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The necessity of prophylactic antibiotics in uncomplicated appendicitis during childhood
The Necessity
of Prophylactic Antibiotics in Uncomplicated Appendicitis During Childhood
By F. Kizilcan, F.C. Tanyel, N. BijyiikpamukFu, Ankara, l A prospective, randomized, clinical study was done to evaluate the place of prophylactic antibiotics in uncomplicated childhood appendicitis. One hundred patients with uncomplicated appendicitis were randomly assigned to one of four groups, each consisting of 25 cases. Group 1 patients did not receive prophylactic antibiotic. Group 2, group 3, and group 4 patients received ornidazole, penicillin plus tobramytine, and piperacillin. respectively. The use of prophylactic antibiotics did not yield better results than the use of placebos. The rarity of infectious complications after uncomplicated appendicectomy may be unique for children. Although the need for antibiotic prophylaxis is well documented in adults, the rarity of infectious complications makes it highly questionable in the treatment of uncomplicated appendicitis in children. Copyright o 1992 by W.B. Saunders Company INDEX WORDS: Appendicitis; tion; antibiotic prophylaxis.
postoperative
wound
infec-
R
EMOVAL OF a normal appendix, without preoperative antibiotics, may result in a wound infection rate of up to 10%. This incidence may jump to 30% if the appendix is inflamed.’ In recent years, the use of prophylactic antibiotics for the prevention of infection following appendicectomy has become an acceptable practice. 2 Although good results are reported with a single antianaerobic agent,i4 the majority of articles published since 1980 recommend both aerobic and anaerobic coverage in the antibiotic prophylaxis3 However, the increase in the number of publications during the last 25 years reflects the absence of a universally acceptable solution to the problem of wound sepsis after appendicectomy.3 Additionally the majority of publications dealing with antibiotic prophylaxis in acute appendicitis are confined to adult patients with only limited number of papers written about acute appendicitis in children. Therefore, a prospective randomized clinical trial was planned to evaluate the place of antibiotic prophylaxis in the treatment of acute appendicitis in children.
and A. Hiqsiinmez
Turkey MATERIALS AND METHODS One hundred patients treated for acute appendicitis in the Department of Pediatric Surgery of Hacettepe Children’s Hospital, between December 1987 and June 1990, were included in the present study. The patients who were diagnosed to have acute appendicitis were accepted to be candidates for inclusion in the study group. In the presence of parameters suggesting complicated appendicitis, such as symptoms longer than 36 hours, diffuse abdominal pain and tenderness, temperature over 38°C white blood cell (WBC) count exceeding 13,000/mm3~~h a history of previously diagnosed renal or gastrointestinal disease, drug hypersensitivity reaction. or antibiotic treatment during the recent 72 hours, the patients were not included into the study group. One hundred forms were prepared with each 25 denoting different prophylaxis protocols. Patients were assigned to one of the four treatment groups. In group 1, the regimen included placebo; in group 2.20 mgikgld of Ornidazole in 2 divided doses; in group 3, penicillin, 200.000 U/kg/d in 8 doses, plus 4 mglkgid of Tobramycine in 3 doses; in group 4,200 mg/kg/d of Piperacillin Na in 3 doses. The medications according to the protocols were given 30 minutes prior to operations. Hemoglobin, WBC count, urinalysis, blood urea nitrogen (BUN), creatinine, total protein-albumin, and plain abdominal radiographs were evaluated preoperatively. After the fluid and electrolyte resuscitation, the patients underwent operation under general anesthesia through identical RockeyDavis incisions. Standardized operative procedures were used. Immediately after opening the peritoneal cavity, the peritoneal swab was taken for the bacteriological examination, which included aerobic and anaerobic culture by conventional methods. The stumps were inverted with purse string. No abdominal lavages or drains were used. All the incisions were closed in layers. If the preoperative diagnosis of uncomplicated appendicitis was not confirmed at surgery, the patient was withdrawn from the study group and an identical form was recruited to the remaining protocols. The antibiotic prophylaxis was continued for 48 hours. The infectious complications and drug side effects were closely monitored. Blood BUN and creatinine values were reevaluated 24 hours after the withdrawal of antibiotics. The specimen were examined pathologically. If the pathological examination did not confirm the diagnosis, the patient was also withdrawn from the study, and an identical form was recruited to the remaining protocols. The prospective randomized clinical trial was done until the completion of 100 patients. The statistical comparisons were performed by x’ tests and ANOVA; P < .05 was considered to be significant. RESULTS
From the Department of Pediatric Surgery, Hacettepe University, Children’s Hospital, Ankara, Turkey. Date accepted: November 7, 1990. Address reprint requests to F.C. Tanyel, MD, Department of Pediattic Surgery, Hacettepe University, Children’s Hospital, 06100 Sihh&e, Ankara, Turkey. Copyright 0 I992 by W B. Saunders Company 0022-346819212705-OOI3$03.00/0
586
The study groups included 66 boys and 34 girls, of whom 54% were older than 11 years of age. The age and sex distributions in groups did not differ significantly (P > .05; Table 1). The preoperative BUN, creatinine, and blood protein values of patients did not show significant difference (P > .05; Table 2). The postoperative BUN and creatinine vaiues also
Journal of Pediatric Surgery, Vol 27, No 5 (May), 1992: pp 586-588
UNCOMPLICATED
587
CHILDHOOD APPENDICITIS
Table 1. Age and Sex Distribution of the Patients Group 1
Age (vr)
M
o-5
1
6-8
3
Group 2
F
M
T
1
M
F
1
1
1
2
2
4
2
3
5
2
3
Total
Group 4
Group 3 T
F
T
M
F
T
M
2 5
2
1
3
F
T
4
1
5
9
8
17 24
9-11
4
2
6
5
2
7
3
3
6
3
2
5
15
9
12-15
10
4
14
6
5
11
8
4
12
14
3
17
38
16
54
Total
18
7
25
14
11
25
15
10
25
19
6
25
66
34
100
Abbreviations: M, male; F, female; T, total.
did not differ significantly from preoperative values (P > .05). Swabs from peritoneum yielded aerobic microorganism in 27 patients (Table 3). However, none of them yielded positive anaerobic cultures. The most frequently isolated microorganism in aerobic cultures, was E coli in all groups (50%). It was followed by Stuphylococcus aureus ( 11.1%) and hemolytic Sfreptococcus (7.4%). The numbers of positive cultures in groups didn’t differ significantly (P > .05). None of the patients had had complicating infections, including wound infection and intraabdominal abscess. No drug side effects were recorded in patients who had undergone antibiotic prophylaxis. All of the patients were discharged on the fourth postoperative day and all of them were found to be in good condition during the outpatient clinical control 1 week after discharge. DISCUSSION
Appendicitis is the most common condition requiring urgent abdominal operations.i*7 When the diagnosis of appendicitis is established, it is uncomplicated in 55% to 70% of cases.8 It is generally accepted that an antibiotic prophylaxis is beneficial in reducing the wound sepsis in uncomplicated cases.2s3 However, most of the articles on this subject dealt with adults. Although it is the most common urgent surgical condition in children, the number of publications dealing with children is few. Therefore, the place of antibiotic prophylaxis, which is reasonable for adults, has not heretofore been thoroughly evaluated for uncomplicated appendicitis in children. In our study groups composed of patients with similar age and sex distributions and nutritional
status, the diagnosis of uncomplicated appendicitis was confirmed histopathologically. Cultures yielded positive results only for aerobic microorganisms in 27 patients. The incidence of aerobic cultures were similar in the study groups. Anaerobic cultures were negative in all of the cases. It was reported that one third of patients with uncomplicated appendicitis show positive aerobic cultures, but anaerobic cultures remain negative until complication occurs.9 The number of positive aerobic culture results in this study correlates with this finding. The negative anaerobic cultures in these patients, which may reflect true negatives, may also result from the technical insufficiency of the Microbiology Department of our hospital or some additional technical factors.4 There were no infectious complications in any of the patients, including those patients with positive peritoneal cultures. The use of prophylactic antibiotics did not show a superiority compared with the use of placebo. Age, obesity, duration of the operation, and nutritional status are among the factors known to influence infectious complications.iO Our study groups, which included similar patient populations, had similar risk of infectious complications. Because none of the patients with uncomplicated appendicitis had infectious complications, this may reflect a character unique for children. During laparotomy in children, it is easy to pass through the thin abdominal wall with minimal tissue trauma. There is a lower risk of contamination during extracting the appendix through the incision. The closed space created during the closure of the wound, which contains minimal fat layer, is small. The time period required for appendicectomy is shorter in children than in adults.
Table 2. Preoperative and Postoperative
Blood Chemistry Values
Preoperation Groups
BUN
1
13.8 + 5.2
Creatinine 0.75 + 0.34
Postoperation
Total Protein
Albumin
BUN
7.59 2 0.80
4.61 2 0.75
14.21 k 3.67
Creatinine 0.71 2 0.18
2
15.71 + 4.34
0.72 + 0.18
7.23 k 0.69
4.31 + 0.74
15.12 + 4.19
0.73 + 0.30
3
13.11 f 3.25
0.64 f 0.15
7.62 + 0.53
4.47 + 0.64
14.17 r 5.05
0.63 -c 0.12
4
14.64 k 3.00
0.80 k 0.15
7.52 + 0.66
4.47 + 0.61
15.14 + 3.89
0.84 + 0.13
NOTE. Values are given in mg/dL. There were no significant differences among groups.
588
KIZILCAN ET AL
Table 3. Aerobic Bacteria Isolated From Peritoneal Swabs
tis, the antibiotics should be discontinued in patients who are found to have an uncomplicated appendicitis during operation.
of 27 Patients GVXIDS 1
Microorganism E coli
2
s a”reiJS u-Hemolytic
-
3
3
3
-
Streptococcus
E coli + Klebsiella
1
-
Klebsieila
1
-
Micrococcus Streptococcus
2
5
3
-
2
-
-
1
2 faecalis
-
1
Proteus
-
-
1
Pseudomonas
-
1
-
Diphteroid
-
1
-
Total
4
6
7
8
6
Therefore, appendicectomy for uncomplicated appendicitis in children may carry a minimal risk of infectious complications. Because the infectious complications are negligible, the place of prophylactic antibiotics is very questionable in children with uncomplicated appendicitis. We recommend that if an uncomplicated appendicitis is diagnosed, the use of antibiotics for prophylaxis is not required. If the treatment has been initiated with the diagnosis of complicated appendici-
REFERENCES 1. Stevenson RJ: Abdominal pain unrelated to trauma. Surg Clin North Am 65:1181-12151985 2. McAllister TA, Fyfe AHB, Young DG, et al: Cefotaxime lavage in children undergoing appendicectomy. Drugs 35127-132, 1988 (suppl2) 3. Krukowski ZH, Irwin ST, Denholm S, et al: Preventing wound infection after appendicectomy: A review. Br J Surg 75:1023-1033, 1988 4. Ford WDA, MacKellar A, Richardson CJL: Pre- and postoperative rectal metronidazole for the prevention wound infection in children appendicitis. J Pediatr Surg 15:160-163,198O 5. Stone HH, Sanders SL, Martin JD: Perforated appendicitis in children. Surgery 69:673-679, 1971 6. King DR, Browne AF, Birken GA, et al: Antibiotic management of complicated appendicitis. J Pediatr Surg 18:945-950, 1983 7. Kottmeier PK: Appendicitis, in Welch KJ, Randolp JG, Ravitch MM, et al (eds): Pediatric Surgery. Chicago, IL, Year Book, 1986, pp 989-995 8. Savrin RA, Clatworthy HW: Appendiceal rupture: A continuing diagnostic problem. Pediatrics 63:37-43,1979 9. Stone HH: Bacterial flora appendicitis in children. J Pediatr Surg 11:37-42, 1976 10. Schwartz SI: Complications, in Schwartz SI, Shires GT, Spencer FC, et al (eds): Principles of Surgery. New York, NY, McGraw-Hill. 1984, pp 455-484
of Prophylactic Antibiotics in Uncomplicated Appendicitis During Childhood
By F. Kizilcan, F.C. Tanyel, N. BijyiikpamukFu, Ankara, l A prospective, randomized, clinical study was done to evaluate the place of prophylactic antibiotics in uncomplicated childhood appendicitis. One hundred patients with uncomplicated appendicitis were randomly assigned to one of four groups, each consisting of 25 cases. Group 1 patients did not receive prophylactic antibiotic. Group 2, group 3, and group 4 patients received ornidazole, penicillin plus tobramytine, and piperacillin. respectively. The use of prophylactic antibiotics did not yield better results than the use of placebos. The rarity of infectious complications after uncomplicated appendicectomy may be unique for children. Although the need for antibiotic prophylaxis is well documented in adults, the rarity of infectious complications makes it highly questionable in the treatment of uncomplicated appendicitis in children. Copyright o 1992 by W.B. Saunders Company INDEX WORDS: Appendicitis; tion; antibiotic prophylaxis.
postoperative
wound
infec-
R
EMOVAL OF a normal appendix, without preoperative antibiotics, may result in a wound infection rate of up to 10%. This incidence may jump to 30% if the appendix is inflamed.’ In recent years, the use of prophylactic antibiotics for the prevention of infection following appendicectomy has become an acceptable practice. 2 Although good results are reported with a single antianaerobic agent,i4 the majority of articles published since 1980 recommend both aerobic and anaerobic coverage in the antibiotic prophylaxis3 However, the increase in the number of publications during the last 25 years reflects the absence of a universally acceptable solution to the problem of wound sepsis after appendicectomy.3 Additionally the majority of publications dealing with antibiotic prophylaxis in acute appendicitis are confined to adult patients with only limited number of papers written about acute appendicitis in children. Therefore, a prospective randomized clinical trial was planned to evaluate the place of antibiotic prophylaxis in the treatment of acute appendicitis in children.
and A. Hiqsiinmez
Turkey MATERIALS AND METHODS One hundred patients treated for acute appendicitis in the Department of Pediatric Surgery of Hacettepe Children’s Hospital, between December 1987 and June 1990, were included in the present study. The patients who were diagnosed to have acute appendicitis were accepted to be candidates for inclusion in the study group. In the presence of parameters suggesting complicated appendicitis, such as symptoms longer than 36 hours, diffuse abdominal pain and tenderness, temperature over 38°C white blood cell (WBC) count exceeding 13,000/mm3~~h a history of previously diagnosed renal or gastrointestinal disease, drug hypersensitivity reaction. or antibiotic treatment during the recent 72 hours, the patients were not included into the study group. One hundred forms were prepared with each 25 denoting different prophylaxis protocols. Patients were assigned to one of the four treatment groups. In group 1, the regimen included placebo; in group 2.20 mgikgld of Ornidazole in 2 divided doses; in group 3, penicillin, 200.000 U/kg/d in 8 doses, plus 4 mglkgid of Tobramycine in 3 doses; in group 4,200 mg/kg/d of Piperacillin Na in 3 doses. The medications according to the protocols were given 30 minutes prior to operations. Hemoglobin, WBC count, urinalysis, blood urea nitrogen (BUN), creatinine, total protein-albumin, and plain abdominal radiographs were evaluated preoperatively. After the fluid and electrolyte resuscitation, the patients underwent operation under general anesthesia through identical RockeyDavis incisions. Standardized operative procedures were used. Immediately after opening the peritoneal cavity, the peritoneal swab was taken for the bacteriological examination, which included aerobic and anaerobic culture by conventional methods. The stumps were inverted with purse string. No abdominal lavages or drains were used. All the incisions were closed in layers. If the preoperative diagnosis of uncomplicated appendicitis was not confirmed at surgery, the patient was withdrawn from the study group and an identical form was recruited to the remaining protocols. The antibiotic prophylaxis was continued for 48 hours. The infectious complications and drug side effects were closely monitored. Blood BUN and creatinine values were reevaluated 24 hours after the withdrawal of antibiotics. The specimen were examined pathologically. If the pathological examination did not confirm the diagnosis, the patient was also withdrawn from the study, and an identical form was recruited to the remaining protocols. The prospective randomized clinical trial was done until the completion of 100 patients. The statistical comparisons were performed by x’ tests and ANOVA; P < .05 was considered to be significant. RESULTS
From the Department of Pediatric Surgery, Hacettepe University, Children’s Hospital, Ankara, Turkey. Date accepted: November 7, 1990. Address reprint requests to F.C. Tanyel, MD, Department of Pediattic Surgery, Hacettepe University, Children’s Hospital, 06100 Sihh&e, Ankara, Turkey. Copyright 0 I992 by W B. Saunders Company 0022-346819212705-OOI3$03.00/0
586
The study groups included 66 boys and 34 girls, of whom 54% were older than 11 years of age. The age and sex distributions in groups did not differ significantly (P > .05; Table 1). The preoperative BUN, creatinine, and blood protein values of patients did not show significant difference (P > .05; Table 2). The postoperative BUN and creatinine vaiues also
Journal of Pediatric Surgery, Vol 27, No 5 (May), 1992: pp 586-588
UNCOMPLICATED
587
CHILDHOOD APPENDICITIS
Table 1. Age and Sex Distribution of the Patients Group 1
Age (vr)
M
o-5
1
6-8
3
Group 2
F
M
T
1
M
F
1
1
1
2
2
4
2
3
5
2
3
Total
Group 4
Group 3 T
F
T
M
F
T
M
2 5
2
1
3
F
T
4
1
5
9
8
17 24
9-11
4
2
6
5
2
7
3
3
6
3
2
5
15
9
12-15
10
4
14
6
5
11
8
4
12
14
3
17
38
16
54
Total
18
7
25
14
11
25
15
10
25
19
6
25
66
34
100
Abbreviations: M, male; F, female; T, total.
did not differ significantly from preoperative values (P > .05). Swabs from peritoneum yielded aerobic microorganism in 27 patients (Table 3). However, none of them yielded positive anaerobic cultures. The most frequently isolated microorganism in aerobic cultures, was E coli in all groups (50%). It was followed by Stuphylococcus aureus ( 11.1%) and hemolytic Sfreptococcus (7.4%). The numbers of positive cultures in groups didn’t differ significantly (P > .05). None of the patients had had complicating infections, including wound infection and intraabdominal abscess. No drug side effects were recorded in patients who had undergone antibiotic prophylaxis. All of the patients were discharged on the fourth postoperative day and all of them were found to be in good condition during the outpatient clinical control 1 week after discharge. DISCUSSION
Appendicitis is the most common condition requiring urgent abdominal operations.i*7 When the diagnosis of appendicitis is established, it is uncomplicated in 55% to 70% of cases.8 It is generally accepted that an antibiotic prophylaxis is beneficial in reducing the wound sepsis in uncomplicated cases.2s3 However, most of the articles on this subject dealt with adults. Although it is the most common urgent surgical condition in children, the number of publications dealing with children is few. Therefore, the place of antibiotic prophylaxis, which is reasonable for adults, has not heretofore been thoroughly evaluated for uncomplicated appendicitis in children. In our study groups composed of patients with similar age and sex distributions and nutritional
status, the diagnosis of uncomplicated appendicitis was confirmed histopathologically. Cultures yielded positive results only for aerobic microorganisms in 27 patients. The incidence of aerobic cultures were similar in the study groups. Anaerobic cultures were negative in all of the cases. It was reported that one third of patients with uncomplicated appendicitis show positive aerobic cultures, but anaerobic cultures remain negative until complication occurs.9 The number of positive aerobic culture results in this study correlates with this finding. The negative anaerobic cultures in these patients, which may reflect true negatives, may also result from the technical insufficiency of the Microbiology Department of our hospital or some additional technical factors.4 There were no infectious complications in any of the patients, including those patients with positive peritoneal cultures. The use of prophylactic antibiotics did not show a superiority compared with the use of placebo. Age, obesity, duration of the operation, and nutritional status are among the factors known to influence infectious complications.iO Our study groups, which included similar patient populations, had similar risk of infectious complications. Because none of the patients with uncomplicated appendicitis had infectious complications, this may reflect a character unique for children. During laparotomy in children, it is easy to pass through the thin abdominal wall with minimal tissue trauma. There is a lower risk of contamination during extracting the appendix through the incision. The closed space created during the closure of the wound, which contains minimal fat layer, is small. The time period required for appendicectomy is shorter in children than in adults.
Table 2. Preoperative and Postoperative
Blood Chemistry Values
Preoperation Groups
BUN
1
13.8 + 5.2
Creatinine 0.75 + 0.34
Postoperation
Total Protein
Albumin
BUN
7.59 2 0.80
4.61 2 0.75
14.21 k 3.67
Creatinine 0.71 2 0.18
2
15.71 + 4.34
0.72 + 0.18
7.23 k 0.69
4.31 + 0.74
15.12 + 4.19
0.73 + 0.30
3
13.11 f 3.25
0.64 f 0.15
7.62 + 0.53
4.47 + 0.64
14.17 r 5.05
0.63 -c 0.12
4
14.64 k 3.00
0.80 k 0.15
7.52 + 0.66
4.47 + 0.61
15.14 + 3.89
0.84 + 0.13
NOTE. Values are given in mg/dL. There were no significant differences among groups.
588
KIZILCAN ET AL
Table 3. Aerobic Bacteria Isolated From Peritoneal Swabs
tis, the antibiotics should be discontinued in patients who are found to have an uncomplicated appendicitis during operation.
of 27 Patients GVXIDS 1
Microorganism E coli
2
s a”reiJS u-Hemolytic
-
3
3
3
-
Streptococcus
E coli + Klebsiella
1
-
Klebsieila
1
-
Micrococcus Streptococcus
2
5
3
-
2
-
-
1
2 faecalis
-
1
Proteus
-
-
1
Pseudomonas
-
1
-
Diphteroid
-
1
-
Total
4
6
7
8
6
Therefore, appendicectomy for uncomplicated appendicitis in children may carry a minimal risk of infectious complications. Because the infectious complications are negligible, the place of prophylactic antibiotics is very questionable in children with uncomplicated appendicitis. We recommend that if an uncomplicated appendicitis is diagnosed, the use of antibiotics for prophylaxis is not required. If the treatment has been initiated with the diagnosis of complicated appendici-
REFERENCES 1. Stevenson RJ: Abdominal pain unrelated to trauma. Surg Clin North Am 65:1181-12151985 2. McAllister TA, Fyfe AHB, Young DG, et al: Cefotaxime lavage in children undergoing appendicectomy. Drugs 35127-132, 1988 (suppl2) 3. Krukowski ZH, Irwin ST, Denholm S, et al: Preventing wound infection after appendicectomy: A review. Br J Surg 75:1023-1033, 1988 4. Ford WDA, MacKellar A, Richardson CJL: Pre- and postoperative rectal metronidazole for the prevention wound infection in children appendicitis. J Pediatr Surg 15:160-163,198O 5. Stone HH, Sanders SL, Martin JD: Perforated appendicitis in children. Surgery 69:673-679, 1971 6. King DR, Browne AF, Birken GA, et al: Antibiotic management of complicated appendicitis. J Pediatr Surg 18:945-950, 1983 7. Kottmeier PK: Appendicitis, in Welch KJ, Randolp JG, Ravitch MM, et al (eds): Pediatric Surgery. Chicago, IL, Year Book, 1986, pp 989-995 8. Savrin RA, Clatworthy HW: Appendiceal rupture: A continuing diagnostic problem. Pediatrics 63:37-43,1979 9. Stone HH: Bacterial flora appendicitis in children. J Pediatr Surg 11:37-42, 1976 10. Schwartz SI: Complications, in Schwartz SI, Shires GT, Spencer FC, et al (eds): Principles of Surgery. New York, NY, McGraw-Hill. 1984, pp 455-484