Abstract
Background
Cardiac implantable electronic device (CIED) infection is a costly and highly morbid complication. Perioperative interventions, including the use of antibiotic pouches and intensified perioperative antibiotic regimens, have demonstrated marginal efficacy at reducing CIED infection. Additional research is needed to identify additional interventions to reduce infection risk.
Objective
We sought to evaluate whether adherent skin barrier drape use is associated with a reduction in CIED infection.
Methods
A prospective registry of all CIED implantation procedures was established at our institution in January 2007. The registry was established in collaboration with our hospital infection prevention team with a specific focus on prospectively identifying all potential CIED infections. All potential CIED infections were independently adjudicated by 2 physicians blinded to the use of an adherent skin barrier drape.
Results
Over a 13-year period, 14,225 procedures were completed (mean age 72 ± 14 years; female 4,918 (35%); new implants 10,005 (70%); pulse generator changes 2585 (18%); upgrades 1635 (11%). Of those, 2469 procedures (17.4%) were performed using an adherent skin barrier drape. There were 103 adjudicated device infections (0.73%). The infection rate in patients in the barrier use groups was 8 of 2469 (0.32%) as compared with 95 of 11,756 (0.8%) in the nonuse group (P = .0084). In multivariable analysis, the use of an adherent skin barrier drape was independently associated with a reduction in infection (odds ratio 0.32; 95% confidence interval 0.154–0.665; P = .002).
Conclusion
The use of an adherent skin barrier drape at the time of cardiac device surgery is associated with a lower risk of subsequent infection.
Keywords: Infection, Antibiotics, Pacemaker, Implantable cardioverter-defibrillator, Cardiac implantable electronic device, Pulse generator change, Device upgrade, Complication
Key Findings.
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In this prospective observation study of 14,225 procedures, the use of an adherent skin barrier in cardiac implantable electronic device (CIED) implant procedures significantly reduce the risk of hospitalization for device infection by 68% as compared with not using an adherent skin barrier.
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The use of an adherent skin barrier reduces CIED-related infection, specifically device pocket infection rates and CIED-related infections in de novo procedures.
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The use of an adherent skin barrier showed no discernible effect on the incidence of systemic infections and secondary seeding of CIED devices.
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Our study results suggest that the use of an adherent skin barrier during the index procedure may reduce the risk of cardiac device infection.
Introduction
Infection of a cardiac implantable electronic device (CIED) is a common postoperative complication of device implantation, affecting up to 2% of cases.1,2 Device infection is costly and typically requires complete system removal, resulting in prolonged hospitalization and conferring mortality rates of 18%–24%.3,4 Moreover, device infection markedly reduces quality of life and interrupts CIED therapy.4,5 Strategies to define predictors of device infection have identified a number of risk factors.3,6,7 Among these, the most common risk factors include complex device implant (ie, implantable cardioverter-defibrillator [ICD] and cardiac resynchronization therapy [CRT] with defibrillator as compared with simple pacemakers), revision procedures, prolonged procedure times (>1 hour), pocket hematoma, and patient comorbidities (eg, advanced age, diabetes mellitus, and renal failure).2,5,8, 9, 10, 11, 12, 13, 14 Also more recently, researchers have started to define factors associated with subtypes of CIED infection, specifically systemic infection and pocket infection.8,10 To prevent CIED infection, a number of routine perioperative interventions have been widely adopted, including prophylactic antibiotics, hair removal, and antiseptic skin washes around the incisional site.15 In higher-risk patients, use of absorbable antibiotic envelopes is recommended to reduce bacterial biofilm formation; in such patients, there is an absolute risk reduction of 0.5% as seen in the Worldwide Randomized Antibiotic Envelope Infection Prevention Trial (WRAP-IT).3 Despite these measures, rates of CIED infection remain unacceptably high and regimens to prevent or treat CIED are highly desirable.
Among the strategies proposed to reduce the risk of CIED infection, the use of an adherent skin barrier drape over the wound during surgery has emerged as a promising option. Although a recent Cochrane review of barrier drapes in other types of operations (including cardiac surgery) failed to demonstrate a meaningful difference in the risk of infection,16, 17, 18 CIED surgery is inherently different as a foreign material is retained within a poorly perfused site (ie, a pocket fashioned within adipose tissue above the pectoralis muscle). In support of this strategy, a recent study showed that the use of an adherent skin barrier drape reduced the risk of contamination during primary knee arthroplasty.19 Given that there have been no studies evaluating the use of an adherent skin barrier drape in patients undergoing CIED implantation, we examined the potential effect of adherent skin barrier drape use on the risk of infection after CIED implantation by using a prospective single-center registry that was established in 2007 to monitor postoperative CIED infections.
Methods
Patients and registry details
A prospective registry of all CIED implantation procedures was established at our institution in January 2007. The registry was established in collaboration with the Division of Infectious Diseases to prospectively identify all CIED infections. The project was reviewed by our institutional ethics committee, which indicated that the project falls within the context of quality initiative and quality improvement, and hence as per the Tri-Council Policy Statement 2, Article 2.5, full review by the ethics committee was not required. The registry was developed within the institution to evaluate and improve the quality of patient care and to collect data on our outcomes. As such, anonymized data were used and patient consent was not required as determined by Health Insurance Portability and Accountability Act of 1996 (HIPPA) Privacy Rules.
Routine perioperative infection prevention measures
Surgical site preparation including hair removal, a 2% chlorhexidine skin wash followed in 2 minutes by a 4% alcohol skin wash, antibiotic use, and periprocedural care was consistent in all procedures as per institutional protocol. During the study period, the institutional protocol mandated that all patients undergoing CIED implantation receive cefazolin within 1 hour before the procedure. In cases of penicillin allergy, vancomycin was used. All patients routinely had the device pocket washed with bacitracin before closure of the incision. The only exception to this standardized regime was during the period our center participated in the Prevention of Arrhythmia Device Infection Trial (PADIT) between 2012 and 2015. PADIT was a cluster randomized 4-period crossover study comparing incremental (preprocedural cefazolin plus vancomycin, intraprocedural bacitracin pocket wash, and 2-day postprocedural oral cephalexin) with conventional (preprocedural cefazolin) perioperative CIED management.20 Our site underwent 4 sequences of protocol change every 6 months as follows: incremental, conventional, incremental, and conventional.20,21 After the publication of the PADIT risk score, we incorporated this in our institutional protocol and specifically used incremental antibiotics for all patients with PADIT risk score > 4.2
In addition, our center contributed to WRAP-IT (2012–2016) that investigated the effectiveness of using an antibiotic-impregnated pouch (Tyrx, Medtronic, MN) during high-risk device surgery as compared with standard of care. However, cost constraints have greatly limited our use of the antibiotic pouch during the initial procedure and subsequently we have used a total of 37 Tyrx pouches during the reported period.22
Adherent skin barrier
Barrier use was at the discretion of individual physicians; these were either Tegaderm 3M or Ioban (3M, St. Paul, MN). Tegaderm is a sterile transparent adhesive skin dressing that offers waterproof properties, whereas Ioban, in addition to being waterproof, features an antimicrobial coating enriched with iodine.
Outcome
The primary outcome of the study was admission to hospital for proven CIED- or pocket-related infection within 1 year of the procedure.1,23 Device infection was defined as pocket infection, bloodstream infection, and endocarditis. The definitions were exactly as used in PADIT.21 The adjudication process was also exactly as in PADIT. Specifically blinded adjudication of all possible end points was performed by 2 investigators (N.M.B. and R.O.) blinded to the treatment received, with all discrepancies resolved by an additional investigator (M.G.).
Variable definitions
Variables used and defined as in PADIT21
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1.
Renalinsufficiency was defined as estimated glomerular filtration rate < 30 mL/min
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2.Procedure type definitions
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a.Pacemaker: New pacemaker or pacemaker generator change
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b.ICD: New ICD or ICD generator change
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c.CRT: New CRT with pacemaker or defibrillator or CRT generator change
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d.Revision/upgrade: Pocket and/or lead revision and/or system upgrade (ie, addition of new lead(s))
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a.
It should be noted that the 4 groups within procedure type are mutually exclusive. For example, if a patient is undergoing upgrade to CRT device, then they are counted as “revision/upgrade.”
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3.
Number of previous procedures
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4.
PADIT score: CIED infection risk is determined by incorporating several factors, including prior procedures (P), age (A), depressed renal function (D), immunocompromised status (I), and procedure type (T). This yields a score that spans from 0 to 15 points. The score stratifies patients into 3 risk categories: low risk (0–4 points), intermediate risk (5–6 points), and high risk (≥7 points). These risk categories correspond to distinct rates of hospitalization for infection, namely, 0.51% for low-risk patients, 1.42% for intermediate-risk patients, and 3.41% for high-risk patients.2
Statistical analysis
Continuous variables and categorical variables were summarized as mean ± SD and frequency (percentage), respectively. Baseline characteristics were compared between patients with and without hospitalization for device infection by using the 2-sample t test for continuous variables and the χ2 test or Fisher exact test for categorical variables, as appropriate. A multivariable model was fit by including all variables identified in univariable analysis with P < .25 for inclusion by using a backward elimination approach. All statistical analyses were performed with SAS version 9.4 (SAS Institute, Inc., Cary, NC).
Results
Population and primary end points
A total of 14,225 procedures were included in the registry between 2007 and 2020. Of those 2469 procedures (17.4%) were performed using an adherent skin barrier drape (Tegaderm 3M or Ioban). All patients had a minimum of 1-year follow-up. Because of the hospital’s unique geographical position and it being the only device clinic and CIED extraction site in our catchment area of Ontario, previous research has shown that >99% of implanted patients would have their follow-up completed at our center.21 There were 103 of 14,225 (0.73%) adjudicated primary end points (hospitalization for device infection). The infection rate in patients in the barrier use groups was 8 of 2469 (0.32%) compared with 95 of 11,756 (0.8%) in the nonuse group (P = .0084).
Analysis of the full cohort
The baseline characteristics of patients with or without CIED infection are compared in Table 1. Among these patients, those who had CIED infection were younger (66.0 ± 14.9 years vs 72.2 ± 13.8 years; P < .0001), more likely to have undergone previous CIED operations (P < .0001), and less likely to have used a skin barrier drape over the wound during surgery (8% vs 18%; P = .01). In multivariable analysis, patients who underwent >2 prior procedures demonstrated a 2-fold increased risk in requiring hospitalization for CIED infection (95% confidence interval [CI] 1.14–3.56; P = .016) (Table 2). The type of CIED implantation was associated with an increased risk of infection, as ICD and/or CRT implants demonstrated an odds ratio (OR) of 1.93 (95% CI 1.15–3.24; P = .013) and 3.16 (95% CI 1.78–5.63; P < .001) for infection, respectively. When restricting the analysis to patients with only a pocket infection and no evidence for systemic infection, the predictors for infection remained unchanged (ie, younger age, absence of adherent skin barrier drape use, and a history of ≥3 procedures).
Table 1.
Baseline characteristics of patients with and without hospitalization for device infection
| Characteristic | No infection (n = 14,122) | CIED infection (n = 103) | P† |
|---|---|---|---|
| Sex | 9231 (65.4) | 76 (73.8) | .073 |
| Age (y) | 72.2 ± 13.8 | 66.0 ± 14.9 | <.0001 |
| Adherent skin barrier drape use | 2461 (17.4) | 8 (7.8) | .010 |
| Procedure number for the implant site | <.0001 | ||
| First | 9942 (70) | 63 (61) | |
| Second | 2939 (21) | 18 (18) | |
| Third | 847 (6) | 10 (10) | |
| More than 3 | 394 (3) | 12 (12) | |
| Procedure type | <.0001 | ||
| Pacemaker (new implant or PGC) | 7784 (55) | 32 (31) | |
| ICD (new implant or ICD PGC) | 3259 (23) | 33 (32) | |
| CRT (new CRT-P, new CRT-D, or CRT PGC) | 1462 (10) | 20 (19) | |
| Pocket revision and/or insertion of new lead(s) | 1617 (12) | 18 (18) | |
| Procedure complexity | .080 | ||
| Initial procedure | 9942 (70) | 63 (61) | |
| PGC only | 2563 (18) | 22 (21) | |
| Other | 1617 (12) | 18 (18) | |
| Creatinine (μmol/L) | 105 ± 71 | 113 ± 105 | .879 |
| MDRD CrCl | 68.2 ± 30.3 | 70.1 ± 26.6 | .248 |
| PADIT definition of renal dysfunction 1 = <30 | 888 (6.5) | 7 (6.9) | .892 |
Values are presented as mean ± SD or n (%).
CIED = cardiac implantable device; CRT = cardiac resynchronization therapy; CRT-D = cardiac resynchronization therapy with defibrillator; CRT-P = cardiac resynchronization therapy with pacemaker; ICD = implantable cardioverter-defibrillator; MDRD = glomerular filtration rate = 175 × (serum creatinine)−1.154× (age)−0.203 × 1.212 (if patient is black∗) × 0.742 (if female): creatinine in mg/dL for this formula; PADIT definition = prior procedures ≥2 4 points, age (<60 → 2 points, 60–69 → 1 point), depressed renal function (glomerular filtration rate <30 mL/min → 1 point), immunocompromised status 3 points, and procedure type (implantable cardioverter-defibrillator → 2 point, CRT → 4 point, revision/upgrade → 5 point); PGC = pulse generator change.
Revision or upgrade: Pocket and/or lead revision and/or system upgrade, that is, adding new lead(s).
P value is from the χ2 test or Fisher exact test for categorical variables and the 2-sample t test for continuous variables.
Table 2.
Multivariable model using all variables identified in univariable analysis with P < .25 for inclusion by using a backward elimination approach
| Cohort and primary end point | No infection | CIED infection | Variable | OR (95% CI) | P |
|---|---|---|---|---|---|
| Hospitalization for any device infection | 14,112 | 103 | Age | 0.98 (0.97–0.99) | .0016 |
| Adherent skin barrier use | 0.32 (0.15–0.67) | .0022 | |||
| ≥3 Procedures vs initial | 2.01 (1.14–3.56) | .0158 | |||
| ICD/ICD PGC vs PPM/PPM PGC | 1.93 (1.15–3.24) | .0131 | |||
| CRT-P/CRT-D/CRT PGC vs PPM/PPM PGC | 3.16 (1.78–5.63) | <.001 | |||
| Pocket revision and/or insertion of new lead(s) vs PPM/PPM PGC | 2.24 (1.1–4.55) | .0264 | |||
| Hospitalization for a device infection in patients with ≥1 previous device operations (non–de novo procedure) | 4220 | 40 | Age | 0.98 (0.96–1.00) | .0467 |
| Procedure no. ≥3 vs 2 | 2.76 (1.47–5.18) | .0016 | |||
| Hospitalization for a device infection after the initial CIED implantation (de novo implant) | 10,005 | 63 | Adherent skin barrier use | 0.34 (0.15–0.80) | .0139 |
| ICD/ICD PGC vs PPM/PPM PGC | 3.65 (2.05–6.49) | <.0001 | |||
| CRT-P/CRT-D/CRT PGC vs PPM/PPM PGC | 5.81 (2.94–11.49) | <.0001 | |||
| Hospitalization for pocket infection without evidence of systemic infection | 14,154 | 71 | Age | 0.98 (0.96–0.99) | .0025 |
| Adherent skin barrier yes vs no | 0.35 (0.14–0.87) | .0239 | |||
| Procedure no. ≥3 vs 1 | 3.54 (2.01–6.24) | <.0001 | |||
| Hospitalization for systemic infection and/or pocket infection | 14,193 | 32 | Age | 0.96 (0.95–0.99) | .0012 |
| Neutrophil count | 0.80 (0.64–0.99) | .0475 |
Variables with effect size change by >10% are shown in boldface.
CI = confidence interval; CIED = cardiac implantable device; CRT = cardiac resynchronization therapy; CRT-D = cardiac resynchronization therapy with defibrillator; CRT-P = cardiac resynchronization therapy with pacemaker; ICD = implantable cardioverter-defibrillator; OR = odds ratio; PGC = pulse generator change; PPM = permanent pacemaker.
The overall infection rate over the 13 years was 0.73% with range from 0.58% to 1.01% in each 2-year time interval (Figure 1). The mean PADIT score was 2.4 ± 2.4. We found no significant difference in mean PADIT scores or the proportion of infections with time (Figure 1). In addition, there was no difference in time to presentation with pocket infection between patients with barrier use and those without barrier use.
Figure 1.
Annualized cardiac implantable electronic device (CIED) infections and mean Prevention of Arrhythmia Device Infection Trial (PADIT) score for all implanted CIEDs per 2-year time interval. Two-sided t test comparing mean PADIT score or infection rate with 2-year interval data.
Analysis of the full cohort stratified by barrier use
The baseline characteristics of patients with and without adherent skin barrier use are compared in Online Supplemental Table 1. In the cohort with adherent skin barrier use, patients were younger (70.5 ± 13.8 vs 72.5 ± 13.8; P < .0001) and had higher average PADIT scores (3.0 ± 2.4 vs 2.3 ± 2.4; P < .0001). Moreover, procedural categories had greater complexity in the adherent skin barrier group, featuring a higher incidence of ICD, CRT, or pocket revisions (59.9% vs 42.1%; P < .0001). However, there was a lower number of pulse generator change or upgrades in the group with adherent skin barrier use (27% vs 30.3%; P < .0001). It is important to note that all these variables were factored into the multivariable model when evaluating the potential effect of adherent skin barrier use on the incidence of CIED infection.
Patients undergoing non–de novo procedures (pulse generator change)
As shown in Table 3, patients who had CIED infection were more likely to be younger (66.6 ± 15.1 years old vs 71.8 ± 14.3 years old; P = .02), were undergoing their third or more procedure (P < .0005), and had an elevated PADIT score (5.6 ± 2.0 vs 4.5 ± 2.3; P = .005). The use of an adherent skin barrier was associated with a trend to decreased infections (5% vs 15.9%; P = .06). In multivariable analysis, patients who underwent ≥3 procedures had a significantly increased risk of CIED infection (OR 2.76; 95% CI 1.47–5.18; P = .0016).
Table 3.
Characteristics of patients undergoing non–de novo procedures
| Characteristic | No infection (n = 4180) | CIED infection (n = 40) | P |
|---|---|---|---|
| Male sex | 2824 (67.6%) | 27 (67.5%) | .9936 |
| Age (y) | 71.8 ± 14.3 | 66.6 ± 15.1 | .0231 |
| Adherent skin barrier drape use | 664 (15.9) | 2 (5.0) | .0602 |
| Procedure number for the implant site | .0005 | ||
| Second | 2939 (70.3) | 18 (45.0) | |
| Third or more | 1241 (29.7) | 22 (55.0) | |
| PADIT score | 4.5 ± 2.3 | 5.6 ± 2.0 | .0045 |
| Procedure type | .7879 | ||
| Pacemaker PGC | 1418 (34) | 12 (30) | |
| ICD PGC | 688 (17) | 5 (13) | |
| CRT PGC | 457 (11) | 5 (13) | |
| Pocket revision and/or insertion of new lead(s) | 1617 (39) | 18 (45) | |
| Procedure complexity | .4145 | ||
| PGC only | 2563 (61) | 22 (55) | |
| Other | 1617 (39) | 18 (45) | |
| Creatinine (μmol/L) | 103.6 ± 58.4 | 121.2 ± 141.7 | .2986 |
| MDRD CrCl | 67.7 ± 27.8 | 71.5 ± 28.1 | .2010 |
| PADIT definition of renal dysfunction 1 = <30 | 235 (5.7) | 3 (7.5) | .4989 |
| WBC (U) | 7.4 ± 5.1 | 7.2 ± 2.3 | .7736 |
Values are presented as mean ± SD or n (%).
CIED = cardiac implantable device; CRT = cardiac resynchronization therapy; ICD = implantable cardioverter-defibrillator; MDRD = glomerular filtration rate = 175 × (serum creatinine)−1.154× (age)−0.203 × 1.212 (if patient is black∗) × 0.742 (if female): creatinine in mg/dL for this formula; PADIT score = prior procedures ≥2 4 points, age (<60 → 2 points, 60–69 → 1 point), depressed renal function (glomerular filtration rate <30 mL/min → 1 point), immunocompromised status 3 points, and procedure type (implantable cardioverter-defibrillator → 2 point, CRT → 4 point, revision/upgrade → 5 point); PGC = pulse generator change; WBC = white blood cells.
Patients undergoing de novo procedures (first CIED implantation)
Table 4 provides a comparison of infected CIED cases in patients who underwent the index procedure as their first operation. Patients in the infected group were younger (65.6 ± 14.9 years old vs 72.4 ± 13.6 years old; P < .0001) and more likely to have undergone implantation of an ICD or CRT device (P < .0001). Patients with device infection were also more likely to be male (77.8 vs 64.4%; P = .03) and had an elevated PADIT score (2.8 ± 2.0 vs 1.5 ± 1.8). Finally, there was a nonsignificant trend for fewer CIED infections in patients who used an adherent skin barrier drape (9.5% vs 18.1%; P = .08).
Table 4.
Characteristics of patients undergoing de novo CIED implantation
| Characteristic | No infection (n = 9942) | CIED infection (n = 63) | P |
|---|---|---|---|
| Males | 6407 (64.4) | 49 (77.8) | .0274 |
| Age (y) | 72.4 ± 13.6 | 65.6 ± 14.9 | <.0001 |
| Surgeon = 1 | 1814 (18.3) | 5 (7.9) | .0344 |
| Adherent skin barrier drape use | 1797 (18.1) | 6 (9.5) | .0784 |
| PADIT score | 1.5 ± 1.8 | 2.8 ± 2.0 | <.0001 |
| Procedure type | <.0001 | ||
| Pacemaker (new implant or PGC) | 6366 (64) | 20 (32) | |
| ICD (new implant or ICD PGC) | 2571 (26) | 28 (45) | |
| CRT (new CRT-P, new CRT-D, or CRT PGC) | 1005 (10) | 15 (24) | |
| Creatinine (μmol/L) | 105.5 ± 75.7 | 107.8 ± 72.0 | .5522 |
| MDRD CrCl | 68.4 ± 31.3 | 69.2 ± 25.7 | .6207 |
| PADIT definition of renal dysfunction 1 = <30 | 653 (6.9) | 4 (6.5) | .99 |
| WBC (U) | 7.7 ± 3.4 | 7.5 ± 2.2 | .4542 |
| Neutrophil (U) | 5.1 ± 2.2 | 5.0 ± 2.0 | .8756 |
| Lymphocyte (U) | 1.8 ± 2.3 | 1.6 ± 0.5 | .3417 |
| Platelet (U) | 223.9 ± 85.6 | 220.0 ± 78.2 | .9292 |
| HbA1c (%) | 6.2 ± 1.2 | 6.3 ± 1.4 | .9496 |
Patients with pocket infection
Table 5 shows that patients in the infected group were younger (67.0 ± 15.0 years old vs 72.2 ± 13.8 years old; P = .0015) and had higher PADIT scores (3.97 ± 2.43 vs 2.45 ± 2.38; P < .0001). There was a lower rate of infection in the adherent skin barrier drape group (7.0% vs 17.4%; P = .02). Infected pockets were more likely to have >3 operations (25% vs 9%; P < .0001). In multivariable analysis (Table 2), the use of an adherent skin barrier drape was significantly associated with lower rates of pocket infection (OR 0.35; 95% CI 0.14–0.87; P = .0239).
Table 5.
Characteristics of patients with pocket infection only compared to the noninfected cohort
| Characteristic | No infection (n = 14,122) | Pocket infection alone (n = 71) | P |
|---|---|---|---|
| Male sex | 9231 (65.4) | 50 (70.4) | .3717 |
| Age (y) | 72.2 ± 13.8 | 67.0 ± 15.0 | .0015 |
| Adherent skin barrier drape use | 2461 (17.4) | 5 (7.0) | .0212 |
| Procedure number for the implant site | <.0001 | ||
| First | |||
| Second | 9942 (70) | 38 (54) | |
| Third | 2939 (21) | 15 (21) | |
| More than 3 | 1241 (9) | 18 (25) | |
| PADIT score | 2.5 ± 2.4 | 4.0 ± 2.4 | <.0001 |
| Procedure type | .0019 | ||
| Pacemaker (new implant or PGC) | 7784 (55) | 24 (34) | |
| ICD (new implant or ICD PGC) | 3259 (23) | 21 (30) | |
| CRT (new CRT-P, new CRT-D, or CRT PGC) | 1462 (10) | 14 (20) | |
| Pocket revision and/or insertion of new lead(s) | 1617 (12) | 12 (17) | |
| Procedure complexity | .0076 | ||
| Initial procedure | 9942 (70.45) | 38 (53.5) | |
| PGC only | 2563 (18.2) | 21 (29.6) | |
| Other | 1617 (11.5) | 12 (16.9) | |
| Creatinine (μmol/L) | 104.9 ± 70.9 | 117.4 ± 120.4 | .7292 |
| MDRD CrCl | 68.2 ± 30.3 | 69.4 ± 26.1 | .2954 |
| PADIT definition of renal dysfunction 1 = <30 | 888 (6.5) | 6 (8.6) | .4627 |
| WBC (U) | 7.63 ± 4.01 | 7.72 ± 2.36 | .5749 |
Patients with endocarditis and/or systemic infection
Table 6 shows that patients with endocarditis and/or systemic infection were younger (63.8 ± 14.9 years old vs 72.2 ± 13.8 years old; P = .0006), had higher PADIT scores (3.8 ± 2.4 vs 2.5 ± 2.4; P = .0019), and had more often undergone CRT or another more complex procedure (P = .0032) (Table 6). The use of an adherent skin barrier drape was not associated with a reduction in CIED infection (9.4% vs 17.4%; P = .23). In multivariable analysis (Table 2), only younger age and lower neutrophil count were found to be associated with CIED infection.
Table 6.
Characteristics of patients with systemic infection (bloodstream and/or endocarditis) compared with those without infection
| Characteristic | No infection (n = 14,122) | CIED infection secondary to systemic infection with or without endocarditis (n = 32) | P |
|---|---|---|---|
| Male sex | 9231 (65.4) | 26 (81.3) | .0592 |
| Age (y) | 72.2 ± 13.8 | 63.8 ± 14.9 | .0006 |
| Adherent skin barrier drape use | 2461 (17.4) | 3 (9.4) | .2302 |
| Procedure number for the implant site | .2491 | ||
| First | 9942 (70) | 25 (78) | |
| Second | 2939 (21) | 3 (9) | |
| More than 3 | 1241 (9) | 4 (13) | |
| PADIT score | 2.5 ± 2.4 | 3.8 ± 2.4 | .0019 |
| Procedure type | .0032 | ||
| Pacemaker (new implant or PGC) | 7784 (55) | 8 (25) | |
| ICD (new implant or ICD PGC) | 3259 (23) | 12 (38) | |
| CRT (new CRT-P, new CRT-D, or CRT PGC) | 1462 (10) | 6 (19) | |
| Pocket revision and/or insertion of new lead(s) | 1617 (12) | 6 (19) | |
| Procedure complexity | .0569 | ||
| Initial procedure | 9942 (70) | 25 (78) | |
| PGC only | 2563 (18) | 1 (3) | |
| Other | 1617 (12) | 6 (19) | |
| Creatinine (μmol/L) | 104.9 ± 70.9 | 103.6 ± 56.5 | .8098 |
| MDRD CrCl | 68.2 ± 30.3 | 71.5 ± 28.0 | .6043 |
| PADIT definition of renal dysfunction 1 = <30 | 888 (6.5) | 1 (3.1) | .7207 |
| Baseline WBC (U) | 7.63 ± 4.01 | 6.53 ± 1.71 | .0122 |
Discussion
The use of an adherent skin barrier drape was associated with a significant 68% decrease in hospitalization for device infection. This association was specifically in 2 subsets of patients (Figure 2):
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1.
Patients with device pocket infections. Not unsurprisingly, the benefit did not extend to secondary seeding from endocarditis or bloodstream infections.
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2.
Patients undergoing de novo procedures.
Figure 2.
Forest plot demonstrating the value of an adherent skin barrier drape at reducing the risk of cardiac implantable electronic device infection. CI = confidence interval.
Consistent with previous studies, the risk factors that consistently predicted an increased risk of device infection included younger age, patients undergoing multiple device operations (>3 procedures), and those undergoing more complex procedures (CIED upgrade and ICD or CRT device implant procedures).2,8,9,11, 12, 13, 14,22,23
The guidelines recommend preoperative CIED infection prevention strategies including hair removal, prophylactic antibiotics, and antiseptic skin cleaning.15 In WRAP-IT, 6983 patients at high risk of CIED infection—undergoing procedures such as CIED generator replacement, system upgrades, pocket or lead revision, or CRT with defibrillator—were randomized to receive an antibacterial envelope in addition to standard of care. The study aimed to assess whether the risk of device infection could be reduced by adding an antibacterial envelope emitting rifampin and minocycline to the standard of care.24 After 3-year follow-up, the major CIED infection rate was 1.3% in the antibiotic envelope arm compared with 1.9% in the standard of care arm (hazard ratio 0.63; 95% CI 0.4–0.98).24 Notably, the number needed to treat to prevent 1 infection was 200 patients. This therapeutic approach has received endorsement in the European Heart Rhythm Association guidelines specifically for high-risk patients.1 High-risk patients are considered those with end-stage renal disease, those with a history of CIED-related infection, those who were immunosuppressed, those who underwent redo procedures, those with diabetes, or those with skin disorders.1 Despite these recommendations, the use of an antibiotic envelope is limited in many centers because of high cost. We found that the use of an adherent skin barrier drape in addition to these established techniques was associated with a lower risk of infection. To our knowledge, only PADIT reported infection rates stratified by use of an adherent skin barrier drape. In PADIT, there was a trend for the use of an adherent skin barrier drape to reduce the OR of CIED infection (OR 0.81; 95% CI 0.54–1.21).21 However, in that study, adherent skin barrier drape use was categorized by the center and was not adjusted for individual operator or procedures. As a result, centers where some, but not all, operators used an adherent skin barrier drape were binarily categorized as a barrier site in the analysis,21 thereby possibly underestimating the protective effect of an adherent skin barrier drape.
There exists considerable literature examining the use of an adherent skin barrier drape in other surgical procedures. In 2 Cochrane reviews of adherent skin barrier drape use in cardiac, general, gynecological, or orthopedic surgeries, there was no difference in the risk of infection (relative risk ratio 1.03; 95% CI 0.06–1.66; P = .89).16,25 Interestingly, the use of an adhesive dressing (ie, not antimicrobial) increased the risk of postoperative infections (relative risk ratio 1.23; 95% CI 1.02–1.48; P = .03).16,25 These discouraging results are tempered by the progressive improvement in surgical techniques as the first studies included in these reviews date back to the 1970s. The studies also included a relatively small number of patients and included a number of different types of operations with varying infection rates. Given that none of the trials included patients undergoing CIED procedures, the generalizability of these conclusions to CIED infection rates is problematic. As such, the 2020 update by the National Institute for Health and Care Excellence has no specific recommendation on adherent skin barrier drape use for the prevention of surgical site infection.26 The Centers for Disease Control and Prevention 2017 Guideline for the Prevention of Surgical Site Infection leaves the use of an adherent skin barrier drape to the discretion of the operator with a weak recommendation.27 Consistently, the 2020 European Heart Rhythm Association CIED management guidelines did not make any specific recommendations regarding the use of skin barriers during CIED implantation, citing a lack of supporting evidence.1
The operations that are arguably most relevant to CIED implantation include those involving indwelling vascular catheters. In an underpowered randomized controlled trial of 100 patients with cancer undergoing insertion of a completely implantable vascular access port, the use of an adherent skin barrier drape did not affect infection rates.28 In contrast, a recent study involving 355 patients undergoing joint arthroplasty (ie, implantation of a foreign material into an avascular space) revealed that only 3.8% of scalpels in the adherent skin barrier drape arm showed bacterial growth on scalpel cultures as compared with 12.2% in the control arm.29 Although positive scalpel culture was not predictive of a surgical site infection, these data suggest that the use of an adherent skin barrier drape may reduce skin bacterial translocation. Likewise, in a randomized controlled study involving 1187 total knee arthroplasty procedures, Hesselvig et al19 reported a 35% relative reduction in wound contamination in procedures that used an adherent skin barrier drape. Moreover, Rezapoor et al30 demonstrated that an adhesive drape prevented bacterial colonization on wound swabs (12% vs 27%; P < .05) in a randomized prospective study of 101 hip operations. It follows that the potential benefits of adherent skin barrier drape use may be more pronounced in cases involving foreign prostheses that remains in the body, such as in the use of CIED or joint replacement. In such cases, the formation of an avascular capsule around the prosthesis may limit the access of immune cells to the area of injury and afford colonizing pathogens the opportunity to proliferate into a fulminant infection. The potential benefit conferred by using an adherent skin barrier drape could be due to a reduction in bacterial translocation and “loading” into the pocket. This plausible mechanism could provide an explanation for the observed association seen in our study.
The use of an adherent skin barrier drape was not associated with a reduced rate of infection in patients with ≥1 prior surgeries. Many prior studies have shown that the risk of infection is proportional to the number of procedures.2,8,10, 11, 12,31 The reason for this is not clear, and one hypothesis that would tie together that observation with the findings is the bacterial inoculation load. While device and pocket DNA analysis is frequently positive for bacteria (47.2%) at the end of device surgery, it is uncommon for an associated infection to develop subsequently.32 Presumably in most patients, the immune system overcomes the inoculated bacteria. The immune system is more likely to be successful in a relatively vascular setting (ie, de novo procedure) than the subsequent procedure (with an established avascular capsule). Therefore, if an adherent skin barrier drape reduces, but does not eliminate, the bacterial load, smaller inoculums may still be “successful” in causing infections in non–de novo procedures.
In our database, the cohort without the use of an adherent skin barrier dressing during the procedure included a higher number of cardiac surgeon operators (0% vs 22.7%; P < .0001), and this subgroup exhibited higher infection rates. However, in our multivariable analysis, the distinction between cardiac surgeon operators and electrophysiologist implanters did not correlate with an elevated risk of infection nor did it emerge as an independent predictor. Notably, the comprehensive evaluation of complications based on operator types by Chui et al33 revealed that electrophysiologists had the lowest overall complication rates in CIED procedures as compared with interventionalists, general cardiologists, thoracic surgeons, and other specialties. However, it is worth mentioning that the infection rates between electrophysiologists and “other specialties” were similar at 2% and 2.3%, respectively.33
Given the study design, our results are hypothesis generating and highlight the need for an adequately powered randomized controlled trial to evaluate the potential benefit of adherent skin barrier drape use at reducing the risk of CIED infection. A small randomized controlled trial of barrier use in CIED surgery is underway, but it should be noted that it is using an unvalidated surrogate (end of the index procedure pocket swab positivity) as a primary outcome and is underpowered for the end point of infection (ClinicatTrials.gov identifier NCT04591366). Interventions aimed at reducing the risk of infection can be costly. For instance, when assessing the cost-effectiveness of the absorbable antibiotic pouch, the base-case incremental cost-effectiveness ratio for the antibacterial envelope was found to be $112,603 per quality-adjusted life years. This calculation was based on a conservative estimate of a 40% reduction in infection rates with use of the envelope.3 In contrast, an adherent skin barrier drape would be a much less costly intervention than an antibiotic envelope. For example, in our institution at the present time, the charge of the envelope is CAN$1495 and of the barrier is CAN$1.75.
Limitations
Our study has several limitations, including its design, which limits our ability to infer causality. While we achieved a remarkably high follow-up rate at our site, it is important to acknowledge that some patients may have sought follow-up care at other centers or may have relocated to a different province. Also, it is possible that there were other confounders that we did not control for (e.g., differential surgical technique/ability). Ultimately, we will need a randomized controlled trial to investigate whether a barrier actually reduces infection. In addition, information on immunocompromised status was obtained using only white blood cells as a surrogate marker at the time of the operation. Data on the presence of other disease states known to reduce immune system function such as rheumatologic conditions, cancer, or chronic immunosuppressive therapy were not available.
Conclusion
This is the first study to suggest that the use of an adherent skin barrier drape is associated with a reduced rate of CIED infection. Further studies in the form of randomized controlled trials are warranted to robustly define the benefit of adherent skin barrier drape use at reducing the risk of CIED-related infections.
Acknowledgments
Funding Sources
This research did not receive any grant support from funding agencies in the public, commercial, or not-for-profit sectors.
Disclosures
The authors have no conflicts of interest to declare.
Authorship
All authors attest they meet the current ICMJE criteria for authorship.
Patient Consent
Anonymized data were used and patient consent was not required as determined by Health Insurance Portability and Accountability Act of 1996 (HIPPA) Privacy Rules.
Ethics Statement
The project falls within the context of quality initiative and quality improvement, and hence as per the Tri-Council Policy Statement 2, Article 2.5, full review by the ethics committee was not required.
Footnotes
Supplementary data associated with this article can be found in the online version at https://doi.org/10.1016/j.hroo.2023.12.002.
Appendix. Supplementary Data
References
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