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Whodunnit: The Mysterious Case of Mediastinitis After Continuous Interscalene Block

Horlocker, Terese T. MD*; Weiss, William T. RPh; Olson, Cheryl A. PharmD, RPh

doi: 10.1213/ane.0b013e318184b977
Editorial: Editorial

From the Departments of *Anesthesiology and †Pharmacy, the Mayo Clinic, Rochester, Minnesota.

Accepted for publication June 20, 2008.

Address correspondence and reprint request to Terese T. Horlocker, MD, Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905. Address e-mail to horlocker.terese@mayo.edu.

The Whodunnit (“Who done it?”) is a complex, plot-driven variety of the detective story in which the puzzle is paramount. The reader is provided with clues from which the identity of the perpetrator of the deed may be deduced before the solution is revealed in the final moments of the case. Often, the reader is lead down the wrong path; an “obviously guilty” party is initially implicated, but the least likely suspect is eventually revealed as the true villain of the story. Such is the chilling case of infectious complications of regional anesthesia.

Historically, the frequency of serious infections after regional anesthetic techniques was considered to be extremely low and cases were reported as individual cases or small series.1–5 Initial interest focused on the risk factors and sources of infections of the central nervous system (CNS), including meningitis and abscess. Often, a true causality was difficult to prove. When an infectious complication occurred, the “usual suspects” considered to be the likely source were either a distant localized infection with subsequent hematogenous spread and CNS invasion or colonization of an aseptically placed neuraxial catheter with skin flora and consequent ascending infection to the epidural or intrathecal space. Conversely, direct transmission of microorganisms into the CNS by catheter insertion or contamination through a break in aseptic technique was considered to be potential, but unlikely, etiologies. As a result, recommendations for decreasing the risk of infectious complications after regional anesthesia were directed at patient selection—avoidance of needle or catheter placement in patients with untreated infections and those likely to experience perioperative bacteremia or viremia.6 Although meticulous aseptic technique was uniformly advocated, the term was not defined and standards were only developed in the last several years.7

However, epidemiologic series from Europe suggest that the frequency of infectious complications associated with neuraxial techniques is increasing.8,9 In a national study conducted from 1997 to 1998 in Denmark, Wang et al.9 calculated the risk of persisting neurologic deficits to be 1:4343 after epidural analgesia. Epidural abscess was most likely to occur in immunocompromised patients with prolonged durations of epidural catheterization. The most common causative organism was Staphylococcus aureus, suggesting that colonization and subsequent infection from normal skin flora as the pathogenesis. Likewise, Moen et al.8 reviewed the Swedish experience from 1990 to 1999 and reported an alarming association of postspinal block meningitis with α-hemolytic streptococcal cultures, with the source of the organism being the nasopharynx of the proceduralist. The trail of evidence leads directly to us! “Once you eliminate the impossible, whatever remains, no matter how improbable, must be the truth.” (Sherlock Holmes, A Scandal in Bohemia). Thus, the occurrence of both of these serious complications may be affected by our actions. Techniques to reduce infection are literally in our hands and include increased vigilance in hand-washing with an antimicrobial soap,7 the use of sterile gloves, the proper wearing of masks,7,10 and skin preparation with alcohol-based chlorhexidine solutions.7

In this issue of Anesthesia & Analgesia, another source of infectious complications is uncovered: contaminated infusate. Capdevila et al.11 report a case of acute neck cellulitis and mediastinitis complicating continuous interscalene block. The catheter had been placed after skin disinfection with povidone iodine; the anesthesiologist wore a cap, facemask, and sterile gloves. Postoperatively, a continuous infusion of bupivacaine was provided through an elastomeric pump. Importantly, solution preparation and pump filling were performed outside of current recommended compounding requirements (i.e., without appropriate garb and outside of a laminar airflow workbench), according to United States Pharmacopeia (USP) Chapter 797. When the catheter was removed 39 h later to allow hospital discharge, the patient complained of neck pain. Three days later, he was readmitted with neck edema, erythema, and fever. Imaging revealed abscess of the interscalene and sternocleidomastoid muscles with extension into the mediastinum. Blood cultures were positive for S. aureus. After a complicated and prolonged hospital course involving surgical drainage and antibiotic therapy, the patient was discharged neurologically intact and without evidence of continuing infection. It was determined that the most likely infectious source was the infusate, which became contaminated during the repeated manipulations required for solution admixture and pump filling. This case emphasizes “the importance of strict aseptic conditions during puncture, catheter insertion, and postoperative infusion of local anesthetics.”11 However, many anesthesiologists are unaware of the standards of asepsis, particularly related to sterile compounding procedures and microbiological stability of regional anesthetic infusions. The timely review by Head and Enneking12 provides strategies for the prevention of infusate contamination, which includes adherence to USP 797 requirements, standards that were established, but not enforced, by the Food and Drug Administration (FDA) at the time of the reported case.

Since 1820, the USP has set standards to ensure good pharmaceutical care. The mission of the organization is to “promote the public health by developing and disseminating quality standards and information for medicines, healthcare delivery, and related products and practices. Our standards and information help patients and practitioners maintain and improve health.”13

During the 1990s, several different professional and regulatory groups published guidelines concerning the preparation of compounded sterile products, including the American Society of Health System Pharmacists, USP, and FDA.14 In 2003, a survey of hospitals to determine compliance with the 2000 American Society of Health System Pharmacists guidelines on Quality Assurance for Pharmacy-Prepared Sterile Products was performed with disturbing results.15 Despite the availability of guidelines, the practice standards had not been widely adopted. There were substantial gaps between practice and the guidelines.15 Very low compliance rates were also reported; for example, a 5.2% compliance rate with garbing recommendations for the lowest risk compounds.15

In January 2004, the USP updated its guidelines on the compounding of sterile pharmaceuticals. Full compliance has been required since January 2008.14 Notably, the USP also changed the location of Chapter 797 “Pharmaceutical Compounding-Sterile Preparations”16 within the document. Chapters with numbers from 1 to 999 are enforceable by the FDA, chapters with numbers higher than 1000–1999 are informational.14

The Chapter 797 guidelines apply to all health care settings that make sterile products. The intent was to decrease the risk of harm or death as a result of microbial or bacterial endotoxin contamination, chemical or physical contaminants, variability of dose of ingredients, or incorrect types and quantity of ingredients.16 On the basis of these factors and procedures, the risk of microbiological contamination is delineated as low, medium, or high.16 For example, reconstitution of a single-dose vial represents low risk of contamination, whereas solutions made from nonsterile bulk ingredients are high risk.12 Solutions at medium risk for contamination include local anesthetic admixtures. To reduce the risk, USP specifies that all solutions not for immediate use must be prepared in an ISO Class 5 environment, with air quality testing and appropriate garbing of personnel. An ante area or “gown room” is also required. These conditions are not met in a patient room, preoperative waiting area/block room, or even in an operating suite with high-efficiency particulate air filtration, an ISO 6 class environment where the number of particles greater than 0.5 mcg/m3 is still 10 times that allowed for compounding of solutions. “It has long been an axiom of mine that the little things are infinitely the most important” (Sherlock Holmes, A Case of Identity).

The exceptions to the previously mentioned compounding standards are solutions prepared for “immediate use” as defined by the USP.17 The following conditions are required: emergency or immediate patient care, not more than three sterile nonhazardous commercial products, preparation time does not exceed 1 h, product is aseptically prepared, administration to begin within 1 h, and appropriately labeled if not prepared by the person administering the compound.17 The proposed revisions also state that single-dose containers are to be used within 1 h and any remaining contents discarded.17 In addition, the following requirements must be met for a new category created in the revision, low-risk level compounded sterile products with 12 h or less beyond use date.17 The following conditions are required: primary engineering control maintains ISO Class 5 environment; segregated area; low traffic area; personnel cleansing and garbing apply; no sinks adjacent to area; environmental testing; and personnel training, quality assurance, and media-fill tests.17 This revision places additional limitations on the ability to perform compounding outside the pharmacy, including in the operating suite. It is imperative that anesthesiologists are aware of USP 797 requirements and their institutional compliance with these policies.

Finally, USP 797 specifies the conditions for compounding solutions and admixtures, but does not deal with the clinical administration. A solution may be prepared under sterile conditions, but may become contaminated during infusion due to breeches in asepsis, including line manipulations (and disconnects), dressing changes, and infusate/reservoir exchanges. For example, the catheter hub accounts for nearly half of the sources of entry for microorganisms into the epidural space.18,19 In the case by Capdevila et al.,11 the continuity of the system was not interrupted, but two dressing changes were performed. Additional information is needed to determine the optimal infusion time for a given bag or reservoir, balancing the potential for bacterial growth in a solution over time (with consideration for the antimicrobial properties of local anesthetic solutions) and the risk of contamination during manipulation of the infusion system.

In summary, the source of infections complicating regional anesthetic techniques continues to evolve. Initial interrogations pointed to the patient, but after careful review of the facts, it appears that the proceduralist and pharmacy play prominent roles. Thus, in The Mysterious Case of Mediastinitis After Continuous Interscalene Block, we can theorize according to the board game Clue, “the nurse unwittingly did it in the preinduction room with a contaminated infusate.”

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