Infectious complications following abdominal hysterectomy in Karachi, Pakistan

International Journal of Gynecology & Obstetrics 73 Ž2001. 27᎐34

Article

Infectious complications following abdominal hysterectomy in Karachi, Pakistan F. AhmedU , S. Wasti Department of Obstetrics and Gynecology, The Aga Khan Uni¨ ersity Hospital, Karachi, Pakistan Received 22 July 1998; received in revised form 4 March 2000; accepted 10 March 2000

Abstract Objecti¨ e: In this paper we studied the prevalence of post-operative infections after total abdominal hysterectomy in Karachi, Pakistan and their associated risk factors. Method: A retrospective analysis was conducted by reviewing the case notes of 827 consecutive total abdominal hysterectomies. Results: The post-operative infection rate was 22%. Of the patients, 6% Ž49. developed operative site infections including wound and vaginal cuff infections and pelvic abscesses while 16% Ž133. developed non-operative site infections including urinary tract infections and thrombophlebitis. Six risk factors were found to be significantly associated with post-operative infections: a pre-operative hospitalization of more than 2 days Ž P- 0.02.; additional non-gynecological procedures performed intra-operatively Ž P- 0.02.; indwelling catheterization for more than 7 days Ž P- 0.001.; patient’s age greater than 50 years Ž P- 0.02.; an underlying malignancy Ž P - 0.0001.; and developing a hematoma post-operatively Ž P - 0.04.. Conclusion: The results of this study may serve as a baseline for future comparison and indicate interventions which may contribute to a reduction in the post-operative infection rate. 䊚 2001 Published by International Federation of Gynecology and Obstetrics. Keywords: Pakistan; Total abdominal hysterectomy; Post-operative infections; Antibiotic prophylaxis

1. Introduction Hysterectomy is the most frequently performed major operation in gynecology w1x. In fact it is only exceeded by appendectomy among all major

U

Corresponding author. Tel.: q92-315-428-0261.

surgical procedures performed in the United States where approximately 800 000 hysterectomies are performed annually w2,3x. Currently, one in three women in the United States and one in five women in the United Kingdom have a hysterectomy before the age of 60 w4x. Although no concrete data exist regarding the prevalence of total abdominal hysterectomies in Pakistan, it is

0020-7292r01r$20.00 䊚 2001 Published by International Federation of Gynecology and Obstetrics. PII: S 0 0 2 0 - 7 2 9 2 Ž 0 0 . 0 0 2 4 6 - 0

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F. Ahmed, S. Wasti r International Journal of Gynecology & Obstetrics 73 (2001) 27᎐34

believed to be a commonly performed procedure in Pakistan also. Hysterectomy is associated with a significant complication rate; one-quarter to one-half of women undergoing this procedure will sustain one or more complications w5x. Post-operative complications serve only to exacerbate the unique medical, emotional, sexual, and psychological challenges posed by this procedure by increasing patients’ physical discomfort, emotional distress, expenditure, and prolonging both the duration of hospitalization and recovery. Post-operative infections, despite modern standards of pre-operative preparation, antibiotic prophylaxis, and advances in anesthetic and operative techniques, remain a leading cause of morbidity after both elective and emergent gynecological surgical procedures w6x. The most common infections associated with total abdominal hysterectomy are nosocomial urinary tract infection, wound infection, and pelvic abscess w7x. Risk factors that have been identified in the past include inexperience of the surgeon, undergoing additional surgical procedures, catheterization, and excessive blood loss. Other high-risk patients included women who were obese, of advanced age, diabetic, postmenopausal, or anemic w6,8x. Infection rates, however, may vary significantly among hospitals and patient populations. Factors that may contribute to this variation include the criteria used to define the various infections that may develop, the types of surgical procedures performed and, perhaps most importantly, the patient populations treated. Also, fewer investigators have commented on risk factors for postoperative infection after abdominal hysterectomy than after vaginal hysterectomy w6x. The purpose of the present study was to determine the prevalence of post-operative infections after total abdominal hysterectomy at the Aga Khan University Hospital in Karachi, Pakistan, and the risk factors that influence this rate.

2. Materials and methods A non-randomized retrospective analysis was conducted of 827 total abdominal hysterectomies

ŽTAH. performed on women during the 6-year period between January 1990 and December 1995 in the form of an ongoing audit. The study was conducted at the Aga Khan University Hospital ŽAKUH. in Karachi, Pakistan which is a 600-bed referral center for secondary and tertiary care and is supported by a medical college and a school of nursing. In reviewing these 827 cases, the prevalence of post-operative infections and their associated risk factors was determined. Antibiotic prophylaxis for gynecological procedures at AKUH is routinely done with cefazolin and metronidazole. According to the protocol established for elective total abdominal hysterectomy, 1 g of cefazolin was administered intravenously 2 h prior to the patients’ surgery and post-operatively two 500-mg doses were administered intravenously at 6-h intervals. Also, 2 g of metronidazole were administered orally the night before the surgery and post-operatively two 500mg doses were administered intravenously at 8-h intervals. This protocol was followed for most of the patients studied; however, a minority received these antibiotics according to schedules with minor deviations from that mentioned above. To determine the prevalence of in-hospital post-operative infections, septic morbidity was calculated using parameters divided into the following two categories: operative site infections including wound infection, vaginal cuff infection, and pelvic abscesses; and non-operative site infections including urinary tract infection and thrombophlebitis. The diagnosis of a wound infection was based on hospital note descriptions of wound erythema, oozing, dehiscence, and tenderness or a positive wound swab culture and sensitivity report. The occurrence of a pelvic abscess was ascertained by documented evidence of such in the hospital notes. The presence of a vaginal cuff infection was determined by a positive high vaginal swab culture and sensitivity report. The occurrence of a urinary tract infection was suspected by the presence of moderate bacteria or white blood cells in the urine microscopy and then confirmed by a positive urine culture and sensitivity report. Diagnosis of thrombophlebitis was based on documented findings of leg pain associated with increased calf size, erythema and ten-

F. Ahmed, S. Wasti r International Journal of Gynecology & Obstetrics 73 (2001) 27᎐34

derness. Febrile morbidity was not used as a primary indicator of post-operative infectious morbidity in our study. However, its prevalence was determined using the following criteria: an oral temperature of more than 38⬚C on two or more occasions, at least 6 h apart, during any consecutive 48-h period excluding the first 24 h after surgery. Next, various risk factors were evaluated for their association with the development of the post-operative infections. These risk factors were divided into three broad categories, namely: factors related to the operative procedure; factors related to catheterization of the patients; and factors related to the pre- and post-operative status of the patients. The risk factors that were studied relating to the operative procedure included: any gynecological or non-gynecological operative procedures performed in addition to a total abdominal hysterectomy; the surgeon’s experience Ždetermined by whether a consultant or resident performed the operation.; amount of blood loss; length of pre-operative hospitalization; and whether the operation was an emergency or an elective procedure. Factors related to patient catheterization included: whether or not the patient was catheterized and if so, the type Žsupra-pubic or urethral .; place of insertion Žthe ward or the operating room.; and duration of catheterization. The patient factors that were studied included: the patient’s age; menopausal status; presence of diabetes mellitus or a malignancy; and the development of a hematoma or seroma post-operatively. EPIINFO6 was used both for data entry and analysis. Statistical significance of the association between these risk factors and the prevalence of post-operative infections was determined by ␹ 2 analysis and a P-value of - 0.05 was taken as significant.

3. Results At the Aga Khan University Hospital, a total of 827 cases of total abdominal hysterectomy were

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Table 1 Post-operative infection rates Ž N s 827. Number Operati¨ e site infections Wound infection Vaginal cuff infection Pelvic abscess

%

49 42 4 3

6.0 5.1 0.5 0.4

Non-operati¨ e site infections Urinary tract infection Thrombophlebitis

133 131 2

16.0 15.8 0.2

Total

182

22.0

performed between January 1990 and December 1995. On analysis, the prevalence of in-hospital septic morbidity was determined to be 22%. Of the 827 cases reviewed, 182 developed post-operative infections including 49 Ž6%. patients with operative site infections and 133 Ž16%. patients with nonoperative site infections. The operative site infections included 42 cases of wound infection, four cases of vaginal cuff infection and three pelvic abscesses. The non-operative site infections included 131 cases of urinary tract infection and two cases of thrombophlebitis ŽTable 1.. Of our patients, 178 Ž21.5%. also met the defined criteria for febrile morbidity. Of these patients, 67 Ž8.1%. were febrile post-operatively but had no other clinical evidence of infection. The risk factors that were considered to influence the rate of post-operative infection were divided into the following three groups: factors related to the operative procedure; factors related to catheterization of the patients; and factors related to the pre- and post-operative status of the patients. When reviewing the prevalence of risk factors related to the operative procedure, only five patients underwent a total abdominal hysterectomy as an emergency procedure. The length of pre-operative hospitalization was divided into the following three categories ᎏ 1 day, 2 days, and more than 2 days; 618 Ž74.7%. patients stayed 1 day; 105 Ž12.7%. stayed 2 days; and 104 Ž12.6%.

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stayed more than 2 days before their operation. Regarding the designation of the surgeon, consultants operated on 814 Ž98.4%. cases while residents conducted the remaining 13 Ž1.6%. operations. Although all the patients reviewed underwent total abdominal hysterectomy, 488 Ž57%. also had one or more additional gynecological procedures done at the time of their surgery. The most common of these were bilateral salpingo-ophorectomy performed on 334 patients and unilateral salpingo-ophorectomy performed on 99 patients. Fifty-five patients underwent other gynecological procedures including colposuspension, cystectomy, peritoneal adhesiolysis, and ovarian biopsy. We also looked at additional non-gynecological procedures that were done with the total abdominal hysterectomies and found that 103 Ž12.3%. patients underwent such combined procedures. The more common of these additional procedures were omentectomy, incisionalrumbilical hernia repair, cholecystectomy, cystoscopy, and appendectomy. Excessive intra-operative blood loss was defined as blood loss of more than 500 ml and 192 Ž23.2%. patients met this criteria. On examining the catheterization status of our patients, it was found that 713 Ž86.1%. patients were catheterized while 115 Ž13.9%. were not. Of the 713 patients who were catheterized, 707 had urethral and five had supra-pubic catheterization;

63 catheterizations were performed in the ward while the remaining 650 were done in the operating theater. Nineteen patients had an indwelling catheter in place for more than 7 days. When reviewing patient-related risk factors among the 827 women included in our study, it was found that 98 Ž11.9%. were over the age of 50 and 99 Ž12.0%. were postmenopausal Ži.e. had not menstruated for 1 year or more.; 91 Ž11%. patients were known diabetics at the time of their surgery; 70 Ž8.5%. patients had a malignancy of gynecological origin or otherwise; and 11 patients developed a hematoma post-operatively while five developed a seroma. Then, using ␹ 2 analysis, we evaluated the association between the above-mentioned risk factors and the overall post-operative infection rate. Of all the risk factors studied, six were found to have a statistically significant association with the development of post-operative infections after total abdominal hysterectomy ŽTable 2.. These six risk factors were: a pre-operative hospitalization of greater than 2 days Ž P- 0.02.; additional nongynecological procedures performed intra-operatively Ž P - 0.02.; a duration of indwelling catheterization greater than 7 days Ž P- 0.001.; patient’s age greater than 50 years Ž P- 0.02.; the presence of a malignancy Ž P- 0.0001.; and the development of a hematoma post-operatively Ž P - 0.04..

Table 2 Factors associated with the development of post-operative infections

Number

%

Number

%

P-value significance

3 37 49 37 2 187 10 36 31 26 33 5 3

23.1 36.0 25.5 35.6 40.0 26.2 52.6 36.7 31.3 28.6 47.1 45.5 60.0

13 103 192 104 5 713 19 98 99 91 70 11 5

1.6 12.6 23.2 12.6 0.6 86.2 2.3 11.9 12.0 11.0 8.5 1.3 0.6

NS P- 0.02 NS P- 0.02 NS NS P- 0.001 P- 0.02 NS NS P- 0.0001 P- 0.04 NS

Infected

Resident surgeon Additional procedure Excessive blood loss Post-op hosp ) 2 days Emergency procedure Catheterization Catheter ) 7 days Age ) 50 years Postmenopausal Diabetic Malignancy Hematoma Seroma

Total

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4. Discussion The results of our study showed the prevalence of post-operative septic morbidity in patients who underwent a total abdominal hysterectomy at the Aga Khan University Hospital between January 1990 and December 1995, to be 22%. This rate falls between the extremes reported by others w9᎐11x. Our operative site infection rate of 6% compares favorably with rates of 9᎐14% reported in the literature w6,7x. Likewise, our rates of postoperative wound infection, vaginal cuff abscess, and pelvic abscess were consistent with other reports w10᎐15x. Of our patients, 16% Ž133r827. developed non-operative site infections including 131 cases of urinary tract infection which constitute the largest segment of our infectious morbidity. Widely divergent rates of urinary tract infection after total abdominal hysterectomy, ranging from 5 to 30%, have been reported in the literature w3,10,11,14,15x. This variation is the result of several factors including: different patient populations being evaluated; varying hospital infection rates; predisposing patient factors such as diabetes and malignancy; and perhaps most importantly, different practices regarding urinary catheterization. Although our finding of 15.8% is between the extremes reported, it does merit some scrutiny. While reviewing catheterization practices at the AKUH, it was found that there was a deficiency in standardization and restraint when it came to this intervention. Based on these findings, guidelines were recommended for gynecology ward staff education, the most important of these which outlined which patients required catheterization and the duration and proper care of indwelling catheters. It has been found that increasing the professional training of personnel responsible for catheterization leads to decreased infection rates w16x. Our findings were also in agreement with previous results which indicate that thrombophlebitis is an uncommon complications after hysterectomy w3,10᎐12,15x. Of the patients, 178 Ž21.5%. were febrile post-operatively and 67 Ž8.1%. showed no other clinical evidence of infection. Both of these results are in agreement with data reported by other investigators w11,18x. We did not use febrile morbidity as a

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primary indicator of post-operative infectious morbidity because of the current confusion in literature about the definitions and clinical implications of this entity. Six of our risk factors were shown to have a statistically significant association with the prevalence of post-operative infections after total abdominal hysterectomy. As in our series, the length of pre-operative hospitalization has previously also been shown to be a risk factor for post-operative infections w8,13,14x. Previous reports have shown, in fact, that colonization occurs in virtually all patients with nosocomial bacteria within 2 weeks of hospital admission. These colonizations usually occur with hospital acquired antibioticresistant microorganisms. While the majority of our patients Ž74.7%. were admitted 1 day prior to their surgery, 104 Ž12.6%. patients were admitted more than 2 days pre-operatively, primarily for social indications. The Aga Khan University Hospital serves not only Karachi’s urban population of 13 million but also the rural population of the surrounding population of Sind. For many of these patients, the great distances involved in travelling to the hospital often necessitates such early admission. The greater risk of post-operative infections among those of our patients undergoing additional surgical procedures intra-operatively confirms the observations of others w6x. These additional procedures usually prolong the duration of the operation and although the numbers of microorganisms present after a surgical scrub are low, they tend to increase with the length of the operation. One study found that prophylactic antibiotics significantly reduce the post-operative infection rate but the protective effect diminished as the length of the operation increased and by 3 h and 20 min, the prophylactic antibiotics ceased to have an effect w17x. Our results were also in agreement with most authors in finding that patients of advanced age have a greater risk of infection w8,10,12,18x. While our study found that women over the age of 50 have an increased risk of developing post-operative infections after hysterectomy, a previous study has found that the risk increases after the age of 60 w19x. Our study conformed with previous studies in finding that post-operative hematomas

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predispose to the development of infection w12x. Most authors agree about the increased risk of infection in patients with an underlying malignancy w10,18x. Chryssikopolous and Loghis w10x, after comparing 486 patients undergoing hysterectomy for a malignancy with 2924 patients undergoing the operation for benign disease, found a doubling of the overall post-operative morbidity in the patients with a malignancy. In our study, 41.7% Ž33r70. of the patients with a malignancy developed a post-operative infection compared to only 19.5% of patients operated on for benign indications. The duration of indwelling catheterization has been previously found to be of particular importance and this study also found that catheterization for more than 7 days was significantly related to the development of postoperative infections w6x. Grimmond et al. w16x found that the infection rates rise by 5% per day of indwelling catheterization. The prominence of urinary tract infections in our series and the contributing role of urinary catheterization has already been discussed. A number of risk factors evaluated in this study were found not to have a significant association with the development of post-operative infections in contradiction to previously reported findings w6,12,18x. Three of the risk factors, the development of a post-operative seroma, and performing the operation as an emergency case or by an inexperienced surgeon, each occurred in less than 2% of our patient population and this low prevalence most likely resulted in them not being found significant. Previous studies have shown that excessive intra-operative blood loss and anemia were significant predispositions to developing postoperative infections w6x. Although nearly 25% Ž192r827. of our patients lost a significant amount of blood intra-operatively, we did not find a significant association between this risk factor and the development of infection. Why was this so? The most likely explanation for this is the liberal use of blood transfusions for our patients. This may also explain why, despite the documented prevalence of anemia in Pakistani women w20x, only one of our patients went into surgery anemic. While there may be a questionable benefit of blood transfusion, both pre-operatively and

intra-operatively, in reducing post-operative morbidity, there are a number of potentially serious complications that may result from such a practice. Besides the attending cost, injudicious use of blood transfusion carries the risk of transmitting blood-borne infections of which hepatitis B and hepatitis C are the most important in the Pakistani context. Also, several risk factors found by previous studies to be significantly associated with the development of a post-operative infection were not examined in our study. These risk factors, including obesity, atherosclerotic disease, the type of surgical drainage used, and duration of surgery w12,13,18x, may be examined in future studies investigating Pakistani women undergoing hysterectomy. Recently, two carefully conducted metaanalyses of all randomized controlled studies of antibiotic prophylaxis for total abdominal hysterectomy since 1971 conclusively demonstrated that antibiotics are highly protective against serious infectious morbidity after this procedure and it is no longer justified not to use antibiotic prophylaxis w7,9x. However, there is still controversy regarding the benefits of different antibiotics. As mentioned previously, all our patients received prophylactic antibiotics in the form of metronidazole and cefazolin Ža first generation cephalosporin.. Most of our patients were given an initial dose of each pre-operatively and then the prophylaxis was continued with two doses given postoperatively. Mittendorf et al. w7x found that cefazolin, metronidazole, and tinidazole were each effective individually in preventing serious infectious morbidity associated with this surgical procedure and recommended future randomized controlled trials, comparing metronidazole and cefazolin in particular, to determine which is the most efficacious. In their meta-analysis, Tanos and Rojansky w9x reviewed 17 prospective trials that, with 2752 study and control patients, evaluated cephalosporin prophylaxis alone. They found that prophylactic cephalosporins were clearly effective in decreasing post-operative infections and febrile morbidity and also met most of the criteria outlined by Ledger et al. w21x in their description of the ‘perfect’ antibiotic for prophylaxis. Based on these findings, they recommended a single

F. Ahmed, S. Wasti r International Journal of Gynecology & Obstetrics 73 (2001) 27᎐34

pre-operative intravenous dose of an inexpensive first generation cephalosporins Že.g. cefazolin., with proven safety and tolerance, as probably the most cost-effective responsible choice for prophylaxis for this procedure. Hemsell w6x has also suggested prophylaxis with a single dose of cefazolin Ž1᎐2 g. administered intravenously in the operating room after i.v. line placement and before anesthesia. In light of these findings, it is recommended that the prophylactic antibiotic administration protocol for total abdominal hysterectomy at AKUH and other major hospitals in Pakistan be re-evaluated, possibly in favor of a shorter, simpler, one drug regimen. No discussion of healthcare data would be complete without considering it in the context of its relevant healthcare system. This is especially important when evaluating the health services of a developing country such as Pakistan. A cursory glance at the state of Pakistan’s healthcare services, with 45% of the population having no access to healthcare facilities, a ratio of one doctor for every 2000 people and less than 2% of the GNP spent on health, makes the need for careful resource allocation and the necessity of practicing cost-effective medicine acutely apparent w22x. Post-operative complications, including operative site and distant site infections, both increase the cost of health services and result in the diversion and utilization of limited resources. These infections, therefore, need to be minimized. Our results identified frequently occurring risk factors associated with these infections and this knowledge can be used to launch preventive efforts to avert these complications. The results of this study serve as a baseline for future comparison and emphasize the repercussions of post-operative infections on the healthcare system of a developing country like Pakistan. The results also indicate some interventions which may contribute to a decrease in the infection rate after total abdominal hysterectomy. A review of the policies for antibiotic prophylaxis and blood transfusions at AKUH are also recommended. Total abdominal hysterectomy done for the right indications and performed carefully to minimize post-operative complications has the potential for relieving much suffering in women. All efforts

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must be made to evaluate and improve the outcomes of this procedure. References w1x Boyd ME. Postoperative gynecologic infections. Can J Surg 1987;30:7᎐9. w2x Thompson JD, Birch HW. Indications for hysterectomy. Clin Obstet Gynecol 1981;24Ž4.:1245᎐1258. w3x Schwarz RH, Minkoff HL. Postoperative infections. In: Monif GRG, editor. Infectious diseases in obstetrics and gynecology. Omaha: IDI Publishers, 1993:470᎐478. w4x Clark A, Black N, Rowe P, Mott S, Howle K. Indications for and outcome of total abdominal hysterectomy for benign disease: a prospective cohort study. Br J Obstet Gynaecol 1995;102:611᎐620. w5x Easterday CL, Grimes DA, Riggs JA. Hysterectomy in the United States. Obstet Gynecol 1983;62Ž2.:203᎐212. w6x Hemsell DL. Prophylactic antibiotics in gynecologic and obstetric surgery. Rev Infect Dis 1991;13ŽSuppl 10.: S821᎐S841. w7x Mittendorf R, Aronson MP, Berry RE, Williams MA, Kopelnick B, Klickstein A et al. Avoiding serious infections associated with abdominal hysterectomy: a metaanalysis of antibiotic prophylaxis. Am J Obstet Gynecol 1993;169Ž5.:1119᎐1124. w8x Yalcin AN, Bakir M, Bakici Z, Dokmetas I, Sabir N. Postoperative wound infections. J Hosp Infect 1995; 29:305᎐309. w9x Tanos V, Rojansky N. Prophylactic antibiotics in abdominal hysterectomy. J Am Coll Surg 1994;179: 593᎐600. w10x Chryssikopoulos A, Loghis C. Indications and results of total hysterectomy. Int Surg 1986;71:188᎐194. w11x Dicker RC, Greenspan JR, Strauss LT. Complications of abdominal and vaginal hysterectomy among women of reproductive age in the United States ŽThe Collaborative Review of Sterilization.. Am J Obstet Gynecol 1982;144Ž7.:841᎐848. w12x Hemsell DL. Infections after gynecologic surgery. Obstet Gynecol Clin North Am 1989;16Ž2.:381᎐400. w13x Eltahawy ATA, Mokhtar AA, Khalaf RMF, Bahnassy AA. Postoperative wound infection at a university hospital in Jeddah, Saudi Arabia. J Hosp Infect 1992;21:79᎐83. w14x Clarke A, Rowe P, Black N. Does a shorter length of hospital stay affect the outcome and costs of hysterectomy in Southern England? J Epidemiol Community Health 1996;50:545᎐550. w15x Grant JM, Hussein IY. An audit of abdominal hysterectomy over a decade in a district hospital. Br J Obstet Gynaecol 1984;91:73᎐77. w16x Grimmond TR, Sinclair G, Marshall VR. Catheter associated urinary infections. In: Watts JM, McDonald PJ, O’Brien PE, Marshall VR, Finlay-Jones JJ, editors. Infections in surgery ᎏ basic and clinical aspects. Melbourne: Churchill Livingstone, 1981:389᎐398.

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F. Ahmed, S. Wasti r International Journal of Gynecology & Obstetrics 73 (2001) 27᎐34

w17x Shapiro M, Munoz A, Tager IB, Schoenbaum SC, Polk F. Risk factors for infection at the operative site after abdominal or vaginal hysterectomy. N Engl J Med 1982;307Ž27.:1661᎐1666. w18x Harris WJ. Early complications of abdominal and vaginal hysterectomy. Obstet Gynecol Surv 1995;50Ž11.: 795᎐805. w19x Keighley MRB, Burdon DW. Antimicrobial prophylaxis in surgery. Kent: Pittman Medical Publishing, 1979:1᎐22.

w20x Hamedani P, Hashmi KZ, Manji M. Iron depletion and anaemia: prevalence, consequences, diagnostic and therapeutic implications in a developing Pakistani population. Curr Med Res Opin 1987;10Ž7.:480᎐485. w21x Ledger WJ, Gee C, Lewis WP. Guidelines for antibiotic prophylaxis in gynecology. Am J Obstet Gynecol 1975; 121:1038᎐1045. w22x Haq MU. Human development in South Asia 1997. Karachi: Oxford University Press, 1997:37᎐42.