Efficiency of Hyperbaric Oxygen Therapy in Iatrogenic Spinal Infections

Mehmet Resid Onen, MD,? Evren Yuvruk, MD,? Gul Karagoz, MD,y and Sait Naderi, MD?

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Study Design. Retrospective clinical study.
Objective. The aim of this study is to reveal the effectiveness of HBO therapy in iatrogenic spinal infections intractable to antibiotic therapy alone.
Summary of Background Data. The efficiency of hyperbaric oxygen (HBO) therapy, which is currently being used in many areas, has been proven in infections in deep and superficial locations and in osteomyelitis. The aim of this study is to reveal effectives of HBO therapy in iatrogenic spinal infections intract- able to antibiotic alone therapy.
Methods. HBO therapy was given to 19 cases of iatrogenic spinal infection between 2008 and 2013. Adjuvant HBO therapy was applied to cases that had exhibited no improvement in clinical and laboratory findings despite medical treatment for at least 3 weeks. Several parameters including demographic characteristics, surgical area, etiology and the surgical treatment modality, microbiology (culture material and causative organ- ism), clinical and laboratory results, duration of HBO therapy, and outcome were reviewed.
Results. The mean age was 54.6 years (range: 32–75 years). Iatrogenic spinal infections were most frequent in the lumbar region. It occurred after spine instrumentation in 12 cases and after micro-discectomy in 7 cases. The average number of HBO therapy sessions applied was 20.1 (range: 10–40). Wound discharge and clinical and laboratory findings recovered in all cases at the end of the therapy course. No revision or removal of the instrumentation was necessary in the instrumented cases. Conclusion. HBO therapy is a treatment modality, which is safe and efficient as an adjuvant therapy in the treatment of infections. It was also seen to be effective in the prevention of

From the ?Departments of Neurosurgery; and yInfectious Diseases, Umra- niye Teaching and Research Hospital, Istanbul, Turkey.

Acknowledgment date: March 18, 2015. First revision date: June 4, 2015. Acceptance date: July 1, 2015.

The device(s)/drug(s) that is/are the subject of this manuscript is/are being evaluated as part of an ongoing FDA-approved investigational protocol (IDE) or corresponding national protocol.

No funds were received in support of this work.

No relevant financial activities outside the submitted work.

Address correspondence and reprint requests to Mehmet Resid Onen, MD, Department of Neurosurgery, Umraniye Teaching and Research Hospital, Istanbul, Turkey; E-mail: mresid@gmail.com

DOI: 10.1097/BRS.0000000000001065

revision procedures and instrumentation failures in iatrogenic osteomyelitis cases, which had occurred following spinal instru- mentation.
Key words: hyperbaric oxygen treatment, iatrogenic spine infections, infection.

Level of Evidence: 4 Spine 2015;40:1743-1748

Iatrogenic spinal infections (ISE) are included in the possible complications after spinal procedures. ISEs are seen at rates of 0.7% to 16%, depending on the procedure and comorbidities present in the preoperative period.1 – 6 Although they are seen at a rate of 0.5% to 2.4% in discectomy cases, the rate can be higher in spinal instrumentation cases and go up to 1.5% to 7.5%.3,4,7 – 9 ISEs are pathologies with long treatment periods and can cause deformities. Inadequately treated spondylodiscitis may result in serious deformities. The standard treatment in these cases includes biopsy, debridement, and revision or removal of the instruments in instrumented cases, depending on the local- ization and extent of the infection. After applying culture- antibiogram to the specimen collected during the surgical procedure, antibiotic therapy is given for 2 to 6 weeks, depending on the pathogenic organism and level of infection. This period can be even longer in osteomyelitis cases. Spinal infections are pathologies for which treatment is difficult, despite appropriate medical and surgical treatments.

Hyperbaric oxygen (HBO) therapy is a treatment option used in resistant osteomyelitis, severe organ damage, acute ischemic organ damage, burns, radiation necrosis, muscular ischemic necrosis, compartment syndrome, and infec- tions.10 – 13 Its mechanism of action was attributed to an increase in the oxygen saturation in the ischemic tissue, with resultant increase in microcirculation, and direct antimicro- bial effect against microorganisms.

The aim of this study is to evaluate the effectiveness of HBO therapy in iatrogenic spinal infections intractable to antibiotherapy.

MATERIALS AND METHODS

HBO therapy was applied to 19 cases with iatrogenic spinal infection that neither improved clinically nor showed a

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TABLE 1. Infections and Biopsy Distribution
	Culture Positive (N1⁄416)	Preferred Antibiotherapy
Gram negative 10 Cefazolin, imipenem, ceftriaxone
MRSA 3 Vancomycin, linezolid
Enterococcus spp 1 Linezolid
Pseudomonas 1 Imipenem, amikacin aeruginosa
Acinetobacter spp 1 Tigecycline, ciprofloxacin
MRSA indicates methicillin-resistant Staphylococcus aureus.

decrease in infection markers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]) despite appropriate antibiotic therapy for at least 3 weeks. Patients in whom HBO therapy was applied were evaluated with regard to demographic characteristics (age and gender), surgical area, etiology and the surgical treatment modality, microbiology (culture material and causative organism), clinical and laboratory results, duration of HBO therapy, and the find- ings of posttreatment follow-up examinations. The follow- up of these patients was conducted as outpatient clinic examinations and with phone calls at periodic intervals.

Hyperbaric Oxygen Therapy

On the basis of clinical findings and laboratory values, cases that did not respond to at least a 3-week course of antibiotic therapy were administered HBO therapy. The patients were given HBO therapy simultaneously with antibiotherapy. HBO was administered in 120-minute sessions compliant with 9 depth/time profile at 2.5 ata (pure atmospheric pressure) pressure. Patients were allowed to breathe 100% oxygen through masks or helmets, based on their general medical status (Fig. 1A, B). The number of HBO therapy sessions to be applied was determined by the HBO specialist doctor on the basis of the extension and depth of the infection and the response obtained.

RESULTS

The mean age of the 19 cases (9 females and 10 males) was 54.6 years (range: 32–75 years). The mean interval between the primary surgical procedure and infection was 29.4 days (range: 6–60 days). Locations of the spinal infections were determined as cervical in 1 (5.2%), thoracic in 4 (21.1%), and lumbar in 14 (73.7%) cases. Discectomy had been done in 7 cases (36.8%), and instrumentation plus decompression procedures with a posterior approach were undertaken in 12 cases (63.2%) as the initial interventions.

The cases were evaluated with regard to the risk factors. Eleven cases were obese (BMI > 30 kg/m2), 7 had diabetes mellitus, 2 had chronic anemia, 1 had chronic steroid use for rheumatoid arthritis, and 6 had hypertension.

The culture material was obtained with open debride- ment under general anesthesia in 7 (36.8%) cases, but the sample was obtained with a minimally invasive procedure performed percutaneously under local anesthesia in 12

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(63.2%) cases. For this, a vertebroplasty working channel was inserted into the infected intervertebral disc and, then, tissue sampling, debridement, and lavage were carried out with a percutaneous endoscopic alligator, punch, and cur- ettes. This minimally invasive approach was used in cases in which infection was limited to the intervertebral disc with- out significant dural sac compression.

Gram-negative enteric bacteria grew in 10 cases (62.5%), methicillin-resistant Staphylococcus aureus (MRSA) in 3, and Enterococcus spp., Pseudomonas aeruginosa, and Aci- netobacter spp. grew in 1 case each (Table 1). First-gener- ation cephalosporins were started empirically in all cases. Treatment was continued with antibiotics appropriate to the antibiogram results in culture-positive cases. Cefazolin was continued in 3 cases where no growth was found in cultures. The duration of the treatments was planned in accordance with the recommendations of the infectious diseases specialist.

HBO therapy was started in cases with infection intract- able to at least 3 weeks of antibiotic therapy where no significant improvements were seen in clinical findings and laboratory values, with continued wound discharge.

There was no meaningful improvement in infection markers after antibiotic alone therapy alone. The ESR reduced from 55 (range: 44–88) before antibiotic alone therapy to 49.0 (range: 42–86) after antibiotic alone therapy (before HBO) and the CRP reduced from 7.7 (range: 6.3–18.4) before antibiotic alone therapy to 7.1 (range: 5– 17.8) after antibiotic alone therapy (before HBO). After the use of combined antibiotic and HBO therapy, the mean ESR

Figure 1. (A) Hyperbaric oxygen therapy tank. (B) The patient compartment for hyperbaric oxygen treatment.

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TABLE 2. Erythrocyte Sedimentation Rate (ESR) and C-reactive Protein (CRP) Changes Before AB (Antibiotic) Treatment, 3 Weeks After Antibiotic Treatment, and After Combined Treatment using AB þ HBO (Hyperbaric Oxygen)

Before Antibiotic After Antibiotic After Combined Antibio- Treatment Treatment tic þ HBO Treatment

ESR 55 (range: 44–88) 49.0 (range: 42–86) 24.5 (range: 5–33)

CRP 7.7 (range: 6.3–18.4) 7.1 (range: 5–17.8) 0.8 (range: 0.2–2.6)

value reduced from 49.0 (range: 42 – 86) to 24.5 (range: 5 – 33), whereas the mean CRP level reduced from 7.1 (range: 5 – 17.8) to 0.8 (range: 0.2 – 2.6; normal limits for ESR: 15 – 20 mm/hr, and normal limits for CRP: 0 – 1) (Table 2; Fig. 2).

An average of 20.1 (range: 10 – 40) sessions of HBO therapy were applied to the patients. Discharge from the wound site stopped in all cases at the end of the treatment, and improvements in the clinical evaluations and laboratory findings were observed (Fig. 3A – D), Fig. 4A – D), Fig. 5A – C), Fig. 6A–D).

Patients were followed up for a mean duration of 23 months (range: 10 – 50 mo) after the HBO therapy. Follow- up evaluations included the infection markers (ESR and CRP), clinical findings (pain, neurological functions, and wound site), and radiological studies (MRI and contrast MRI). During the follow-up period, no recurrence of infec- tion, spinal instability, or deformity was seen in any of the patients.

DISCUSSION

The results of this study showed the efficiency of HBO therapy in patients with iatrogenic spinal infections who were unresponsive to medical treatment alone. HBO therapy, which can be successfully used in other bone infections, can also be used with success in ISEs and can prevent the need for instrument removal or surgical revision in instrumented patients.

It has been reported that iatrogenic infection develops at a rate of 0.2% to 4.7% in spinal surgeries with implants despite prophylactic antibiotic therapy.14 Postoperative infections have been reported to range between 3% and 7% in cases where posterior spinal instruments have been

Figure 2. The change in erythrocyte sedimentation rate and C-reac- tive protein values with hyperbaric oxygen therapy.

used.15,16 It has been suggested that the instruments used

inoculate microorganisms into the wound environment.15

The type of implant material and surface roughness at the

microlevel are important factors for microorganism growth.4,15,17 – 19

Many medical and surgical factors may play a role in iatrogenic spinal infections. The major medical factors that increase risk of the postoperative infections include the extension of the surgical period, perioperative blood loss exceeding 1000 mL, diabetes mellitus, advanced age, obesity, cardiac insufficiency, and anemia.10,20 – 23 In the current study, obesity was present in 8, diabetes mellitus in 7, and anemia in 2 cases.

Surgical factors include tissue necrosis related to soft tissue dissection, destruction of vascular structures related to exploration, spreading of necrotic tissues related to cauterization around the surgical area, and the transfer of infectious agents into the bony tissue by spinal implants.15

All of these factors cause hypo-oxygenation at the sur- gical site, making treatment of infection difficult. Oxygen saturation in bony tissue with osteomyelitis is 30% to 40% less than in normal bone. This ratio can exceed the same for

Figure 3. MRI image of spondylodiscitis on postoperative day 10 fol- lowing surgery of L5–S1 spondylolisthesis. A, Sagittal T1-weighted con- trast-enhanced image. B, Sagittal T2-weighted image. C, Axial T2- weighted image. D, Axial T1-weighted contrast-enhanced image.

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Figure 4. Case of FIGURE 3; patient with spondylodiscitis after surgery of L5–S1 spondylolisthesis. MRI images after HBO treatment. A, Sagittal T1-weighted contrast-enhanced image. B, Sagittal T2- weighted image. C, Axial T1-weighted contrast-enhanced image. D, Axial T2-weighted image.

healthy bony tissue with HBO.24 Therefore, HBO therapy has been used as an effective treatment for osteomyelitis. Chen et al conducted 20 sessions of HBO therapy together with surgical debridement and antibiotherapy for resistant osteomyelitis, which developed in 10 hemodialysis cases, and reported that the osteomyelitis recovered completely in 8 cases after this treatment.25 Similarly Davis et al reported that recovery was achieved with 40 sessions of HBO therapy in 34 of 38 chronic nonhematogenous osteomyelitis cases after surgical debridement and antibiotherapy.26 In another study, Ahmed et al reported successful results in 5 out of 6 patients with medical comorbidities and a poor general medical status in a series of primary and secondary osteo- myelitis cases.27

The reported successful results encouraged the use of HBO in spinal infections. However, there are a few studies on the use of HBO therapy in spine infections. Larsson et al reported that postoperative HBO therapy in pediatric patients with neuromuscular spinal deformities reduces the need for removal or revision of the instrument in infections at deep locations by reducing the need for antibiotherapy.28 In another study, Larson et al reported the effectiveness of HBO therapy in craniospinal

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Figure 5. MRI images of spondylodiscitis and epidural abscess occurred on postoperative day 15 after surgery of L5–S1 microdis- cectomy. A, Sagittal T1-weighted image. B, Sagittal T1-weighted contrast-enhanced image. C, Axial T1-weighted contrast-enhanced image.

infections. This treatment was reported to be effective in shortening the treatment period and in reducing the need for reoperation, particularly in 7 cases with spinal implants.29

This study is the largest study reporting the effectiveness of HBO therapy in spine infections and shows the efficiency of HBO in both short- and long-term outcomes and against all agents.

A literature search showed that minor complications occurred at a rate of 19.9%, and major complications (epileptic seizures) occurred at a rate of 0.1% after the use of HBO therapy.11 In the current study, no serious complications related to HBO therapy were seen.

Another important issue during the use of HBO therapy is the timing and duration of HBO therapy. To date, there has been no consensus on the timing for starting and the duration of HBO therapy. In literature, applications of 10

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Key Points

Iatrogenic spinal infections (ISEs) are included among the possible complications after spinal procedures.

ISEs are pathologies with long treatment periods and can cause deformities.

HBO therapy seems to be a safe and efficient treatment modality in cases intractable to antibiotic alone therapy.

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Figure 6. Case of FIGURE 5; patient with spondylodiscitis and epi- dural abscess after surgery of L5–S1 microdiscectomy. MRI images after surgical debridement and hyperbaric oxygen therapy. A, Sagit- tal T2-weighted image. B, Sagittal T1-weighted contrast-enhanced image. C, Axial T1-weighted image. D, Axial T1-weighted contrast- enhanced image.

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In the current study, the criteria for starting the HBO therapy were determined as a lack of response to antibiotic therapy for at least 3 weeks and no significant decrease in the ESR and CRP level. HBO therapy was applied for a mean of 20.1 sessions (range: 10 – 40 sessions). The duration of the HBO therapy to be applied was determined by both the HBO specialist and clinician based on the depth of infection, wound discharge, laboratory findings, and whether or not instrumentation had been applied. The predetermined number of sessions was increased in some cases according to the response to therapy.

CONCLUSION

Iatrogenic spinal infections constitute a significant problem in spinal surgery. They can cause long hospital stays, repeated surgeries, and morbidities. HBO therapy seems to be a safe and efficient treatment modality in cases intract- able to antibiotic therapy alone.

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