetic resonance (MR) imaging.

Inclusion criteria comprised monoradicular pain, lumbar disk herniation on CT or MR images, herniation site congruous with the neurologic level, and Oswestry Disability Index (20) greater than 30%. All patients complained of pain for at least 8 weeks. They had received conservative therapy (physiotherapy and/or nonsteroidal antiinflammatory drugs and/or intramuscular steroids) for 2–4 weeks, with no or poor clinical improvement.

Exclusion criteria comprised pregnancy, referred allergy to proposed drugs, and major neurologic deficits. We also excluded any patients who had clinically diagnosed syndromes that are able to mimic the symptoms of a lumbar disk herniation: facet syndrome, sacroileitis, bone lesions (infective, inflammatory, or neoplastic), or previous spine surgery.

The level to be treated was chosen on the basis of results from a neurologic examination performed by the neurosurgeons and correspondence between imaging and clinical findings. Discography was performed only in few patients at the beginning of our practice, but we abandoned this procedure. According to our experience and the literature (21), discography does not add important information because only patients with discogenic pain are identified with this procedure. Moreover, a contrast agent injected during discography fills the potential intradiscal space that may be used for therapeutic agents (ie, steroids and O2-O3), which prevents injection of the optimal amount of these drugs. However, in our experience, O2-O3 itself has a discographic effect.

The 159 enrolled patients were all the ones who met our criteria and who were treated during the study time. The patients were randomly assigned to one of two groups (A and B) by means of a randomization grid. Group A included 77 patients (43 men and 34 women; mean age, 41 years), and group B included 82 patients (45 men and 37 women; mean age, 40 years) (Table). Group A underwent intraforaminal and intradiscal injections of 2 mL of triamcinolone acetonide (40 mg/mL Kenacort; Bristol-Myers Squibb, Sermoneta, Italy), with 1 mL injected in the epidural space and 1 mL injected inside the disk, and 2–4 mL of 2% ropivacaine (Naropina; AstraZeneca, Basiglio, Italy), about 2 mL injected in the epidural space and 1 mL injected inside the disk. Group B received the same treatment with the addition of an O2-O3 mixture, with an ozone concentration of 28 μg/mL . We injected 5–7 mL of O2-O3 at intraforaminal level (mean, 6.5 mL) and 5–7 mL of O2-O3 inside the disk (mean, 5.8 mL). We chose a steroid injection for comparison because of the effectiveness of this treatment and the similar degree of invasiveness of both interventions (22,23). Patients were blinded as to whether they had received O2-O3 as part of the treatment.

Patient Characteristics

Procedures

The procedures were always performed on an outpatient basis by two neuroradiologists (M.G., 8 years experience in spinal interventions; N.L., 2 years experience). Before every procedure, the patients received premedication with intravenously administered 1 g of cefazoline (Totacef; Bristol-Myers Squibb), 30 mg of ketorolac (Toradol; Recordati, Milan, Italy), and 50 mg of ranitidine (Ranidil; Menarini, Florence, Italy). All procedures were performed with CT guidance (Somatom Plus 4; Siemens Medical Systems, Erlangen, Germany) with the patient in the prone position. Transverse scans (3 mm thick) were used to choose the needle path and to calculate the entry point.

The O2-O3 gas mixture was achieved by using an ozone generator (OZO2 Futura; Alnitec, Cremosano, Italy). Intradiscal and intraforaminal injections were administered with a paravertebral approach in 147 (92.4%) patients and an interlaminar approach in 12 (7.6%) patients by using a 9- or 15-cm 22-gauge spinal needle. The side of the injection was chosen on the basis of the main location of symptoms.

After local anesthesia, the needle was advanced to the intraforaminal space, with an angle usually between 45° and 60°, following a needle tip position with use of CT scans (Fig 1a). After confirmation of the position, the drugs were injected at this level (Fig 1b). The needle was subsequently advanced toward the disk to inject the drugs inside the nucleus pulposus. When the needle entered the disk, a soft resistance was felt. Before injection inside the disk, a CT scan was used to confirm that the needle tip was inside the nucleus pulposus to avoid injection into the outer annulus (Fig 1c). The drugs were slowly injected inside the disk.

Figure 1a:

Figure 1a:

Transverse CT images of consecutive phases of O2-O3 chemodiscolysis with right paravertebral approach at L4-5 level in 65-year-old man in prone position. (a)Entry path with a 45° angle.(b) Tip of the needle (arrow) is in periradicular position.(c) Needle is advanced inside the disk following the same path; the position is confirmed by evidence of needle tip (arrow). (d)Distribution of gas after intradiscal and periradicular injections; the needle is still on site (white arrow). The O2-O3 mixture is distributed inside the disk (*) and in epidural space (black arrow).

Figure 1b:

View larger version:

  • In this page
  • In a new window
  • Download as PowerPoint Slide
Figure 1b:

Transverse CT images of consecutive phases of O2-O3 chemodiscolysis with right paravertebral approach at L4-5 level in 65-year-old man in prone position. (a)Entry path with a 45° angle.(b) Tip of the needle (arrow) is in periradicular position.(c) Needle is advanced inside the disk following the same path; the position is confirmed by evidence of needle tip (arrow). (d)Distribution of gas after intradiscal and periradicular injections; the needle is still on site (white arrow). The O2-O3 mixture is distributed inside the disk (*) and in epidural space (black arrow).

Figure 1c:

Figure 1c:

Transverse CT images of consecutive phases of O2-O3 chemodiscolysis with right paravertebral approach at L4-5 level in 65-year-old man in prone position. (a)Entry path with a 45° angle.(b) Tip of the needle (arrow) is in periradicular position.(c) Needle is advanced inside the disk following the same path; the position is confirmed by evidence of needle tip (arrow). (d)Distribution of gas after intradiscal and periradicular injections; the needle is still on site (white arrow). The O2-O3 mixture is distributed inside the disk (*) and in epidural space (black arrow).

In group B, O2-O3 was injected immediately after anesthetic and steroid injections. A mild resistance was usually felt during O2-O3 injection; if the resistance was strong, the injection was stopped. A CT scan was acquired to evaluate eventual complications and O2-O3 distribution. O2-O3 delivery was considered satisfactory when the gas was homogeneously distributed inside the nucleus pulposus and when it showed diffusion in the epidural space, with involvement of the periganglionic space (Fig 1d). If epidural diffusion was absent or poor (gas only near the root and not in the epidural space, or vice versa), the needle was pulled out of the disk and was repositioned deeper in the foramen or in the epidural space, and O2-O3 was injected again. Epidural gas diffusion could help confirm the proper positioning. After this last evaluation, the needle was removed and the procedure was concluded. The interlaminar access was only performed when the lumbar bone anatomy made needle positioning in the center of the disk impossible with a paravertebral approach and conventional spinal needles. CT guidance always prevented injections into or puncture of the dural sac (Fig 2).

Figure 1d:

Figure 1d:

Transverse CT images of consecutive phases of O2-O3 chemodiscolysis with right paravertebral approach at L4-5 level in 65-year-old man in prone position. (a)Entry path with a 45° angle.(b) Tip of the needle (arrow) is in periradicular position.(c) Needle is advanced inside the disk following the same path; the position is confirmed by evidence of needle tip (arrow). (d)Distribution of gas after intradiscal and periradicular injections; the needle is still on site (white arrow). The O2-O3 mixture is distributed inside the disk (*) and in epidural space (black arrow).

Figure 2a:

Figure 2a:

Transverse CT images of consecutive phases of O2-O3 chemodiscolysis with left interlaminar approach at L5-S1 level in 21-year-old man in prone position. (a)Preprocedural image shows right paracentral disk extrusion (arrow). (b) Tip of needle (arrow) is positioned close to the herniation; dural theca is not located along needle entry path. (c) Needle (arrow) is inside the disk and its position is extrathecal. After further needle entry, drugs are injected. (d) Postprocedural image shows wide distribution of gas (*) inside the disk.

Figure 2b:

Figure 2b:

Transverse CT images of consecutive phases of O2-O3 chemodiscolysis with left interlaminar approach at L5-S1 level in 21-year-old man in prone position. (a)Preprocedural image shows right paracentral disk extrusion (arrow). (b) Tip of needle (arrow) is positioned close to the herniation; dural theca is not located along needle entry path. (c) Needle (arrow) is inside the disk and its position is extrathecal. After further needle entry, drugs are injected. (d) Postprocedural image shows wide distribution of gas (*) inside the disk.

Figure 2c:

Figure 2c:

Transverse CT images of consecutive phases of O2-O3 chemodiscolysis with left interlaminar approach at L5-S1 level in 21-year-old man in prone position. (a)Preprocedural image shows right paracentral disk extrusion (arrow). (b) Tip of needle (arrow) is positioned close to the herniation; dural theca is not located along needle entry path. (c) Needle (arrow) is inside the disk and its position is extrathecal. After further needle entry, drugs are injected. (d) Postprocedural image shows wide distribution of gas (*) inside the disk.

Figure 2d:

Figure 2d:

Transverse CT images of consecutive phases of O2-O3 chemodiscolysis with left interlaminar approach at L5-S1 level in 21-year-old man in prone position. (a)Preprocedural image shows right paracentral disk extrusion (arrow). (b) Tip of needle (arrow) is positioned close to the herniation; dural theca is not located along needle entry path. (c) Needle (arrow) is inside the disk and its position is extrathecal. After further needle entry, drugs are injected. (d) Postprocedural image shows wide distribution of gas (*) inside the disk.

Overall, the average injected volume in group A was 3 mL at intraforaminal level and 2 mL inside the disk. In group B, the average injected volume was 9.5 mL at the intraforaminal level and 6.8 mL inside the disk. The average injected volume of O2-O3 in group B patients was 12.3 mL. Mean surgical time was 27 minutes (range, 12–40 minutes) for group A and 30 minutes (range, 12–45 minutes) for group B. After treatment, the patients rested in the supine decubitus position for 2 hours. At discharge, the patients were advised to take a 4-day rest and to gradually resume motion activity.

Outcome Evaluation

To determine the effectiveness of the procedures, a 6-month follow-up was performed. We administered the Oswestry Low Back Pain Disability Questionnaire (24) to all patients the day of the procedure, 2 weeks later, and 3 and 6 months later. Data about possible complications were also collected. The questionnaire was administered by two individuals (E.S., L.Z.) who were blinded to patient distribution in the two groups. During follow-up, the questionnaire was administered by phone. Every patient was randomly assigned to one of the two clinicians, with each clinician administering the questionnaire to each of the patients in the subset over the full course of follow-up. Clinician A (E.S.) interviewed 37 (48%) group A patients and 39 (47%) group B patients. Clinician B (L.Z.) interviewed 40 (52%) group A patients and 43 (52%) group B patients.

The results of the questionnaire were used to calculate the Oswestry Disability Index, which was applied to assess clinical outcome. The response to treatment was considered binary; classified as successful if the Oswestry Disability Index was no greater than 20% at follow-up, and unsuccessful otherwise. Ten group B patients with unsuccessful results had second intraforaminal and intradiscal O2-O3injections, and 6-month follow-up was performed.

During and after the procedures, all patients were carefully evaluated by the neuroradiologist who performed the procedure in order to recognize any complications. During phone consultation, patients were asked to report any possible late complication. Considered complications were allergic reactions, high or low blood pressure induced by drugs, infections, and permanent neurologic deficits.

Statistical Analysis

An evaluation of the success rate was performed for both groups on the basis of the Oswestry Disability Index. The results of the Oswestry pain questionnaire were entered in a database. The success rates at 2-week, 3-month, and 6-month follow-up for groups A and B were compared by means of the χ2 test. P < .01 was considered to indicate a statistically significant difference.

The success rate of group B patients who underwent a second intraforaminal and intradiscal O2-O3 injection session was calculated; however, no formal statistic was used because of the low number of patients. The success and complication rates of the patients treated with the interlaminar approach were also considered separately to evaluate both the effectiveness and the safety of this approach.

The software used for statistical analysis was Stata (version 8.2; StataCorp, College Station, Tex).

Previous SectionNext Section

RESULTS

Group A

In group A, the treatment was a success in 69 (90%) of 77 patients (95% confidence interval [CI]: 80.6%, 95.4%) after 2 weeks, 52 (67%) patients (95% CI: 55.9%, 77.8%) after 3 months, and 36 (47%) patients (95% CI: 35.3%, 58.5%) after 6 months. The treatment was unsuccessful in 41 (53%) patients after 6 months.

Group B

In group B, the treatment was a success in 72 (88%) of 82 patients (95% CI: 78.8%, 93.4%) after 2 weeks, 64 (78%) patients (95% CI: 67.5%, 86.4%) after 3 months, and 61 (74%) patients (95% CI: 63.6%, 83.3%) after 6 months. At 6-month follow-up, the treatment was unsuccessful in the remaining 21 (26%) group B patients. Among the 10 group B patients who underwent a second O2-O3procedure, the 6-month follow-up revealed a satisfactory outcome in five (50%) patients.

Groups A and B Comparison

The statistical analysis with χ2 test showed that the different outcome at 2 weeks was not significant (χ2 = 0.13, P = .72). After 3 months, the difference was also not significant (χ2 = 2.23, P = .136). On the contrary, the χ2 test showed that after 6 months, the success rate difference between group A and group B was statistically significant (χ2 = 12.75, P < .001) (Fig 3).

Figure 3:

Figure 3:

Graph shows outcomes of group A and group B patients whose treatment was deemed a success according to their responses to the Oswestry pain questionnaire. At 2 weeks and 3 months, outcome of group B patients is similar to that of group A patients. Difference becomes appreciable after 6-month follow-up, when the procedure was successful in 74% of group B and in 47% of group A patients (P < .01).

Interlaminar Approach

Five of the 12 patients treated by means of an interlaminar approach were part of group A, and seven were part of group B. After 6 months, the treatment was successful in two (40%) of five group A patients and in five (71%) of seven group B patients.

Complications

During or after the procedures, no major or minor complications were observed.

Previous SectionNext Section

DISCUSSION

In our series, we administered an intradiscal steroid and an anesthetic. Intradiscal anesthetics are useful for discogenic pain diagnosis and treatment (20). Intradiscal steroid injection is not a definitively established treatment, and studies have shown discordant results (25,26). Intradiscal steroids and anesthetics can be useful mainly in patients with reactive endplate changes (25). Pain reduction can also depend on the block of Luschka nerve fibers that enter the annulus.

Periganglionic and intradiscal injections of O2-O3 have been proposed since the late 1990s as a treatment for lumbar disk herniation (14–18). Ozone is an unstable form of oxygen that, in water, reacts with organic molecules containing double or triple bonds: Ozone causes an oxide reduction called ozonolysis. This reaction involves mainly molecules for which ozone has affinity (27). Intradiscal O2-O3mixture injection produces a chemodiscolysis, with ozonolysis of nucleus pulposus proteoglycans, loss of water, and dehydration. Progressive degeneration with fibrous replacement occurs followed, finally, by disk shrinkage. In this way, chemodiscolysis leads to loss of disk volume and direct reduction of root compression. Chemodiscolysis has been shown experimentally in rabbit and human disks, with histopathologic evidence of dehydration of the fibrillary matrix of the nucleus pulposus, vacuole formation, and collagen fragmentation (15,28,29). The reduction of herniated disk volume decreases root edema and venous stasis, stopping the demyelination process (28).

The mixture also has analgesic and antiinflammatory effects. Ozone, by means of direct ozonolysis, inhibits the synthesis and release of prostaglandins, bradykinin, and various algogenic molecules (27). Moreover, ozone increases the release of antagonists of proinflammatory cytokines (27). Thus, O2-O3 can solve or decrease chemical radiculitis (28,30). The effect of ozone on chemical radiculitis can also explain the clinical effectiveness of intraforaminal O2-O3 injection without intradiscal therapy (19).

The reported effectiveness of the procedure is promising, with clinical success in 70%–80% of patients (14–18). In our practice, we inject a steroid and a local anesthetic in addition to the O2-O3 mixture, because the combination of these agents has been proved to be more effective than the injection of the O2-O3mixture alone (15).

Group B had a successful outcome in 74% of patients after 6 months, while group A had a successful outcome in 47% of patients. The statistical analysis demonstrated that this difference was significant (P < .01); consequently, the combined injection of O2-O3, a steroid, and an anesthetic at the intradiscal and intraforaminal levels should be considered more effective than a simple steroid and anesthetic injection. The injection of O2-O3 is the only difference between the two treatments we compared; therefore, the better outcome of group B patients should be due to the pharmacologic actions of O2-O3. Our results are similar to those reported in other studies (14–18) in which intradiscal O2-O3 injections were not compared with other percutaneous interventional treatments. Small differences between our and other studies may be related to patient selection and evaluation methods.

We observed that 2 weeks and 3 months after the procedure, the difference in success rate between group A and group B was not significant. The difference became significant only after 6 months, probably because the effectiveness of steroids and anesthetics administered to both groups is temporary, while O2-O3has long-acting effects. Therefore, in comparison to conventional steroid injections, O2-O3 therapy appears to be a more effective treatment.

The 6-month success rate of group B patients is similar to that obtained with other percutaneous intradiscal interventions (11–13). Intradiscal and intraforaminal O2-O3injections are less invasive for many reasons, such as a narrower needle and absence of probes and of toxicity. O2-O3 therapy is also cost-effective, because it can be performed on an outpatient basis and thus has favorable implications for cost, as does the equipment needed for the procedure. In our experience, there were no complications, which helped confirm that O2-O3 chemodiscolysis is a safe procedure (14–18).

In our series, we performed all procedures with CT guidance instead of fluoroscopy, as was done in other studies (18). The main reason was practicality, since at our institution we have three CT units. There is no published evidence that CT guidance is superior to fluoroscopy. However, in our opinion, this approach ensures more precise needle positioning in the central part of the disk and reduces the risk of complications and incorrect injection sites. Moreover, CT allows verification of correct gas diffusion, which is more difficult with fluoroscopy. Another advantage of CT is the lack of operator exposure.

The main limitations of our study were the low number of enrolled patients and the short follow-up interval. Future studies are necessary to demonstrate whether O2-O3 therapy effects are limited over time.

In conclusion, intraforaminal and intradiscal injections of an O2-O3 mixture, a steroid, and an anesthetic with CT guidance lead to rapid pain relief, with good outcome in most patients. This treatment is easy to perform and is safe. Moreover, it is more effective than the injections of pure steroids and anesthetic in the same sites; therefore, O2-O3 seems to play a role in pain relief. In our opinion, O2-O3chemodiscolysis should be regarded as a useful treatment for the management of lumbar disk herniation.

Ozone Injections for disc herniation

Minimally Invasive Oxygen-Ozone Therapy for Lumbar Disk Herniation

Minimally Invasive Oxygen-Ozone Therapy for Lumbar Disk Herniation

Abstract

BACKGROUND AND PURPOSE: Oxygen-ozone therapy is a minimally invasive treatment for lumbar disk herniation that exploits the biochemical properties of a gas mixture of oxygen and ozone. We assessed the therapeutic outcome of oxygen-ozone therapy and compared the outcome of administering medical ozone alone with the outcome of medical ozone followed by injection of a corticosteroid and an anesthetic at the same session.

METHODS: Six hundred patients were treated with a single session of oxygen-ozone therapy. All presented with clinical signs of lumbar disk nerve root compression, with CT and/or MR evidence of contained disk herniation. Three hundred patients (group A) received an intradiscal (4 mL) and periganglionic (8 mL) injection of an oxygen-ozone mixture at an ozone concentration of 27 μg/mL. The other 300 patients (group B) received, in addition, a periganglionic injection of corticosteroid and anesthetic. Therapeutic outcome was assessed 6 months after treatment by using a modified MacNab method. Results were evaluated by two observers blinded to patient distribution within the two groups.

RESULTS: A satisfactory therapeutic outcome was obtained in both groups. In group A, treatment was a success (excellent or good outcome) in 70.3% and deemed a failure (poor outcome or recourse to surgery) in the remaining 29.7%. In group B, treatment was a success in 78.3% and deemed a failure in the remaining 21.7%. The difference in outcome between the two groups was statistically significant (P < .05).

CONCLUSION: Combined intradiscal and periganglionic injection of medical ozone and periganglionic injection of steroids has a cumulative effect that enhances the overall outcome of treatment for pain caused by disk herniation. Oxygen-ozone therapy is a useful treatment for lumbar disk herniation that has failed to respond to conservative management.

Noninvasive procedures, minimally invasive percutaneous injection, and surgery represent the gamut of treatments available in the management of lumbar disk herniation. Noninvasive treatments are plainly the first choice in most cases (1), but when patients fail to respond, minimally invasive percutaneous injection or surgery is warranted. Minimally invasive treatments were developed to offer good clinical results combined with a well-tolerated, low-cost procedure. In recent years, these procedures were further boosted by a growing number of reports of 5–20% treatment failure rate after surgical diskectomy, with failed back surgery syndrome in 15% of cases (2–9).

Oxygen-ozone therapy is one of the different minimally invasive treatments currently available (10–13). It is used in medicine to treat different conditions (14, 15) and is based on exploiting the chemical properties of ozone, an unstable allotropic form of oxygen with the symbol O3 and a molecular weight of 48 kDa. A vast bibliography on the topic can be found in a recent study on how oxygen-ozone therapy works (16).

A reduction in herniated disk volume is one of the therapeutic aims of intradiscal administration of medical ozone, as disk shrinkage may reduce nerve root compression (17). Another reason for using medical ozone to treat disk herniation is its analgesic and antiinflammatory effects (15, 18).

In the wake of reports on the efficacy of periganglionic administration of steroids to treat pain from disk herniation (19–22), we combined an intradiscal injection of medical ozone with subsequent periganglionic injection of a mixture containing a corticosteroid and an anesthetic in one group of patients.

We assessed the results obtained in treating 600 patients with oxygen-ozone therapy and compared the outcome in patients receiving medical ozone alone with that in patients who also received a corticosteroid and anesthetic mixture injected at the same session.

Previous SectionNext Section

Methods

From January 1999 to March 2001, 600 patients aged 20–80 years were treated with a single session of oxygen-ozone therapy. The patients observed in this multicenter study had not been randomized, nor was the treatment compared with an accepted reference standard since ethical constraints precluded a randomized blind study design (23). These patients represent a consecutive sequence of patients who presented with lumbar disk herniation during the 2 years and who were judged not to be surgical candidates for clinical or anatomic reasons. Informed consent was obtained from all patients.

Three hundred patients (group A, Bellaria Hospital, Bologna, Italy) received an intradiscal (4 mL) and periganglionic (8 mL) injection of an oxygen-ozone mixture with an ozone concentration of 27 μg/mL. The other 300 patients (group B, Anthea Hospital, Bari, Italy) received identical oxygen-ozone injections, followed by a periganglionic injection of corticosteroid (1 mL of Depo-Medrone 40 mg [Pharmacia & Upjohn, Milan, Italy]) and anesthetic (2 mL of Marcain 0.5% [Biologici Italia Laboratories, Novate Milanese, MI, Italy]) at the same session. The oxygen-ozone gas mixture was obtained by using a Multiossigen PM95 generator (Multiossigen s.r.l., Gorle, BG, Italy).

Intradiscal and periganglionic injection was administered by means of an extraspinal lateral approach, using a 22-gauge 17.78-cm Becton Dickinson spinal needle (Quincke Type Point; Becton Dickinson & Co., Franklin Lakes, NJ), as used for discography under fluoroscopic guidance (group A) (12, 24, 25) or CT guidance (group B) (26) (Fig 1), from the same side as the main location of symptoms. The gas mixture was injected by using a polypropylene syringe with the interconnection of a millipore filter (Fig 2). Time for injection was globally 15 seconds. A longer time is not suitable because of the unstable condition of medical ozone, which starts decaying (2 μg/mL) after about 20 seconds. No premedication or anesthesia was given to either group, and the procedure was performed at an outpatient facility. The L4–5 level was the most frequently treated (61.8%); L1–2, 0.7%; L2–3, 1.2%; L3–4, 8.7%; L5-S1, 27.6%.

Fig 1.

View larger version:

  • In this page
  • In a new window
FIG 1.

Puncture at L4-L5 performed under CT guidance.

Fig 2.

View larger version:

  • In this page
  • In a new window
FIG 2.

Injection of the oxygen-ozone mixture through a millipore filter.

Selection criteria for oxygen-ozone therapy were the following. Clinical criterion was low back pain resistant to conservative management (drugs, physiotherapy, and others), lasting at least 3 months. Neurologic criterion was low back pain with positive signs of nerve root involvement, with or without paraesthesia or hypaesthesia, with appropriate dermatome distribution. Neuroradiologic criteria were CT and/or MR evidence of contained disk herniation, in line with the patient’s clinical symptoms, with or without disk degeneration, and residues of surgical microdiskectomy with recurrent herniation.

Exclusion criteria for oxygen-ozone therapy were neuroradiologic evidence of disk prolapse or free fragments of herniated disk, and major neurologic deficit correlated to disk disease. In these cases, the patients underwent surgical treatment.

At the end of treatment, patients were advised to rest in supine decubitus position for 2 hours. All patients were discharged on the same day as treatment. On discharge, patients were instructed to gradually resume motor activity. All patients underwent follow-up examinations 2 weeks, 2 months, and 6 months after treatment.

Clinical outcome was assessed 6 months after treatment by applying the modified MacNab method (Table ) (8, 27). Results were evaluated by two observers (R.R., F.d.S.) who were blinded to patient distribution within the two groups, by using a questionnaire and direct patient interviews. Statistical analysis was performed by means of the χ2 test.

View this table:

  • In this window
  • In a new window

Modified MacNab method for assessing clinical outcome after oxygen-ozone therapy

Previous SectionNext Section

Results

Treatment was a success in 211 patients (70.3%) in group A and 235 patients (78.3%) in group B. In the remaining 89 patients (29.7%) in group A and 65 patients (21.7%) in group B, treatment was deemed a failure. The difference in outcome in the two groups was statistically significant at χ2 test (P < .05).

Among the group A patients whose treatment was a success, outcome was excellent in 151 patients (50.3%) and good in 60 (20%). Among the patients in group A whose treatment was a failure, this was poor in 75 (25%) and poor with recourse to surgery in 14 (4.7%) (Fig 3). Among the patients in group B whose treatment was a success, outcome was excellent in 160 cases (53.3%) and good in 75 (25%). Among the patients in group B whose treatment was a failure, this was poor in 50 (16.7%) and poor with recourse to surgery in 15 (5%) (Fig 3).

Fig 3.

View larger version:

  • In this page
  • In a new window
FIG 3.

Therapeutic outcome 6 months after oxygen-ozone therapy. Light gray bars indicate group A (n=300); dark gray bars, group B (n=300). Numbers at top of bars are percentages.

Complications occurred in two group B patients, who presented with episodes of impaired sensitivity in the lower limb ipsilateral to the treatment; the episode resolved spontaneously within 2 hours.

Previous SectionNext Section

Discussion

The appropriate treatment of lumbar sciatica and disk herniation is a challenge, particularly because the concept of a disk hernia represents only a simplification of the problem. So many largely unknown or poorly understood factors are involved in the pathophysiology of this disease that the right treatment is very difficult to pinpoint; this is the main reason so many treatments are continuously proposed. In addition, many specialists are convinced that conservative treatment offers the same level of results, if checked at a late follow-up, with surgery being undertaken less frequently. In this setting, attention has focused on minimally invasive treatments. Our study addressed the use of an oxygen-ozone mixture, the least invasive technique currently available.

Oxygen-ozone therapy exploits the chemical properties of ozone, an unstable allotropic form of oxygen with the symbol O3 and a molecular weight of 48 kDa. Many biologic effects have been attributed to ozone: increased glycolysis (28); effects on red blood cells (29, 30); effects on rheology (31); bactericidal, fungicide, and virustatic (28); immunomodulating action (29, 32); and analgesic and antiinflammatory effects (15, 18). This broad spectrum of action explains the many indications for medical ozone administration (14).

The dose of ozone administered is crucial (33) and must not exceed the capacity of antioxidant enzymes (superoxide dismutase and catalase)and glutathione to prevent accumulation of the superoxide anion (O2-) and hydrogen peroxide (H2O2) (34–36), which can cause cell membrane degradation (33, 37). Free radicals are mainly formed by ozone in a medium with a pH higher than 8, whereas at a pH less than 7.5 the ozonolysis mechanism prevails, mainly leading to the formation of peroxides (35, 38).

In oxygen-ozone therapy, ozone is administered in the form of an oxygen-ozone gas mixture, medical ozone, at nontoxic concentrations varying from 1 to 40 μg of ozone per milliliter of oxygen (14). Empirical studies performed in vivo on rabbits and in vitro on resected human disk specimens have demonstrated that for intradiscal administration the optimal concentration of ozone per milliliter of oxygen is 27 μg. At this concentration, ozone has a direct effect on the proteoglycans composing the disk’s nucleus pulposus, resulting in its release of water molecules and subsequent cell degeneration of the matrix, which is replaced by fibrous tissues in the space of 5 weeks and the formation of new blood cells. Together, these events result in a reduction in disk volume (15).

In our series, these effects were confirmed in five histologic disk specimens removed during surgical microdiskectomy from patients who had received intradiscal injections of medical ozone at a concentration of 27 μg/mL. The specific feature of oxygen-ozone therapy noted in these specimens was dehydration of the fibrillary matrix of the nucleus pulposus, revealing collagen fibers and signs of regression (vacuole formation and fragmentation)—a sort of disk “mummification.” The other findings such as chondrocyte hyperplasia at the lesion margin, proliferating and large, and signs of new blood cell formation accompanied by mainly lymphocyte inflammatory tissue are commonly encountered at histopathologic examination of a herniated disk not treated with medical ozone (39) (Fig 4). A reduction in herniated disk volume is one of the therapeutic motives for intradiscal administration of medical ozone, as a reduction in disk size may reduce nerve root compression (17). Disk shrinkage may also help to reduce venous stasis caused by disk compression of vessels, thereby improving local microcirculation and increasing the supply of oxygen. This effect has a positive effect on pain as the nerve roots are sensitive to hypoxia. Another reason for using medical ozone to treat disk herniation is its analgesic and antiinflammatory effects (15, 18), which may counteract disk-induced pain (40, 41). This action is correlated to inhibited synthesis of proinflammatory prostaglandins or release of bradykinin or release of algogenic compounds; increased release of antagonists or soluble receptors able to neutralize proinflammatory cytokines like interleukin (IL)-1, IL-2, IL-8, IL-12, IL-15, interferon-α, and tumor necrosis factor-α; and increased release of immunosuppressor cytokines like transforming growth factor-β1 and IL-10 (15, 18).

Fig 4.

FIG 4.

A, Low-magnification photomicrograph of histologic specimen of the intervertebral disk shows chronic inflammatory infiltrate (hematoxylin & eosin stain; original magnification, × 4).

B, Higher magnification photomicrograph of histologic disk specimen discloses the lymphocytic nature of the infiltrate (hematoxylin & eosin stain; original magnification, × 10).

In the wake of literature reports on the efficacy of periganglionic administration of steroids to treat disk-induced pain (19–22), this study combined intradiscal injection of medical ozone with subsequent periganglionic injection of a corticosteroid and anesthetic mixture (group B) and compared the outcome to findings in patients receiving intradiscal ozone injection alone (group A). The mechanisms underlying the periganglionic administration of steroids are correlated to both the substance administered and the strategic role of the spinal ganglion in causing and transmitting pain (14, 42–44). Therapeutic outcome evaluated 6 months after treatment was a success in 70.3% of group A patients and 78.3% of group B patients, whereas the failure rate was 29.7% in group A and 21.7% in group B. Group B therefore presented a cumulative effect of corticosteroid and ozone effects that enhanced the therapeutic success rate. The combined intradiscal and periganglionic injection of medical ozone and periganglionic injection of a corticosteroid is thought to affect both the mechanical and inflammatory components of pain caused by disk herniation, enhancing the effect of periganglionic injection of steroids alone (19–22).

In our group B patients, anesthetic administration may have led to early improvement in pain, as most patients with an excellent or good outcome had a clinical course as follows: 1) immediate total or partial remission of pain, 2) stability or mild worsening of pain in the subsequent 2 weeks, and 3) a second improvement phase in the space of 6–8 weeks. The initial phase of immediate pain relief was much less evident in group A patients in whom symptoms improved gradually.

Comparison of our results with those of other percutaneous treatments for disk herniation indicates that the outcome in our series was satisfactory. In particular, our success rates are similar to those of enzymatic chemonucleolysis (5–7, 45, 46). This is important as these two procedures are similar, although oxygen-ozone therapy is less invasive for the following reasons: the needle used is narrower and hence less traumatic; there are no allergic or anaphylactic reactions (0.5% and 0.05%, respectively) and hence premedication is not required; discomfort after treatment and recommended bed rest are 2–3 days compared with the 1–2 weeks advised after enzymatic chemonucleolysis; and treatment can be repeated. Also, ozone has a well known antiseptic activity, reducing the risk of infectious complications (25).

The patients in our series who failed to benefit from oxygen-ozone therapy subsequently underwent surgery. In all cases, the previous oxygen-ozone treatment had no negative effect on the surgical procedure. The complications we encountered in two of our group B patients are thought to have been caused by the periganglionic injection of anesthetic.

Conclusion

Our study provides evidence that the combined intradiscal and periganglionic injection of medical ozone and periganglionic injection of steroids has a cumulative effect that enhances the overall outcome of treatment. For this reason, oxygen-ozone therapy is an option to treat lumbar disk herniation that has failed to respond to conservative management, before recourse to surgery or when surgery is not possible.

References

  1. Eckel TS. Advances in spinal imaging and interventions (abstr). Presented at the 40th annual meeting of the American Society of Neuroradiology, Vancouver, May 11–17,2002
  2. Crock HV. Observation on the management of failed spinal operations. J Bone Joint Surg Br 1976;58:193–199
  3. Greenwood J, McGuire TH, Kimbell F. A study of the causes of failure in the herniated intervertebral disc operation: an analysis of 67 reoperated cases.J Neurosurg 1952;9:15–20
    Medline
  4. Law JD, Lehman RW, Kirsc WM. Reoperation after lumbar intervertebral disc surgery. J Neurosurg 1978;48:259–263
    Medline
  5. Matsui H, Terahata N, Tsuji H. Familial predisposition and clustering for juvenile lumbar disc herniation. Spine 1992;17:1323–1328
    Medline
  6. Pheasant HC. Sources of failure in laminectomies. Orthop Clin North Am1975;6:319–329
    Medline
  7. Spaziante R. La terapia chirurgica nel conflitto disco-radicolare. Riv Neuroradiol 1997;10:545–550
  8. Muto M, Avella F. Percutaneous treatment of herniated lumbardisc by intradiscal oxygen-ozone injection. Intervent Neuroradiol 1998;4:279–286
  9. Iliakis E. Ozone treatment in low back pain. Orthopaedics 1995;1:29–33
  10. Onik G, Helms CA, Ginsburg L, et al. Percutaneous lumbar diskectomy using a new aspiration probe. AJNR Am J Neuroradiol 1985;6:290–293
  11. Choy D, Ascher P, Ranu HS, et al. Percutaneous laser decompression.Spine 1992;17:949–956
    Medline
  12. Smith L. Chemonucleolysis. J Bone Joint Surg Am 1972;54:1795–1802
  13. Leonardi M, Fabris G, Lavaroni A. Percutaneous discectomy and chemonucleolysis. In: Valavanis A, ed. Medical Radiology: Interventional Neuroradiology. Heidelberg: Springer-Verlag;1993 :173–190.2
  14. Viebahn R. The Use of Ozone in Medicine. Heidelberg: Karl F. Haug Publisher;1994
  15. Iliakis E, Valadakis V, Vynios DH, Tisiganos CP, Agapitos E.Rationalization of the activity of medical ozone on intervertebral disc: a histological and biochemical study. Riv Neuroradiol 2001;14(suppl 1):23–30
  16. Bocci V. Oxygen-Ozone Therapy, a Critical Evaluation. Doordrecht: Kluwer Academic Publishers;2002
  17. Suguro T, Degema JR, Bradford DS. The effects of chymopapain on prolapsed human intervertebral disc. Clin Orthop 1986;213:223–231
  18. Bocci V, Luzzi E, Corradeschi F, et al. Studies on the biological effects of ozone: III, an attempt to define conditions for optimal induction of cytokines. Lymphokine Cytokine Res 1993;12:121–126
    Medline
  19. Zennaro H, Dousset V, Viaud B, et al. Periganglionic foraminal steroid injections performed under CT control. AJNR Am J Neuroradiol1997;19:349–352
  20. Cuckler JM, Bernini PA, Wiesel SW, et al. The use of epidural steroids n the treatment of radicular pain. J Bone Joint Surg Am 1985;67:63–66
    Medline
  21. Nelemens PJ, deBie RA, deVet HC, Sturmans F. Injection therapy for subacute and chronic low back pain. Spine 2001;26:501–515
    CrossRefMedline
  22. Bebelski B, Beraneck L. Traitment par infiltration périradiculaire des cruralgies et des sciatiques par conflit disco-radiculaire. Rev Rhum1989;56:795–796
  23. Eckel TS. New techniques: intradiscal electrothermal therapy (abstr).Presented at the 40th annual meeting of the American Society of Neuroradiology, Vancouver, May 11–17,2002
  24. Leonardi M. Discography: how-to workshop (abstr). Radiology1993;189(suppl 1):78
  25. Leonardi M. Disc puncture under fluoroscopic guidance. Riv Ital Ossigeno-Ozonoterapia 2002;1:73–78
  26. Andreula CF. Lumbosacral disc herniation and correlated degenerative disease: spinal interventional chemodiscolysis with O3. Riv Neuroradiol2001;14(suppl 1):81–88
  27. MacNab I. Negative disc exploration. J Bone Joint Surg Am 1971;53:891–903
    Medline
  28. Rilling S, Viebahn R. The Use of Ozone in Medicine. 2nd ed. Heidelberg: Karl F. Haug Publisher;1987 :7–187
  29. Bocci V. Autohaemotherapy after treatment of blood with ozone: a reappraisal. J Int Res 1994;22:131–144
  30. Coppola L, Verazzo G, Giuta R, et al. Oxygen-ozone therapy and hemorrheological parameters in peripheral chronic arterial occlusive disease. Trombosi e Aterosclerosi 1992;3:85–89
  31. Rokitansky O, Rokitansky A, Steiner J, et al. Ozontherapie bei peripheren, arteriellen. Durchblutungsstorungen: klinik, biochemishe und blutgasanalytische untersuchungen. In: Wasser, IOA, ed. Ozon-Weltkongress. Berlin:1981 :53–75
  32. Wenzel DG, Morgan DL. Interactions of ozone and antineoplastic drugs on rat lung fibroblasts and Walker rat carcinoma cells. Res Commun Chem Pathol Pharmacol 1983;40:279–287
    Medline
  33. Mirabelli F, Salis A, Bellomo G, et al. Surface blebbing and cytoskeletal abnormalities caused by sulphydril reagents in isolated hepatocytes, II: oxidizing reagents. Med Biol Environ 1988;16:201–211
  34. Bertè F, Varietti M, Richelmi P. Ozono:problemi tossicologici con particolare riguardo alla formazione di radicali liberi. In: the Proceedings ofCongresso nazionale della Società di Ossigeno-Ozono Terapia, Punta Ala (Gr), Italy1990;1–6
  35. Richelmi P, Valdenassi L. Aspetti biochimici ed implicazioni tossicologiche in ossigeno-ozono terapia. Attualità e prospettive in terapia antalgica. Ed. ESM1995 :185–204
  36. Bellomo G, Mirabelli F, Richelmi P, et al. Glutathione-mediated mechanism of defence against oxygen free radical-induced hepatotoxicity.Hum Toxicol 1989;8:152
  37. Bellomo G, Mirabelli F, Richelmi P, et al. Oxidative stress-induced plasma membrane blebbing and cytoskeletal alterations in normal and cancer cells. Ann NY Acad Sci 1989;551:128–130
  38. Richelmi P, Valdenassi L, Bertè F. Basi farmacologiche dell’azione dell’ossigeno-ozono terapia. Riv Neuroradiol 2001;14(suppl 1):17–22
  39. Leonardi M, Simonetti L, Barbara C. Effetti dell’ozono sul nucleo polposo: reperti anatomo-patologici su un caso operato. Riv Neuroradiol2001;14(suppl 1):57–59
  40. Simonetti L, Agati R, Cenni P, de Santis F, Leonardi M. Mechanism of pain in disc disease. Riv Neuroradiol 2001;14:171–174
  41. Siddal PJ, Cousins MJ. Spine update spinal pain mechanism. Spine1997;22:98–104
    CrossRefMedline
  42. Weistein J. Mechanisms of spinal pain: the dorsal root ganglion and its role as a mediator of low back pain. Spine 1986;11:999–1001
    CrossRefMedline
  43. Rydevik B, Myers R, Powell H. Pressure increase in the dorsal root ganglion following mechanical compression: closed compartment syndrome in nerve roots. Spine 1989;14:574–576
    Medline
  44. Rabishong P. Comprehensive approach to the discoradicular conflict.Riv Neuroradiol 1997;10:515–518
  45. De Nardi E, Ceccotto C, Pomelli L, et al. La chemonucleolisi nell’ernia discale lombare, 1° parte: analisi clinica dei risultati. Riv Neuroradiol1988;1:53–61
  46. Fabris G, Lavaroni A, Zappoli F, et al. La chemonucleolisi nell’ernia discale lombare. Riv Neuroradiol 1989;2(suppl 1):93–102

Call us at (941) 330-8553

Featured

We are currently involved in a Research Study on a special process of purifying bone marrow or BMA using a system designed by Emcyte Corporation. We are working with Bio Sciences Research Center at Harvard and offering a great opportunity for special pricing on treatment. Call our office for details.

Prolotherapy & Platelet Rich Plasma with

Wellington Chen, M.D. & John Lieurance, D.C.

& the Gecko Team.

Clinic Tour Wood St from Dr. John Lieurance on Vimeo.

Years of experience and training in the field of regenerative injections are why you might choose Dr. Chen as your doctor for these treatments. Platelet Rich Plasma Therapy or PRP is Prolotherapy using your own blood. Your blood is placed into a machine that looks like a record player. The platelet rich plasma is spun down and this solution is then injected into area’s that are damaged or arthritic.

Click on one of the button’s below to explore videos and information on how Gecko’s Regenerative therapies work on some specific conditions.

This is a video explaining PRP.

This video shows how ligament damage can often be the cause of chronic neck pain.

Watch this video on PRP regenerating Cartilage.

Screen Shot 2013-07-13 at 8.31.20 AM