Infectious Risks of Chronic Pain Treatments: Injection Therapy, Surgical Implants, and Intradiscal Techniques James P. Rathmell, M.D., Tiffini Lake, M.D., and Mary B. Ramundo, M.D.
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he scope of the field of pain medicine now ventures well beyond that of the typical regional anesthesiologist and into the purview of the surgeon. The pain medicine specialist is called on to perform a range of spinal injection techniques and also to perform minor surgical implantation procedures to place devices capable of providing longterm analgesic effects. The infectious risks associated with injection techniques are similar to those for regional anesthetic techniques performed to provide surgical anesthesia and perioperative pain control. The risk of superficial and deep infections rises as the duration of infusion increases. Implanted infusion ports, reservoirs, and programmable drug delivery systems carry less risk of infection than tunneled, percutaneous epidural catheters. The most common types of infections associated with these implantable devices are superficial and confined to the area immediately surrounding the implanted device. We can learn much about the prevention, diagnosis, and management of implanted devices from those learned by practitioners who implant cardiac pacemakers and defibrillators. Diagnostic discography and intradiscal treatments like intradiscal electrothermal therapy (IDET) and percutaneous discectomy are emerging as important treatment techniques. Common to all of these techniques is the percutaneous placement of a needle or other treatment device into an intervertebral disc, carrying the risk of introducing bacteria. Prevention, early diagnosis, and appropriate management of
See Editorial page 289
From the University of Vermont College of Medicine, Burlington, VT; and The Center for Pain Medicine, Fletcher Allen Health Care, Burlington, VT. Accepted for publication March 10, 2006. Reprint requests: James P. Rathmell, M.D., Center for Pain Medicine, Fletcher Allen Health Care, 62 Tilley Drive, South Burlington, VT 05403. E-mail:
[email protected] © 2006 by the American Society of Regional Anesthesia and Pain Medicine. 1098-7339/06/3104-0009$32.00/0 doi:10.1016/j.rapm.2006.03.004
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spondylodiscitis are also essential elements of the pain medicine specialist’s clinical acumen. The aim of this review is to define specific recommendations for pain medicine practitioners who manage patients receiving various injection techniques, longterm epidural infusions, implanted epidural and intrathecal drug-delivery devices, and various types of percutaneous intradiscal therapies.
Infectious Risks Associated With Injection Therapies Used in Chronic Pain Treatment Both superficial and deep infections have been reported after injection therapies for pain including: epidural steroid injections,1-3 facet injections,4 and trigger-point injections.5 Injection therapy for pain treatment carries a small risk of both superficial and deep infection, including neuraxial infection such as epidural abscess. It is not possible to discern the actual incidence of infection from the available published data. Considerations regarding sterile technique and use of disinfectant solutions are similar to those recommended for single-shot regional anesthetic techniques performed in the perioperative period.6,7 Pain practitioners should establish written postprocedural guidelines for their patients that include a clear description of the signs and symptoms of evolving infection and a clear process for contacting pain clinic personnel to report the appearance of any worrisome signs or symptoms.
Infectious Risks Associated With Permanent Epidural Catheters The advent of portable, programmable infusion pumps and silicone epidural catheters that could be tunneled beneath the skin and fixed in position, with or without subcutaneous access ports (Fig 1), provided a significant advance allowing application of neuraxial blockade to the control of severe cancer-related pain.8,9 Although the use of long-term, continuous epidural analgesia has been largely supplanted by implantable intrathecal drug delivery systems, this approach still proves useful for treat-
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likely than catheters with an implanted subcutaneous reservoir to become infected in the first weeks after placement.12 This is likely because of the direct portal for bacterial entry at the location where percutaneous catheters pass through the skin. Epidural catheters with an implanted subcutaneous reservoir are accessed percutaneously by using a sterile needle; however, the access needle is changed periodically and this fact may also contribute to the lower rate of infection. The risk of infection in those receiving epidural therapy for more than 70 days approaches 15%, whereas the incidence of infection extending to the epidural space is about 1%.12 Entry-site infections can generally be managed conservatively by using local incision and drainage, dressing changes, and oral antibiotics.13 It is notable that superficial infections associated with percutaneous catheters (i.e., those that are not totally implanted but have a catheter that enters through the skin) can often be managed without removal of the device; perhaps this is because of the open skin entry site allowing an avenue for egress of drainage. Deep infections along the subcutaneous catheter track can extend to involve the epidural space and generally mandate removal of the indwelling epidural catheter and/or subcutaneous injection port followed by appropriate wound management and antibiotic therapy.11-13 Most superficial infections present with erythema, swelling, and pain with or without purulent discharge at or near the site of the catheter’s skin-entry site or surrounding the subcutaneous reservoir. Similar signs and symptoms extending along the course of the subcutaneous catheter toward the epidural space or in the paraspinous Fig 1. Implanted epidural catheters systems: (A) percutaneous tunneled silicone rubber catheter with subcutaneous, antibiotic impregnated cuff (DuPen epidural catheter; Bard Access Systems, Murray Hill, NJ; reproduced with permission from Du Pen SL, Peterson DG, Williams A, Bogosian AJ. Infection during chronic epidural catheterization: diagnosis and treatment. Anesthesiology 1990; 73:905-909). Infection may occur along the epidural catheter (1) within the epidural space or within the (2) deep or (3) superficial tissues along the course of the catheter. (B) Tunneled epidural catheter with subcutaneous port (Port-a-Cath; Deltec, Inc., St. Paul, MN; illustration reproduced with permission from Deltec, Inc).
ment of pain in some patients near the end of life. Indwelling epidural catheters carry a significant risk of infection that increases in direct proportion to the duration of therapy (Fig 2).10 Infections can occur at the entry site, in deeper tissues along the course of the tunneled epidural catheter, and within the epidural space.11 Percutaneous catheters are more
Fig 2. Cumulative risk of infection with implanted epidural catheters for treatment of pain associated with advanced cancer. (Redrawn from Smitt PS, Tsafka A, Tengvan de Zande F, van der Holt R, Elswijk-de Vries I, Elfrink E, van den Bent MJ, Vecht CJ. Outcome and complications of epidural analgesia in patients with chronic cancer pain. Cancer 1998;83:2015-2022.)
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Fig 3. (A) Illustration of a totally implanted intrathecal drug delivery pump. The drug reservoir and delivery pump are placed in a subcutaneous pocket within the abdominal wall, and the catheter is tunneled subcutaneously from the pump to the subarachnoid space. The pump is refilled periodically (typically at 4- to 6-week intervals) by accessing the reservoir percutaneously; the delivery rate of some systems is fixed at a constant rate, whereas the delivery rate of other systems can be reprogrammed by using wireless technology similar to that used for pacemaker devices. (B) Anteroposterior radiograph of the intrathecal catheter tip (arrow) of an implanted intrathecal drug-delivery system in final position with tip adjacent to the L2/3 intervertebral disc. (Reproduced with permission from Rathmell JP. Atlas of Image-Guided Injection in Regional Anesthesia and Pain Medicine. Lippincott Williams & Wilkins, Philadelphia, 2006, pp. 164, 169.)
region in which the catheter is typically sutured to the subcutaneous fascia suggest deep-tissue infection that carries high risk for extension to the epidural space.
Infectious Risks Associated With Implantable Devices Infection associated with surgical implants account for about half of the 2 million cases of nosocomial infection that occur each year in the United States.14 The majority of device-related infections are associated with orthopedic fracture-fixation devices followed by vascular graft and pacemaker-defibrillator infections.14 Implanted devices used in the treatment of chronic and cancer-related pain include spinal cord stimulators, implanted epidural catheters, and im-
planted intrathecal drug delivery pumps (Fig 3). There are only limited data available regarding the need for antibiotic prophylaxis during implantation and the management of infection associated with these implanted pain-control modalities. However, both spinal cord stimulators and implanted intrathecal pumps are constructed of identical materials and placed by using operative techniques similar to those used for pacemaker-defibrillators; thus, many recommendations can be extrapolated directly from the extensive experience preventing and managing infections associated with these devices. Antibiotic Prophylaxis During Implantation The Centers for Disease Control and Prevention (CDC) published an extensive Guideline for Pre-
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vention of Surgical Site Infection in 1999 that discussed all aspects of prevention in detail, including assessment of patient risk, surgical site preparation, and the use of antimicrobial prophylaxis.15 Pain medicine practitioners performing surgical implantation should be familiar with these guidelines. The most common organisms causing surgical-site infection after pacemaker implantation are Staphylococcus aureus and Staphylococcus epidermidis.16 A cumulative meta-analysis of 7 randomized trials including 2,023 patients examining the use of prophylactic antibiotics during pacemaker implantation suggested a consistent protective effect of antibiotic pretreatment (P ⫽ .0046; odds ratio: 0.256; 95% confidence interval, 0.10-0.656).16 In applying the CDC guidelines for antibiotic prophylaxis to the implanted devices used in pain medicine, it is notable that each of the implanted devices extends to the neuraxis. Thus, surgical-site infection could extend to the neuraxis, thereby proving catastrophic. With the consistent protective effect of prophylactic antibiotic use seen during pacemaker implantation and the possibility of catastrophic infection, routine antimicrobial prophylaxis is warranted in all patients undergoing implantation of a spinal cord stimulator or implanted spinal drugdelivery system (epidural or intrathecal, with or without a subcutaneous port). The current antimicrobial drugs of choice for prophylaxis have recently been reviewed by Gyssens17 and are shown in Table 1. Implanted drug-delivery systems are often placed in patients with advanced cancer, and these groups of patients who are receiving concomitant cancer treatment are not infrequently neutropenic at the time of implantation. A recent systematic review suggests that infection-related mortality because of bacterial causes is reduced with the use of oral prophylactic antibiotics throughout the duration of the neutropenic episode in afebrile, neutropenic oncology patients.18 There are no data
Table 1. Antimicrobial Drugs of Choice for Prophylaxis During Implantation of Spinal Cord Stimulator or Implanted Spinal Drug-Delivery Systems Drug
Preoperative Dose
Cefazolin
Comments
1-2 g IV 30 minutes before incision Clindamycin 600 mg IV 30 In patients with -lactam minutes before allergy incision Vancomycin 1 g IV over 60 In patients who are minutes before documented carriers of incision methicillin-resistant Staphylococcus aureus Abbreviation: IV, intravenously.
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available to guide the selection of antimicrobial agents or the duration of phophylactic therapy for neutropenic patients undergoing surgery. Managing the Patient With an Infected Implantable Device The incidence of any type of infection (superficial or deep) after placement of a spinal cord stimulator implanted pulse generator and tunneled electrode ranges from 2% to 5% in case series reporting results in more than 100 patients.19-21 The risk of deep infections including epidural abscess and meningitis ranges from 0% to 0.5% in the same series. Follett et al.22 recently detailed the incidence of infection associated with intrathecal drug-delivery systems and spinal cord stimulators. Their analysis included data reported in 4 prospective trials using various implanted drug delivery systems. A total of 36 infections involving 35 separate patients were reported in a total of 700 patients for an overall infection rate of 5% (range in infection rate among the 4 studies was 2.5%-9.0%). Infections involved the pump pocket in 57% to 80% of patients and the lumbar site in 13% to 33% of patients, and led to meningitis in 0% to 14% of patients. Complete details of the implantation procedure, including comment on the use of prophylactic antibiotics, were not given. Reported infection rates for implanted cardiac defibrillators range from 1% to 7% and are primarily infections involving the implanted generator site.23 There are case descriptions of successful management of superficial epidural entry site infections and pocket infections using oral and parenteral antibiotics selected through culture and sensitivity testing obtained directly from the infected site without removal of the implanted device.11 In the cumulative analysis reported by Follett et al.,22 the device was totally explanted in 55% to 80% of patients and left in place in the remainder. All infections resolved; however, these authors caution that antibiotic treatment alone without device removal rarely cured an established device-related infection. How or why a few reported infections were treated successfully without device removal is unclear. Treatment must be individualized with the recognition that surgical-site infection could extend to the neuraxis, thereby proving catastrophic. Removal of the implanted device is recommended in those patients who have erythema, swelling, pain, or fluctuance along the length of the tunneled catheter or electrode that suggests deep-tissue infection. Progression of these infections to involve the epidural space has been well documented.24,25 Extensive experience with implanted pacemakers suggests that
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conservative treatment with parenteral antibiotics alone is rarely successful, and complete removal of all components of the implanted device is typically required to eradicate infection.23,26-28 Infectious Risks Associated With Discography Provocative discography and intradiscal treatment techniques like IDET are frequently performed by pain medicine practitioners. These techniques all involve the percutaneous introduction of a hollow needle or cannula through the posterior portion of the annulus fibrosis and into the nucleus pulposus of an intervertebral disc. Infection within the disc space is a well-recognized complication of diagnostic discography, with an overall incidence of less than 0.15% per patient and less than 0.08% per disc injected.29 Discitis appears to result from infection introduced by the needle tip.30 The most common organisms identified are S aureus and S epidermidis.30 Antibiotic Prophylaxis During Discography Animal studies suggest that both intravenous and intradiscal administration of antibiotics can prevent the development of discitis even when bacteria are directly introduced into the disc.31,32 Because discitis can be classified as potentially catastrophic, the 1999 CDC Guideline for Prevention of Surgical Site Infection supports the use of routine antimicrobial prophylaxis during discography and other intradiscal treatment techniques.15 There are only limited animal data available to guide the selection of antimicrobial agent and the route of administration for prophylaxis during discography and intradiscal treatments. Discography is commonly performed with use of radiographic contrast material injected into the intervertebral disc; cefazolin and clindamycin both remain active in vitro when mixed with radiographic contrast (iohexol).32 Extrapolation from animal data31,32 and the CDC recommendations15 support the routine use of intradiscal or intravenous antibiotics before discography and other intradiscal techniques (Table 2); the advantage of one route of administration over another is not clear. Diagnosis and Management of Discitis Discitis is an insidious infection that presents initially with worsening back pain. The clinical presentation and time course are highly variable. A detailed discussion of the diagnosis and management of discitis is beyond the scope of this manuscript but is available in several recent review articles.33,34 Early in the course of discitis, there are few
Table 2. Antimicrobial Drugs of Choice for Prophylaxis During Discography and Other Intradiscal Treatment Techniques Drug
Dose
Comments
Cefazolin
1-2 g IV 30 minutes before discography or Cefazolin 1-10 mg/mL with intradiscal contrast Clindamycin 600 mg IV 30 minutes In patients with before discography -lactam allergy or Clindamycin 7.5 mg/mL with intradiscal contrast Vancomycin 1 g IV over 60 minutes In patients who are before discography documented carriers of methicillin-resistant Staphylococcus aureus Abbreviation: IV, intravenously.
systemic symptoms because the disc space is poorly vascularized, and systemic bacteremia is uncommon. In a series of 29 consecutive patients with spontaneous disc-space infections, 10 patients (34%) had an elevated serum leukocyte count and 21 patients (72%) had an elevated erythrocyte sedimentation rate.34 Diagnosis is dependent on maintaining a high index of suspicion and is confirmed by characteristic changes seen within the disc space on magnetic resonance imaging.35 Practitioners should suspect discitis in patients who report worsening back pain during the weeks after discography, particularly a change in the pattern of longstanding back pain. Successful conservative treatment of discitis relies on early detection.34 Pain practitioners should establish written postprocedural guidelines for their patients that include a clear description of the signs and symptoms of evolving infection and a clear process for contacting pain clinic personnel to report the appearance of any worrisome signs or symptoms. Practitioners performing discography should be familiar with the principles of diagnostic evaluation and management of the patient with discitis.
Recommendations Infectious Risks Associated With Injection Therapies Used in Chronic Pain Treatment Considerations regarding sterile technique are identical to those recommended for single-shot regional anesthetic techniques performed in the perioperative period (evidence level Ib, recommendation grade A). Pain practitioners should establish written postprocedural guidelines that include a de-
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scription of the signs and symptoms of evolving infection and a clear process for contacting appropriate personnel to report the appearance of worrisome signs and symptoms (evidence level IV, recommendation grade C). Infectious Risks Associated With Permanent Epidural Catheters Exit-site infections can generally be managed conservatively by using local incision and drainage, dressing changes, and oral antibiotics (evidence level III, recommendation grade B). Deep infections along the subcutaneous catheter track can extend to involve the epidural space and generally require removal of the indwelling device followed by appropriate wound management and antibiotic therapy (evidence level IIb, recommendation grade B). The decision to remove an infected system must be tailored to each clinical situation; in patients suffering with pain near the end of life, effective symptom control may be more important than eradicating infection (evidence level IIb, recommendation grade B). Infectious Risks Associated With Implantable Devices: Antibiotic Prophylaxis During Implantation Because implanted devices used for chronic pain therapy extend to the neuraxis and infection can prove to be catastrophic, routine antimicrobial prophylaxis is warranted in all patients (evidence level Ia, recommendation grade A). Infectious Risks Associated With Implantable Devices: Managing the Patient With an Infected Implantable Device Exit site and pocket infections may respond to conservative management by using local incision and drainage, dressing changes, and oral antibiotics but will require device removal in the majority of cases (evidence level IIb, recommendation grade B). Deep infections along the subcutaneous catheter or electrode track can extend to involve the epidural space and generally require removal of the indwelling device followed by appropriate wound management and antibiotic therapy (evidence level IIb, recommendation grade B). Infectious Risks Associated With Discography: Antibiotic Prophylaxis During Discography Discitis is a deep-seated, difficult infection to treat and can prove to be catastrophic, thus routine antibiotic prophylaxis is warranted (evidence level Ia, recommendation grade A).
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Infectious Risks Associated With Discography: Diagnosis and Management of Discitis Pain practitioners should establish written postprocedural guidelines that include a clear description of the signs and symptoms of evolving infection and a clear process for contacting appropriate personnel to report the appearance of worrisome signs and symptoms (evidence level IV, recommendation grade C).
Conclusions The pain medicine specialist is called on to perform a range of spinal injection techniques, to perform minor surgical implantation procedures, and to perform intradiscal diagnostic and treatment techniques. The infectious risks of each technique and an approach to prevention, diagnosis, and management of associated infection should become a core part of the knowledge of the pain medicine practitioner.
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