Grochowski, Jan A

Górecki, Wojciech

Medical Science Monitor

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Jagiellonian Univeristy Repository

Clinical Research289Med Sci Monit, 2001; 7(2): 289-292Are antibiotics necessary in nonperforated appendicitis in children?A double blind randomized controlled trialWojciech J. Grecki, Jan A. GrochowskiDepartment of Pediatric Surgery, ChildrenÕs Hospital, Jagiellonian University, Cracow, Polandkey words: appendicitis in children, antibioticsSUMMARYBackground: The use of antibiotics in uncomplicated appendicitis in children, remains the area of controversy.The aim of the study was to assess the necessity of antibiotic administration in nonperforated appendicitis inchildren.Material and methods: The design of the study was a double blind randomized controlled trial, with a follow-upof 4 to 20 months. Setting: Surgical Department in a University Pediatric Hospital. Patients: One hundred andeighty seven out of 249 children subjected to emergency appendectomies met the inclusion criteria, with 35 eligi-ble but not included in the study. The remaining 152 patients were randomized; 41 had complicated appendici-tis, 3 other diagnosis, 108 were analyzed within 3 study groups: 1 (n=31) no antibiotic, 2 (n=41) one dose, 3(n=36) 5-day course. Open appendectomy was a surgical procedure and Ceftriaxone 1.0 g i.v. was administe-red. Investigated parameters were: body temperature, WBC, bowel sounds, wound healing, recovery and morbi-dity.Results: Valid outcome data were available for 90 of 108 randomized patients. Protocols of 18 children due tofever >39¡C, upper airway infection or allergy were disclosed. In the remaining 90 children, there were no diffe-rences in WBC and oral feeding between groups 1 (n=24), 2 (n=35) and 3 (n=31). Group 1 and 2 had a hi-gher mean temperature on day 1 post-op, without any clinical significance. A higher mean temperature was no-ted on day 5 post-op in group 1, due to wound infection in one patient. There were no intraabdominal absces-ses. The only other complications were 2 adhesion small bowel obstructions (in groups 1 and 2 each).Conclusion: Routine use of antibiotics in nonperforated appendicitis in children is not necessary.Received: 2001.01.18Accepted: 2001.03.02Correspondence address: Wojciech Grecki MD PhD, Department of Pediatric Surgery, ChildrenÕs Hospital, Jagiellonian University, 265 Wielicka St., 30-663 Cracow, Poland, e-mail: migoreck@cyf-kr.edu.plBACKGROUNDThe major improvement in appendicitis outcomebegan with the antibiotic era. A mortality of 40% atthe turn of the century was significantly diminishedto 2.4% in the early 1940s [1]. With the advent ofantibiotics, complications of appendectomy out-numbered mortality and further efforts were pursu-ed in their reduction. Since then, however, relati-vely little progress has been made in lowering theoverall morbidity [2]. Numerous papers publishedin the next decades dealt with new antibiotics, the-ir combinations and route of administration. Thewound infection rate of 45% [3] ceased to occur,after King et al. [4] announced the standard ofusing ampicillin, gentamicin and clindamycin inpediatric complicated appendicitis. Employing thisprotocol for a decade, Lund and Murphy achievedthe lowest published wound infection rate of 3% inperforated appendicitis in children [5]. After thethird-generation cephalosporins were introduced,this popular ÔtripleÕ regimen became obsolete [6].Preoperative administration of antibiotics has pro-ven to be effective in reducing the wound infectionrate after potentially contaminated surgical proce-dures [7—9]. Controversy, however, persists in ap-290Clinical Researchpendectomies for nonperforated appendicitis, par-ticularly in children. Some authors find prophylac-tic antibiotics effective in reducing septic complica-tions after appendectomy for nonperforated ap-pendicitis [10], others conclude that antibiotic pro-phylaxis in uncomplicated appendicitis, particularlyin children, is highly questionable [11].If it is assumed that:— the inflamed appendix, without a perforation orperitoneal involvement, represents a resectableinfection;— children with acute appendicitis do not meet ne-ither patient related nor perioperative and intra-operative criteria determined by factors of incre-ased risk of postoperative infection;— inappropriate use of prophylactic antibiotics mayincrease costs, side effects, and selection of resi-stant organisms [7];we hypothesized, that routine antibiotic use inchildren with nonperforated appendicitis might beavoided.MATERIAL AND METHODSIn order to verify this statement, we performeda prospective, double blind, randomized and pla-cebo controlled clinical trial in children.PatientsÕ characteristicsThe study protocol and consent form were appro-ved by the institutional review board and researchcommittee prior to the initiation of the trial. Infor-med consent was obtained from the parents or le-gal guardians of the children. The study was con-ducted in the surgical department of the 600-bedJagiellonian University ChildrenÕs Hospital in Kra-kow, Poland, between December 1993 and March1995. During this time, 249 children were subjec-ted to emergency appendectomies with the pre-sumptive diagnosis of acute appendicitis. Theircharacteristics are presented in Table 1. Exclusioncriteria from the study comprised: body weight lessthan 15 kg, allergy to penicillin or cephalosporin,antibiotic therapy within the previous 72 h or un-derlying illness requiring antibiotic therapy, eviden-ce of diffuse peritonitis, or lack of written informedconsent.One hundred and eighty seven children were eligi-ble for the study. One hundred and fifty two weresuccessfully randomized. Those patients who werefound intraoperatively to have a perforated appen-dicitis or intraabdominal abscess (n=41), or thosemisdiagnosed (n=3), were excluded from the pro-tocol. The double blind study was conducted on108 children.AntibioticAll patients were treated with the same agent. Dueto the hospital pharmacy policy, identical but onlytwo doses were prepared for the day and for theon call time. Ceftriaxone had been chosen. The wi-de range of the dosage (20—80 mg per kg of bodyweight), allowed the administration of 1.0 g to allchildren. Moreover, the drug could be administe-red once a day, witch was beneficial for the chil-dren in the placebo group. Antibiotics used forprophylaxis for postappendectomy infections sho-uld control E. coli and Bacteroides fragillis [8]. Ce-ftriaxone seems to meet these requirements [6,12].Protocol:The patients were randomized into 3 stu-dy groups. The details of randomization were ba-sed on a table of random numbers and were unk-nown to anybody but the hospital pharmacy,which kept the master key and dispensed thedrugs. The antibiotic and placebo were packedidentically in opaque, numbered, ready for use i. v.bags. Each patient was administered intravenouslythe content of a bag every 24 hours for 5 days. Thefirst dose was given 30—45 minutes before the skinincision. Group 1(n=31) received no antibiotic.Group 2 (n=41) received one preoperative dose.Group 3 (n=36) received a 5-day course startedEligible, subjected to study and randomized 152Double blind studyPerforated appendixMisdiagnosed (Meckel diverticulitis,omental torsion, intususception)Eligible, not subjected to studyHospital pharmacy limitsNegligence to administerPhysicians refusal(endocarditis prophylaxis,2 handicapped children, family member)Did not meet inclusion criteriaLack of consentAntibiotic < 72 hPeritonitisBody weight < 15 kgKnown allergy108413352384623023432Table 1. PatientsÕ characteristics n = 249.291Grecki WJ et al — Are antibiotics necessary in nonperforated appendicitis in childrenÉpreoperatively. At the time of manuscript prepara-tion a 5-day antibiotic course after appendectomywas routinely employed in our department.All operations were performed by the on duty te-am. To maintain uniformity in the operative proce-dure a standard protocol of open appendectomywas followed. The appendiceal stump was inver-ted. All specimens were sent to pathology, whichestablished the final diagnosis. The peritoneumand the wound were irrigated with normal saline.No drains were inserted and the wound was closedprimarily.Study parametersAll patients were examined daily by the authors orby designated staff physicians and carefully asses-sed for the development of wound, intraabdominalor other infectious complications. For the purposeof this study wound infection was defined afterBurnweit [13] as peri-incisional cellulitis or seropu-rulent wound drainage, whether culture positive ornot. In addition to monitoring septic complications,body temperature was taken three times daily,WBC was counted daily and bowel sounds wereexamined with a stethoscope three times dailyuntil they reappeared. Attention was also paid topossible side effects of the antibiotic.If in any circumstance, observers or parents feltÔunsafeÕ with the effect of the masked drug, theprotocol was disclosed. This situation occurred in18 children out of 108 in whom the study had be-en started. Complete postoperative monitoring wasperformed in 90 children.Upon discharge all patients were reevaluated attwo weeks and one month after operation for thedevelopment of late complications. A questionna-ire was also mailed 4 to 20 months after dischargeto the parents in order to rule out possible late ab-dominal problems. The questionnaire was returnedby 70% of the parents.Statistical analysisChi-squared test was performed in the analysis ofqualitative variables. The differences in quantitativevariables within groups were identified usingANOVA and analyzed between groups by the Stu-dentÕs t-test. The normality of variables distributionwas assessed with the Kolmogorov-Smirnov test. Si-gnificance was determined at p<0.05.RESULTSThere were no significant differences in age, sex,body weight, WBC and temperature within groups1—3 at admission.The reasons for protocol disclosure are shown inTable 2. Table 3 presents the distribution of thechildren and pathology of the appendix in the 90randomized children with valid outcome data.The differences in appendix pathology withingroups 1—3 were non-significant.The side effects of ceftriaxone therapy were com-prised of allergic reactions (rash) in 2 patients andcolitis with massive Candida infection in 1 patientafter a single dose in each case.Group N Temp. WBC OralfeedingWoundinfectionOthermorbidity*123243531YesYesn.s.n.s.n.s.n.s.n.s.n.s.n.s.1 (4,2%)001 (4,18%)1 (2.7%)0*Small bowel obstruction after 3 and 2 months postoperativelyTable 4. Observed differences of monitored variables of 90 children ingroups 1-3.Group 1 Group 2 Group 3 TotalFeverURTI*AllergyCandida colitisHuman errorTotalStudy completedTotal* Upper respiratory tract infection; Û Non-significant difference in the numbers ofdisclosed protocols in groups 1-3 (chi2 3x2 matrix)420017Û24Û31311106Û35Û41221005Û31Û36952111890108Table 2. Reasons for disclosure of 18 patients in the study.Normal SimpleacutePhlegm-onous Gangrenous TotalGroup 1Group 2Group 3Total2226Û231615191650511122824353190ÛNon significant difference in pathology within groups 1-3 (chi2 4x3 matrix)Table 3. Distribution of randomized children and pathology of appendix.292Clinical ResearchThe differences of monitored variables in groups1—3 are shown in Table 4. Group 1 and 2 had a hi-gher mean temperature on first postoperative day.A higher mean temperature was also noted on fifthpostoperative day in group 1. Resolution of leuco-cytosis did not differ in groups 1—3. There was onlyone wound infection with Pseudomonas aerugino-sa in a child from group one. This child was suc-cessfully treated with incision and drainage. Nowound infection occurred in groups 2 or 3. Theonly other complications were two small bowel ob-structions due to adhesions (in groups 1 and 2each, occurred 3 and 2 months postoperatively).DISCUSSIONAntibiotic prophylaxis in appendicitis, particularlyin children, has been an area of controversy. A listof all known attempts for prevention of wound in-fection is very extensive and beyond the scope ofthis paper. Our clinical results of a randomized do-uble blind study in 90 children were as follow: onewound infection in group one (4.2%); two smallbowel obstructions due to adhesions (1 of 24 ingroup 1 and 1 of 35 in group 2, occurred beyond30 post-op day) and temperature shifts in somemeasurements in group 1 and 2. The temperatureaverage was higher on the first postoperative day ingroup 1 and 2, than in group 3. We did not finda clinical correlation to this phenomenon. The ave-rage temperature increase in group 1 on the fifthpostoperative day was due to the wound infectionin one patient. The wound exudate of this childcultured Pseudomonas aeruginosa. These bacteriawere also isolated from peritoneum and appendixin this patient. Pseudomonas growth from the peri-toneum may predict an infection even after anti-biotic prophylaxis [14,15].The wound infection rate of 4.2% without prophy-laxis in our study seemed to be acceptable. Inother placebo controlled trials, Ôno antibioticÕ wo-und infection rates ranged from 4% to 9% for sim-ple appendicitis [7].The reasons for opening the protocol of three outof 18 patients were the following side effects of theantibiotic therapy: two allergic reactions (rash) andone candida colitis.The question remains whether all children withnonperforated appendicitis should be consideredfor routine prophylaxis. Prophylactic antibiotics arerecommended when the risk of postoperative in-fection is high or in lower risk cases, when the con-sequence of the infection is extreme morbidity ormortality [7]. Postappendectomy wound infectionin children does not constitute extreme morbidity.The most serious complication — intraabdominalabscess — did not occur in our study.CONCLUSIONSWe suggest that routine use of antibiotics in non-perforated appendicitis in children is not necessa-ry. The potential minimal reduction of the woundinfection rate is counterbalanced by the side effectsof antibiotics and the risk of emergence of resistantflora and opportunistic infections. REFERENCES:1. Maxwell JM, Ragland JR: Appendicitis. Improvements in Diagnosisand Treatment. Am Surg, 1991; 57: 282-2842. Cooperman M: Complication of appendectomy. Surg Clin N Am,1983; 63: 1223-12473. Andersen B, Bendtsen A, Holbraad L, Schantz A: Wound infectionsafter appendicectomy. Acta Chir Scand, 1972; 138: 531-5364. King DR, Browne AF, Birken GA et al: Antibiotic management ofcomplicated appendicitis. J Pediatr Surg, 1983; 18: 945-9505. Lund DP, Murphy EU: Management of perforated appendicitis inchildren: a decade of aggressive treatment. J Pediatr Surg, 1994; 29:1130-11346. Wittmann DH, Schein M, Condon RE: Management of secondary pe-ritonitis. Ann Surg, 1996; 224: 10-187. Page CP, Bohnen JMA, Fletcher JR et al: Antimicrobial Prophylaxisfor Surgical Wounds. Guidelines for Clinical Care. Arch Surg, 1993;128: 79-888. Bohnen JM, Solomkin JS, Dellinger EP et al: Guidlines for clinicalcare: anti-infective agents for intraabdominal infection. A Surgical In-fection Society policy statement Arch Surg, 1992; 127: 83-909. Gorbach SL: State-of-art clinical article. Intraabdominal infections.Clin Infect Dis, 1993; 17: 961-96710. Busutill RW, Davidson RK, Marjorie F, Tompkins RK: Effect of pro-phylactic antibiotics in acute nonperforated appendicitis. Ann Surg,1981; 194: 502-50911. Kizilcan F, Tanyel FC, Buynkpamukcu N, Hiesonmez R: The necessi-ty of prophylactic antibiotics in uncomplicated appendicitis duringchildhood. J Ped Surg, 1992; 27: 586-55812. Aldridge KE, Gelfand M, Reller LB et al: A five year multicenter studyof the susceptibility of the Bacteroides fragilis group isolates to cepha-losporins, cephamins, penicillins, clindamycin, and metronidazole inthe United States. Diagn Microbiol Infect Dis, 1994; 18: 235-24113. Burnweit C, Bilik R, Shandfing B: Primary closure of contaminatedwounds in perforated appendicitis. J Pediatr Surg, 1991; 26: 1362-136514. Lau WY, Teoch-Chan CH, Fan ST et al: The bacteriology and septiccomplication of patients with appendicitis. Ann Surg, 1984; 200: 576-58115. Yellin AE, Heseltine PNR, Berne TV: The role of pseudomonas spe-cies in patients with ampicillin and sulbactam for gangrenous and per-forated appendicitis. Surg Gynecol Obstet. 1985; 161: 303-307

Are antibiotics necessary in nonperforated appendicitis in children? : a double blind randomized controlled trial

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Are antibiotics necessary in nonperforated appendicitis in children? : a double blind randomized controlled trial

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