- Email: [email protected]
Risk Factors Associated with Infection of Lower Extremity Revascularization: Analysis Of 365 Procedures Performed at a Teaching Hospital
Risk Factors Associated with Infection of Lower Extremity Revascularization: Analysis Of 365 Procedures Performed at a Teaching Hospital Jeanette K. Chang, MD,1 Keith D. Calligaro, MD,1 Sean Ryan, MD,1 Debra Runyan, CIC,2 Matthew J. Dougherty, MD,1 and John J. Stern, MD,2 Philadelphia, Pennsylvania
Infection of arterial reconstructions is associated with high rates of mortality and limb loss despite optimal treatment. Lower extremity revascularization procedures performed at a teaching hospital were reviewed to identify risk factors associated with wound infection. Medical records, postoperative infection surveillance forms, and a computerized vascular registry for lower extremity revascularizations involving a common femoral or more distal artery during a 3year period were reviewed. There were 335 bypass operations (184 femoral-distal, 36 poplitealdistal, 17 aortofemoral, 13 femorofemoral, 11 axillofemoral, 74 graft revisions) and 30 other vascular procedures (arterial thrombectomy or endarterectomy). Factors analyzed included age, gender, diabetes mellitus, dialysis dependence, malnutrition, obesity, ipsilateral foot ulcer or gangrene, separate admissions within the month preceding surgery, length of hospital stay before surgery, length of operation, wound hematoma requiring reoperation, vein or prosthetic grafts, or redo surgery. Risk factors commonly thought to increase wound infection following lower extremity revascularizations, such as diabetes, obesity, renal failure, redo surgery, and prosthetic grafts, did not predict this complication in this series. Given the correlation of operative time with infection, efforts to minimize operative time by ‘‘double-teaming’’ staff participation in teaching cases may decrease infection rates, although this is speculative. Vascular services should institute strategies to ensure that appropriate prophylactic antibiotics are administered in a timely fashion before lower extremity revascularizations.
INTRODUCTION
1
Section of Vascular Surgery, Pennsylvania Hospital, Philadelphia,
2
Section of Infectious Disease, Pennsylvania Hospital, Philadelphia,
PA. PA. Presented at the Twenty-seventh Annual Meeting of the Peripheral Vascular Surgery Society, Boston, MA, June 8, 2002. Correspondence to: K.D. Calligaro, MD, Section of Vascular Surgery, Pennsylvania Hospital, 700 Spruce Street, Suite 101, Philadelphia, PA 19106, USA, E-mail: [email protected]. Ann Vasc Surg 2003; 17: 91-96 DOI: 10.1007/s10016-001-0337-8 Ó Annals of Vascular Surgery Inc. Published online: 15 January 2003
Infection of arterial bypasses is a devastating complication associated with high rates of limb loss and mortality.1,2 Prominent surgeon R.S. Shaw stated in 1962 that infections of arterial grafts could ‘‘lead to the loss of the patient or a large part of him.’’3 Unfortunately, infectious complications associated with arterial grafts are not uncommon. Various reports from the literature have cited an incidence of wound infection of between 7 and 44%.4,5 Not only are patients susceptible to the consequences of infection such as sepsis or hemorrhage, but they are also subjected to the threat of 91
92 Chang et al.
limb ischemia if revascularization is unsuccessful or not possible, such as when ligation or resection of the involved artery or bypass graft is necessary. The rates of amputation and death after peripheral rascular graft infections have been reported to be 8 to 52% and 14 to 58%, respectively.1,6-8 Additionally, wound and graft complications lengthen hospitalization and utilize expensive resources. In the current medical climate emphasizing cost efficiency, avoidance of complications and protracted medical care is critically important. The gravity of infection associated with peripheral revascularization has been well established and understanding the etiology and course of these infections is helpful in devising its treatment. We have previously identified specific bacterial strains, namely Staphylococcus aureus and Pseudomonas aeruginosa, as particularly aggressive organisms, and identified late-onset infections (i.e., more than 2 months after surgery) as more virulent than earlier infections.1,6 In this study, we attempted to identify predisposing factors for wound and graft infections in a retrospective analysis of 365 lower extremity arterial revascularizations procedures performed at a tertiary care teaching hospital.
PATIENTS AND METHODS Medical records, postoperative infection surveillance surveys, and a vascular registry were reviewed for lower extremity revascularizations involving a common femoral or more distal artery between July 1, 1997 and June 30, 2000 at Pennsylvania Hospital in Philadelphia. Information regarding potential risk factors for arterial infections was available for 365 patients: 335 underwent a revascularization with a bypass procedure (184 femoral-distal, 36 popliteal-distal, 17 aortofemoral, 13 femorofemoral, 11 axillofemoral, 74 revisions) and 30 had other vascular procedures (thromboembolectomy or endarterectomy). All procedures were performed at a single institution by a staff vascular surgeon and the vascular fellow or a general surgery resident. Our protocol for antibiotic prophylaxis included administration of antibiotics by anesthesia personnel upon arrival in the operating room, rather than administration on the surgical floors or holding area. Most patients received an intravenous firstgeneration cephalosporin (cefazolin) before skin incision and at 4-h intervals intraoperatively. Vancomycin and gentamycin were given to patients who were allergic to penicillins or cephalosporins. Additionally, this combination was frequently administered to patients who were
Annals of Vascular Surgery
considered at high risk for infection. Antibiotics were not continued postoperatively unless there was a preexisting infection requiring continued treatment. Factors analyzed included age, gender, and the presence of diabetes mellitus or end-stage renal disease requiring dialysis. Nutritional status was also examined. Malnutrition was defined as albumin <3.0 mg/dL and obesity as 130% of ideal body weight. An ipsilateral foot ulcer or gangrene was considered evidence of concomitant infection or tissue loss. Admission occurring within a month before surgery and length of hospital stay before surgery were analyzed as possible factors predisposing to nosocomial infection. We analyzed several operative factors, including the length of operation, type of conduit used, and whether the procedures were primary or secondary. The development of a postoperative wound hematoma requiring reoperation was also considered a potential risk factor. The criteria for wound infections were in accordance with the definition of the Centers for Disease Control (CDC) and implemented for the surveillance of nosocomial infections.9 For this report, the overall wound infection rate included cellulitis, superficial infections involving the subcutaneous tissue, and deep soft tissue infections (including arterial or graft infections). Cellulitis was defined as erythema of the skin warranting treatment with antibiotics as deemed necessary by the treating physician, as defined by the CDC.9 Superficial wound infection was defined as involvement of only the skin and subcutaneous tissue along with purulent drainage, positive cultures of the wound, one of the signs or symptoms of infection (pain, swelling, erythema, or heat), and diagnosis of infection by the attending surgeon.9 A deep wound infection was defined as involvement of the fascia and muscle layers along with purulent drainage, opening of the incision spontaneously or by an attending surgeon when the patient had fever, pain, or tenderness, and diagnosis of infection by the attending surgeon.9 Arterial or graft infection was defined as direct involvement of an underlying artery or graft (vein or prosthetic) with positive bacterial cultures taken from perilarterial or perigraft tissues. Patients with pus along the majority of the graft or with sepsis due to graft infection were treated by total graft excision.1,2 Patients with a disrupted infected anastomosis were treated by excision of the infected part of the graft with revascularization through sterile routes to salvage the uninfected segment of the graft. Infected occluded grafts were
Vol. 17, No. 1, 2003
Infection of lower extremity revascularization 93
Table I. Wound infections analyzed according to risk factors
Risk factor
Wound infections/ Patients with risk factor (%)
Wound infections/ Patients without risk factor (%)
pb
pc
Gender (male) Diabetes mellitus Dialysis dependence Malnutritiond Obesitye Ipsilateral ulcer Ipsilateral gangrene Recent hospitalizationf Wound hematoma Use of prosthetic graft Redo surgery Operative time (min)
12/177 (6.8) 13/175 (7.4) 0/14 (0) 1/24 (4.2) 7/57 (12.3) 12/150 (8.0) 5/79 (6.3) 2/67 (3.0) 1/8 (12.5) 7/150 (4.7) 1/35 (2.9) 318 (mean)
15/160 (3.1) 13/156 (8.3) 17/175 (9.7) 2/33 (6.1) 12/120 (10) 15/183 (8.2) 21/246 (8.5) 25/268 (9.3) 18/186 (9.7) 21/185 (11.4) 27/330 (8.2) 265 (mean)
0.25 0.70 0.25 0.62 0.41 0.60 0.81 0.99 0.57 0.13 0.53 0.03
0.97 0.52 0.99 0.90 0.64 0.68 0.18 0.08 0.46 0.35 0.72 0.02
a
Data were not available for all patients. p-value based on two-tailed t-test and Fisher’s exact test. c p-value based on logistic regression multivariate analysis. d Defined as albumin <3.0 mg/dL. e Defined as 130% of ideal body weight. f Defined as a hospital stay with a discharge date within 30 days of new admission. b
treated by subtotal excision of the graft, leaving an oversewn segment of intact graft at an anastomosis to maintain preservation of an underlying artery often critical for limb salvage. Complete graft preservation was frequently attempted if the anastomosis was intact, the patient was not septic, the graft was patent, and pseudomonas was not cultured from the wound.1,2 We have previously reported that this strategy was associated with approximately a 10% mortality and 10% amputation rate.1,2,6 Data were analyzed using a two-tailed t-test and Fisher’s exact test with Epi Info (version 6, word processing, database, statistic program distributed by CDC) and logistic regression multivariate analysis was done using Stat-View (version 5.01, SAS Institute Inc.).
RESULTS The wound infection rate for all lower extremity revascularizations, including superficial infections such as cellulitis or skin infections, deep wound infections not involving a graft or artery, and arterial or graft infections, was 8.0% (27/365). Mean onset of infection was 21 days (range, 3-135 days). Follow-up averaged 6 months (range, 1-16 months). The average age of patients with wound infection was 67.3 years, compared to 70.2 years in patients without infection (p = NS). Comorbidities such as diabetes mellitus, end-stage renal disease,
concomitant infection, tissue loss, or revision surgery did not predispose patients to infection of the revascularization site in this series (Table I). The only factor that correlated with wound infection was operative time. Mean operative time for revascularization procedures in patients who ultimately developed a wound or graft infection was 318 min vs. 265 min for patients who did not have an infectious complication (two-tailed t-test and Fisher exact test, p = 0.03; logistic regression multivariate analysis, p = 0.02). There were no predictors of early versus late infection. Location of infection and bypass type are delineated in Table II. Despite the surgeons’ intent, appropriate prophylactic antibiotics were not administered according to our protocol in 8.1% (27/335) cases. Vein grafts were associated with a significantly higher rate of superficial wound infection, including cellulitis or subcutaneous infection (9.2% [17/ 185]), than were prosthetic grafts (0.3% [1/129]) (p = 0.02). Of the bypass procedures performed, graft infections occurred in 2.6% (9/335). All graft infections presented with concomitant wound infections also (draining sinus, erythema, purulent drainage). Of the nine graft infections, six involved prosthetic material and three involved vein grafts. Prosthetic grafts therefore tended to have higher rates of graft infection (4.7% [6/129]) than did autogenous venous conduits (1.6% [3/185]), although statistical significance was not achieved (p = NS).
94 Chang et al.
Annals of Vascular Surgery
Table II. Patients with wound infections by procedure (365 total) Procedure
Axillofemoral bypass with PTFE Iliotibial bypass with veina Femoral-femoral bypass with PTFE Femoral-popliteal bypass in situ vein veina Femoral-tibial bypass in situ vein veina veina (revision) PTFE Femoral-dorsalis pedis bypass in situ vein veina Popliteal-tibial bypass with veina Popliteal-dorsalis pedis bypass with veina Total
n (%)
2 (0.5) 1 (0.3) 1 (0.3) 4 (1.0) 2 (0.5) 2 5 1 4
(0.5) (1.4) (0.3) (1.0)
2 1 1 1 27
(0.5) (0.3) (0.3) (0.3) (8.0)
PTFE, polytetrafluoroethylene. a Reversed, translocated, and/or composite grafts using upper and/or lower extremity veins.
DISCUSSION Previous reports have cited numerous factors predisposing patients to infectious complications after surgery, including medical comorbidities. Diabetes mellitus and poor glucose control are thought to contribute to the development of infection.10 Nutritional status has also been postulated to be relevant to infection. Both malnutrition, frequently measured by albumin levels, and obesity have been suggested as risk factors for adverse effects and infection.11,12 Other predisposing factors for wound complications have been cited, including female gender, chronic steroid therapy, low preoperative hematocrit and high preoperative blood urea nitrogen level, low postoperative hematocrit, use of a continuous incision, ipsilateral limb ulcer, indication for revascularization (i.e., limb salvage), in situ bypass, bypass to the dorsalis pedis artery, previous infection, and methicillin-resistant Staphylococcus aureus colonization.13,14 In contrast, conflicting reports have suggested that age, race, gender, hypertension, coronary artery disease, smoking, diabetes, end-stage renal disease, preoperative leukocytosis or hyperglycemia, ipsilateral arteriography, use of prosthetic graft material, previous groin surgery, preoperative gangrene or ulcer, mean Ankle/brachial index (ABI) type of incision, method of wound closure, infected ipsilateral lymph node, type of revascu-
larization procedure, early reoperation, and occurrence of graft-related complications are not associated with the development of wound problems.5,13,15,16 In our series, patient demographics and comorbidities did not predict infection, and the only factor that correlated with infection was a prolonged operative time, based on logistic regression multivariate analysis. We speculate that prolonged operative time exposes the open wound to greater risk of direct or airborne contamination. Prolonged operative time may reflect cases that are more technically difficult with more scar tissue or extensive tissue dissection.8 Further, more distal surgery generally requires more operative time, and one might therefore expect that more difficult operations would have a higher incidence of graft infection. Edwards et al.8 reviewed patients undergoing prosthetic aortobifemoral procedures and femorodistal bypasses. Within each group, patients who suffered infectious complications had a longer mean operative time. Longer operative time therefore appeared to be an independent predictor of infection.8 Nonetheless, we readily admit that prolonged operative times may be a reflection of other factors that could not be isolated in our study. Efforts to reduce operative time, especially for procedures expected to be particularly prolonged, should be examined. For instance, an additional team of surgeons could be employed to operate simultaneously to expedite surgical procedures, especially in a teaching hospital environment where instruction and inexperience of residents and fellows may prolong operative time. However, this strategy of double-teaming staff surgeons may not yield lower infection rates and we do not have data to support this conclusion. Autogenous vein grafts were associated with superficial wound infection in our series, while prosthetic grafts tended to be associated more frequently with graft infection. These findings are likely attributable to the difference in technique and properties of the conduit.5,17 Specifically, harvesting vein involves more extensive incisions and dissection and therefore introduces more potential for tissue trauma and wound healing problems. We did not analyze the exact length of the incision(s) in each patient since we utilized continuous skin incisions to harvest vein in all patients; the length of incision to harvest vein is determined by the distance from the proximal to distal arterial anastomosis. Prosthetic grafts are foreign bodies and are prone to developing infection of the graft itself. In 1978, Kaiser et al. demonstrated decreased wound infections and a trend toward decreased
Vol. 17, No. 1, 2003
graft infections with use of prophylactic cephalosporins.18 Antimicrobial prophylaxis has become the standard of care for vascular surgery, and the antibiotic used should be effective against a wide variety of gram-positive and gram-negative pathogens. It should be administered 30 to 60 min prior to incision and repeated to maintain adequate serum levels throughout the operative procedure.19 Unfortunately, adherence to this protocol is not always observed. Edwards et al. documented that prophylactic antibiotics were given according to their proscribed practice in only 29.5% of patients.8 Silver et al. reported that antibiotic prophylaxis is frequently not standardized and that adherence to protocols deteriorated throughout the day.20 In our series, adherence to our antibiotic prophylaxis protocol occurred in only 92% of cases, despite the fact that our institution has demonstrated a particular interest in arterial graft infections.1,2,6 We were disappointed by this finding that 8% of patients did not receive prophylactic antibiotics in a timely fashion by the anesthesia team. To address this problem, signs have since been posted on a wall near the head of the patient in the vascular operating rooms, reminding the anesthesia team to administer prophylactic antibiotics in a timely fashion, and the vascular surgeons have made a determined effort to routinely ask if prophylactic antibiotics have been given for all patients undergoing revascularization procedures. Although we routinely administered cefazolin in straightforward cases, we utilized the combination of vancomycin and gentamycin in patients perceived to be at increased risk, such as those with diabetes, renal failure, obesity, and prior revascularization procedures.8,13,15 Also, patients with preexisting infections were usually treated with broad-spectrum antibiotics before surgery. Only a prospective randomized study would protect against bias such as this. We postulate that administration of broader and more potent prophylactic antibiotics in patients with potential risk factors for infection may be beneficial and may account for our finding that no risk factors were associated with revascularization procedures except for prolonged operative time.
CONCLUSION In this series of lower extremity arterial revascularizations, the only risk factor associated with infectious complication was prolonged operative time. We believe that reasonable measures should
Infection of lower extremity revascularization 95
be taken to shorten operative time, although we cannot provide data to support this recommendation. The suggestion of double-teaming staff vascular surgeons for particularly challenging, lengthy operations to decrease wound infections is speculative and may not ultimately prove beneficial. Strict attention should be paid to improve conformity to prophylactic antibiotic protocols. Randomized, prospective studies will be necessary to ascertain whether more potent and broader-spectrum antibiotic prophylaxis would be beneficial for patients who have traditionally been regarded as being at high risk for infection.
REFERENCES 1. Calligaro KD, Veith FJ, Schwartz ML, et al. Differences in early versus late extracavitary arterial graft infections. J Vasc Surg 1995;22:680-688. 2. Calligaro KD, Veith FJ, Schwartz ML, et al. Selective preservation of infected prosthetic arterial grafts: analysis of a 20-year experience with 120 extracavitary-infected grafts. Ann Surg 1994;220:461-471. 3. Shaw RS, Baue AE. Management of sepsis complicating arterial reconstructive surgery. Surgery 1962;53:75-86. 4. Donaldson MC, Whittemore AD, Mannick JA. Further experience with an all-autogenous tissue policy for infrainguinal reconstruction. J Vasc Surg 1993;18:41-48. 5. Reifsnyder T, Bandyk D, Seabrook G, et al. Wound complications of the in situ saphenous vein bypass technique J Vasc Surg 1992;15:843-850. 6. Calligaro KD, Veith FJ, Schwartz, et al. Management of infected lower extremity autologous vein grafts by selective graft preservation. Am J Surg 1992;164:291-294. 7. Bunt TJ. Synthetic vascular graft infections. I. Graft infections. Surgery 1983;6:733-746. 8. Edwards WH, Martin RS, Jenkins JM, Edwards WH, Mulherin JL. Primary graft infections. J Vasc Surg 1987; 6:235-239. 9. Garner JS, Jarvis WR, Emori TG, et al. CDC definitions for nosocomial infections, 1988. Am J Infect Control 1988;16: 128-140. 10. Pomposelli JJ, Baxter III JK, Babineau TJ, et al. Early postoperative glucose control predicts nosocomial infection rate in diabetic patients. J Parenter Enteral Nutr 1998;22:7781. 11. Gibbs J, Cull W, Henderson W, et al. Preoperative serum albumin level as a predictor of operative mortality and morbidity: results from the National VA Surgical Risk Study. Arch Surg 1999;134:36-42. 12. Forse RA, Karam B, MacLean LD, et al. Antibiotic prophylaxis for surgery in morbidly obese patients. Surgery 1989; 106:750-757. 13. Wengrovitz M, Atnip RG, Gifford RR, et al. Wound complications of autogenous subcutaneous infrainguinal arterial bypass surgery: predisposing factors and management. J Vasc Surg 1990;11:156-163. 14. Mest DR, Wong DH, Shimoda KJ, et al. Nasal colonization with MRSA on admission to the surgical ICU increases the risk of infection. Anesth Analg 1994;78:644-650. 15. Schwartz ME, Harrington EB, Schanzer H. Wound complications after in situ bypass. J Vasc Surg 1988;7:802-807.
96 Chang et al.
16. Josephs LG, Cordts PR, DiEdwardo CL, et al. Do infected inguinal lymph nodes increase the incidence of postoperative groin wound infection? J Vasc Surg 1993;17:10771082. 17. Londrey GL, Ramsey DE, Hodgson KJ, et al. Infrapopliteal bypass for severe ischemia: comparison of autogenous vein, composite and prosthetic grafts. J Vasc Surg 1991;13:631636.
Annals of Vascular Surgery
18. Kaiser AG, Clayson KR, Mulherin JL, et al. Antibiotic prophylaxis in vascular surgery. Ann Surg 1978;88:283-289. 19. Kaiser A. Zero infection rate: an achievable irreducible minimum in clean surgery? Infect Control 1986;7:107109. 20. Silver A, Eichorn A, Krai J, et al. Timeliness and use of antibiotic prophylaxis in selected inpatient surgical procedures. Am J Surg 1996;171:548-552.
Infection of arterial reconstructions is associated with high rates of mortality and limb loss despite optimal treatment. Lower extremity revascularization procedures performed at a teaching hospital were reviewed to identify risk factors associated with wound infection. Medical records, postoperative infection surveillance forms, and a computerized vascular registry for lower extremity revascularizations involving a common femoral or more distal artery during a 3year period were reviewed. There were 335 bypass operations (184 femoral-distal, 36 poplitealdistal, 17 aortofemoral, 13 femorofemoral, 11 axillofemoral, 74 graft revisions) and 30 other vascular procedures (arterial thrombectomy or endarterectomy). Factors analyzed included age, gender, diabetes mellitus, dialysis dependence, malnutrition, obesity, ipsilateral foot ulcer or gangrene, separate admissions within the month preceding surgery, length of hospital stay before surgery, length of operation, wound hematoma requiring reoperation, vein or prosthetic grafts, or redo surgery. Risk factors commonly thought to increase wound infection following lower extremity revascularizations, such as diabetes, obesity, renal failure, redo surgery, and prosthetic grafts, did not predict this complication in this series. Given the correlation of operative time with infection, efforts to minimize operative time by ‘‘double-teaming’’ staff participation in teaching cases may decrease infection rates, although this is speculative. Vascular services should institute strategies to ensure that appropriate prophylactic antibiotics are administered in a timely fashion before lower extremity revascularizations.
INTRODUCTION
1
Section of Vascular Surgery, Pennsylvania Hospital, Philadelphia,
2
Section of Infectious Disease, Pennsylvania Hospital, Philadelphia,
PA. PA. Presented at the Twenty-seventh Annual Meeting of the Peripheral Vascular Surgery Society, Boston, MA, June 8, 2002. Correspondence to: K.D. Calligaro, MD, Section of Vascular Surgery, Pennsylvania Hospital, 700 Spruce Street, Suite 101, Philadelphia, PA 19106, USA, E-mail: [email protected]. Ann Vasc Surg 2003; 17: 91-96 DOI: 10.1007/s10016-001-0337-8 Ó Annals of Vascular Surgery Inc. Published online: 15 January 2003
Infection of arterial bypasses is a devastating complication associated with high rates of limb loss and mortality.1,2 Prominent surgeon R.S. Shaw stated in 1962 that infections of arterial grafts could ‘‘lead to the loss of the patient or a large part of him.’’3 Unfortunately, infectious complications associated with arterial grafts are not uncommon. Various reports from the literature have cited an incidence of wound infection of between 7 and 44%.4,5 Not only are patients susceptible to the consequences of infection such as sepsis or hemorrhage, but they are also subjected to the threat of 91
92 Chang et al.
limb ischemia if revascularization is unsuccessful or not possible, such as when ligation or resection of the involved artery or bypass graft is necessary. The rates of amputation and death after peripheral rascular graft infections have been reported to be 8 to 52% and 14 to 58%, respectively.1,6-8 Additionally, wound and graft complications lengthen hospitalization and utilize expensive resources. In the current medical climate emphasizing cost efficiency, avoidance of complications and protracted medical care is critically important. The gravity of infection associated with peripheral revascularization has been well established and understanding the etiology and course of these infections is helpful in devising its treatment. We have previously identified specific bacterial strains, namely Staphylococcus aureus and Pseudomonas aeruginosa, as particularly aggressive organisms, and identified late-onset infections (i.e., more than 2 months after surgery) as more virulent than earlier infections.1,6 In this study, we attempted to identify predisposing factors for wound and graft infections in a retrospective analysis of 365 lower extremity arterial revascularizations procedures performed at a tertiary care teaching hospital.
PATIENTS AND METHODS Medical records, postoperative infection surveillance surveys, and a vascular registry were reviewed for lower extremity revascularizations involving a common femoral or more distal artery between July 1, 1997 and June 30, 2000 at Pennsylvania Hospital in Philadelphia. Information regarding potential risk factors for arterial infections was available for 365 patients: 335 underwent a revascularization with a bypass procedure (184 femoral-distal, 36 popliteal-distal, 17 aortofemoral, 13 femorofemoral, 11 axillofemoral, 74 revisions) and 30 had other vascular procedures (thromboembolectomy or endarterectomy). All procedures were performed at a single institution by a staff vascular surgeon and the vascular fellow or a general surgery resident. Our protocol for antibiotic prophylaxis included administration of antibiotics by anesthesia personnel upon arrival in the operating room, rather than administration on the surgical floors or holding area. Most patients received an intravenous firstgeneration cephalosporin (cefazolin) before skin incision and at 4-h intervals intraoperatively. Vancomycin and gentamycin were given to patients who were allergic to penicillins or cephalosporins. Additionally, this combination was frequently administered to patients who were
Annals of Vascular Surgery
considered at high risk for infection. Antibiotics were not continued postoperatively unless there was a preexisting infection requiring continued treatment. Factors analyzed included age, gender, and the presence of diabetes mellitus or end-stage renal disease requiring dialysis. Nutritional status was also examined. Malnutrition was defined as albumin <3.0 mg/dL and obesity as 130% of ideal body weight. An ipsilateral foot ulcer or gangrene was considered evidence of concomitant infection or tissue loss. Admission occurring within a month before surgery and length of hospital stay before surgery were analyzed as possible factors predisposing to nosocomial infection. We analyzed several operative factors, including the length of operation, type of conduit used, and whether the procedures were primary or secondary. The development of a postoperative wound hematoma requiring reoperation was also considered a potential risk factor. The criteria for wound infections were in accordance with the definition of the Centers for Disease Control (CDC) and implemented for the surveillance of nosocomial infections.9 For this report, the overall wound infection rate included cellulitis, superficial infections involving the subcutaneous tissue, and deep soft tissue infections (including arterial or graft infections). Cellulitis was defined as erythema of the skin warranting treatment with antibiotics as deemed necessary by the treating physician, as defined by the CDC.9 Superficial wound infection was defined as involvement of only the skin and subcutaneous tissue along with purulent drainage, positive cultures of the wound, one of the signs or symptoms of infection (pain, swelling, erythema, or heat), and diagnosis of infection by the attending surgeon.9 A deep wound infection was defined as involvement of the fascia and muscle layers along with purulent drainage, opening of the incision spontaneously or by an attending surgeon when the patient had fever, pain, or tenderness, and diagnosis of infection by the attending surgeon.9 Arterial or graft infection was defined as direct involvement of an underlying artery or graft (vein or prosthetic) with positive bacterial cultures taken from perilarterial or perigraft tissues. Patients with pus along the majority of the graft or with sepsis due to graft infection were treated by total graft excision.1,2 Patients with a disrupted infected anastomosis were treated by excision of the infected part of the graft with revascularization through sterile routes to salvage the uninfected segment of the graft. Infected occluded grafts were
Vol. 17, No. 1, 2003
Infection of lower extremity revascularization 93
Table I. Wound infections analyzed according to risk factors
Risk factor
Wound infections/ Patients with risk factor (%)
Wound infections/ Patients without risk factor (%)
pb
pc
Gender (male) Diabetes mellitus Dialysis dependence Malnutritiond Obesitye Ipsilateral ulcer Ipsilateral gangrene Recent hospitalizationf Wound hematoma Use of prosthetic graft Redo surgery Operative time (min)
12/177 (6.8) 13/175 (7.4) 0/14 (0) 1/24 (4.2) 7/57 (12.3) 12/150 (8.0) 5/79 (6.3) 2/67 (3.0) 1/8 (12.5) 7/150 (4.7) 1/35 (2.9) 318 (mean)
15/160 (3.1) 13/156 (8.3) 17/175 (9.7) 2/33 (6.1) 12/120 (10) 15/183 (8.2) 21/246 (8.5) 25/268 (9.3) 18/186 (9.7) 21/185 (11.4) 27/330 (8.2) 265 (mean)
0.25 0.70 0.25 0.62 0.41 0.60 0.81 0.99 0.57 0.13 0.53 0.03
0.97 0.52 0.99 0.90 0.64 0.68 0.18 0.08 0.46 0.35 0.72 0.02
a
Data were not available for all patients. p-value based on two-tailed t-test and Fisher’s exact test. c p-value based on logistic regression multivariate analysis. d Defined as albumin <3.0 mg/dL. e Defined as 130% of ideal body weight. f Defined as a hospital stay with a discharge date within 30 days of new admission. b
treated by subtotal excision of the graft, leaving an oversewn segment of intact graft at an anastomosis to maintain preservation of an underlying artery often critical for limb salvage. Complete graft preservation was frequently attempted if the anastomosis was intact, the patient was not septic, the graft was patent, and pseudomonas was not cultured from the wound.1,2 We have previously reported that this strategy was associated with approximately a 10% mortality and 10% amputation rate.1,2,6 Data were analyzed using a two-tailed t-test and Fisher’s exact test with Epi Info (version 6, word processing, database, statistic program distributed by CDC) and logistic regression multivariate analysis was done using Stat-View (version 5.01, SAS Institute Inc.).
RESULTS The wound infection rate for all lower extremity revascularizations, including superficial infections such as cellulitis or skin infections, deep wound infections not involving a graft or artery, and arterial or graft infections, was 8.0% (27/365). Mean onset of infection was 21 days (range, 3-135 days). Follow-up averaged 6 months (range, 1-16 months). The average age of patients with wound infection was 67.3 years, compared to 70.2 years in patients without infection (p = NS). Comorbidities such as diabetes mellitus, end-stage renal disease,
concomitant infection, tissue loss, or revision surgery did not predispose patients to infection of the revascularization site in this series (Table I). The only factor that correlated with wound infection was operative time. Mean operative time for revascularization procedures in patients who ultimately developed a wound or graft infection was 318 min vs. 265 min for patients who did not have an infectious complication (two-tailed t-test and Fisher exact test, p = 0.03; logistic regression multivariate analysis, p = 0.02). There were no predictors of early versus late infection. Location of infection and bypass type are delineated in Table II. Despite the surgeons’ intent, appropriate prophylactic antibiotics were not administered according to our protocol in 8.1% (27/335) cases. Vein grafts were associated with a significantly higher rate of superficial wound infection, including cellulitis or subcutaneous infection (9.2% [17/ 185]), than were prosthetic grafts (0.3% [1/129]) (p = 0.02). Of the bypass procedures performed, graft infections occurred in 2.6% (9/335). All graft infections presented with concomitant wound infections also (draining sinus, erythema, purulent drainage). Of the nine graft infections, six involved prosthetic material and three involved vein grafts. Prosthetic grafts therefore tended to have higher rates of graft infection (4.7% [6/129]) than did autogenous venous conduits (1.6% [3/185]), although statistical significance was not achieved (p = NS).
94 Chang et al.
Annals of Vascular Surgery
Table II. Patients with wound infections by procedure (365 total) Procedure
Axillofemoral bypass with PTFE Iliotibial bypass with veina Femoral-femoral bypass with PTFE Femoral-popliteal bypass in situ vein veina Femoral-tibial bypass in situ vein veina veina (revision) PTFE Femoral-dorsalis pedis bypass in situ vein veina Popliteal-tibial bypass with veina Popliteal-dorsalis pedis bypass with veina Total
n (%)
2 (0.5) 1 (0.3) 1 (0.3) 4 (1.0) 2 (0.5) 2 5 1 4
(0.5) (1.4) (0.3) (1.0)
2 1 1 1 27
(0.5) (0.3) (0.3) (0.3) (8.0)
PTFE, polytetrafluoroethylene. a Reversed, translocated, and/or composite grafts using upper and/or lower extremity veins.
DISCUSSION Previous reports have cited numerous factors predisposing patients to infectious complications after surgery, including medical comorbidities. Diabetes mellitus and poor glucose control are thought to contribute to the development of infection.10 Nutritional status has also been postulated to be relevant to infection. Both malnutrition, frequently measured by albumin levels, and obesity have been suggested as risk factors for adverse effects and infection.11,12 Other predisposing factors for wound complications have been cited, including female gender, chronic steroid therapy, low preoperative hematocrit and high preoperative blood urea nitrogen level, low postoperative hematocrit, use of a continuous incision, ipsilateral limb ulcer, indication for revascularization (i.e., limb salvage), in situ bypass, bypass to the dorsalis pedis artery, previous infection, and methicillin-resistant Staphylococcus aureus colonization.13,14 In contrast, conflicting reports have suggested that age, race, gender, hypertension, coronary artery disease, smoking, diabetes, end-stage renal disease, preoperative leukocytosis or hyperglycemia, ipsilateral arteriography, use of prosthetic graft material, previous groin surgery, preoperative gangrene or ulcer, mean Ankle/brachial index (ABI) type of incision, method of wound closure, infected ipsilateral lymph node, type of revascu-
larization procedure, early reoperation, and occurrence of graft-related complications are not associated with the development of wound problems.5,13,15,16 In our series, patient demographics and comorbidities did not predict infection, and the only factor that correlated with infection was a prolonged operative time, based on logistic regression multivariate analysis. We speculate that prolonged operative time exposes the open wound to greater risk of direct or airborne contamination. Prolonged operative time may reflect cases that are more technically difficult with more scar tissue or extensive tissue dissection.8 Further, more distal surgery generally requires more operative time, and one might therefore expect that more difficult operations would have a higher incidence of graft infection. Edwards et al.8 reviewed patients undergoing prosthetic aortobifemoral procedures and femorodistal bypasses. Within each group, patients who suffered infectious complications had a longer mean operative time. Longer operative time therefore appeared to be an independent predictor of infection.8 Nonetheless, we readily admit that prolonged operative times may be a reflection of other factors that could not be isolated in our study. Efforts to reduce operative time, especially for procedures expected to be particularly prolonged, should be examined. For instance, an additional team of surgeons could be employed to operate simultaneously to expedite surgical procedures, especially in a teaching hospital environment where instruction and inexperience of residents and fellows may prolong operative time. However, this strategy of double-teaming staff surgeons may not yield lower infection rates and we do not have data to support this conclusion. Autogenous vein grafts were associated with superficial wound infection in our series, while prosthetic grafts tended to be associated more frequently with graft infection. These findings are likely attributable to the difference in technique and properties of the conduit.5,17 Specifically, harvesting vein involves more extensive incisions and dissection and therefore introduces more potential for tissue trauma and wound healing problems. We did not analyze the exact length of the incision(s) in each patient since we utilized continuous skin incisions to harvest vein in all patients; the length of incision to harvest vein is determined by the distance from the proximal to distal arterial anastomosis. Prosthetic grafts are foreign bodies and are prone to developing infection of the graft itself. In 1978, Kaiser et al. demonstrated decreased wound infections and a trend toward decreased
Vol. 17, No. 1, 2003
graft infections with use of prophylactic cephalosporins.18 Antimicrobial prophylaxis has become the standard of care for vascular surgery, and the antibiotic used should be effective against a wide variety of gram-positive and gram-negative pathogens. It should be administered 30 to 60 min prior to incision and repeated to maintain adequate serum levels throughout the operative procedure.19 Unfortunately, adherence to this protocol is not always observed. Edwards et al. documented that prophylactic antibiotics were given according to their proscribed practice in only 29.5% of patients.8 Silver et al. reported that antibiotic prophylaxis is frequently not standardized and that adherence to protocols deteriorated throughout the day.20 In our series, adherence to our antibiotic prophylaxis protocol occurred in only 92% of cases, despite the fact that our institution has demonstrated a particular interest in arterial graft infections.1,2,6 We were disappointed by this finding that 8% of patients did not receive prophylactic antibiotics in a timely fashion by the anesthesia team. To address this problem, signs have since been posted on a wall near the head of the patient in the vascular operating rooms, reminding the anesthesia team to administer prophylactic antibiotics in a timely fashion, and the vascular surgeons have made a determined effort to routinely ask if prophylactic antibiotics have been given for all patients undergoing revascularization procedures. Although we routinely administered cefazolin in straightforward cases, we utilized the combination of vancomycin and gentamycin in patients perceived to be at increased risk, such as those with diabetes, renal failure, obesity, and prior revascularization procedures.8,13,15 Also, patients with preexisting infections were usually treated with broad-spectrum antibiotics before surgery. Only a prospective randomized study would protect against bias such as this. We postulate that administration of broader and more potent prophylactic antibiotics in patients with potential risk factors for infection may be beneficial and may account for our finding that no risk factors were associated with revascularization procedures except for prolonged operative time.
CONCLUSION In this series of lower extremity arterial revascularizations, the only risk factor associated with infectious complication was prolonged operative time. We believe that reasonable measures should
Infection of lower extremity revascularization 95
be taken to shorten operative time, although we cannot provide data to support this recommendation. The suggestion of double-teaming staff vascular surgeons for particularly challenging, lengthy operations to decrease wound infections is speculative and may not ultimately prove beneficial. Strict attention should be paid to improve conformity to prophylactic antibiotic protocols. Randomized, prospective studies will be necessary to ascertain whether more potent and broader-spectrum antibiotic prophylaxis would be beneficial for patients who have traditionally been regarded as being at high risk for infection.
REFERENCES 1. Calligaro KD, Veith FJ, Schwartz ML, et al. Differences in early versus late extracavitary arterial graft infections. J Vasc Surg 1995;22:680-688. 2. Calligaro KD, Veith FJ, Schwartz ML, et al. Selective preservation of infected prosthetic arterial grafts: analysis of a 20-year experience with 120 extracavitary-infected grafts. Ann Surg 1994;220:461-471. 3. Shaw RS, Baue AE. Management of sepsis complicating arterial reconstructive surgery. Surgery 1962;53:75-86. 4. Donaldson MC, Whittemore AD, Mannick JA. Further experience with an all-autogenous tissue policy for infrainguinal reconstruction. J Vasc Surg 1993;18:41-48. 5. Reifsnyder T, Bandyk D, Seabrook G, et al. Wound complications of the in situ saphenous vein bypass technique J Vasc Surg 1992;15:843-850. 6. Calligaro KD, Veith FJ, Schwartz, et al. Management of infected lower extremity autologous vein grafts by selective graft preservation. Am J Surg 1992;164:291-294. 7. Bunt TJ. Synthetic vascular graft infections. I. Graft infections. Surgery 1983;6:733-746. 8. Edwards WH, Martin RS, Jenkins JM, Edwards WH, Mulherin JL. Primary graft infections. J Vasc Surg 1987; 6:235-239. 9. Garner JS, Jarvis WR, Emori TG, et al. CDC definitions for nosocomial infections, 1988. Am J Infect Control 1988;16: 128-140. 10. Pomposelli JJ, Baxter III JK, Babineau TJ, et al. Early postoperative glucose control predicts nosocomial infection rate in diabetic patients. J Parenter Enteral Nutr 1998;22:7781. 11. Gibbs J, Cull W, Henderson W, et al. Preoperative serum albumin level as a predictor of operative mortality and morbidity: results from the National VA Surgical Risk Study. Arch Surg 1999;134:36-42. 12. Forse RA, Karam B, MacLean LD, et al. Antibiotic prophylaxis for surgery in morbidly obese patients. Surgery 1989; 106:750-757. 13. Wengrovitz M, Atnip RG, Gifford RR, et al. Wound complications of autogenous subcutaneous infrainguinal arterial bypass surgery: predisposing factors and management. J Vasc Surg 1990;11:156-163. 14. Mest DR, Wong DH, Shimoda KJ, et al. Nasal colonization with MRSA on admission to the surgical ICU increases the risk of infection. Anesth Analg 1994;78:644-650. 15. Schwartz ME, Harrington EB, Schanzer H. Wound complications after in situ bypass. J Vasc Surg 1988;7:802-807.
96 Chang et al.
16. Josephs LG, Cordts PR, DiEdwardo CL, et al. Do infected inguinal lymph nodes increase the incidence of postoperative groin wound infection? J Vasc Surg 1993;17:10771082. 17. Londrey GL, Ramsey DE, Hodgson KJ, et al. Infrapopliteal bypass for severe ischemia: comparison of autogenous vein, composite and prosthetic grafts. J Vasc Surg 1991;13:631636.
Annals of Vascular Surgery
18. Kaiser AG, Clayson KR, Mulherin JL, et al. Antibiotic prophylaxis in vascular surgery. Ann Surg 1978;88:283-289. 19. Kaiser A. Zero infection rate: an achievable irreducible minimum in clean surgery? Infect Control 1986;7:107109. 20. Silver A, Eichorn A, Krai J, et al. Timeliness and use of antibiotic prophylaxis in selected inpatient surgical procedures. Am J Surg 1996;171:548-552.