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Routine surgery in addition to chemotherapy for treating spinal tuberculosis

  1. Paul C Jutte1,*,
  2. Joke H van Loenhout-Rooyackers2

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 17 MAR 2010

Assessed as up-to-date: 21 OCT 2007

DOI: 10.1002/14651858.CD004532.pub2

Database Title

Additional Information

How to Cite

Jutte PC, van Loenhout-Rooyackers JH. Routine surgery in addition to chemotherapy for treating spinal tuberculosis. Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD004532. DOI: 10.1002/14651858.CD004532.pub2.

Author Information

  1. 1

    University Medical Center Groningen, Groningen, Netherlands

  2. 2

    GGD Regio Nijmegen (Public Health Office), Department of Tuberculosis, Nijmegen, Netherlands

*Paul C Jutte, University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, Groningen, 9700 RB, Netherlands. p.c.jutte@orth.umcg.nl.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 17 MAR 2010

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Characteristics of included studies [ordered by study ID]
ICMR/MRC 1989
MethodsRandomized controlled trial

Generation of allocation sequence: unclear

Allocation concealment: sealed envelopes

Blinding: assessor only

Inclusion of all randomized (enrolled) participants in the final analysis for primary outcomes:
1. Deformity: 73/130 (56%) at 3 years (73/94 available as x-rays technically inadequate or x-ray series incomplete for 21 participants); 65/130 (50%) at 5 years (15 participants not assessed for x-rays not being available on 0 or 60 months follow up)
2. Neurology: 68% (89/130) at 3 years; 62% (80/130) at 5 years; 5 participants excluded for neurological assessment (2 died of nontuberculous causes and 3 defaulted, all after 18 months)

Length of follow up: 5 years, with assessment at 18 months, 3 years, and 5 years
ParticipantsNumber (further details in Appendix 2): 201 enrolled and randomized

168 available for analysis at 3 years; losses to follow up due to no tuberculosis (3), refused surgery (2), considered unfit for the anaesthetic (1), considered unfit for surgery (3), no evidence of active spinal tuberculosis on radiographs (7), defaulted from 4 to 25 months (1), died of nontuberculous causes (6), operated at wrong level (1), missed considerable amount (> 6 weeks) of chemotherapy (9)

164 available for analysis at 5 years; losses to follow up due to reasons detailed above (33), excluded due to death of unrelated cause, default, or additional chemotherapy due to tuberculosis in other location (4; no details given)

156 available for analysis at 10 years; losses to follow up due to reasons detailed above during 0 to 5 years (37), and excluded for nontuberculous death (4) or default from follow up (4)

Inclusion criteria: presence of clinical and radiographic evidence of tuberculosis of any vertebral body from the first thoracic to the first sacral, inclusive, that is excluding cervical and sacral disease; disease was active clinically and/or radiographically (radiographic active disease: (a) loss of the thin cortical outline and (b) rarefaction of the affected vertebral bodies); availability for observation over a period of 3 years

Exclusion criteria: paraplegia or paraparesis severe enough to prevent walking; active tuberculosis in a lower limb requiring rest in bed; pulmonary tuberculosis of a type considered likely to complicate the management; history of previous antituberculosis chemotherapy for 12 months or more; serious nontuberculous disease likely to prejudice the response to treatment or its assessment; contraindication to the methods of the treatment under comparison
Interventions1. Chemotherapy
Adults (≥ 45 kg): daily streptomycin sulphate (1 g) by intramuscular injection for the first 3 months plus isoniazid (300 mg) and sodium p-amino salicylic acid (PAS) (10 g), both for 18 months

Children (< 15 years) and adults (< 45 kg): daily streptomycin sulphate (20 mg/kg bodyweight) by intramuscular injection for the first 3 months plus isoniazid (6 mg/kg bodyweight; maximum 300 mg) and sodium PAS (0.2 mg/kg bodyweight; maximum 10 g), both for 18 months

Participants randomized to this regimen or the same regimen without the initial 3 months of streptomycin

2. Chemotherapy plus debridement surgery
Same chemotherapy regimen with debridement surgery: an operation to remove all necrotic and diseased tissue without reconstruction
Outcomes1. Kyphosis angle
2. Neurological deficit
3. Bony fusion
4. Absence of spinal tuberculosis
5. Deaths from any cause
6. Regained activity level
7. Change of allocated treatment
NotesLocation: Bulawayo, Rhodesia (now Zimbabwe)

Date: 3-year follow up in 1974; 5-year follow up in 1978

The 5-year report contains information about a study from Hong Kong performed by the same group of investigators, the British Medical Research Council (MRC), with the same criteria; we excluded this part of the report from the analysis because participants were not randomized between chemotherapy or chemotherapy plus surgery




MRC 1974a
MethodsRandomized controlled trial

Generation of allocation sequence: unclear

Allocation concealment: sealed envelopes

Blinding: assessor only

Inclusion of all randomized (enrolled) participants in the final analysis for primary outcomes:
1. Deformity: 39% (79/201) at 5 years; 34% (69/201) at 10 years; not available at 3 years; lumbar lesions excluded for deformity measurements, so total number less than 201, and, as a consequence, the percentages are higher than 39% and 34%, but exact figures cannot be reconstructed from article
2. Neurology: 80% (161/201) at 5 years; 78% (156/201) at 10 years; not available at 3 years

Length of follow up: 10 years, with assessment at 18 months, and 3, 5, and 10 years
ParticipantsNumber (further details in Appendix 2): 130 enrolled and randomized

94 available for analysis at 3 years, 36 lost to follow up due to no evidence on radiographs of tuberculosis (5), permanent default (6), excessive interruption (17), major drug change (3 toxicity, 1 brucellosis), death nontuberculous cause (3), admitted in error 1)

80 available for analysis at 5 years, 50 lost to follow up due to earlier exclusion (36 at 3 years), defaulted from follow up between 3 and 5 years (6), died of unrelated cause (3), not explained (5)

Inclusion criteria: presence of clinical and radiographic evidence of tuberculosis of any vertebral body from the first thoracic to the first sacral, inclusive, that is excluding cervical and sacral disease; disease was active clinically and/or radiographically (radiographic active disease: (a) loss of the thin cortical outline and (b) rarefaction of the affected vertebral bodies); availability for observation over a period of 3 years

Exclusion criteria: paraplegia or paraparesis severe enough to prevent walking; active tuberculosis in a lower limb requiring rest in bed; pulmonary tuberculosis of a type considered likely to complicate the management; a history of previous antituberculosis chemotherapy for 12 months or more; serious nontuberculous disease likely to prejudice the response to treatment or its assessment; a contraindication to the methods of the treatment under comparison
Interventions1. Chemotherapy
Isoniazid plus rifampicin (1 dose daily for 6 months)
2. Chemotherapy plus surgery
Isoniazid plus rifampicin (1 dose daily for 6 months) with an operation consisting of debridement (removal of all necrotic and diseased tissue) and stabilization with a bone graft (reconstruction)

Not included in review because it has a different chemotherapy regimen without a comparable surgical intervention group:

3. Chemotherapy
Isoniazid plus rifampicin (1 dose daily for 9 months)
Outcomes1. Kyphosis angle
2. Neurological deficit
3. Bony fusion
4. Absence of spinal tuberculosis
5. Deaths from any cause
6. Regained activity level
7. Change of allocated treatment
NotesLocation: Madras, India

Date: 3-year follow up in 1989; 5-year follow up in 1999; and 10-year follow up in 1999

The 5-year report also includes information from studies done in Hong Kong (all surgical) and Korea (all chemotherapy); we excluded these results from analysis because they did not randomize between chemotherapy alone and chemotherapy plus surgery


 
Characteristics of excluded studies [ordered by study ID]
StudyReason for exclusion
Jain 2004Not randomized
Loembe 1994Not randomized
MRC 1973aNo surgical group
MRC 1973bNo surgical group
MRC 1974bAll participants had surgery
MRC 1976No surgical group
MRC 1978aAll participants had surgery
MRC 1982All participants had surgery
MRC 1985No surgical group
MRC 1986All participants had surgery
MRC 1993No surgical group
MRC 1998No randomization for conservative or surgical treatment: 2 locations, Korea (all chemotherapy without surgery) and Hong Kong (all chemotherapy plus surgery)
Rajasekaran 1998No surgical group
Rajeswari 1997bNot a randomized controlled trial, poor methodological quality, randomization method and concealment are unclear; study reports on 33 participants of whom the first 10 were not randomized but all operated because of participation in another trial (one of the included trials ICMR/MRC 1989); the other 23 patients were allocated to chemotherapy only, 4 were lost to follow up for various reasons; of the 19 included in the analysis 3 were operated for neurological deterioration
Seddon 1976Description of several MRC studies, not a study itself
Upadhyay 1993All participants had surgery
Upadhyay 1994aAll participants had surgery
Upadhyay 1994bAll participants had surgery
Upadhyay 1994cAll participants had surgery
Upadhyay 1996All participants had surgery


 
Comparison 1. Chemotherapy plus surgery versus chemotherapy alone
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Change of allocated treatment2Odds Ratio (M-H, Fixed, 95% CI)Subtotals only
    1.1 At 18 months
2262Odds Ratio (M-H, Fixed, 95% CI)0.75 [0.27, 2.09]
    1.2 At 3 years
2262Odds Ratio (M-H, Fixed, 95% CI)0.67 [0.25, 1.82]
    1.3 At 5 years
2244Odds Ratio (M-H, Fixed, 95% CI)0.69 [0.25, 1.92]
    1.4 At 10 years
1156Odds Ratio (M-H, Fixed, 95% CI)1.0 [0.28, 3.60]
 2 Clinically significant increase in kyphosis angle2Odds Ratio (M-H, Fixed, 95% CI)Subtotals only
    2.1 Deterioration > 10 ° at 3 years
178Odds Ratio (M-H, Fixed, 95% CI)0.88 [0.36, 2.16]
    2.2 Deterioration > 10 ° at 5 years
2144Odds Ratio (M-H, Fixed, 95% CI)1.08 [0.54, 2.15]
 3 Improvement in neurological deficit2Odds Ratio (M-H, Fixed, 95% CI)Subtotals only
    3.1 At 18 months
223Odds Ratio (M-H, Fixed, 95% CI)3.18 [0.47, 21.67]
    3.2 At 3 years
223Odds Ratio (M-H, Fixed, 95% CI)1.84 [0.33, 10.19]
    3.3 At 5 years
220Odds Ratio (M-H, Fixed, 95% CI)2.14 [0.35, 13.13]
    3.4 At 10 years
110Odds Ratio (M-H, Fixed, 95% CI)0.27 [0.01, 8.46]
 4 Bony fusion2Odds Ratio (M-H, Fixed, 95% CI)Subtotals only
    4.1 At 18 months
2256Odds Ratio (M-H, Fixed, 95% CI)0.97 [0.59, 1.59]
    4.2 At 3 years
2247Odds Ratio (M-H, Fixed, 95% CI)0.76 [0.45, 1.27]
    4.3 At 5 years
2236Odds Ratio (M-H, Fixed, 95% CI)1.07 [0.57, 2.00]
    4.4 At 10 years
1156Odds Ratio (M-H, Fixed, 95% CI)1.27 [0.58, 2.81]
 5 Absence of spinal tuberculosis2Odds Ratio (M-H, Fixed, 95% CI)Subtotals only
    5.1 At 18 months
2261Odds Ratio (M-H, Fixed, 95% CI)1.17 [0.67, 2.05]
    5.2 At 3 years
2262Odds Ratio (M-H, Fixed, 95% CI)1.32 [0.58, 3.02]
    5.3 At 5 years
2244Odds Ratio (M-H, Fixed, 95% CI)0.78 [0.36, 1.68]
    5.4 At 10 years
1156Odds Ratio (M-H, Fixed, 95% CI)1.67 [0.52, 5.35]
 6 Deaths from any cause2Odds Ratio (M-H, Fixed, 95% CI)Subtotals only
    6.1 At 18 months
2262Odds Ratio (M-H, Fixed, 95% CI)2.65 [0.60, 11.64]
    6.2 At 3 years
2262Odds Ratio (M-H, Fixed, 95% CI)1.45 [0.42, 4.95]
 7 Regained activity level2Odds Ratio (M-H, Fixed, 95% CI)Subtotals only
    7.1 At 18 months
2262Odds Ratio (M-H, Fixed, 95% CI)0.66 [0.26, 1.66]
    7.2 At 3 years
2262Odds Ratio (M-H, Fixed, 95% CI)0.60 [0.24, 1.50]
    7.3 At 5 years
2244Odds Ratio (M-H, Fixed, 95% CI)0.81 [0.35, 1.85]
    7.4 At 10 years
1156Odds Ratio (M-H, Fixed, 95% CI)1.67 [0.52, 5.35]
 8 Deterioration of bone loss2Odds Ratio (M-H, Fixed, 95% CI)Subtotals only
    8.1 At 3 years
1161Odds Ratio (M-H, Fixed, 95% CI)0.58 [0.31, 1.09]
    8.2 At 5 years
2220Odds Ratio (M-H, Fixed, 95% CI)0.73 [0.41, 1.29]
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