Journal of Investigative Surgery

ISSN: 0894-1939 (Print) 1521-0553 (Online) Journal homepage: http://www.tandfonline.com/loi/iivs20

Predicting Postoperative Complications After Pediatric Perforated Appendicitis G. Frongia, A. Mehrabi, L. Ziebell, J.P. Schenk & P. Günther To cite this article: G. Frongia, A. Mehrabi, L. Ziebell, J.P. Schenk & P. Günther (2016): Predicting Postoperative Complications After Pediatric Perforated Appendicitis, Journal of Investigative Surgery, DOI: 10.3109/08941939.2015.1114690 To link to this article: http://dx.doi.org/10.3109/08941939.2015.1114690

Published online: 29 Jan 2016.

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Journal of Investigative Surgery, Early Online, 1–10, 2016 C 2016 Taylor & Francis Copyright  ISSN: 0894-1939 print / 1521-0553 online DOI: 10.3109/08941939.2015.1114690

Predicting Postoperative Complications After Pediatric Perforated Appendicitis 1 ¨ G. Frongia,1 A. Mehrabi,2 L. Ziebell,1 J.P. Schenk,3 P. Gunther

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1

Division of Pediatric Surgery, Department of General, Visceral and Transplantation Surgery 2 Department of General, Visceral and Transplantation Surgery 3 Division of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Heidelberg, Germany

ABSTRACT Purpose: Assessment of risk factors for postoperative complications following surgical treatment of pediatric perforated appendicitis (PA) is necessary to identify those patients in need of closer monitoring. In this study, we have investigated the impact of different risk factors on the occurrence of complications after an appendectomy in children with PA. Material and Methods: The study was a retrospective, single-centre analysis of all pediatric PA conducted over a 10-year period. Preoperative clinical and laboratory results, intraoperative findings, and postoperative complications were analyzed. Risk factors were defined and a risk score was determined for postoperative complications and reinterventions. Results: Surgical treatment for appendicitis was performed in 840 pediatric patients during the observation period. 163 of the included patients were diagnosed with PA (mean age 8.9 ± 3.6 years). 19 (11.7%) patients developed postoperative complications, 17 (10.4%) of which required complication-related intervention. We identified five predictors of postoperative complications: the C-related protein value at admission, purulent peritonitis, open appendectomy (primary, secondary, or converted), placement of an abdominal drain, and administration of antibiotics not compliant to results from the subsequent antibiogram. The determined risk score was significantly higher in the complication group (p < .0001) and reintervention group (p < .001). Conclusions: Postoperative complications following pediatric PA can be predicted using specific preoperative, intraoperative, and postoperative risk factors. In the high-risk group, an active prevention, detection, and intervention of any occurring complication is necessary and we present a new specific pediatric risk score to define patients at risk for complications. Keywords: perforated appendicitis; risk factors; risk score; Outocome; complications; prevention; pediatric; children

INTRODUCTION

pediatric patients with PA have not been conclusively defined. The aim of this study was to determine the preoperative, intraoperative, and postoperative risk factors that can reliably predict the development of postoperative complications following PA.

A perforated appendix (PA) is one of the most frequent indications for an emergency operation in children, occurring in about 35% of all cases of pediatric appendicitis [1, 2]. Postoperative complications are significantly higher following surgical treatment of PA compared to nonperforated appendicitis, occurring in 20%–30% of cases [1, 3, 4]. PA, therefore, demands a higher rate of reintervention and longer hospital stays [4] creating a high burden for both patients and the pediatric health care system [5]. An evaluation of the risk factors in pediatric patients presenting with PA is necessary to identify those high-risk patients in need of closer monitoring following surgery. However, factors that can reliably predict postoperative complications in

PATIENTS AND METHODS Study Design Ethical approval for the study was obtained from the local ethics committee. The study included all patients aged 15 years and under, who received an appendectomy for PA at our tertiary referral center for pediatric surgery between January 1, 2003, and December 31,

Received 17 July 2015; accepted 27 October 2015. Address correspondence to Giovanni Frongia, Division of Pediatric Surgery, Department of General, Visceral and Transplantation Surgery, University Hospital of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. E-mail: [email protected]

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2 G. Frongia et al. 2012. PA was defined intraoperatively as a visible hole in the appendix or a fecalith in the abdomen, as previously described [6]. Patients with an appendicitis not matching this definition were excluded from this study, regardless of the reported diagnosis in the medical reports. Demographic, preoperative, intraoperative, and postoperative data were extracted by retrospective review of the patient charts. Predictors of postoperative complications as a whole, defined as the sum of all complications, were analyzed initially by comparing the group developing complications to the group not developing complications. The predictors of specific postoperative complications and the need for reintervention were analyzed by independently comparing the occurrence of each individual complication.

tion, with (for IIIb) or without (for IIIa) general anesthesia. A combination of multiple complications for each patient was possible. Postoperative complications were defined as follows: abscess formation (defined as an intraabdominal hypoechoic enclosed collection identified by ultrasound), intestinal obstruction (defined as an ileus or clinically relevant subileus requiring adhesiolysis), wound infection (defined as a dehiscence of wound margins with purulent secretion), dehiscence of the abdominal fascia (defined as a wound healing deficit leading to dehiscence of the abdominal fascia and possible evisceration). Purulent peritonitis was intraoperatively defined as an abdominal infection with a diffuse purulence in more than one abdominal quadrant.

Surgical Procedure

Data Analysis

Open and laparoscopic appendectomies were performed under general anesthesia. The surgical method was determined primarily by the surgeon’s personal experience and preference. For a laparoscopic appendectomy, a 10 mm trocar was introduced periumbilically for the camera and each one 5 mm trocar into both the right and left lower quadrants for the instruments. The pneumoperitoneum pressure ranged from 8 to 12 mmHg of CO2 . Laparoscopic appendectomy was performed using endoloop-sutures. Open appendectomy was performed by an abdominal incision in the right lower quadrant or by median laparotomy. During open appendectomy, the appendicular stump was sewed over. No stapling devices were used.

R Statistical analysis was performed using SPSS ver R sion 21 (SPSS Corp., Chicago, IL, USA). Categorical variables were expressed as frequency distributions and continuous variables as mean values ± standard error of the mean (SEM). Categorical data were compared using a chi-squared and Fisher’s exact test, while continuous variables were compared using an independent-samples t-test. A new and arbitrary risk score was calculated as the number of risk factors occurring in a patient (defined in the results section) multiplied by the CRP value at admission (mg/dl). The minimal risk score value is 0, while theoretically there is no upper value. Cut-off values were determined using a receiver operating characteristic (ROC) curve analysis. Odds ratios were calculated using binary logistic regression. A p < .05 was considered significant.

Variables Admission, in-patient stay and postoperative course variables were evaluated. Admission variables included age, sex, body mass index (BMI), fever (> 38.5◦ C), infection parameters (C-related protein (CRP) and leucocyte levels), abdominal ultrasound findings, and abdominal complaints prior to admission. In-patient stay variables included operative access for appendectomy (laparoscopic, open and conversion rates), the type and duration of preoperative and postoperative antibiotic treatments as well as infection parameters at the time of discharge (CRP and leucocyte levels). The occurrence of severe complications during the postoperative course was monitored in this study. Only grades II and IIIa/IIIb (according to Clavien classification) complications were recorded in this study [7]. Grade II complications require pharmacological treatment with drugs other than antiemetics, antipyretics, analgetics, diuretics, and electrolytes and physiotherapy, e.g., antibiotics; grade III complications require surgical, endoscopic, or radiological interven-

RESULTS Patient Demographics and Findings at Admission During the study period a total of 840 pediatric patients were operated for appendicitis at our center. 163 patients (19.4%) with a PA met the inclusion criteria for this study. The demographic and diagnostical findings at admission are presented in Table 1.

In-Patient Stay Procedures Appendectomies to treat PA were started laparoscopically in 106 cases (65%), of which 63 cases (38.7%) were concluded laparoscopically and 43 cases (26.4%) were converted into an open appendectomy during surgery. Open appendectomies were performed primarily in 57 cases (35%). Overall, an open appendectomy was Journal of Investigative Surgery

Risk Factors Pediatric Perforated Appendicitis 3 TABLE 1 Demographics and diagnostical findings at admission Patients

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Age (years) Sex (male) BMI (Kg/m2 ) Findings at admission Length of abdominal complaints (days) Fever (>38.5◦ C) CRP (mg/l) Leucocytes (/nl) Suspected PA in abdominal ultrasound

163 8.9 ± 0.3 97 (59.5%) 17.5 ± 0.3 3.5 ± 0.3 61 (42%) 108.4 ± 5.6 18.4 ± 0.5 23 (14%)

performed (either primarily or by conversion) in 100 cases (61.3%). One ileostomy was performed during intervention for PA. Intraabdominal drainage was used in 123 cases (76%). Intravenous antibiotic treatment with cefotaxime and metronidazole was provided to every patient during surgery. In 79% of patients, this treatment was postoperatively prolonged for a mean duration of 7.3 ± 0.2 days for cefotaxime and 5.7 ± 0.2 days for metronidazole. In 21% of cases, the antibiotic therapy was adapted according to the subsequently obtained microbiological and antibiogram. Until antibiogram was available, patients continued to receive cefotaxime and metronidazole. In accordance with the antibiogram results, ampicillin, ceftazidine, cefuroxime, ciprofloxacine, imipenem, meropenem, and taicoplanin were used. The antibiotics were provided intravenously either alone or in combination for a mean duration of 7.6 ± 0.9 days. At the time of discharge, the mean CRP value was 14.8 ± 1.3 mg/l (internal standard value < 5 mg/l) and the mean leucocyte value was 8.3 ± 0.2 /nl (internal standard value 5–13 /nl).

Postoperative Course 19 (11.7%) patients developed postoperative complications, 17 (10.4%) of which required surgical intervention (Table 2). Of the 12 patients developing a postoperative intrabdominal abscess, nine required a surgical debridement, while three were successfully managed with antibiotic treatment. No computed tomography (CT)-guided drain placement was performed as the abscesses were anatomically not easily accessible. An abdominal adhesiolysis was performed for all seven clinically relevant intestinal obstructions. Six out of eight wound infections needed a surgical wound debridement, while antibiotic therapy after spontaneous wound draining was sufficient in two cases. Both cases of abdominal fascia dehiscence occurred after converting to an open appendectomy. The patients were seven and 13 years old, with repsective BMIs of 15.3 and 29.3 Kg/m2 . After closure of the fascia, vacuum assisted closure was performed for six and 12 days, respectively,  C

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TABLE 2 Postoperative course

Intraabdominal abscess Intestinal obstruction Wound infection Dehiscence abdominal fascia

Postoperative complications

Reintervention necessary

12 (7.4%) 7 (4.3%) 8 (4.9%) 2 (1.2%)

9 (5.5%) 7 (4.3%) 6 (3.7%) 2 (1.2%)

before secondary wound closure was possible. Intervention was necessary in two patients (1.2%) for other reasons; in one case the ileostomy performed during the appendectomy was closed and in the second case a wound revision was performed due to an omental prolapse following removal of an abdominal drain.

Risk Factors of Postoperative Complications as a Whole The sum of all complications is shown in Table 3. The complication and noncomplication groups were comparable with regard to demographics, clinical, laboratory, and ultrasound findings at admission, except for the CRP value at admission, which was significantly higher in the complication group. The duration of surgery and the surgical method (laparoscopic or open) had no significant impact on the occurrence of complications, in general. However, subgroup analysis revealed significantly more conversions from laparoscopy to open surgery in the complication group. The risk ratio for the development of complications following conversion was 4 (95% confidence interval (CI): 1.2–13.9, p = 0.028). The rate of purulent peritonitis and abdominal drain placement were also significantly higher in the complication group. 15.4% of patients with a drain developed complications, while no complications were observed in patients without a drain (p = 0.004). Significantly more patients with purulent peritonitis developed complications (31.6% vs. 11.1%, p = 0.025) and 90.9% of children with purulent peritonitis had a drain placed (p = 0.07). Purulent peritonitis did not affect the conversion rate (50% vs. 41.9%, p = 0.576). The CRP value at admission was similar in converted and primarily open appendectomies (131 ± 11 vs. 118.4 ± 10.2, p = 0.407). Furthermore, significantly more patients developing postoperative complications received initial antibiotic treatment that was not compliant to the subsequent antibiogram, necessitating a change in antibiotics (47.4% vs. 17.4%, p = 0.005), although this was not affected by the occurence of purulent peritonitis (31.8% vs. 19.1%, p = 0.256). The CRP and leucocyte values at discharge were comparable in both groups.

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TABLE 3 Predictors of postoperative complications as a whole p-value

Complication group

Noncomplications group

19 (11.7%)

144 (88.3%)

9.7 ± 0.9 90% 18.5 ± 1.2

8.8 ± 0.3 61.1% 17.4 ± 0.3

0.272 0.321 0.228

4.7 ± 0.5 31.6% 149 ± 14.3 17.6 ± 1.8 15.8%

3.3 ± 0.3 38.2% 103 ± 5.9 18.5 ± 0.5 13.9%

0.173 0.621 0.008 0.568 1

98.5 ± 8.3 26.3% 73.7% 52.6% 31.6% 100%

82.6 ± 3.2 40.3% 59.7% 22.9% 11.1% 72.2%

0.091 0.319 0.319 0.039 0.025 0.004

47.4%

17.4%

0.005

13.8 ± 3.2 7.8 ± 0.7

14.9 ± 1.4 8.4 ± 0.3

0.753 0.512

Number of patients (%) Demographics Age Gender (male) BMI (Kg/m2 ) Clinical and laboratory findings at admission Duration abdominal complaints (days) Fever (>38.5◦ C) CRP (mg/l) Leucocytes (/nl) Sonographic suspicion of PA Appendectomy Duration of surgery (min) Laparoscopic Open (primarily or by conversion) Open after conversion from laparoscopy Purulent peritonitis Drain placement Postoperative antibiotics Antibiogram noncompliant Laboratory findings at discharge CRP (mg/l) leucocytes (/nl)

Risk Factors of Specific Postoperative Complications and Need for Reintervention Specific complications could be predicted with statistical significance by the following risk factors: the CRP value at admission, purulent peritonitis, open appendectomy (either primarily or secondarily after conversion from laparoscopy), and an initial antibiotic treatment not compliant to the antibiogram (Table 4). CRP Value at Admission A CRP value higher then 100 mg/dl at admission was associated with a higher rate and reintervention for intrabdominal abscesses and wound infections (Table 4). The CRP value at admission could accurately predict a postoperative abdominal fascia dehiscence (area under the ROC curve 0.953 ± 0.025, 95% CI: 0.905–1, p = 0.028), with a cut-off value of 205 mg/dl having a sensitivity of 100% and specifity of 92.5%. Furthermore, the CRP value at admission predicted postoperative wound infection with fair accuracy (area under the ROC curve 0.732 ± 0.111, 95% CI: 0.514–0.949, p = 0.027), with a cut-off value of 151 mg/dl having a sensitivity of 75% and specifity of 76.8%. The occurrence of a postoperative intestinal obstruction was not accurately predicted by the CRP value at admission (area under the ROC curve 0.580 ± 0.057, 95% CI: 0.469–0.691, p = 0.474). Open Appendectomy An open appendectomy (either primarily or secondarily following conversion) was associated with a higher rate of postoperative wound infections (8% vs. 0%, p =

0.024) and consequent reinterventions (6% vs. 0%, p = 0.048) compared to a laparoscopic appendectomy. Indeed, all wound infections and necessary reinterventions were observed in the open appendectomy group. Subgroup analysis revealed that conversion to an open appendectomy during surgery was associated with a higher postoperative abscess rate (14% vs. 1.8%, p = 0.04) and abscess related reintervention rate (11.6% vs. 1.8%, p = 0.04) compared to a primarily open appendectomy. Intestinal obstruction and wound dehiscence rates were also higher in open compared to laparascopic appendectomies (intestinal obstruction: 5% vs. 0.03%, p = 0.707; wound dehiscence: 100% vs. 0%, p = 0.523). Purulent Peritonitis Significantly, more children with purulent peritonitis developed a wound infection (13.6% vs. 3.5%, p = 0.042) and had a higher rate of reinterventions for wound infection, although this difference was not stastistically significant (9.1% vs. 2.8%, p = 0.186). Futhermore, purulent peritonitis was associated with a higher rate of postoperative abscesses (13.6% vs. 6.4%, p = 0.208), wound dehiscence (4.5% vs. 0%, p = 0.252), and ileus (0% vs. 4.9%, p = 0.595), although these differences were not significant. Lack of Compliance of Initial Antibiotic Treatment With Subsequent Antibiogram Results Antibiotic treatment that did not comply with the subsequent antibiogram was associated with a higher occurrence of abscesses (14.7% vs. 5.4%, p = 0.065), wound infection (11.8% vs. 3.1%, p = 0.037), and Journal of Investigative Surgery

Risk Factors Pediatric Perforated Appendicitis 5

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TABLE 4 Predictors of specific complications and reinterventions

CRP > 100 mg/dl at admission Intraabdominal abscess (n = 12) Reinterventions due to intraabdominal abscess (n = 9) Wound infection (n = 8) Reinterventions due to wound infection (n = 6) Open appendectomy (primarily or after conversion) Wound infection (n = 8) Reintervention due to wound infection (n = 6) Purulent peritonitis Wound infection (n = 8) Reintervention due to wound infection (n = 6) Initial antibiotics not compliant to antibiogram Dehiscence of the abdominal fascia (n = 2) Reintervention due to dehiscence of the abdominal fascia (n = 2)

abdominal fascia dehiscence (5.9% vs. 0%, p = 0.042). The need for reintervention did not increase for abscesses and wound infection following uncompliant antibiotic treatment (abscesses: 11.8% vs. 3.9%, p = 0.073; wound infection: 5.9% vs. 3.1%; p = 0.606), but more interventions were required for dehiscence of abdominal fascia (5.9% vs. 0%, p = 0.042).

Abdominal Drainage The placement of an abdominal drain was associated with a higher overall complication rate (100% vs. 72.2%, p = 0.004) and a higher overall reintervention rate (100% vs. 72.6%, p = 0.014), but these differences were not significant on an individual basis (intraabdominal abscess: 8.9% vs. 2.5%, p = 0.297; ileus: 5.7% vs. 0%, p = 0.196; wound infection: 6.5% vs. 0%, p = 0.201; dehiscence of the abdominal fascia: 1.7% vs. 0%, p = 1).

Risk Score The risk score, calculated as the number of risk factors occurring in one patient multiplied by the CRP value at admission (mg/dl), was significantly higher in the complication compared to the noncomplication group (547.8 ± 78.1 vs. 267.2 ± 21.1, 95% CI: 150.3–411, p < .0001) and significantly higher in the reintervention group compared to the nonreintervention group (506.4 ± 74.4 vs. 275.8 ± 22.6, 95% CI: 90.8–370.4, p < .001). The risk score cut-off value of 281 has a sensitivity of 79% and a specificity of 60.4% in predicting a postoperative complication (odds ratio: 1.99, 95% CI: 1.47–2.71) and a sensitivity of 76.5% and a specificity of 60% in predicting the need for a reintervention (odds ratio: 1.89, 95% CI: 1.36–2.63). The risk score demonstrated fair accuracy as a predictor of complications (area under the ROC curve 0.753 ± 0.61, 95% CI: 0.634–0.872, p = 0.001).  C

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Occurrence of(%) risk factor (%)

No occurrence of(%) risk factor (%)

p-value

11.8 10.6 8.2 5.9

2.6 0 1.3 1.3

0.034 0.003 0.04 0.119

100 100

0 0

0.024 0.048

13.6 9.1

3.5 2.8

0.042 0.186

100 100

0 0

0.042 0.042

DISCUSSION PA is associated with a high complication rate leading to elevated patient burden, frequent surgical reintervention, longer hospital stays, and higher costs for the pediatric health care system [4, 5]. Predictors of PAassociated postoperative complications are necessary for more stringent monitoring of at-risk patients, permitting early intervention and management of postoperative complications following surgical treatment of PA. In our study, we detected a lower rate of postoperative complications in patients with PA compared to previous studies, reporting rates of about 20%–30% [1, 3, 4]. Possibly, this is because we only evaluated severe postoperative complications with a Clavien grade of II-III. However, we identified the following significant risk factors for postoperative complications in children with PA: CRP value at admission, purulent peritonitis, conversion to open surgery, drain placement, and an initial antibiotic therapy not compliant to the subsequent antibiogram. The information we gathered regarding the patient history and physical examination may also have prospective value in predicting postoperative complications and assuring optimal therapy in future cases. CRP is an acute phase inflammatory marker and higher levels signify a more intense local inflammatory reaction and more severe appendicitis [8, 9]. Only a few studies have identified the CRP value at admission as a marker for complications in appendicitis [8, 10]. However, these were mainly studies of adult patients [8, 10] and dealt with appendicitis in general rather than PA specifically [8]. In our study, a CRP level of > 100 mg/l was significantly associated with a five to seven times higher intraabdominal abscess and wound infection rate, as well as a five to nine times higher reintervention rate. According to other publications, the CRP level at admission can be used to distinguish PA from

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TABLE 5 Published predictors of postoperative complications following PA and comparison to the results of present study (OR odds ratio) Reference

Population

Predictors

Complication

Fraser 2010 [12]

Children

Demographics, history, clinic, and serum values

Abdominal abscess formation

Henry 2007 [3]

Children

Diarrhea at presentation, intraoperative fecalith

Abdominal abscess formation

Van Wijck 2010 [41]

Children

Gender

Abdominal abscess formation

Kokoska 1998 [35]

Children

Symptoms duration Abdominal abscess before surgical formation referral; drain placement

Emil 2014 [24]

Children

Abdominal abscess Serum values, formation presence of bowel obstruction or severe ileus at presentation

Obinwa 2015 [47]

Children

Pyrexia

Complications in general

Predictive value

Comparison to our results

Increasing age (p = 0.003), Mentioned items were highly predictive for weight (p = 0.001), BMI abscess formation (p = 0.008), diarrhea (p following PA in children. = 0.005), increased These risk factors were white blood cell count not confirmed by our on day five (p < .001) study (all p > .05). highly predictive of abscess The two factors are Diarrhea at presentation described to be OR 3.63 (95% CI: predictive of abscess 1.29–10.21), development, but were intraoperative fecalith not tested in our study. OR 8.77 (95% CI: 1.50–51.40) Male OR 1.06 (95% CI: Female gender was a risk 0.18–0.97, p = 0.042) factor for abscess formation, however, this risk factor was not confirmed by our study (male:female, p = 0.321). Development of More than five days of postoperative abscess symptoms before occurs in children with a operation (p < .01) and longer (> five days) no drain placement was duration of symptoms highly predictive of before surgical referral abscess and is significantly less frequent after drain placement. In our study the duration of complains was not predictive for complications (p = 0.173), and drain placement was associated with significantly more complications (p = 0.004). Elevated white blood cell Higher white blood cell count at presentation count OR 1.08 (95% CI: was predictive of 1.01–1.16, p = 0.02). abdominal abscess Presence of bowel formation. This was not obstruction or severe confirmed by our data, ileus at presentation OR as mentioned variable 6 (95% CI: 2.2–20, p = was not significantly 0.001) elevated in the complication group (p = 0.568). We did not evaluate the impact of bowel obstruction/ileus at presentation in our study. Preoperative body Preoperative pyrexia was temperature > 37.5◦ C highly associated with OR 1.82, 95% CI: development of 1.07–3.08) postoperative complications. We could not confirm this risk factors by our study (fever > 38.5◦ C, p > .05). (Continued on next page)

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TABLE 5 Published predictors of postoperative complications following PA and comparison to the results of present study (Continued) Reference

Population

Predictors

Complication

Shelton 2014 [8]

Adults

Preoperative CRP-value

Complications in general

Abe 2013 [9]

Adults

Preoperative CRP-value

Conversion to open appendectomy

Shelton 2014 [8]

Adults

Open appendectomy

Complications in general

nonperforated appendicitis [11] and is a reliable predictor of conversion from laparoscopic to open appendectomy [8, 10]. Although we did not confirm this in our study, the CRP value was indicative of a more challenging surgical intervention and increased postoperative complications. The cut-off CRP value of 151 mg/dl might be predicative of wound infections, while the cut-off value of 205 mg/dl could be indicative of an abdominal fascia dehiscence. Many previously identified risk factors for preoperative and postoperative complications were not confirmed by our study. Increasing age [12], increasing BMI [5, 12–14], and diarrhea [3, 5, 12] have been reported to be preoperative risk factors for abscess formation, but we did not confirm this, neither could we confirm that demographics, duration of complaints, occurrence of fever, leucocyte count, and sonographic suspi-

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Predictive value

Comparison to our results

CRP of > 150 mg/l was an independent predictor for complications. Our study confirms this data, as in our data a similar cut-off CRP value of 151 mg/dl was predictive of complications, in our case wound infections. High CRP level (> Higher preoperative CRP 10 mg/dl) OR 3.44 (95% level (> 10 mg/dl) was a CI: 1.22–9.71, p = 0.019) significant risk factors for conversion from laparoscopic to open appendectomy. However, we could not confirm this in our study (p = 0.998). OR 2.084 (95% CI: The authors state that not 1.152–3.771, p = 0.015) enough information was available to draw statistically significant conclusions. According to our study, a complication is fourfold more likely after open appendectomy, as the risk ratio for the development of complications following conversion was 4 (95% CI: 1.2–13.9, p = 0.028). Further, an open appendectomy in our study was associated with a higher rate of postoperative wound infections (p = 0.024) and reinterventions (p = 0.048).

CRP 150–199.9 mg/l OR 2.159 (95% CI: 1.004–4.639, p = 0.049) to CRP > 350 + OR 8.234 (95% CI: 1.398–48.517 p = 0.020)

cion of PA were predictors of postoperative complaints. Although obesity in children has been linked to an increased incidence of wound infections [13, 15, 16], abscess formation [12, 14], and longer hospital-stay [13, 14], we did not find any predictive value for the BMI for postoperative complaints, possibly due to the relatively low average BMI in our study group. We have identified an open appendectomy as an intraoperative risk factor for postoperative complications, particularly wound infections. This is in agreement with published findings attesting the advantages of laparoscopic appendectomy over open appendectomy in children with PA [17–22]. These advantages include reduced postoperative infection, particularly wound infections, reduced abdominal scarring, less postoperative pain, earlier recovery, shorter hospital stays, and fewer clinical visits [17–22]. Consequently,

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8 G. Frongia et al. laparoscopic appendectomy is widely considered a safe and effective first-line procedure for the treatment of PA in children [17]. In our study, we observed a slightly higher conversion rate than previous publications [18, 23], possibly due to the strict definition of PA in our study [6]. Conversion from laparoscopic to open surgery was associated with postoperative abscess formation, surgical reintervention, and abdominal fascia dehiscence, which is in agreement with a previous report that described an increased risk of wound infections and readmissions following conversion to open surgery [18]. We believe that the need for conversion represents a more difficult operation, which explains the increased complications rate and propose that appendectomies should be performed laparoscopically and conversions avoided whenever possible [18]. A longer surgical time has previously been associated with a higher abscess formation rate [24], but we, together with others, have not confirmed this [12]. We found purulent peritonitis to be significantly associated with a higher rate of complications as a whole and particularly with wound dehiscence. Copious irrigation of four abdominal quadrants has been recommended to prevent postoperative intraabdominal abscesses [25], although it has also been suggested that this measure has not proven effective in reducing postoperative abscesses [26, 27]. We observed increased abscess development postoperatively in the purulent peritonitis group, despite placement of a drain in 90.9% of these patients. Multiple studies have demontrated that placement of drains during the operation increases abscess formation, prolongs the initial hospital stay [24] and increases the likelihood of other complications [28, 29]. This in accordance with our finding that there are significantly more postoperative complications as a whole following drain placement. However, these findings must be interpreted with caution as the majority of patients with a drain placement in our study also had purulent peritonitis. That being said, a wound revision due to omental prolapse was necessary following the removal of an abdominal drain and would most likely have been unnecessary if the original drain placement had been avoided. We routinely use endoloops rather than an endostapler to close the appendical stump during a laparoscopic appendectomy. It has recently been shown that an endo stump closure during a laparoscopic appendectomy is safe and effective in children with PA [30]. PA in children might be triggered by specific bacterial pathogens, in particular, E. coli, Streptococci, and Pseudomonas aeruginosa [31]. We found that postoperative complications occured more frequently when the initial antibiotic therapy did not comply with the subsequent antibiogram results. We tailored antibiotic treatment in one fifth of children with PA whose antibiogram results revealed resistance to the typical antibiotic regimens and continued to do so for one week on

average. Like others [32], we feel that tailoring antibiotic therapy may help to reduce postoperative complications, although we acknowledge that it is not sufficient to completely remove the threat of postoperative complications. Some groups have even abandoned the practice of tailoring the antibiotic regimen altogether, as it does not guarantee an improved outcome [24, 33–36]. The optimum duration for antibiotic therapy has not been determined. We continued postoperative antibiotic treatment for five to seven days on average. A minimum of five days has been recommended [37], although no difference was reported in complication rate after three days of treatment compared to longer periods [38]. It is possible and even recommended to stop antibiotic therapy under certain clinical criteria, such as a return of bowel function and absence of fever [24, 39]. Prolonging antibiotic treatment once the symptoms have resolved has proven ineffective in preventing complications [5, 40, 41]. Intravenous antibiotic therapy followed by an outpatient conversion to oral antibiotics is reported to be an efficient therapeutic approach for pediatric patients with PA [42]. Table 5 presents the published predictors of postoperative complications following PA including a comparison to the results of present study. The published risk factors could only, in part, be confirmed by our study, possibly due to the differences in the studied cohorts, especially in age of the patients. However, the CRP at admission seems to be a risk factor for complications in adults [8], as well as in children, as shown by present data. Here, we describe a novel risk score, which is easily calculated and reliably predicts postoperative complications and reinterventions based on the presence of risk factors in children with PA. A cut-off value accurately discriminates the subset of patients at higher risk. These higher-risk patient groups can then be monitored more closely after surgical treatment of PA, promoting early prevention, detection, and intervention of complications. Ultrasound and MRI are sensible diagnostic tools for this purpose in pediatric patients, while cross-sectional imaging with CT should be avoided where possible, due to the high radiation dose [43–45]. In the literature, the only comparable score to predict the risk of postoperative intraabdominal collections is the Sunshine Appendicitis Grading System (SAGS) [46]. However, this score was only evaluated for adults. A risk ratio of 2.594 (95% CI: 0.655–4.065; p = 0.001) for intraabdominal collection was found using SAGS score as a predictor. The discriminative ability of SAGS score was supported by an area under the curve value of 0.850 (95% CI: 0.799–0.892; p < .001). Compared to the SAGS evaluated in adults, our score has a similar risk ratio of 1.99 (95% CI: 1.47–2.71) for occurring complications, however, the value of the area under the curve was lower (0.753 ± 0.61, 95% CI: 0.634–0.872, p = 0.001). The present study is limited by its retrospective nature and potential bias, such as undetectable Journal of Investigative Surgery

Risk Factors Pediatric Perforated Appendicitis 9 confounding factors. To avoid any potential bias regarding the definition of PA, we used an unequivocal intraoperative definition [6] and considered only a closely circumscribed study population. However, the limited number of patients and occurring complications may have restricted the statistical analysis and the impact of the detected risk factors may not have been fully validated, as also evident by the comparison to the available literature (Table 5). Therefore, further studies including more patients are needed to confirm which specific surgical and conservative measures should be taken in the event of certain risk factors in pediatric patients with PA.

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CONCLUSIONS 16.

Predicting postoperative complications in children with PA is possible through the assessment of specific preoperative, intraoperative, and postoperative risk factors. These factors and the present new risk score can help to define a high-risk subgroup of children prone to complications, who will likely benefit from early and active prevention, detection, and intervention of occurring complications. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

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