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Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 408 - 408
1 Sep 2005
Walters R Moore R Fraser R
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Introduction Infection is a risk following surgical procedures that violate the disc. Bacteria, often from normal skin flora, can be introduced into the disc space causing inflammation with destruction of the adjacent vertebrae. The incidence of iatrogenic discitis is thought to be reduced with the use of prophylactic antibiotics. Although there is substantial evidence from animal studies that prophylactic antibiotics reduce the incidence of discitis, evidence in humans is not strong. The aim of this study was to determine if levels of cephazolin in human disc and serum reached the stated minimum inhibitory concentration (MIC > 1 mg/L) against Staphylococcus aureus following intravenous administration.

Methods Thirty patients (15 female and 15 male) with a mean age 42 years, (range 21–63 years) received 1g cephazolin prior to one or two level lumbar spinal fusion surgery. Venous blood was collected prior to intravenous administration of cephazolin and again at the time of disc removal to measure its concentration in serum and disc tissue.

Results The interval between cephazolin administration and tissue sampling ranged from 7 to 137 minutes. Cephazolin concentration in the serum (31.1 – 148 mg/L) was greater than in the disc (0 – 9.5 mg/L). The concentration of cephazolin peaked in the serum at 7 minutes and in the disc between 37 and 53 minutes. Over 70% of the disc samples had detectable levels of cephazolin at the time the disc was removed, although only half had cephazolin levels above 1 mg/L.

Discussion For a given time period the antibiotic concentration in the disc varies between patients. Only one measurement was taken from the disc using the method described when in fact if multiple measurements were taken over time there may be an antibiotic concentration peak in the disc followed by a steady decline. Variability between peak antibiotic concentration in the disc may be attributed to patient size, weight, gender, co-morbidities (diabetes, rheumatoid arthritis) and degree of disc degeneration. However the most critical variable for all patients is timing of administration of antibiotic to achieve optimal concentration in the disc when it is at greatest risk of inadvertent inoculation.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 221 - 221
1 Sep 2005
Freeman B Walters R Moore R Fraser R
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Objective: To investigate the effects of intra-discal electro-thermal therapy (IDET) on an experimentally induced posterolateral annular inter vertebral disclesion in sheep.

Summary of Background Data: IDET is being used increasingly as a minimally-invasive treatment for chronic discogenic low back pain, with success reported in up to 70% of cases. The mechanism of action however is poorly understood. Proposed mechanisms include the contraction of collagen and the coagulation of annular nociceptors. An ovine model was used to assess the innervation of peripheral posterolateral annular lesions and the potential for IDET to denervate this region.

Methods: Posterolateral annular incisions were made in 36 lumbar discs of 18 sheep. After twelve weeks the sheep underwent IDET at one level and a sham treatment at the other level. IDET was performed using a modified intradiscal catheter (SpineCATH™, Oratec Interventions Inc., Menlo Park, CA). Temperatures were recorded in the nucleus (TN) and the posterior annulus (TPa). The spines were harvested at intervals up to eighteen months. Histological sections of the discs were stained with haematoxylin and eosin and an antibody to the general neuronal marker PGP 9.5.

Results: The target temperature of 90°C at the catheter was tip was reached in all cases. The mean maximum TPa was 63.6°C and the mean maximum TN 67.8°C. Vascular granulation tissue consistent with a healing response was observed in the region of the posterior annulus tear of all incised discs from 12 weeks. PGP 9.5 positive nerve fibres were clearly identified in the adjacent periannular tissue, but were scarce within the outer few lamellae of the annulus. There were no fewer nerve fibres identified in those specimens that had undergone IDET. From six weeks after IDET there was evidence of thermal necrosis in the inner annulus, sparing the periphery of the disc.

Conclusions: IDET delivered at 90°C in the sheep consistently heats the posterior annulus and the nucleus to a temperature range associated with coagulation of nociceptors and collagen contraction. Thermal necrosis was observed within the inner annulus from six weeks after IDET. In this model IDET did not produce denervation of the experimentally induced posterior annular lesion.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 34 - 34
1 Mar 2005
Freeman BJC Walters R Moore R Fraser RD
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Objectives: Posterolateral annular lesions were experimentally induced and allowed to mature for 12 weeks in the intervertebral discs of sheep. IDET was performed in an attempt to denervate and repair the annular lesion. The histological and immunohistochemical effects of IDET were studied.

Summary of Background Data: IDET continues to be used as a minimally-invasive treatment for chronic discogenic low back pain, with success rates reported in up to 70% of cases. The mechanism of action by which IDET exerts its effect is poorly understood. Proposed mechanisms include the contraction of collagen and the coagulation of annular nociceptors. An ovine model was used firstly to induce a posterolateral annular lesion, secondly to assess the innervation of such a lesion, and thirdly to assess the effect of IDET on this innervation.

Methods: Posterolateral annular incisions were made in 40 lumbar discs of 20 sheep. Twelve weeks were allowed for each annular lesion to mature. IDET was then performed in the disc with the posterolateral annular tear and in another control level. IDET was performed using a modified intradiscal catheter. Temperatures were recorded in the nucleus (TN) and the posterior annulus (TPA). The spines were harvested at predetermined intervals up to eighteen months. Histological sections of the discs were graded for disc morphology to assess degeneration and immunohistochemical staining to assess potential denervation.

Results: Vascular granulation tissue consistent with a healing response was observed in the posterior annular tear of all incised discs from 12 weeks. PGP 9.5 positive nerve fibres were clearly identified in the adjacent periannular tissue and the outer few lamellae of the posterior annulus. During the IDET procedure the mean maximaximum TPA was 63.6°C and the mean maximaximum TN was 67.8°C. At sacrifice the number of nerve fibres identified in the posterior annular tear was the same for those specimens that had undergone IDET and those that had not. From six weeks after IDET there was evidence of thermal necrosis in the inner annulus and adjacent nucleus but sparing the periphery of the disc.

Conclusions: IDET delivered at 90°C in the sheep consistently heated the posterior annulus and the nucleus to a temperature normally associated with coagulation of nociceptors and collagen contraction. IDET did not denervate the posterior annular lesion. Thermal necrosis was observed within the inner annulus and adjacent nucleus from six weeks after IDET. The reported benefits from IDET appear to be related to factors other than denervation and repair.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 462 - 462
1 Apr 2004
Walters R Moore R Rahmat R Shimamura Y Fraser R
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Introduction: Although prophylactic antibiotic administration is common in spinal surgery, the choice of drug, dose, and timing of administration often varies. Little is known about the activity of antibiotics in the spine and indeed if they are distributed throughout the disc and if the time intervals are optimal. Because infections that produce iatrogenic discitis generally arise within the disc, the antibiotic concentration of the disc is more relevant than serum concentrations. The aims of the study were to determine if a 2g dose of cephazolin was effective at preventing discitis over a four-hour period in immature ovine discs that were both non-degenerate and degenerate; and also to determine the concentration of cephazolin in serum and disc tissue.

Methods: In 10 Merino wethers aged 12 weeks, three lumbar discs were “degenerated” by incising the posterolateral annulus with a scalpel blade and using ronguers, removing the bulk of the nucleus pulposus. After 12 weeks nine animals were anaesthetised and given a 2g dose of cephazolin (David Bull Laboratories, Australia) at predetermined time intervals over a four-hour period. The antibiotic was chosen for effectiveness against Staphylococcus aureus a common discitis-causing organism. One sheep (control) did not receive any antibiotics to follow the natural progression of infection. All animals had discography with radiographic contrast that contained S. aureus at two incised levels and at two non-incised levels. Lateral radiographs of the lumbar spine were taken at two, six and 12 weeks to monitor the bony changes. At 12 weeks all sheep were given a 2g intravenous dose of cephazolin at time intervals before being killed. The spines were removed and prepared for light microscopy to assess pathology of the discs and for biochemical analysis of antibiotic concentration. Success of treatment was judged using histologic and radiographic features.

Results: The control sheep that did not receive any antibiotics developed discitis at four levels. Histology at 12 weeks confirmed discitis in 10/36 “prophylactic discs”. Of these “prophylactic discs” 7/10 had previously been “degenerated”. Discitis only developed in immature discs that were administered cephazolin two hours prior to inoculation. When antibiotic was administered after inoculation discitis was prevented. Biochemistry results confirmed that antibiotic diffused throughout the disc but was concentrated in the annulus more than the nucleus. Antibiotic levels in the disc peaked at 15 minutes (annulus mean concentration 15.5 mg/L, nucleus mean concentration 3.2 mg/L). Serum levels at 15 minutes were up to 50 times greater at this time (serum mean concentration 178 mg/L).

Discussion: The discs that were “degenerate” had a higher incidence of discitis compared to “non-degenerate” discs. However the concentration of antibiotic in degenerate discs was not significantly different than in non-degenerate discs. A 2 gram dose of cephazolin is reasonably effective (approx 70% success rate) at preventing discitis over a four-hour period.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 95 - 95
1 Jan 2004
Walters R Rahmat R Moore R Fraser R
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Introduction: Infection can occur after any spinal procedure that involves entry into the disc and although it is not common, the potential consequences are serious. Treatment usually requires identification of the bacteria followed by a course of antibiotics. This treatment remains controversial since it is not clear whether antibiotics actually penetrate the disc and if so, whether they are effective, or even if the outcome would be the same without antibiotics.

For an antibiotic to be effective against the infecting organism it must diffuse through the disc matrix. Blood vessels that surround the disc facilitate the diffusion process, but with age this vascularity decreases and may impede diffusion.

The aims of the pilot study were to assess the effectiveness of antibiotic in treating infection in both normal and degenerate sheep discs and to measure the concentration of antibiotic in non-operated discs at varying ages.

Methods: In each of six Merino wethers aged 12 weeks (n=3) and 24 months (n=3), two lumbar discs were “degenerated” by incising the posterolateral annulus with a scalpel blade. After four weeks all animals had discography with radiographic contrast that contained Staphylococcus aureus at the incised levels and at two non-incised levels. Seven days after infection four animals began IV antibiotic treatment with cephazolin sodium (David Bull Laboratories, Australia) for 21 days at a dose of 50mg/kg/day. The antibiotic was chosen for effectiveness against S. aureus. One control animal from each age group did not receive any antibiotics, to follow the natural progression of infection. Lateral radiographs of the lumbar spine were taken at two, six and 12 weeks. At 12 weeks all sheep were given a single intravenous dose of cephazolin sodium as either a 1, 2 or 3g dose. The sheep were then killed after 30 minutes. The spines were removed and prepared for light microscopy to assess pathology of the discs and for biochemical analysis of antibiotic concentration. Success of treatment was judged using histologic and radiographic features.

Results: Discitis was evident radilogically as early as two weeks after inoculation in all animals. Histology at 12 weeks confirmed discitis in all discs regardless of treatment. Biochemistry results confirmed that antibiotic diffused throughout the disc but was more concentrated in the annulus than the nucleus. At all doses disc concentration of antibiotic was higher in lambs than sheep.

Discussion: Treatment with cephazolin sodium at a dose of 50mg/kg/day for 21 days administered from seven days after inoculation, did not prevent discitis. This does not appear to be due to inability of antibiotic diffusion into the disc.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 85 - 85
1 Jan 2004
Freeman B Walters R Moore R Vernon-Roberts B Fraser R
Full Access

Introduction: Intradiscal electrothermal therapy (IDET) is being used increasingly as a minimally-invasive treatment for chronic discogenic low back pain, with success reported in up to 70% of cases. The mechanism of action however is poorly understood. Proposed mechanisms include the contraction of collagen and the coagulation of annular nociceptors. An ovine model was used to assess the innervation of peripheral posterolateral annular lesions and the potential for IDET to denervate this region.

Methods: Posterolateral annular incisions were made in 36 lumbar discs of 18 sheep. After twelve weeks the sheep underwent IDET at one level and a sham treatment at the other level. IDET was performed using a modified intradiscal catheter (SpineCATH™, Oratec Interventions Inc., Menlo Park, CA). Temperatures were recorded in the nucleus and the posterior annulus. The spines were harvested at intervals of up to eighteen months. Histological sections of the discs were stained with haematoxylin and eosin and an antibody to the general neuronal marker PGP 9.5.

Results: The target temperature of 90°C at the catheter tip was reached in all cases. The mean maximum TPa was 63.6°C and the mean maximum TN was 67.8°C. Vascular granulation tissue consistent with a healing response was observed in the region of the posterior annulus tear of all incised discs from 12 weeks. PGP 9.5 positive nerve fibres were clearly identified in the adjacent periannular tissue, but were scarce within the outer few lamellae of the annulus. There were no fewer nerve fibres identified in those specimens that had undergone IDET. From six weeks after IDET there was evidence of thermal necrosis in the inner annulus, sparing the periphery of the disc.

Discussion: IDET delivered at 90°C in the sheep consistently heats the posterior annulus and the nucleus to a temperature associated with coagulation of nociceptors and collagen contraction. Thermal necrosis was observed within the inner annulus from six weeks after IDET. In this model IDET did not appear to produce denervation of the posterior annular lesion.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_III | Pages 280 - 280
1 Mar 2003
Freeman B Walters R Moore R Vernon-Roberts B Fraser R
Full Access

INTRODUCTION: Intradiscal electrothermal therapy (IDET) is being used increasingly as a minimally-invasive treatment for chronic discogenic low back pain, with success reported in up to 70% of cases. The mechanism of action however is poorly understood. Proposed mechanisms include the contraction of collagen and the coagulation of annular nociceptors. An ovine model was used to assess the innervation of peripheral posterolateral annular lesions and the potential for IDET to denervate this region.

METHODS: Posterolateral annular incisions were made in 36 lumbar discs of 18 sheep. After twelve weeks the sheep underwent IDET at one level and a sham treatment at the other level. IDET was performed using a modified intradiscal catheter (SpineCATHTM, Oratec Interventions Inc., Menlo Park, CA). Temperatures were recorded in the nucleus and the posterior annulus. The spines were harvested at intervals of up to eighteen months. Histological sections of the discs were stained with haematoxylin and eosin and an antibody to the general neuronal marker PGP 9.5.

RESULTS: The target temperature of 90°C at the catheter tip was reached in all cases. The mean maximum TPa was 63.6°C and the mean maximum TN was 67.8°C. Vascular granulation tissue consistent with a healing response was observed in the region of the posterior annulus tear of all incised discs from 12 weeks. PGP 9.5 positive nerve fibres were clearly identified in the adjacent periannular tissue, but were scarce within the outer few lamellae of the annulus. There were no fewer nerve fibres identified in those specimens that had undergone IDET. From six weeks after IDET there was evidence of thermal necrosis in the inner annulus, sparing the periphery of the disc.

DISCUSSION: IDET delivered at 90°C in the sheep consistently heats the posterior annulus and the nucleus to a temperature associated with coagulation of nociceptors and collagen contraction. Thermal necrosis was observed within the inner annulus from six weeks after IDET. In this model IDET did not appear to produce denervation of the posterior annular lesion.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_III | Pages 291 - 291
1 Mar 2003
Walters R Rahmat R Moore R Fraser R
Full Access

INTRODUCTION: Infection can occur after any spinal procedure that involves entry into the disc and although it is not common, the potential consequences are serious. Treatment usually requires identification of the bacteria followed by a course of antibiotics. This treatment remains controversial since it is not clear whether antibiotics actually penetrate the disc and if so, whether they are effective, or even if the outcome would be the same without antibiotics.

For an antibiotic to be effective against the infecting organism it must diffuse through the disc matrix. Blood vessels that surround the disc facilitate the diffusion process, but with age this vascularity decreases and may impede diffusion.

The aims of the pilot study were to assess the effectiveness of antibiotic in treating infection in both normal and degenerate sheep discs and to measure the concentration of antibiotic in non-operated discs at varying ages.

METHODS: In each of six Merino wethers aged 12 weeks (n=3) and 24 months (n=3), two lumbar discs were “degenerated” by incising the posterolateral annulus with a scalpel blade. After four weeks all animals had discography with radiographic contrast that contained Staphylococcus aureus at the incised levels and at two non-incised levels. Seven days after infection four animals began IV antibiotic treatment with cephazolin sodium (David Bull Laboratories, Australia) for 21 days at a dose of 50 mg/kg/day. The antibiotic was chosen for effectiveness against S. aureus. One control animal from each age group did not receive any antibiotics, to follow the natural progression of infection. Lateral radiographs of the lumbar spine were taken at two, six and 12 weeks. At 12 weeks all sheep were given a single intravenous dose of cephazolin sodium as either a 1, 2 or 3 g dose. The sheep were then killed after 30 minutes. The spines were removed and prepared for light microscopy to assess pathology of the discs and for biochemical analysis of antibiotic concentration. Success of treatment was judged using histologic and radiographic features.

RESULTS: Discitis was evident radiologically as early as two weeks after inoculation in all animals. Histology at 12 weeks confirmed discitis in all discs regardless of treatment. Biochemistry results confirmed that antibiotic diffused throughout the disc but was more concentrated in the annulus than the nucleus. At all doses disc concentration of antibiotic was higher in lambs than sheep.

DISCUSSION: Treatment with cephazolin sodium at a dose of 50 mg/kg/day for 21 days administered from seven days after inoculation, did not prevent discitis. This does not appear to be due to inability of antibiotic diffusion into the disc.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 165 - 165
1 Feb 2003
Freeman B Walters R Moore R Vernon-Roberts B Fraser R
Full Access

To assess the potential for IDET to ablate nerve fibres in an experimentally induced peripheral annular lesion.

Intradiscal electrothermal therapy (IDET) is being increasingly used as a minimally-invasive treatment for discogenic low back pain, with success reported in up to 70% of cases. One proposed mechanism of IDET is ablation reported in up to 70% of cases. One proposed mechanism of IDET is ablation of nerve fibres in the peripheral annulus. An ovine model was used to assess the innervation of peripheral annular lesions and the potential for IDET to denervate this region of the disc.

Postero-lateral annular incisions were made in 32 lumbar discs of 16 sheep. At twelve weeks the sheep underwent IDET at one level and a sham treatment at the other level. IDET was performed using a modified Intradiscal Catheter (SpineCath, Oratec Interventions Inc., Menlo Park, CA). The spines were harvested at intervals up to six months. Histological sections of the discs were stained with H& E and an antibody to the general neuronal marker PGP 9.5.

Vascular granulation tissue consistent with a healing posterior annular tear was observed in all incised discs from 12 weeks, extending to an average depth of 850 μm at 0 weeks to 690 μm at 6 months. PGP 9.5 positive nerve fibres were clearly identified outside the discs but were scarce within the discs. Nerves were identified up to 300 μm inside the annulus, from the earliest time point, and there was a trend towards less innervation with time. There were no fewer nerve fibres identified in those specimens that had undergone IDET. Specimens obtained six weeks after IDET showed evidence of thermal necrosis in the inner annulus, sparing the periphery of the disc. The reported benefit from IDET appears to be related to factors other than denervation. Thermal necrosis within the annulus six weeks after IDET.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 165 - 165
1 Feb 2003
Freeman B Walters R Moore R Vernon-Roberts B Fraser R
Full Access

Are peak posterior annular and nuclear temperatures obtained during IDET within the temperature range normally associated with nociceptor destruction and contraction of collagen?

Pain relief following intradiscal electrothermal therapy (IDET) has been reported to result from coagulation of annular nociceptors and contraction of collagen. This requires temperatures respectfully of 45°C and 60°C. A cadaveric study using an intradiscal catheter (Spinecath, Oratec Interventions Inc., CA) reported sufficient temperatures for these events to occur. However a human study reported temperatures sufficient only to coagulate nociceptors. This study reports peak posterior annular and nuclear temperatures attained in-vivo with an intradiscal catheter in sheep.

Twenty sheep were anaesthetised and the lumbar spine exposed. In two non-adjacent discs a stab incision was made in the left postero-lateral annulus and the wound closed. Twelve weeks later the animals returned for a second operation. The spine was approached from the right. Under fluoroscopic control the intradiscal catheter was placed into a previously operated disc. One thermocouple sensor needle was placed 2mm posterior to the catheter to record the posterior annular temperature and a second was inserted 2mm anterior to record the nuclear temperature. The process was repeated for a non-operated control disc. Electrothermal energy was delivered according to the recommended heating protocol.

The target temperature of 90°C at the catheter tip was reached in all cases. Data were tabulated with the mean and standard deviation calculated for each site. There was no significant difference between temperatures reached in the ‘degenerate’ discs and those in the control discs. The mean maximum posterior annular temperature was 63.6°C (range 46.8 to 77.7) and the mean maximum nuclear temperature was 67.8°C (Range 51.1 to 81.2).

Intradiscal electrothermal therapy delivered at 90°C in the sheep consistently heats the posterior annulus and the nucleus to a temperature associated both with coagulation of nociceptors and collagen contraction. These findings may contribute to understanding the mechanism of pain relief following IDET.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 211 - 211
1 Nov 2002
Walters R Smith S Hutchinson M Dolan A Vernon-Roberts B Fraser R Moore R
Full Access

Primary disc space infections are thought to occur in children because of the abundant vascularity of the disc prior to skeletal maturity, and while they generally resolve with treatment, little is known about the long-term consequences on the spine.

An ovine model of discitis was used to investigate the effects of discitis on spinal development in the growing sheep. Six-week-old lambs underwent lumbar discography at multiple spinal levels using either radiographic contrast inoculated with Staphylococcus epidermidis (inoculated group) or radiographic contrast only (control group). Plain x-rays of the spines were taken at intervals up to 18 months before the animals were killed and the spines removed for histologic and morphometric analysis.

Discs from animals in the control group were radiologically and histologically normal at all time points, and as expected there was a steady increase in vertebral body and disc dimensions. Although not all inoculated animals showed histologic evidence of discitis, disc abnormalities were evident from an early stage. In particular disc height was significantly reduced from 2 weeks after inoculation and vertebral body dimensions were significantly reduced from one year.

Infection of discs at a young age, whether or not it progresses to discitis, has a significant effect on spinal development.