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Femoral nerve catheter (FNC) insertion is commonly performed for postoperative analgesia following total knee arthroplasty (TKA). High rates of bacterial catheter colonization (57%) complicating FNC insertion have been reported. The Biopatch is a chlorhexidine (CHG) impregnated patch that is designed to inhibit bacterial growth for days. The Biopatch has proven to be effective at decreasing epidural and vascular catheter bacterial colonization. We hypothesized that the Biopatch would be effective at decreasing FNC colonization rates.
Following IRB approval and written informed consent, 100 patients scheduled for TKA were prospectively enrolled. Patients at elevated risk for infection were excluded from analysis. FNCs were inserted and tunneled under sterile conditions using ultrasound guidance following CHG skin cleansing. Participants were then randomized to either have the Biopatch applied to the catheter exit site or not. All patients received pre/postoperative antibiotic therapy. The FNC tip and catheter exit site were cultured for bacterial growth at the conclusion of therapy.
No statistically significant differences in catheter exit site (29.8 vs 25%) or FNC colonization (4.3 vs 6.3%) were found. Local skin inflammation (10.6 vs 2.1%) and FNC exit site colonization by greater than one type of bacteria trended towards increased values in the no Biopatch group.
The baseline rate of bacterial colonization of FNCs placed in the setting of short-term use, CHG skin decontamination, ultrasound guidance, subcutaneous tunneling and perioperative antibiotic therapy is quite low and we were unable to demonstrate any benefit to Biopatch application.
At many institutions, femoral nerve catheter insertion for postoperative analgesia following total knee arthroplasty is considered standard of care. Compared to standard opioid therapy, perineural femoral nerve catheters have demonstrated improved pain control, decreased opioid related side effects and improved functional recovery following total knee arthroplasty.1–4 Unfortunately, any time the integrity of the skin is disturbed the potential for infection exists. Serious case reports of psoas abscess complicating femoral nerve catheter insertion have even been reported.5
Various groups have investigated the incidence of bacterial colonization in patients with femoral nerve catheters and rates as high as 57% have been reported.6 Most studies have found the incidence of femoral nerve catheter colonization to be more moderate and between 9–28.6%.7,8 Various factors have been shown to increase the risk of peripheral nerve catheter bacterial colonization including extended duration of therapy, diabetes mellitus, recent trauma, site of nerve catheter insertion, postoperative care in intensive care unit setting and lack of extended postoperative antibiotic therapy.7–10 Bacterial colonization of invasive devices is of great importance as it has been demonstrated to serve as a surrogate end point for catheter related blood stream infections.11
The Biopatch (Ethicon Inc, Somerville, NJ, U.S.A) is a chlorhexidine impregnated patch that is designed to release chlorhexidine and inhibit bacterial and fungal growth for a number of days. The Biopatch has a low incidence of reported hypersensitivity reactions and has proven to be effective at decreasing epidural and vascular catheter exit site bacterial colonization.12–14 Despite the high rate of reported bacterial colonization of peripheral nerve catheters (specifically femoral nerve catheters) and the potentially devastating consequences of a local abscess or blood stream infection seeding joint hardware, no group has evaluated the Biopatch for use with peripheral nerve catheters. Bacterial colonization of peripheral nerve catheters and the impact of the Biopatch may differ from what has been reported for epidural catheters as the site of peripheral nerve catheter insertion is oftentimes in an anatomical location more conducive to bacterial growth. The impact of the Biopatch on the rate of bacterial colonization of peripheral nerve catheters may differ from what has been reported for vascular catheters secondary to infusions of local anesthetics through peripheral nerve catheters.
The goal of this randomized investigation was to examine the effect of Biopatch placement on the rate of femoral nerve catheter tip bacterial colonization following total knee arthroplasty. We also examined femoral nerve catheter exit site bacterial colonization and clinical signs of infection or inflammation. We hypothesized that the use of a biopatch would significantly reduce both femoral nerve tip and catheter exit site rates of colonization.
This study was approved by the University of Wisconsin Health Sciences IRB (7/2011) and all participants provided written informed consent. Adult patients scheduled for total knee arthoplasty were eligible for the study. Patients aged < 18 years, allergy to local anesthetics, local or generalized infection or inflammation, current antibiotic therapy, compromised immune system, current chronic steroid use, neurological deficits, pregnancy, imprisonment, refusal to participate and primary language other than English were excluded. Randomization was accomplished by inserting a sheet of paper determining patient group (50 stating “Biopatch and 50 stating “Control”) into an opaque envelope. The envelopes where then sealed, well shuffled, and number sequentially by a member of the study team (KS). Consent, envelope retrieval and randomization was done by a member of the study team (staff anesthesiologist) involved in block placement.
For femoral nerve catheter placement, patients were transported to a dedicated area outside of the OR. Nerve catheters were inserted by an anesthesia resident under the supervision of a faculty anesthesiologist. A “time out” procedure was performed to ensure correct patient, correct side and correct procedure. Following application of standard monitors including blood pressure, ECG, and pulse oximetry, the patient was sedated with intravenous midazolam and/or fentanyl. Sedation was titrated to patient comfort. The groin was shaved with electric clippers as needed to allow for adherence of a sterile dressing following catheter placement. Chlorhexidine gluconate 2% / isopropyl alcohol 70% (ChloraPrep, CareFusion, Leawood, KS, USA) was used to decontaminate the skin in the area of needle insertion. A sterile drape was then placed over the needle insertion site. All physicians involved in placement of femoral nerve catheters wore cap, mask, sterile gown and gloves for catheter placement. A Sonosite M-Turbo with a 13-6 MHz ultrasound probe (Sonosite, Bothel, WA, USA) was covered with a sterile probe cover (Bard Access Systems, Inc., Salt Lake City, UT, USA). Sterile ultrasound conducting gel was applied to the probe and ultrasound guidance was utilized to identify the femoral nerve in cross section. Following skin infiltration at the needle insertion site with 1% lidocaine, a 17 gauge touhy needle from an Arrow StimuCath Continuous Nerve Block Procedural kit (Teleflex Medical, Research Triangle Park, NC, USA) was inserted adjacent to the nerve. Current was passed through the needle and when a quadriceps muscle contraction was elicited at a suitable current (variable but typically 0.5–1.5 mAmps) the femoral nerve catheter was advanced through the needle. Current was applied to the catheter as it was advanced through the touhy needle and if the quadriceps muscle contraction dissipated, the catheter was pulled back to within the touhy and then re-advanced following needle repositioning. When catheter insertion continued to result in quadriceps muscle contraction at a current between 0.5–1.5 mAmps, the touhy needle was removed and the catheter was secured. If we were unable to obtain a quadriceps contraction via the stimulating catheter despite repositioning the needle, the needle was positioned adjacent to the femoral nerve and the catheter was threaded 5 cm beyond the needle tip and secured at that location. The femoral nerve catheter was then tunneled 1–2 cm lateral and superior to the initial needle insertion site. Dermabond (Ethicon Inc, Somerville, NJ, U.S.A) was applied at the femoral nerve catheter exit site and site of tunneling.
Once the femoral nerve catheter was placed, the attending anesthesiologist opened the next envelope in the sequence to determine the treatment allocation. The Biopatch group had a Biopatch applied at the catheter exit site prior to application of a tegaderm (3M Healthcare, St. Paul, MN, USA) film dressing. In the no Biopatch group, a tegaderm was applied as the only dressing. Following completion of femoral nerve catheter dressings, the femoral catheter was initially dosed/tested with 3–5 mL of 1.5% lidocaine with 5 mcg/mL epinephrine and then dosed further with an additional 20 mL 0.5% ropivacaine. Patients then received a perineural infusion via a programmable infusion pump (Hospira, Inc., Lake Forest, IL, USA) initiated in the PACU of 0.2% ropivacaine at 6 mL/hr until 0600 on postoperative day 1. The infusion was then changed to 0.1% ropivacaine at 6 mL/hr until 0600 on postoperative day 2. Of note, a bacterial filter is used with all perineural local anesthetic infusions at our institution. For the surgical procedure, patients received either general or neuraxial anesthesia at the discretion of the anesthesia provider and patient. Postoperatively, all patients received additional intravenous and oral opioids as deemed appropriate by the nursing and surgical staff. Following femoral nerve catheter placement, all patients received preoperative and two postoperative doses of appropriate prophylactic antibiotic therapy. Additional postoperative antibiotic doses were given to patients deemed by the orthopedic service to be at high risk of infectious complications.
Upon completion of therapy, a study team member was responsible for femoral nerve catheter removal and culture retrieval. The Tegaderm dressing and any residual Dermabond adhesive was first carefully removed. Residual Dermabond adhesive was removed with a sterile forceps. The skin at the catheter exit site with the catheter still in place was swabbed with a sterile cotton tip applicator moistened with sterile normal saline. The swab was placed in a sterile container and sent immediately to the microbiology laboratory. The staff in the microbiology lab performing the bacterial cultures were blinded with regard to patient group. The swab was inoculated onto a blood agar plate/eosin-methylene blue plate/chocolate agar plate and incubated for 3 days aerobically, then inoculated onto an anaerobic brucella-agar plate and incubated for 7 days anaerobically. Bacterial growth found in the first quadrant of the inoculated plate was defined as low grade growth, in the second and/or third quadrant was moderate growth, and in the fourth quadrant was heavy growth.
Skin around the catheter insertion site was then disinfected with sterile povidone-iodine solution and allowed to dry. The skin was then cleansed with 70% alcohol x2 and allowed to dry between and after each application. The catheter was then removed and 2 cm of the distal portion of the femoral nerve catheter was cut using sterile scissors. The catheter was immediately sent to the microbiology lab for culture in a sterile container. The catheter segments were rolled onto blood agar plates at 35°C under aerobic and anaerobic conditions. Bacterial growth found in the first quadrant of the inoculated plate was defined as low grade growth, in the second and/or third quadrant was moderate growth, and in the fourth quadrant was heavy growth.
The primary outcome of the investigation was bacterial growth present on culture of the femoral nerve catheter. Secondary outcomes included bacterial colonization of the skin at the catheter insertion site and clinical signs of infection or inflammation. Since anesthesia residents would be inserting our femoral nerve catheters, we assumed that our baseline rate of bacterial colonization would approximate that reported by Cuvillon et. al.6 We therefore assumed that the rates of catheter colonization in the control group and treatment group would be 60% and 30%, respectively. A 50% reduction in the rate of colonization was chosen as representing a clinically significant reduction. Using a two sample binomial test, with a type-I error of 5% (2-sided) and a power of 80%, we needed 44 subjects in each group (88 subject in total). The planned enrollment size of 50 subjects per group (100 subjects in total) allowed for potential drop-outs or losses to follow-up. Statistical analysis was performed for primary and secondary outcomes using Fisher’s exact test.
One hundred patients were successfully recruited and randomized between 9/13/2011 and 1/26/2012. Three patients in the no Biopatch and two patients in the Biopatch group were unable to be cultured secondary to premature tegaderm or catheter dislodgement. Baseline patient characteristics were generally similar between groups as documented in Table 1. Importantly, catheter duration was similar between the two groups.
We observed a slightly higher risk of catheter colonization in the Biopatch patients, 3 of 48 (6.3%) versus 2 of 47 (4.3%) control patients (risk ratio = 1.5). However, due to the small number of events the estimation of the risk ratio (RR) is very imprecise (95% CI: 0.3 to 8.4). Thus, the data are compatible with no association (RR = 1.0), a harmful effect of Biopatch (RR > 1.0) and a beneficial effect (RR < 1.0). The results for the secondary outcomes (Table 2) are similarly imprecise.
Skin culture without the Biopatch grew coag negative staph (Staphylococcus epidermidis) in 39% of positive cultures and Gram positive rods/bacillus (actinomyces, propionibacterium, corynebacterium) in 61% of positive cultures. Skin culture with the Biopatch grew coag negative staph (Staphylococcus epidermidis) in 50% of positive cultures and Gram positive rods/bacillus (actinomyces, propionibacterium, corynebacterium) in 42% of positive cultures. Our catheter colonization rate was low (5.3% of all catheters cultured) and culture results revealed predominately coag negative staph (Staphylococcus epidermidis) present in 80% of colonized catheters.
This randomized trial was unable to demonstrate significant reductions in femoral nerve catheter or exit site bacterial colonization with Biopatch application when the catheter is tunneled and used for only 48 hours.
Some of the results and limitations of this study warrant further discussion. Our baseline rate of catheter and exit site colonization appears to be much less than what has been reported thus far in the literature. The baseline rate of bacterial colonization was taken from another study (Cuvillon et. al. 2001) that was 12 years old and utilized different methods of skin preparation. In addition, many of the studies evaluating bacterial colonization of peripheral nerve catheters fail to mention the conditions under which nerve catheters are removed. Cuvillon el al for example, state only that “catheters were carefully removed.” Without adequate skin cleansing prior to catheter removal, significant bacteria from the skin entry site could conceivably contaminate the tip upon removal.6 As the current literature presents a range of reported peripheral nerve catheter colonization rates, it may have been more appropriate to calculate the sample size over a range of parameter values to investigate sensitivity. The most appropriate sample size calculation, given our different catheter insertion and removal conditions, would have utilized recent historical data from our own institution. A pilot study evaluating our current practice of catheter insertion presumably would have demonstrated a much lower rate of baseline bacterial colonization and would therefore have lead us to recruit a larger number of patients to this study.
Multiple factors could have led to our low rate of bacterial colonization. For one, we utilized chlorhexidine gluconate for skin preparation and cleansing instead of povidone iodine, which has been shown in multiple studies to provide superior bactericidal results compared to povidone iodine. 15 Our low rate of bacterial colonization may also be secondary to subcutaneous tunneling which in a previous study was able to reduce the incidence of femoral nerve catheter colonization to 11.7%.10 Patients in this study had preoperative and postoperative antibiotic therapy that was continued for at least two postsurgical doses and this certainly may have played a role in decreasing our rate of contamination.9 This study only examined catheters left in place for two days in a hospital setting and therefore our results may not be able to be applied to catheters of longer duration or those managed in an outpatient setting. Our study also only examines one site of peripheral nerve catheter insertion. It is possible that other sites may benefit to a greater extent from perioperative Biopatch placement. While the microbiology lab was blinded to patient group, those who inserted and removed the femoral nerve catheter were not blinded which could have introduced a source of bias.
Chlorhexidine gluconate has been extensively studied in the medical literature for a variety of indications. Chlorhexidine gluconate functions by altering cell wall permeability, precipitating components of the cell membrane and cytoplasm and rapidly killing gram +/− bacteria in addition to yeasts. Chlorhexidine has the ability to adhere to the skin’s stratum corneum, thereby extending duration, and consistently outperforms povidone iodine when used as a skin antiseptic. Reports of antibacterial resistance to chlorhexidine are rare as are serious reports of adverse reactions to chlorhexidine.15
The Biopatch protective disc is an absorptive foam impregnated with chlorhexidine. The patch provides sustained presence of antibactericidal chlorhexidine at the site of catheter skin penetration. The Biopatch has been approved to reduce device colonization and catheter related blood stream infections for a variety of medical devices including IV catheters, central venous lines, arterial catheters, dialysis catheters, peripherally inserted coronary catheters, mid-line catheter drains, chest tubes, externally placed orthopedic pins and epidural catheters.16 The Biopatch has a proven record in the medial literature for decreasing device contamination. Specific to the field of regional anesthesia, use of the Biopatch has been demonstrated to significantly reduce epidural catheter colonization rates from 29 to 3.8% and epidural catheter exit site contamination from 40.1 to 3.4%.12,13 Cost-benefit analyses have been performed and consistently demonstrate that when used to prevent catheter related blood stream infections from central lines, the use of chlorhexidine dressing is highly cost effective.17,18
There has been concern in the regional anesthesia literature regarding bacterial contamination with the use of continuous peripheral nerve blocks. Concern has been heightened by the recent increase in the number of peripheral nerve catheters inserted. Select catheters are even sent home with patients and health care providers therefore lose the ability to closely monitor the patient for physical signs of infection of inflammation. A study of 628 femoral nerve catheters demonstrated a 0.6% incidence of local inflammation and a 0.5% incidence of local pustule formation.19 A study that evaluated 574 femoral nerve catheters demonstrated a 4% incidence of local inflammation, a 3.3% incidence of infection and a 1.4% incidence of infection requiring surgical drainage.20 In contrast, a study that included 206 outpatient femoral nerve catheters did not report any problems with infection related to nerve catheter placement.21
Cuvillon et al have reported the highest published incidence (57%) of femoral nerve catheter bacterial colonization. The etiology of their increased incidence is unclear but may have been related to the use of iodine for skin preparation.6 Capdevila et al reported one abscess and a 28.6% incidence of femoral nerve catheter colonization out of 683 total femoral nerve catheters. Iodine was again used for skin preparation and the infusion was continued for a longer duration than the previous study so the etiology for the decrease in colonization is unclear.7 Aveline et al reported a bacterial colonization incidence of 9% in femoral nerve catheters placed under ultrasound guidance with either chlorhexidine or iodine skin decontamination.8 Compere et al found that the incidence of colonization could be reduced to 11.7% with catheter tunneling and chlorhexidine skin preparation.10
The pathogenesis of catheter colonization and eventual infection has been well documented. Most catheter related infections of short-term devices are thought to originate from cutaneous sources. Bacteria are thought to migrate extraluminally from the insertion site along the length of the catheter.22 A study of epidural catheter bacterial contamination was able to demonstrate that infection/contamination of the skin surrounding the epidural catheter exit site was associated with an increased risk of catheter colonization. The authors suggested that their results demonstrated the role of bacterial migration along the catheter and the need for strict asepsis of the catheter entry site.23 Bacterial colonization of the catheter has been previously validated as a reasonable surrogate end-point for catheter related bloodstream infections.11
The bacteria isolated in nearly all studies of percutaneous device bacterial colonization represent some form of normal skin flora turned pathogenic following violation of the skin’s protective barrier. Staphylococcus epidermidis represents the most commonly identified pathogen in nearly all studies. Gram-negative bacillus (klebsiella, E. coli, Enterobacter, Citrobacter, serratia, pseudomonas), staphylococcus aureus and gram-positive bacilli are also commonly found when perineural catheters are cultured.6–10 This again demonstrates the importance of strict asepsis when performing placement of peripheral nerve catheters. Handwashing, use of protective barriers (mask, gloves, gowns and drapes) and appropriate selection of skin disinfectants are all clearly highly important with regard to prevention of catheter colonization and infection.
In summary, the baseline rate of bacterial colonization of femoral nerve catheters placed in the setting of short-term use, chlorhexidine skin decontamination, ultrasound guidance, subcutaneous tunneling and perioperative antibiotic therapy is quite low. This prospective randomized trial was unable to demonstrate any benefit to use of the Biopatch in this patient population. Larger trials are likely required to detect a difference in catheter colonization rates and it will then need to be determined if the routine use of the Biopatch is economically responsible to prevent nerve catheter colonization in this patient population.
The authors would like to acknowledge the contributions of our regional anesthesia colleagues (Dr. Michael Ford MD, Dr. Thomas Broderick MD, Dr. Jocelyn Blake MD, Dr. Constance Gilloon MD) for their assistance in carrying out this project. We would also like to acknowledge our surgical colleagues (Dr. John Heiner MD, Dr. Matthew Squire MD, Dr. Richard Illgen) and our statistician Dr. Christopher Warren PhD (Illumavista Biosciences LLC) for their assistance and patience. We would also like to acknowledge the assistance of the University of Wisconsin Office of Clinical Trials; member of the UW Institute for Clinical and Translational Research. Supported by grant 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, National Institutes of Health.
All work was supported by intradepartmental funding.
This work has been submitted in abstract form for the 2012 ASA annual meeting.
Attestations to Authorship:
I, Kristopher Schroeder, attest that I was substantially involved in the attached study. I was involved in conception of project, drafting of manuscript and final approval of the version to be published.
I Robert A Jacobs attest that I contributed to this project through acquisition of data, revision and approval of the final manuscript to be submitted.
I, Melanie Donnelly, attest that I was substantially involved in the attached study. I was involved in conception of project, drafting of manuscript and final approval of the version to be published.
I, Kyle Gassner, contributed significantly to the biopatch study. My specific contributions include study conception and design, article revision, and final approval of the version to be published.
I, Christopher Guite, attest that I was substantially involved in the attached study. I was personally involved in the acquisition of the data presented, revising it critically for important intellectual content and in final approval of the version submitted for publication.
I, Brooke M. Anderson, attest that I was substantially involved in the attached study. I was involved in conception of project, acquisition of the data, drafting of the manuscript, and final approval of the version to be published.
The baseline rate of bacterial colonization of femoral nerve catheters placed in the setting of short-term use, chlorhexidine skin decontamination, ultrasound guidance, subcutaneous tunneling and perioperative antibiotic therapy is quite low. This randomized trial was unable to demonstrate any benefit to use of the Biopatch in this patient population