The American Journal of Surgery 183 (2002) 608 613

Scientic paper

Standardized patient care guidelines reduce infectious morbidity in appendectomy patients

Kenneth S. Helmer, M.D., Emily K. Robinson, M.D.*, Kevin P. Lally, M.D., J. C. Vasquez, B.A., Karen L. Kwong, M.D., Terrence H. Liu, M.D., David W. Mercer, M.D.
Department of Surgery, The University of Texas-Houston Medical School and LBJ General Hospital, 5656 Kelley St., Ste. 3-OS 62008, Houston, TX 77026, USA Manuscript received October 15, 2001; revised manuscript February 2, 2002

Abstract Background: Surgical wound infection and intra-abdominal abscess remain common infectious complications after appendectomy, especially in the setting of a perforated or gangrenous appendix. We therefore developed a clinical protocol for the management of appendicitis to decrease postoperative infectious complications. Methods: Between January 1, 1999, and December 31, 1999, 206 patients with appendicitis were treated on protocol. Retrospectively, the charts were reviewed for all protocol patients as well as for 232 patients with appendicitis treated in the year prior to protocol initiation. Data were collected on surgical wound infections and intra-abdominal abscesses. Results: There were signicantly fewer infectious complications in the protocol group than in the nonprotocol group (20 [9%] versus 8 [4%]; P 0.05). In patients with a perforated or gangrenous appendix, the infectious complication rate was reduced from 33% to 13% (P 0.05). Conclusions: The incidence of infectious complications after appendectomy can be signicantly reduced with a standardized approach to antibiotic therapy and wound management. 2002 Excerpta Medica, Inc. All rights reserved.
Keywords: Appendectomy; Antibiotics; Algorithm; Perforated appendix; Surgical complication; Secondary infectious peritonitis

Appendectomy is the fourth most frequent intra-abdominal operation performed in the United States [1]. Although a simple operation, an appendectomy is often complicated by a postoperative infection, most commonly a wound infection or an intra-abdominal abscess. The rates range from 10% to18%, depending on the degree of contamination found at operation [2]. Although there is little variation among surgeons in the management of early appendicitis, clinical practice differs greatly in the management of a perforated or gangrenous appendix. When surgeons at our institution were surveyed, we found a wide disparity in the choice of antimicrobial therapy, the duration of antimicrobial therapy, the use of

antibiotics in irrigation uid, the role of intraoperative cultures, or the use of delayed primary wound closure. In this setting, we had a 9% incidence of postappendectomy wound infections and intra-abdominal abscess overall. However, in patients with a perforated or gangrenous appendix, the incidence of infectious complications increased to 33%. Given this high rate of infectious complications, we instituted a clinical practice protocol in an attempt to standardize our management of appendicitis, especially in the setting of a gangrenous or perforated appendix. We hypothesized that the rate of infectious complications could be reduced by implementation of an evidence-based clinical practice guideline for the management of appendicitis.

* Corresponding author. Tel.: 1-713-566-5095; fax: 1-713-5664583. E-mail address: emily.k.robinson@uth.tmc.edu These data were presented at the Southwestern Surgical Congress, Cancun, Mexico April 2000.

Methods A clinical practice protocol (Fig. 1) was developed after a critical review of the literature and was introduced as

0002-9610/02/$ see front matter 2002 Excerpta Medica, Inc. All rights reserved. PII: S 0 0 0 2 - 9 6 1 0 ( 0 2 ) 0 0 8 6 0 - 7

K.S. Helmer et al. / The American Journal of Surgery 183 (2002) 608 613

609

Fig. 1. Standardized protocol for appendicitis. ABX

antibiotics; WBC

white blood cell; D/C

discontinue.

standardized guidelines for the management of patients with appendicitis at the Lyndon Baines Johnson County Hospital in Houston, Texas. All patients with a presumptive diagnosis of appendicitis, including pediatric patients (age 17 years), were treated by protocol beginning January 1, 1999. At the end of a 12-month period, the charts of all protocol patients were reviewed. The charts of all patients treated for appendicitis in the 12 months prior to the initiation of the protocol (January 1,1998 to December 31, 1998) were also reviewed to serve as historic controls. There were no exclusion criteria. The following information was recorded for each patient: age, sex, date and time of hospital admission and operation, duration of symptoms, additional diagnosis, white blood cell count, intraoperative and pathologic ndings, antibiotics used preoperatively and postoperatively, the use of intraoperative irrigation, the method of wound closure, and the development and treatment of postoperative infectious complications. Complications were divided into surgical wound infections, intra-abdominal abscess, or both. A surgical wound infection was dened as purulent drainage from the wound, cellulitis requiring antibiotics, or the opening of a closed wound. An intra-abdominal abscess was dened as an intraabdominal uid collection that contained purulent material. A perforated appendix was dened by operative evidence of a hole in the appendix, free uid in the abdomen or an abscess cavity noted during surgery. A gangrenous appendix was dened as the gross appearance of necrosis involv-

ing the appendix as visualized during surgery. The clinical practice guidelines were as follows. Antibiotic therapy All patients with an initial diagnosis of appendicitis received preoperative antibiotics and were taken to the operating room to undergo appendectomy. In patients with suspected nonperforated appendicitis, a single preoperative dose of a second-generation cephalosporin was given within 30 minutes of incision time. Patients with a suspected gangrenous or perforated appendix preoperatively received combination antibiotic therapy effective against facultative gram-negative enteric bacteria as well as against obligate anaerobic bacilli (levooxacin or gentamicin and metronidazole). If the intraoperative ndings conrmed a nonperforated or nongangrenous appendix, then antibiotics were discontinued. If a gangrenous or perforated appendix was found, then combination antibiotic therapy was instituted or continued for a minimum of 7 days or until the patient had defervesced, had a normal white blood cell count, and had return of bowel function; whichever was longer. If patients did not meet these clinical criteria, and no other obvious source of infection was present, then a computed tomography (CT) scan of the abdomen and pelvis was obtained. Identied abscesses were drained percutaneously and cultures sent. Antibiotics were tailored to the identied pathogen and continued until the abscess had resolved and the

610

K.S. Helmer et al. / The American Journal of Surgery 183 (2002) 608 613 Table 1 Infectious complications Complication Nonprotocol (n Adults (n 138) Wound infection Intra-abdominal abscess Both Total 5 3 3 11 (8%) 232) Children (n 94) 3 3 3 9 (9%) 20 (9%) Protocol (n Adults (n 131) 2 3 0 5 (4%) 206) Children (n 75) 1 1 1 3 (4%) 8 (4%)*

above criteria met. If no intra-abdominal abscess was found and there was no surgical wound infection, then a search for another source of infection or another diagnosis was begun and the patient treated accordingly. If the patient continued with signs of infection, there was no abscess, and there was no other identiable source, then imipenem/cilastatin was begun. Pediatric patients with a gangrenous or perforated appendix were treated with gentamicin and metronidazole. Gentamicin was dosed once a day. Wound closure In patients with a gangrenous or perforated appendix, the wound (skin and subcutaneous tissue) was left open. The wound was allowed to heal by secondary intention or delayed primary closure was performed on postoperative day 4 or 5 if the wound was clean. Quantitative wound cultures were not done. In the setting of simple appendicitis, the wound was closed primarily. Peritoneal cultures and irrigation If a diffuse intra-abdominal infection or a localized abscess was found at operation, all infectious uids and particulate matter were removed. Warm saline irrigation, without antibiotics in the irrigation uid, was performed. At initial operation, no peritoneal cultures were obtained. Wound infection If a patient developed a postoperative wound infection as evidenced by purulent drainage, cellulitis, or wound dehiscence, the wound was opened and a sample of uid sent for gram stain and cultures. Wet to dry dressing changes were then instituted. Antibiotics were begun if there was evidence of cellulitis, of deep tissue penetration, of systemic toxicity, or in the presence of an immunosuppresed host or an indwelling prosthetic device. Statistics Statistical signicance was determined using chi-square analysis. A P value of 0.05 was considered to be statistically signicant.

*P

0.05 versus nonprotocol.

Results In the 12 months prior to initiation of our standardized management a total of 232 patients underwent appendectomy. After initiation of our protocol, 206 patients underwent appendectomy. As shown in Table 1, in the historical controls or nonprotocol group, a total of 20 (9%) infectious complications occurred in the 232 patients. Of these infec-

tious complications 8 were surgical wound infections (SWI), 6 were intra-abdominal abscess (IAA), and 6 were both SWI and IAA. The majority of patients with isolated SWI had their complication treated with opening and drainage of the wound that had been previously closed. However, 2 pediatric patients required operative wound debridement, and both recovered without further complications. Twelve patients developed IAA, 2 of which (1 adult, 1 pediatric) were treated with antibiotics alone. Nine patients (5 adults, 4 pediatric) required percutaneous drainage of abscesses and 2 pediatric patients required operative drainage, 1 after failed percutaneous treatment. One pediatric patient required reoperation for an adhesive small bowel obstruction after percutaneous drainage of an abscess. None of the adults required operative intervention for treatment of their infectious complications. Table 1 also demonstrates that there were signicantly fewer infectious complications in the protocol patients than in the nonprotocol patients 4% versus 9% (P 0.05). Among the complications in the protocol group, 3 were SWI, 4 were IAA, and 1 was both. Three patients (1 adult, 2 pediatric) required opening of previously closed wounds for the treatment of SWI, 2 of which (pediatric patients) were closed in violation of the protocol. Three patients (2 adults, 1 pediatric) with IAA required percutaneous drainage whereas 2 others (1 adult, 1 pediatric) were treated with antibiotics alone. No patient in the protocol group required reoperation. There were no deaths in either the protocol or nonprotocol group. The infectious complications in patients who had a gangrenous or perforated appendix are listed in Table 2. In the nonprotocol group 48 (20%) of the 232 patients were found to have a gangrenous or perforated appendix versus 37 (18%) of the 206 patients treated on protocol. As shown, when comparing nonprotocol with protocol patients with a perforated or gangrenous appendix, the infectious complication rate was signicantly reduced from 33% to 13% (P 0.05). There was no signicant improvement in the number of infectious complications in patients with simple ap-

K.S. Helmer et al. / The American Journal of Surgery 183 (2002) 608 613 Table 2 Infectious complications in patients with a perforated or gangrenous appendix Complication Nonprotocol (n Adults (n Wound infection Intra-abdominal abscess Both Total *P 0.05 versus nonprotocol. 2 2 3 7 (24%) 16 (33%) 29) 48) Children (n 3 3 3 9 (47%) 19) Protocol (n Adults (n 1 2 0 3 (10%) 5 (13%)* 37) 28) Children (n 1 0 1 2 (22%)

611

9)

pendicitis when patients treated on protocol were compared with those patients not on protocol (Table 3).

Comments We instituted clinical practice guidelines for the management of appendicitis in an attempt to decrease postoperative infectious complications in a county hospital population. Our protocol was designed to aggressively treat the secondary infectious peritonitis associated with a gangrenous or perforated appendix using guidelines established by the Surgical Infection Society [3]. In addition, the protocol established wound care guidelines and directed management of postoperative infectious complications. In this study, we demonstrated that evidence-based guidelines were superior to surgeon directed management of complicated appendicitis as reected by the reduction in infectious complications after appendectomy. Antibiotics have been shown to reduce the incidence of postoperative infectious complications after operations in patients with secondary infectious peritonitis [35]. Antibiotic therapy in the setting of secondary infectious peritonitis is based on the pathogens likely to be encountered and their presumed contribution to the overall virulence of the infectious process. Thus our protocol design mandated the use of appropriate antibiotics effective against facultative gramnegative enteric bacteria as well as obligate anaerobic bacilli in the setting of gangrenous or perforated appendicitis [3 6]. Although newer single agents could provide similar coverage as our combination therapy, these agents are not
Table 3 Infectious complications in patients with simple appendicitis Complication Nonprotocol (n Adults (n Wound infection Intra-abdominal abscess Both Total 3 1 0 4 (4%) 4 (2%) 109) 184)

available at our facility without approval from the infectious disease staff owing to budget considerations. We therefore chose a combination of antibiotics that would provide adequate coverage that we could dispense without approval thereby decreasing the intricacy of care. The duration of antibiotic usage was also mandated in our protocol. Specifically, antibiotics were continued for a minimum of 7 days or until the patient was afebrile, had resolution of their leukocytosis, and had return of their bowel function. While the optimal duration of antibiotic therapy remains controversial in the treatment of secondary infectious peritonitis [7,8], the probability of a recurrent or residual infection is low if the patient meets the above criteria [9]. Similar clinical algorithms for the treatment of complicated appendicitis in the pediatric population have been used to determine resolution of intra-abdominal sepsis [10,11]. Both studies reported a low incidence of infectious complications, around 3%, which compares favorably with our 4% incidence overall in both adults and children. The majority of the data to support clinical algorithms in the management of complicated appendicitis comes form retrospective reviews of pediatric populations. Lund and Murphy [12] most recently reported a gold standard protocol in 1994. This protocol mandates operative exploration with appendectomy, limited peritoneal debridement, antibiotic irrigation, Penrose drain placement, wound closure, and intravenous antibiotics for 10 days. These authors reported an 8% incidence of major infectious complications in 143 pediatric patients with perforated appendicitis. Prior studies in the pediatric population have reported similar rates [10, 13]. Our infectious complication rate in pediatric patients

Protocol (n Children (n 0 0 0 0 (0%) 75) Adults (n 1 1 0 2 (2%)

169) 103) Children (n 0 1 0 1 (1%) 3 (2%) 66)

612

K.S. Helmer et al. / The American Journal of Surgery 183 (2002) 608 613

with perforated or gangrenous appendicitis (22%) is above the published rate. However, our denition of perforation differed from that used by Lund and Murphy. We included only those patients with obvious gangrene or gross perforation as determined by visual inspection. Their denition included patients with operative evidence of a hole in the appendix, the presence of free pus or an abscess cavity noted during surgery, growth of enteric organisms from peritoneal cultures, or evidence of a perforation noted during pathologic evaluation. Thus it is probable that the degree of contamination in our subset of patients is higher, leading to a higher percentage of postoperative infectious complications. In addition, the sample size for this subset of patients (n 9) in our study is rather small, making interpretation difcult. Our results from a mixed adult and pediatric population are in accord with data published for the adult population that site infectious complication rates ranging from 13% to 18% [2,8]. The role of peritoneal cultures taken at the initial operation to guide systemic therapy for secondary infectious peritonitis remains controversial. It is clear that inadequate empiric antibiotic therapy results in increased postoperative wound infections and abscesses, higher reoperation rates, longer hospital stays, and consequently presents an economic burden to patients [14]. However, the rate of these postoperative complications was not altered by changing antibiotics on the basis of intraoperative culture results alone [14]. In fact, in one study culture results lead to a change in antibiotics in fewer than 10% of patients [15]. Moreover, Soffer et al [16] found that most cultured organisms were sensitive, not resistant, to the antibiotics that were initiated originally. In addition, Hopkins et al [17] demonstrated that while resistant organisms from the intraoperative cultures may contribute to the development of postoperative infection, a signicant number of patients are cured despite their presence. Nonetheless, there are certain patient populations who might benet from obtaining intraoperative cultures such as those who have been on antibiotics previously, patients in whom a recurrent or postoperative infection has occurred, and in immunocompromised patients [4]. Owing to our high incidence of surgical wound infections in the setting of a perforated or a gangrenous appendix (25%), our protocol mandated the wound remain open if either were found at operation. Authors practicing in a county hospital similar to ours found a vefold increase in surgical wound infection if primary wound closure was performed in the setting of perforated appendicitis in the adult population [18]. Consequently, our results conrm and extend these observations. Nonetheless, a recent meta-analysis supports the contention of other authors that wound closure in complicated appendicitis does not increase the rate of incision infection [19]. In this analysis, leaving the wound open did not alter the mean wound infection rate of 4.7%. Burnweit et al [20] advocated wound closure in the pediatric population despite evidence of a perforated or

gangrenous appendix. However, they were willing to accept a slightly higher incidence of wound infection (11%) than the 5% incidence we saw when the wound was left open (ie, excluding protocol violations) in our protocol patients. The 1 pediatric patient with a wound infection in the perforated/ gangrenous subgroup had their wound closed in violation of the protocol guidelines. In our experience, pediatric patients, regardless of age, tolerated delayed primary closure of the wound quite well. The closure was performed with paper tape or by tying nylon sutures placed at the time of operation. In conclusion, our ndings indicate that the incidence of infectious complications after appendectomy can be significantly reduced with a standardized approach to wound treatment and antibiotic therapy in a mixed adult and pediatric population admitted to a county facility. These data are the rst to show a clear improvement in outcome at a single institution by the application of such an algorithm. Our clinical practice guidelines for the treatment of appendicitis signicantly reduced our infectious complication rate in a 12-month period from 9% to 4%. Moreover, in patients that were found to have a gangrenous or perforated appendix, and therefore more likely to have concomitant secondary infectious peritonitis, our protocol signicantly reduced the infectious complication rate from 33% to 13%. Further studies are necessary to determine whether implementation of such practice guidelines is efcacious in other hospital settings. References
[1] Elishauser A. Descriptive statistics by insurance status for the most frequent hospital diagnosis and procedures. Silver Spring, MD: AHCPR Publications Clearinghouse, 1997. [2] Styrud J, Granstrom L. Treatment of perforated appendicitis: an analysis of 362 patients treated during 8 years. Dig Surg 1998;15: 683 6. [3] Bohnen JM, Solomkin MD, Dellinger EP, et al. Guidelines for clinical care: anti-infective agents for intra-abdominal infection. Arch Surg 1992;127:839. [4] Nathens AB, Rotstein OD. Antimicrobial therapy for intraabdominal infection. Am J Surg 1996;172(suppl 6A):1 6. [5] Wittmann DH, Schein M, Condon RE. Management of secondary peritonitis. Ann Surg 1996;224:10 18. [6] Whittmann DH, Bergstein JM, Frantzides C. Calculated empiric antimicrobial therapy for mixed surgical infections. Infection 1991; 19(suppl 6):34550. [7] Condon RE, Whitmann DH. The use of antibiotics in general surgery. Curr Prob Surg 1991;28;803949. [8] Taylor E, Dev V, Shat D, et al. Complicated appendicitis: is there a minimum intravenous antibiotic requirement? A prospective randomized trial. Am Surg 2000;66:88790. [9] Lennard ES, Dellinger EP, Wertz MJ, Minshew BH. Implications of leukocytosis and fever at conclusion of antibiotics for intra-abdominal sepsis. Ann Surg 1982;195:19 23. [10] Keller MS, McBride WJ, Vane DW. Management of complicated appendicitis. Arch Surg 1996;131:261 4. [11] Hoelxer DJ, Zabel DD, Zern JT. Determining duration of antibiotic use in children with complicated appendicitis. Pediatr Infect Dis J 1999;18:979 82.

K.S. Helmer et al. / The American Journal of Surgery 183 (2002) 608 613 [12] Lund DP, Murphy EU. Management of perforated appendicitis in children: a decade of aggressive treatment. J Pediatr Surg 1994;29:11303. [13] Curran TJ, Muenchow SK. The treatment of complicated appendicitis in children using peritoneal drainage: results from a public hospital. J Pediatr Surg 1993;28:204 8. [14] Mosdell DM, Morris DM, Voltura A, et al. Antibiotic treatment for surgical peritonitis. Ann Surg 1991;214:5439. [15] Dougherty SH, Saltzstein EC, Peacock JB, et al. Perforated or gangrenous appendicitis treated with aminoglycosides. Arch Surg 1989; 124:1280 1. [16] Soffer D, Zait S, Klausner J, Kluger Y. Peritoneal cultures and antibiotic treatment in patients with perforated appendicitis. Eur J Surg 2001;167:214 16. [17] Hopkins JA, Lee JC, Wilson SE. Susceptibility of intra-abdominal isolates at operation: a predictor of postoperative infection. Am Surg 1993;59:791 6. [18] Lemieur TP, Rodriquex JL, Jacobs DM, et al. Wound management in perforated appendicitis. Am Surg 1999;65:439 43. [19] Rucinski J, Fabian T, Panagopoulos G, et al. Gangrenous and perforated appendicitis: a meta-analytic study of 2532 patients indicates that the incision should be closed primarily. Surg 2000;127:136 41. [20] Burnweit C, Bilik R, Shandling B. Primary closure of contaminated wounds in perforated appendicitis. J Pediatr Surg 1991;12:13625.

613

Editorial comment It is very uncommon for a paper to be recommended by all of the reviewers to accept as is. Yet that certainly applies to the preceding paper by Helmer and associates. I agree wholeheartedly with the concept of the paper. But one unfortunate thing is their choice of antibiotics that are outmoded. One should also carefully consider the risks associated with the use of standardized antibiotics, especially in an era when patients have many other factors that predispose them to renal failure. Aside from that, this paper is a commendable effort that more of us need to follow. Hiram C. Polk, Jr., M.D. Professor and Chairman Department of Surgery University of Louisville Louisville, KY 40292