Two Days Versus Five Days of Postoperative Antibiotics for Complex Appendicitis: Cost Analysis of a Randomized, Noninferiority Trial.

OBJECTIVE: To compare costs for 2 days versus 5 days of postoperative antibiotics within the antibiotics after an aPPendectomy In Complex appendicitis trial.Background:Recent studies suggest that restrictive antibiotic use leads to a significant reduction in hospital stays without compromising patient safety. Its potential effect on societal costs remains underexplored. METHODS: This was a pragmatic, open-label, multicenter clinical trial powered for noninferiority. Patients with complex appendicitis (age ≥ 8 years) were randomly allocated to 2 days or 5 days of intravenous antibiotics after appendectomy. Patient inclusion lasted from June 2017 to June 2021 in 15 Dutch hospitals. The final follow-up was on September 1, 2021. The primary trial endpoint was a composite endpoint of infectious complications and mortality within 90 days. In the present study, the main outcome measures were overall societal costs (comprising direct health care costs and costs related to productivity loss) and cost-effectiveness. Direct health care costs were recorded based on data in the electronic patient files, complemented by a telephone follow-up at 90 days. In addition, data on loss of productivity were acquired through the validated Productivity Cost Questionnaire at 4 weeks after surgery. Cost estimates were based on prices for the year 2019. RESULTS: In total, 1005 patients were evaluated in the "intention-to-treat" analysis: 502 patients were allocated to the 2-day group and 503 to the 5-day group. The mean difference in overall societal costs was - €625 (95% CI: -€ 958 to -€ 278) to the advantage of the 2-day group. This difference was largely explained by reduced hospital stay. Productivity losses were similar between the study groups. Restricting postoperative antibiotics to 2 days was cost-effective, with estimated cost savings of €31,117 per additional infectious complication. CONCLUSIONS: Two days of postoperative antibiotics for complex appendicitis results in a statistically significant and relevant cost reduction, as compared with 5 days. Findings apply to laparoscopic appendectomy in a well-resourced health care setting.

2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial.

BACKGROUND: The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. METHODS: In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. FINDINGS: Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI -1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. INTERPRETATION: 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. FUNDING: The Netherlands Organization for Health Research and Development.

Multicenter cohort study on the presentation and treatment of acute appendicitis during the COVID-19 pandemic.

PURPOSE: Current studies have demonstrated conflicting results regarding surgical care for acute appendicitis during the COVID-19 pandemic. This study aimed to assess trends in diagnosis as well as treatment of acute appendicitis in the Netherlands during the first and second COVID-19 infection wave. METHODS: All consecutive patients that had an appendectomy for acute appendicitis in nine hospitals from January 2019 to December 2020 were included. The primary outcome was the number of appendectomies for acute appendicitis. Secondary outcomes included time between onset of symptoms and hospital admission, proportion of complex appendicitis, postoperative length of stay and postoperative infectious complications. Outcomes were compared between the pre-COVID group and COVID group. RESULTS: A total of 4401 patients were included. The mean weekly rate of appendectomies during the COVID period was 44.0, compared to 40.9 in the pre-COVID period. The proportion of patients with complex appendicitis and mean postoperative length of stay in days were similar in the pre-COVID and COVID group (respectively 35.5% vs 36.8%, p = 0.36 and 2.0 ± 2.2 vs 2.0 ± 2.6, p = 0.93). There were no differences in postoperative infectious complications. A computed tomography scan was used more frequently as a diagnostic tool after the onset of COVID-19 compared to pre-COVID (13.8% vs 9.8%, p < 0.001, respectively). CONCLUSION: No differences were observed in number of appendectomies, proportion of complex appendicitis, postoperative length of stay or postoperative infectious complications before and during the COVID-19 pandemic. A CT scan was used more frequently during the COVID-19 pandemic.

Postoperative Antibiotics and Time to Reach Discharge Criteria after Appendectomy for Complex Appendicitis.

INTRODUCTION: Postoperative antibiotic treatment is indicated for 3-5 days following appendectomy for complex appendicitis. However, meeting discharge criteria may allow for safe discontinuation of antibiotics and discharge. This study assessed the association between time to reach discharge criteria and duration of postoperative antibiotic use and length of stay. METHODS: This is a multicenter retrospective cohort study including patients who underwent appendectomy for complex appendicitis and received postoperative antibiotics for >24 h. Main outcome measures were time to reach discharge criteria, duration of postoperative antibiotic use, length of hospital stay, and postoperative infectious complications. Discharge criteria were defined as absence of fever (temperature ≤38°C) for 24 h, ability to tolerate oral intake, and pain controlled by oral analgesics. RESULTS: Between May 2014 and January 2015, 124 patients were included. Time to reach discharge criteria was 2 days (interquartile range [IQR] 1-3). Patients received postoperative antibiotics and were in hospital for a median of 5 (IQR 3-5) and 5 (IQR 4-6) days, respectively. Infectious complications occurred in 12% and did not differ between patients reaching discharge criteria before or after 2 postoperative days. DISCUSSION: Discharge criteria were met by a median of 2 days after appendectomy for complex appendicitis. This suggests that postoperative antibiotics duration and thereby hospital stay can be reduced. In daily practice, prescribed antibiotics are not reduced in total days given. Prospective studies that evaluate limited postoperative antibiotic use, based on these criteria, are necessary.

Same-day discharge after appendectomy for acute appendicitis: a systematic review and meta-analysis.

PURPOSE: Patients presenting with acute appendicitis are usually hospitalized for a few days for appendectomy and postoperative recovery. Shortening length of stay may reduce costs and improve patient satisfaction. The purpose of this study was to assess the safety of same-day discharge after appendectomy for acute appendicitis. METHODS: A systematic review was performed according to PRISMA guidelines. A literature search of EMBASE, Ovid MEDLINE, Web of Science, Cochrane Central, and Google Scholar was conducted from inception to April 14, 2020. Two reviewers independently screened the literature and selected studies that addressed discharge on the same calendar day as the appendectomy. Risk of bias was assessed with the ROBINS-I tool. Main outcomes were hospital readmission, complications, and unplanned hospital visits in the postoperative course. A random effects model was used to pool risk ratios for the main outcomes. RESULTS: Of the 1912 articles screened, 17 comparative studies and 8 non-comparative studies met the inclusion criteria. Most only included laparoscopic procedure for uncomplicated appendicitis. Most studies were considered at moderate or serious risk of bias. In meta-analysis, same-day discharge (vs. overnight hospitalization) was not associated with increased rates of readmission, complication, and unplanned hospital visits. Non-comparative studies demonstrated low rates of readmission, complications, and unplanned hospital visits after same-day discharge. CONCLUSION: This study suggests that same-day discharge after laparoscopic appendectomy for uncomplicated appendicitis is safe without an increased risk of readmission, complications, or unplanned hospital visits. Hence, same-day discharge may be further encouraged in selected patients. TRIAL REGISTRATION: PROSPERO registration no. CRD42018115948.

Disease burden of appendectomy for appendicitis: a population-based cohort study.

BACKGROUND: Few large-scale epidemiologic studies evaluate the clinical and economic burden of appendicitis. These data may impact future research and treatment strategies. In this study, the objective was to determine the burden of appendectomy for appendicitis in terms of incidence rates, length of hospital stay (LOS) and hospital costs on a national level. In addition, outcomes were compared for subgroups based on surgical treatment, age and hospital setting. METHODS: Observational retrospective population-based cohort study using the national Dutch healthcare reimbursement registry, which covers hospital registration and reimbursement for 17 million inhabitants. Patients with a diagnosis of appendicitis who underwent appendectomy between 2006 and 2016 were included. Primary outcomes were incidence rates, LOS and hospital costs. RESULTS: A total of 135,025 patients were included. Some 53% of patients was male, and 64% was treated in a general hospital. The overall incidence rate of appendectomy was 81 per 100,000 inhabitants and showed a significant decreasing trend across time and age. Mean ± SD LOS per patient was 3.66 ± 3.5 days. LOS showed a significant increase with age and was significantly longer for open versus minimally invasive appendectomy. Mean ± SD hospital costs per patient were €3700 ± 1284. Costs were initially lower for open compared to minimally invasive appendectomy, but were similar from 2012 onward. Compared to non-university hospitals, patients treated in university hospitals had a significantly longer LOS and higher costs. CONCLUSIONS: Appendectomy for appendicitis represents a substantial clinical and economic burden in the Netherlands. A preference for minimally invasive technique seems justified.

Systematic Review and Meta-Analysis of Postoperative Antibiotics for Patients with a Complex Appendicitis.

Postoperative antibiotics are recommended after appendectomy for complex appendicitis to reduce infectious complications. The duration of this treatment varies considerably between and even within institutions. The aim of this review was to critically appraise studies on duration of antibiotic treatment following appendectomy for complex appendicitis. A systematic literature search according to the PRISMA guidelines was performed. Comparative studies evaluating different durations of postoperative antibiotic therapy. Primary endpoint was intra-abdominal abscess (IAA) after appendectomy. Secondary endpoints were surgical site infection, readmission and length of hospital stay. The quality of evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Pooled event rates were calculated using a random-effects model. Nine studies reporting 2006 patients with complex appendicitis were included. The methodological quality of the included articles was poor. IAA was seen in 138 patients (8,6%). Meta-analysis revealed a statistically significant difference in IAA incidence between antibiotic treatment of ≤5 vs. >5 days (risk ratio (OR) 0.36 [95% CI 0.23-0.57] (p < 0.0001)) but not between ≤3 vs. >3 days (OR 0.81 [95% CI 0.38-1.74] (p = 0.59)). Descriptive statistics were used for secondary endpoints. The duration of postoperative antibiotic treatment is not associated with IAA following appendectomy for complex appendicitis.

Postoperative Outcomes of Patients With Nonperforated Gangrenous Appendicitis: A National Multicenter Prospective Cohort Analysis.

BACKGROUND: Controversy exists regarding the use of postoperative antibiotics for nonperforated gangrenous appendicitis. OBJECTIVE: The aim of this study was to evaluate the rate of postoperative infectious complications and the effect of postoperative antibiotic use among patients with nonperforated gangrenous appendicitis. DESIGN: This was a prospective cohort study conducted during 2 months. SETTINGS: A national multicenter observational study was conducted in 62 Dutch hospitals. PATIENTS: All of the consecutive patients who had surgery for suspected acute appendicitis were included. Patients were excluded if no appendectomy was performed or appendectomy was performed for pathology other than acute appendicitis. MAIN OUTCOMES MEASURES: Type of appendicitis was categorized as phlegmonous, gangrenous, or perforated. The primary end point was the rate of infectious complications (intra-abdominal abscess and surgical site infection) within 30 days after appendectomy. Univariable and multivariable logistic regression analyses were performed to identify predictors of infectious complications. RESULTS: A total of 1863 patients were included: 1321 (70.9%) with phlegmonous appendicitis, 181 (9.7%) with gangrenous appendicitis, and 361 (19.4%) with perforated appendicitis. Infectious complications were more frequent in patients with gangrenous versus phlegmonous appendicitis (7.2% vs 3.8%; p = 0.03). This association was no longer statistically significant in multivariable analysis (OR = 1.09 (95% CI, 0.49-2.44)). There was no significant difference in infectious complications between ≤24 hours (n = 57) of postoperative antibiotics compared with >24 hours (n = 124; 3.6% vs 8.9%; p = 0.35) in patients with gangrenous appendicitis. LIMITATIONS: Possible interobserver variability in the intraoperative classification of appendicitis was a study limitation. CONCLUSIONS: Patients with nonperforated gangrenous appendicitis are at higher risk of infectious complications than patients with phlegmonous appendicitis, yet gangrenous disease is not an independent risk factor. Postoperative antibiotic use over 24 hours was not associated with decreased infectious complications. See Video Abstract at http://links.lww.com/DCR/A1000. RESULTADOS POSTOPERATORIOS DE PACIENTES CON APENDICITIS GANGRENOSA NO PERFORADA: UN ANÁLISIS DE COHORTE PROSPECTIVO MULTICÉNTRICO NACIONAL:: Existe controversia sobre el uso de antibióticos postoperatorios para la apendicitis gangrenosa no perforada.El objetivo de este estudio fue evaluar la tasa de complicaciones infecciosas postoperatorias y el efecto del uso de antibióticos postoperatorios en pacientes con apendicitis gangrenosa no perforada.Estudio de cohorte prospectivo realizado durante dos meses.Estudio observacional multicéntrico nacional en 62 hospitales holandeses.Todos los pacientes consecutivos sometidos a cirugía por sospecha de apendicitis aguda. Los pacientes fueron excluidos si no se realizó una apendicectomía o si se realizó una apendicectomía para otra patología que no fuera la apendicitis aguda.El tipo de apendicitis se clasificó como flegmonosa, gangrenosa o perforada. El criterio de valoración primario fue la tasa de complicaciones infecciosas (absceso intraabdominal e infección en el sitio quirúrgico) dentro de los 30 días posteriores a la apendicectomía. Se realizaron análisis de regresión logística univariables y multivariables para identificar predictores de complicaciones infecciosas.Se incluyeron un total de 1863 pacientes: 1321 (70,9%) con apendicitis flegmonosa, 181 (9,7%) con apendicitis gangrenosa y 361 (19,4%) con apendicitis perforada. Las complicaciones infecciosas fueron más frecuentes en pacientes con apendicitis gangrenosa frente a flegmonosa (7,2% frente a 3,8%, p = 0,03). Esta asociación ya no fue estadísticamente significativa en el análisis multivariable (OR 1,09; IC del 95%: 0,49 a 2,44). No hubo diferencias significativas en las complicaciones infecciosas entre ≤ 24 h (n = 57) de los antibióticos postoperatorios en comparación con> 24 h (n = 124) (3,6% vs. 8,9%, p = 0,35) en pacientes con apendicitis gangrenosa.Posible variabilidad interobservador en la clasificación intraoperatoria de la apendicitis.Los pacientes con apendicitis gangrenosa no perforada tienen un mayor riesgo de complicaciones infecciosas que los pacientes con apendicitis flegmonosa, aunque la enfermedad gangrenosa no es un factor de riesgo independiente. El uso de antibióticos postoperatorios durante 24 horas no se asoció con una disminución de las complicaciones infecciosas. Vea el Resumen del Video en http://links.lww.com/DCR/A1000.

Variation in Classification and Postoperative Management of Complex Appendicitis: A European Survey.

BACKGROUND: Data on common practice in the management of patients with complex appendicitis are scarce, especially for the adult population. Variation in the definition of complex appendicitis, indications for and the type of prolonged antibiotic prophylaxis have not been well studied yet. The aim of this study was to document current practice of the classification and postoperative management of complex appendicitis on an international level. METHODS: An online survey was dispersed among practicing surgeons and surgical residents. Survey questions pertained to the definition of a complex appendicitis, indications for antibiotic prophylaxis after appendectomy, the duration, route of administration and antibiotic agents used. RESULTS: A total of 137 survey responses were eligible for analysis. Most respondents were from Northern or Western Europe and were specialized in gastrointestinal surgery. Opinion varied substantially regarding the management of appendicitis, in particular for phlegmonous appendicitis with localized pus, gangrenous appendicitis and iatrogenic rupture of appendicitis. The most common duration of postoperative antibiotics was evenly spread over <3, 3, 5 and 7 days. Whereas most respondents indicated a combined intravenous and oral route of administration was common practice, 28% answered a completely intravenous route of administration was standard practice. CONCLUSION: Current practice patterns in the classification and postoperative management of complex appendicitis are highly variable.

Two versus five days of antibiotics after appendectomy for complex acute appendicitis (APPIC): study protocol for a randomized controlled trial.

BACKGROUND: Acute appendicitis is one of the most common indications for emergency surgery. In patients with a complex appendicitis, prolonged antibiotic prophylaxis is recommended after appendectomy. There is no consensus regarding the optimum duration of antibiotics. Guidelines propose 3 to 7 days of treatment, but shorter courses may be as effective in the prevention of infectious complications. At the same time, the global issue of increasing antimicrobial resistance urges for optimization of antibiotic strategies. The aim of this study is to determine whether a short course (48 h) of postoperative antibiotics is non-inferior to current standard practice of 5 days. METHODS: Patients of 8 years and older undergoing appendectomy for acute complex appendicitis - defined as a gangrenous and/or perforated appendicitis or appendicitis in presence of an abscess - are eligible for inclusion. Immunocompromised or pregnant patients are excluded, as well as patients with a contraindication to the study antibiotics. In total, 1066 patients will be randomly allocated in a 1:1 ratio to the experimental treatment arm (48 h of postoperative intravenously administered (IV) antibiotics) or the control arm (5 days of postoperative IV antibiotics). After discharge from the hospital, patients participate in a productivity-cost-questionnaire at 4 weeks and a standardized telephone follow-up at 90 days after appendectomy. The primary outcome is a composite endpoint of infectious complications, including intra-abdominal abscess (IAA) and surgical site infection (SSI), and mortality within 90 days after appendectomy. Secondary outcomes include IAA, SSI, restart of antibiotics, length of hospital stay (LOS), reoperation, percutaneous drainage, readmission rate, and cost-effectiveness. The non-inferiority margin for the difference in the primary endpoint rate is set at 7.5% (one-sided test at ɑ 0.025). Both per-protocol and intention-to-treat analyses will be performed. DISCUSSION: This trial will provide evidence on whether 48 h of postoperative antibiotics is non-inferior to a standard course of 5 days of antibiotics. If non-inferiority is established, longer intravenous administration following appendectomy for complex appendicitis can be abandoned, and guidelines need to be adjusted accordingly. TRIAL REGISTRATION: Dutch Trial Register, NTR6128 . Registered on 20 December 2016.