Single-dose antibiotic prophylaxis for patients undergoing extended pelvic surgery for gynecologic malignancy James W. Orr, Jr., MD: Pamela F. Sisson, RN: Bruce Patsner, MD: Jeffrey M. Barrett, MD: John R. Ellington, Jr., MD: Ralph Henry Jennings, Jr., MD: Keith B. Paredes, MD: Dale L. Taylor, MD: Seng Jaw Soong, PhD/ and Cathy Roe" Lakeland, Florida, and Birmingham, Alabama The comparative efficacy of single-dose antibiotic prophylaxis was retrospectively evaluated in 116 patients undergoing extended pelvic surgical procedures with curative intent. During the 24-month period, other important variables such as surgeon's experience, duration of preoperative hospitalization, preoperative preparation, method of hair removal, suture type, suture size, use of drains, use of cautery, and abdominal closure were controlled. The overall surgical site'infection rate was 4.3% after radical hysterectomy with lymphadenectomy and 4.5% after total hysterectomy with lymphadenectomy. In this clinical situation the use of a single dose of antibiotic prophylaxis theoretically decreases cost and patient exposure and appears to be as efficacious as a multiple-dose regimen. (AM J OasTET GVNECOL 1990;162:718-21.)
Key words: Antibiotic prophylaxis, cancer, surgery The ultimate goal of surgical therapy for reproductive tract malignancy is long-term survival. However, reducing surgical morbidity must be an important part of every gynecologic oncologist's treatment plan. After extended pelvic procedures, infectious morbidity remains a major risk and, when present, increases hospital stay, cost, and patient discomfort and predisposes to additional morbidity. I Although many factors are involved, the use of prophylactic antibiotics has been claimed to reduce the risk of infection after "extended" pelvic procedures!·7 however, some reports question their benefit. 8 • 9 After total hysterectomy, information suggests that a single preoperative dose of antimicrobial prophylaxis is as effective as multiple doses in reducing the risk of postoperative surgical site infection. 1O However, little information is available to indicate that this is true with extended procedures, and most reports evaluate the benefit of multiple-dose prophylaxis. This report details the comparative effects of single-dose antibiotic prophylaxis and a multiple-dose regimen in those patients requiring an extended pelvic surgical procedure.
Methods and material During this 24-month study, the charts of all patients undergoing radical hysterectomy and pelvic lymphadenectomy or total abdominal hysterectomy and pelvic From the Division of Gynecologic Oncology, Watson Clzmc,' and the DIVision of Biostatistics, University of Alabama in B!rmmgham.' Received for pubhcatzon November 28, 1988; revised November 2, 1989; accepted November 15, 1989. Reprint requests: James W. Orr, Jr., MD, D!vision of Gynecologic Oncology, Watson Clmic, Lakeland, FL 33805. 6/1118224
718
lymphadenectomy as primary treatment for cervix or endometrial cancer were evaluated. Patients having preoperative infection, additional contaminated surgical procedures, or recent «72 hours) therapeutic doses of antibiotics were eliminated from further evaluation. No patient had preoperative radiation. All procedures were performed by a gynecologic oncologist and all patients were admitted under a strict protocol of preoperative and intraoperative management. Each had a complete hematologic and biochemical evaluation and chest radiographs. Intravenous pyelography and barium enemas were performed as indicated. All patients underwent' a mechanical (without antibiotic) bowel preparation. Preoperative hospitalization was minimized «48 hours). No preoperative douching was performed. Hair clipping, when deemed necessary, was performed in the operating room. Intraoperative skin and vaginal preparation involved a Betadine preparation scrub. The initial incision was inscribed boldly and electrocautery was used only to secure hemostasis. Only 2-0 polyglycolic acid suture was used during the pelvic operation. Hemostatic clips were used sparingly, not to occlude efferent or afferent lymphatics. The technique of radical hysterectomy and pelvic lymphadenectomy has been described elsewhere. 2 Total lymphadenectomy and periaortic node biopsy were done in those patients undergoing total hysterectomy and pelvic lymphadenectomy. Suprapubic bladder drainage was established in all patients undergoing radical hysterectomy and pelvic lymphadenectomy. At the completion of each procedure, copious (>200 ml) pelvic irrigation was performed with warm sterile water. All fluids were removed. No peritoneal surfaces were closed. Fascial closure incorporated only monofilament sutures. After fascial closure, the subcutaneous
Antibiotic prophylaxis in cancer surgery 719
Volume 162 Number 3
Table I. Characteristics of patients Radical hysterectomy and pelvIc lymphadenectomy Single-dose
No.
I
24 83.3 46.3 :t 14 (28-69) 145.5 :t 31 (99-213) 2.25 :t 0.4 ( 1.6-3.0) 1104 :t 566 (600-3000) 70.8 6.9 :t 1.6 41.7 4.2
White (%) Age (yr) Weight (pounds) Duration of surgery (hr) Estimated blood loss (ml) Transfused (%) Postoperative stay (days) Febrile morbidity (%) Infectious morbidity (%)
Total hysterectomy and pelvIc lymphadenectomy
MultIple-dose
Single-dose
22 86.4 48.6 :t 14 (22-71) 147.8 ± 30 (109-190) 2.45 ± 0.7 ( 1.3-4.5) 1126 ± 756 (400-3000) 68.2 7.1 ± 1.8 45.4 4.5
35 97.1 67.7 ± 11 (39-85) 153.7 ± 40 (88-287) 1.3 ± 0.2 (1.0-1.9) 289 ± 198 (125-800) 2.9 6.4 ± 1.5 17.1 2.9
I
Multiple-dose
31 96.8 65.9 ± 11 (39-83) 170.9 ± 43 (98-245) 1.6 :t 0.5 (1.0-1.9) 397 ± 207 (175-1000) 6.5 6.7 ± 2.5 32.3 6.5
Values are mean ± SD. Ranges are in parentheses.
Table II. Comparison of drugs and dose regimens Radical hysterectomy and pelvic lymphadenectomy M ult!ple-dose
Single-dose Drug
n
Cefoxitin (2 gm) Cefotetan (2 gm) Metronidazole (500 mg)
23
I
%
n
95.8 4.2
I
Single-dose
%
n
20
90.9
2
9.1
19 9 7
tissues were thoroughly irrigated under pressure. No subcutaneous sutures or drains were placed and skin closure involved clips. All patients undergoing radical hysterectomy and pelvic lymphadenectomy had closed suction pelvic drainage. No patient having total hysterectomy and pelvic lymphadenectomy had closed suction drainage. All patients received supplemental (2L by nasal prong) oxygen during the postoperative period for at least 24 hours. No patient received prophylactic heparin, and pneumatic calf compression was done routinely. Antibiotics were administered intravenously after the patient entered the operating room. The maximal time before incision was 45 minutes. In those patients receiving multiple doses, a second intravenous dose was given at 8 and 16 hours. Postoperatively, each patient was evaluated by at least two of us. Standard febrile morbidity was defined as temperature >38 C on two separate occasions at least 4 hours apart, excluding the initial 24 postoperative hours. Infectious morbidity was defined as continued temperature elevation, not responding to conservative measures and pulmonary manipulation. At that time appropriate evaluation and broad spectrum antibiotic therapy, consisting of an aminoglycoside and anaerobic coverage, was begun. No patient was discharged on a regimen of oral antibiotics. 0
Total hysterectomy and pelvic lymphadenectomy
I
M ulttple-dose
%
n
54.3 25.7 20.0
23 6 2
I
% 74.1 19.4 6.5
Results
During the 24 months of this study, 46 patients who underwent radical hysterectomy and pelvic lymphadenectomy as primary treatment for invasive cervical cancer were evaluable. An additional 66 patients (all with a clinical or histologic risk of nodal metastases) underwent total hysterectomy and pelvic lymphadenectomy, as well as periaortic node biopsy, as primary treatment for uterine malignancy. As expected, differences existed between patients undergoing radical hysterectomy and pelvic lymphadenectomy and those having total hysterectomy and pelvic lymphadenectomy (Table I). Patients undergoing radical hysterectomy and pelvic lymphadenectomy had a significantly increased mean operative time (p < 0.001), had a younger mean age (p < 0.001), and weighed less (p < 0.04) than those undergoing total hysterectomy and pelvic lymphadenectomy. There was no patient characteristic difference in those undergoing radical hysterectomy and pelvic lymphadenectomy, regardless of dosage regimen. The same applied for those undergoing radical hysterectomy and pelvic lymphadenectomy. Considering all patients, there was no significant difference in weight, age, presence of medical illness, or postoperative stay when comparing single-dose and multipledose regimens. The majority of patients received cephalosporin prophylaxis (89.3%); however, penicillin-
720
Orr et al.
March 1990 Am J Obstet Gynecol
Table III. Extended hysterectomy and infectious morbidity Author
Orr et al. 2 (l982) Rosenshein et aJ.3 (1983) Sevin et al. 4 (1984) Marsden et al. B (1985) Micha et aI.' (l987) Miyazawa et aI.' (1987)
Febnle morbidity
MflJor morbidity
%
Hospital stay (days)
OperatIVe time (hr)
Blood loss (ml)
Cephalosporin (5-7 days) None
32.4 41.5
18.9 26.8
9.8 12.0
3.7
1800
64.5t 84.5 41.7 88.9 26.6 80.0 109t
11.8 26.7 15.3 52.8 3.0 16.0 6.6 67.7 87.5
16.1 15.6 15.6 18.0 12.0 12.0 10.1 10.4
3.9 3.7 6.1 5.5 3.1 3.6 3.7 4.0 5.4
2400 1600 765 832 840 1013 2196
71
63.6
4.6
1851
26
Doxycycline (1 dose)* None Cefoxitin (12 dose) None Cefoxitin (12 dose) None Mezlocillin (3 dose) None None Cefamandolel doxycycline «48 hr) Cefamandole I doxycycline «48 hr) + cefamandole irrigation
30
3.8
4.4
1544
35 24 25
None Mandol (5 dose) None
2.6 3.2 3.2
525
No. of patients
AntibIOtic
270 41 34 30 26 27 31 43 15 15 8 11
Bendvold and Kjorstad 9 (1987) Creasman et al. 6 (1982)
%
17 12.5 45.8
0 4.2 36.0
10.1 8.2 9.0
*Bowel preparation. tFever index.
allergic patients received metronidazole (Table II). There was no difference in infection rates evaluated by drug used. The overall surgical site infection rate was 4.5% and did not differ between radical hysterectomy and pelvic lymphadenectomy (4.3%) and total hysterectomy and pelvic lymphadenectomy (4.5%). There was no difference in infection rate in patients undergoing radical hysterectomy and pelvic lymphadenectomy or total hysterectomy and pelvic lymphadenectomy, regardless of the antibiotic regimen. In either procedure there was no significant correlation between age, race, duration of surgery. blood loss, and risk of infection. However, if patients developed a postoperative infection, their hospital stay was longer (10 days). Febrile morbidity was common after radical hysterectomyand pelvic lymphadenectomy (43.5%) and total hysterectomy and pelvic lymphadenectomy (24.2%). The usual cause was pulmonary-related; however, pneumonia did not occur in any patients. No patient had a symptomatic pelvic Iymphocyst, and no ureteral vaginal fistulas occurred.
Comment Surgical extirpation with curative intent remains an important treatment aspect of patients with early invasive cervical cancer or endometrial cancer. Both procedures involve extended pelvic surgery, including lymphadenectomy. Occasionally certain inherent risks such as prolonged preoperative diagnostic hospitalization, an altered immunologic system, older age, prolonged procedures, increased blood loss, and altered
nutritional status are present. Faced with this problem, the majority (84%) of gynecologic oncologists use prophylactic antibiotics during radical hysterectomy and pelvic lymphadenectomy, and 16% of those use multiple agents .. To date, only eight studies have evaluated the efficacy of prophylactic antibiotics after extended hysterectomy.2.9 Most indicate a benefit of prophylactic antibiotics during extended hysterectomy (Table III); however, at least two studies question their benefit."' 9 Although retrospective, this study was performed in patients with a standard method of preoperative preparation and control over the variable of surgical experience. Previous studies report patients operated on by surgeons of varied experience with data collected over a long period of time. Operative times, blood loss, socioeconomic status, and the use of preoperative radiation may vary greatly. Only one previous study has evaluated the efficacy of single-dose prophylaxis.' While fever index was lowered, data concerning morbidity were lacking. This information is in contrast to that for non radical hysterectomy, where single-dose prophylaxis has been reported to be as efficacious as a multiple-dose regimen. IO Anecdotal accounts suggest that multiple doses are needed because of prolonged operative times. In nonradical hysterectomy, the benefit of prophylactic antibiotics decreases sharply when operative time approaches 3 hours, II the usual operative time for radical hysterectomy and pelvic lymphadenectomy and reported times for total hysterectomy and pelvic lymphadenectomy.6.12 Some indicate the need to use prolonged preoperative treatment to increase tissue levels of the prophylactic drug.' However. information
Volume 162 ]\;umber 3
regarding commonly used prophylactic drugs indicates that most tissue levels contain more than inhibitory antibiotic levels after a single preoperative dose. 13 This report is the first to compare a single-dose regimen and a multiple-dose regimen and find them to be equally efficacious. Interestingly, one report6 indicates a relatively high risk of drain site infection, which may be explained in part by relatively low antibiotic tissue levels in the subcutaneous fat.I3 While large volumes of fluid may be evacuated with closed suction drainage, 12 when compared with open cuff drainage, there is no protective effect against infection. 12 In fact, one must question the benefit of long-term closed suction drainage with its potential adverse effects on fluid and electrolyte replacement, as well as nutritional status. This study suggests that pelvic drainage may not be necessary to prevent lymphocyst or other complications after certain types of extended pelvic surgery (total hysterectomy and pelvic lymphadenectomy). In fact, drains may predispose to infection as they contaminate the subcutaneous tissues, an area of low blood flow and lowered tissue levels of effective antibiotics. 13 While data are lacking to clearly support the use of a second-generation cephalosporin, we chose to use cefoxitin because of previous studies indicating its efficacy< and its expanded bacterial coverage when compared with first-generation antibiotics. The substitution of cefotetan (because of a change in hospital formulary) in some patients allowed use of a drug with a similar antimicrobial spectrum. Although the serum half-life of the latter drug is reportedly longer, there is little information to indicate an effect on important tissue levels. Although both drugs are effective, approximately 10% of the population claim a penicillin allergy. While cephalosporin "crossover" reactivity may not be common, we chose to administer metronidazole to any patient who claimed a penicillin allergy. While antimicrobial coverage differs, metronidazole is an effective prophylactic agent when used during nonradical gynecologic surgeryl and offers an alternative so as not to place the patient at risk for antimicrobial reaction. In conclusion, this report suggests that attention to preoperative preparation and intraoperative tech-
Antibiotic prophylaxis in cancer surgery
721
nique, when combined with single-dose antimicrobial prophylaxis, is associated with a low risk of infectious morbidity after extended pelvic procedures for the treatment of patients with gynecologic cancer. Future prospective studies must attempt to control for preoperative and intraoperative variables that alter the risk for postoperative infection. REFERENCES 1. Orr JW Jr, Taylor PT. Avoiding postoperative infection in the patient with gynecologic cancer. Infect Surg 1987; 12:666-75. 2. Orr JW Jr, Shingleton HM, Hatch KD, et al. Correlation of perioperative morbidity and conization-radical hysterectomy interval. Obstet Gynecol 1982;59:726-39. 3. Rosenshein NB, Ruth JC, Millar I, et al. A prospective randomized study of doxycycline as a prophylactic antibiotic in patients undergoing radical hysterectomy. GynecoIOncoI1983;15:201-6. 4. Sevin BU, Ramos R, Lichtinger M, et al. Antibiotic prevention of infections complicating radical abdominal hysterectomy. Obstet Gynecol 1984;64:539-45. 5. MichaJP, Kucera PR, BurkettJP, et al. Prophylactic mezlocillin in radical hysterectomy. Obstet Gynecol 1987;69: 251-4. 6. Creasman WT, Hill GB, Weed JC, et al. A trial of prophylactic cefamandole in extended gynecologic surgery. Obstet Gynecol 1982;59:309-14. 7. Miywzawa K, Hernandez E, Dillon MD. Prophylactic topical man dol in radical hysterectomy. Int J Gynecol Obstet 1987 ;25: 133-8. 8. Marsden DE, Cavanagh D, Wisniewski BJ, Roberts WS, Lyman GH. Factors affecting the incidence of infectious morbodity after radical hysterectomy. AM J OBSTET GvNECOL 1985;152:817-21. 9. Bendvold E, Kjorstad KE. Antibiotic prophylaxis for radical abdominal hysterectomy. Gynecol Oncol 1987;28: 201-4. 10. Orr JW Jr, Sisson PF, Barrett JM, Ellington JR, Jennings RH, Taylor DL. Single-center study results of cefotetan and cefoxitin prophylaxis for abdominal or vaginal hysterectomy. AMJ OBSTET GVNECOL 1988;158:714-6. 11. Shapiro M, Munoza, Tager I, et al. Risk factors for infection at the operative site after abdominal or vaginal hysterectomy. N Engl J Med 1982 ;307: 1661-6. 12. Orr JW Jr, Barter JF, Kilgore LC, Soong SJ, Shingleton HM, Hatch KD. Closed suction pelvic drainage after radical pelvic surgical procedures. AM J OBSTET GVNECOL 1986; 155:867-71. 13. Orr JW Jr, Sisson PF, BarrettJM, EliingtonJR,Jennings RH, Taylor DL. Pharmacokinetics and tissue kinetics of 1 gm cefotetan prophylaxis AM J OBSTET GVNECOL 1988;158:742-3.
Key words: Antibiotic prophylaxis, cancer, surgery The ultimate goal of surgical therapy for reproductive tract malignancy is long-term survival. However, reducing surgical morbidity must be an important part of every gynecologic oncologist's treatment plan. After extended pelvic procedures, infectious morbidity remains a major risk and, when present, increases hospital stay, cost, and patient discomfort and predisposes to additional morbidity. I Although many factors are involved, the use of prophylactic antibiotics has been claimed to reduce the risk of infection after "extended" pelvic procedures!·7 however, some reports question their benefit. 8 • 9 After total hysterectomy, information suggests that a single preoperative dose of antimicrobial prophylaxis is as effective as multiple doses in reducing the risk of postoperative surgical site infection. 1O However, little information is available to indicate that this is true with extended procedures, and most reports evaluate the benefit of multiple-dose prophylaxis. This report details the comparative effects of single-dose antibiotic prophylaxis and a multiple-dose regimen in those patients requiring an extended pelvic surgical procedure.
Methods and material During this 24-month study, the charts of all patients undergoing radical hysterectomy and pelvic lymphadenectomy or total abdominal hysterectomy and pelvic From the Division of Gynecologic Oncology, Watson Clzmc,' and the DIVision of Biostatistics, University of Alabama in B!rmmgham.' Received for pubhcatzon November 28, 1988; revised November 2, 1989; accepted November 15, 1989. Reprint requests: James W. Orr, Jr., MD, D!vision of Gynecologic Oncology, Watson Clmic, Lakeland, FL 33805. 6/1118224
718
lymphadenectomy as primary treatment for cervix or endometrial cancer were evaluated. Patients having preoperative infection, additional contaminated surgical procedures, or recent «72 hours) therapeutic doses of antibiotics were eliminated from further evaluation. No patient had preoperative radiation. All procedures were performed by a gynecologic oncologist and all patients were admitted under a strict protocol of preoperative and intraoperative management. Each had a complete hematologic and biochemical evaluation and chest radiographs. Intravenous pyelography and barium enemas were performed as indicated. All patients underwent' a mechanical (without antibiotic) bowel preparation. Preoperative hospitalization was minimized «48 hours). No preoperative douching was performed. Hair clipping, when deemed necessary, was performed in the operating room. Intraoperative skin and vaginal preparation involved a Betadine preparation scrub. The initial incision was inscribed boldly and electrocautery was used only to secure hemostasis. Only 2-0 polyglycolic acid suture was used during the pelvic operation. Hemostatic clips were used sparingly, not to occlude efferent or afferent lymphatics. The technique of radical hysterectomy and pelvic lymphadenectomy has been described elsewhere. 2 Total lymphadenectomy and periaortic node biopsy were done in those patients undergoing total hysterectomy and pelvic lymphadenectomy. Suprapubic bladder drainage was established in all patients undergoing radical hysterectomy and pelvic lymphadenectomy. At the completion of each procedure, copious (>200 ml) pelvic irrigation was performed with warm sterile water. All fluids were removed. No peritoneal surfaces were closed. Fascial closure incorporated only monofilament sutures. After fascial closure, the subcutaneous
Antibiotic prophylaxis in cancer surgery 719
Volume 162 Number 3
Table I. Characteristics of patients Radical hysterectomy and pelvIc lymphadenectomy Single-dose
No.
I
24 83.3 46.3 :t 14 (28-69) 145.5 :t 31 (99-213) 2.25 :t 0.4 ( 1.6-3.0) 1104 :t 566 (600-3000) 70.8 6.9 :t 1.6 41.7 4.2
White (%) Age (yr) Weight (pounds) Duration of surgery (hr) Estimated blood loss (ml) Transfused (%) Postoperative stay (days) Febrile morbidity (%) Infectious morbidity (%)
Total hysterectomy and pelvIc lymphadenectomy
MultIple-dose
Single-dose
22 86.4 48.6 :t 14 (22-71) 147.8 ± 30 (109-190) 2.45 ± 0.7 ( 1.3-4.5) 1126 ± 756 (400-3000) 68.2 7.1 ± 1.8 45.4 4.5
35 97.1 67.7 ± 11 (39-85) 153.7 ± 40 (88-287) 1.3 ± 0.2 (1.0-1.9) 289 ± 198 (125-800) 2.9 6.4 ± 1.5 17.1 2.9
I
Multiple-dose
31 96.8 65.9 ± 11 (39-83) 170.9 ± 43 (98-245) 1.6 :t 0.5 (1.0-1.9) 397 ± 207 (175-1000) 6.5 6.7 ± 2.5 32.3 6.5
Values are mean ± SD. Ranges are in parentheses.
Table II. Comparison of drugs and dose regimens Radical hysterectomy and pelvic lymphadenectomy M ult!ple-dose
Single-dose Drug
n
Cefoxitin (2 gm) Cefotetan (2 gm) Metronidazole (500 mg)
23
I
%
n
95.8 4.2
I
Single-dose
%
n
20
90.9
2
9.1
19 9 7
tissues were thoroughly irrigated under pressure. No subcutaneous sutures or drains were placed and skin closure involved clips. All patients undergoing radical hysterectomy and pelvic lymphadenectomy had closed suction pelvic drainage. No patient having total hysterectomy and pelvic lymphadenectomy had closed suction drainage. All patients received supplemental (2L by nasal prong) oxygen during the postoperative period for at least 24 hours. No patient received prophylactic heparin, and pneumatic calf compression was done routinely. Antibiotics were administered intravenously after the patient entered the operating room. The maximal time before incision was 45 minutes. In those patients receiving multiple doses, a second intravenous dose was given at 8 and 16 hours. Postoperatively, each patient was evaluated by at least two of us. Standard febrile morbidity was defined as temperature >38 C on two separate occasions at least 4 hours apart, excluding the initial 24 postoperative hours. Infectious morbidity was defined as continued temperature elevation, not responding to conservative measures and pulmonary manipulation. At that time appropriate evaluation and broad spectrum antibiotic therapy, consisting of an aminoglycoside and anaerobic coverage, was begun. No patient was discharged on a regimen of oral antibiotics. 0
Total hysterectomy and pelvic lymphadenectomy
I
M ulttple-dose
%
n
54.3 25.7 20.0
23 6 2
I
% 74.1 19.4 6.5
Results
During the 24 months of this study, 46 patients who underwent radical hysterectomy and pelvic lymphadenectomy as primary treatment for invasive cervical cancer were evaluable. An additional 66 patients (all with a clinical or histologic risk of nodal metastases) underwent total hysterectomy and pelvic lymphadenectomy, as well as periaortic node biopsy, as primary treatment for uterine malignancy. As expected, differences existed between patients undergoing radical hysterectomy and pelvic lymphadenectomy and those having total hysterectomy and pelvic lymphadenectomy (Table I). Patients undergoing radical hysterectomy and pelvic lymphadenectomy had a significantly increased mean operative time (p < 0.001), had a younger mean age (p < 0.001), and weighed less (p < 0.04) than those undergoing total hysterectomy and pelvic lymphadenectomy. There was no patient characteristic difference in those undergoing radical hysterectomy and pelvic lymphadenectomy, regardless of dosage regimen. The same applied for those undergoing radical hysterectomy and pelvic lymphadenectomy. Considering all patients, there was no significant difference in weight, age, presence of medical illness, or postoperative stay when comparing single-dose and multipledose regimens. The majority of patients received cephalosporin prophylaxis (89.3%); however, penicillin-
720
Orr et al.
March 1990 Am J Obstet Gynecol
Table III. Extended hysterectomy and infectious morbidity Author
Orr et al. 2 (l982) Rosenshein et aJ.3 (1983) Sevin et al. 4 (1984) Marsden et al. B (1985) Micha et aI.' (l987) Miyazawa et aI.' (1987)
Febnle morbidity
MflJor morbidity
%
Hospital stay (days)
OperatIVe time (hr)
Blood loss (ml)
Cephalosporin (5-7 days) None
32.4 41.5
18.9 26.8
9.8 12.0
3.7
1800
64.5t 84.5 41.7 88.9 26.6 80.0 109t
11.8 26.7 15.3 52.8 3.0 16.0 6.6 67.7 87.5
16.1 15.6 15.6 18.0 12.0 12.0 10.1 10.4
3.9 3.7 6.1 5.5 3.1 3.6 3.7 4.0 5.4
2400 1600 765 832 840 1013 2196
71
63.6
4.6
1851
26
Doxycycline (1 dose)* None Cefoxitin (12 dose) None Cefoxitin (12 dose) None Mezlocillin (3 dose) None None Cefamandolel doxycycline «48 hr) Cefamandole I doxycycline «48 hr) + cefamandole irrigation
30
3.8
4.4
1544
35 24 25
None Mandol (5 dose) None
2.6 3.2 3.2
525
No. of patients
AntibIOtic
270 41 34 30 26 27 31 43 15 15 8 11
Bendvold and Kjorstad 9 (1987) Creasman et al. 6 (1982)
%
17 12.5 45.8
0 4.2 36.0
10.1 8.2 9.0
*Bowel preparation. tFever index.
allergic patients received metronidazole (Table II). There was no difference in infection rates evaluated by drug used. The overall surgical site infection rate was 4.5% and did not differ between radical hysterectomy and pelvic lymphadenectomy (4.3%) and total hysterectomy and pelvic lymphadenectomy (4.5%). There was no difference in infection rate in patients undergoing radical hysterectomy and pelvic lymphadenectomy or total hysterectomy and pelvic lymphadenectomy, regardless of the antibiotic regimen. In either procedure there was no significant correlation between age, race, duration of surgery. blood loss, and risk of infection. However, if patients developed a postoperative infection, their hospital stay was longer (10 days). Febrile morbidity was common after radical hysterectomyand pelvic lymphadenectomy (43.5%) and total hysterectomy and pelvic lymphadenectomy (24.2%). The usual cause was pulmonary-related; however, pneumonia did not occur in any patients. No patient had a symptomatic pelvic Iymphocyst, and no ureteral vaginal fistulas occurred.
Comment Surgical extirpation with curative intent remains an important treatment aspect of patients with early invasive cervical cancer or endometrial cancer. Both procedures involve extended pelvic surgery, including lymphadenectomy. Occasionally certain inherent risks such as prolonged preoperative diagnostic hospitalization, an altered immunologic system, older age, prolonged procedures, increased blood loss, and altered
nutritional status are present. Faced with this problem, the majority (84%) of gynecologic oncologists use prophylactic antibiotics during radical hysterectomy and pelvic lymphadenectomy, and 16% of those use multiple agents .. To date, only eight studies have evaluated the efficacy of prophylactic antibiotics after extended hysterectomy.2.9 Most indicate a benefit of prophylactic antibiotics during extended hysterectomy (Table III); however, at least two studies question their benefit."' 9 Although retrospective, this study was performed in patients with a standard method of preoperative preparation and control over the variable of surgical experience. Previous studies report patients operated on by surgeons of varied experience with data collected over a long period of time. Operative times, blood loss, socioeconomic status, and the use of preoperative radiation may vary greatly. Only one previous study has evaluated the efficacy of single-dose prophylaxis.' While fever index was lowered, data concerning morbidity were lacking. This information is in contrast to that for non radical hysterectomy, where single-dose prophylaxis has been reported to be as efficacious as a multiple-dose regimen. IO Anecdotal accounts suggest that multiple doses are needed because of prolonged operative times. In nonradical hysterectomy, the benefit of prophylactic antibiotics decreases sharply when operative time approaches 3 hours, II the usual operative time for radical hysterectomy and pelvic lymphadenectomy and reported times for total hysterectomy and pelvic lymphadenectomy.6.12 Some indicate the need to use prolonged preoperative treatment to increase tissue levels of the prophylactic drug.' However. information
Volume 162 ]\;umber 3
regarding commonly used prophylactic drugs indicates that most tissue levels contain more than inhibitory antibiotic levels after a single preoperative dose. 13 This report is the first to compare a single-dose regimen and a multiple-dose regimen and find them to be equally efficacious. Interestingly, one report6 indicates a relatively high risk of drain site infection, which may be explained in part by relatively low antibiotic tissue levels in the subcutaneous fat.I3 While large volumes of fluid may be evacuated with closed suction drainage, 12 when compared with open cuff drainage, there is no protective effect against infection. 12 In fact, one must question the benefit of long-term closed suction drainage with its potential adverse effects on fluid and electrolyte replacement, as well as nutritional status. This study suggests that pelvic drainage may not be necessary to prevent lymphocyst or other complications after certain types of extended pelvic surgery (total hysterectomy and pelvic lymphadenectomy). In fact, drains may predispose to infection as they contaminate the subcutaneous tissues, an area of low blood flow and lowered tissue levels of effective antibiotics. 13 While data are lacking to clearly support the use of a second-generation cephalosporin, we chose to use cefoxitin because of previous studies indicating its efficacy< and its expanded bacterial coverage when compared with first-generation antibiotics. The substitution of cefotetan (because of a change in hospital formulary) in some patients allowed use of a drug with a similar antimicrobial spectrum. Although the serum half-life of the latter drug is reportedly longer, there is little information to indicate an effect on important tissue levels. Although both drugs are effective, approximately 10% of the population claim a penicillin allergy. While cephalosporin "crossover" reactivity may not be common, we chose to administer metronidazole to any patient who claimed a penicillin allergy. While antimicrobial coverage differs, metronidazole is an effective prophylactic agent when used during nonradical gynecologic surgeryl and offers an alternative so as not to place the patient at risk for antimicrobial reaction. In conclusion, this report suggests that attention to preoperative preparation and intraoperative tech-
Antibiotic prophylaxis in cancer surgery
721
nique, when combined with single-dose antimicrobial prophylaxis, is associated with a low risk of infectious morbidity after extended pelvic procedures for the treatment of patients with gynecologic cancer. Future prospective studies must attempt to control for preoperative and intraoperative variables that alter the risk for postoperative infection. REFERENCES 1. Orr JW Jr, Taylor PT. Avoiding postoperative infection in the patient with gynecologic cancer. Infect Surg 1987; 12:666-75. 2. Orr JW Jr, Shingleton HM, Hatch KD, et al. Correlation of perioperative morbidity and conization-radical hysterectomy interval. Obstet Gynecol 1982;59:726-39. 3. Rosenshein NB, Ruth JC, Millar I, et al. A prospective randomized study of doxycycline as a prophylactic antibiotic in patients undergoing radical hysterectomy. GynecoIOncoI1983;15:201-6. 4. Sevin BU, Ramos R, Lichtinger M, et al. Antibiotic prevention of infections complicating radical abdominal hysterectomy. Obstet Gynecol 1984;64:539-45. 5. MichaJP, Kucera PR, BurkettJP, et al. Prophylactic mezlocillin in radical hysterectomy. Obstet Gynecol 1987;69: 251-4. 6. Creasman WT, Hill GB, Weed JC, et al. A trial of prophylactic cefamandole in extended gynecologic surgery. Obstet Gynecol 1982;59:309-14. 7. Miywzawa K, Hernandez E, Dillon MD. Prophylactic topical man dol in radical hysterectomy. Int J Gynecol Obstet 1987 ;25: 133-8. 8. Marsden DE, Cavanagh D, Wisniewski BJ, Roberts WS, Lyman GH. Factors affecting the incidence of infectious morbodity after radical hysterectomy. AM J OBSTET GvNECOL 1985;152:817-21. 9. Bendvold E, Kjorstad KE. Antibiotic prophylaxis for radical abdominal hysterectomy. Gynecol Oncol 1987;28: 201-4. 10. Orr JW Jr, Sisson PF, Barrett JM, Ellington JR, Jennings RH, Taylor DL. Single-center study results of cefotetan and cefoxitin prophylaxis for abdominal or vaginal hysterectomy. AMJ OBSTET GVNECOL 1988;158:714-6. 11. Shapiro M, Munoza, Tager I, et al. Risk factors for infection at the operative site after abdominal or vaginal hysterectomy. N Engl J Med 1982 ;307: 1661-6. 12. Orr JW Jr, Barter JF, Kilgore LC, Soong SJ, Shingleton HM, Hatch KD. Closed suction pelvic drainage after radical pelvic surgical procedures. AM J OBSTET GVNECOL 1986; 155:867-71. 13. Orr JW Jr, Sisson PF, BarrettJM, EliingtonJR,Jennings RH, Taylor DL. Pharmacokinetics and tissue kinetics of 1 gm cefotetan prophylaxis AM J OBSTET GVNECOL 1988;158:742-3.
