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.</p

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 α 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

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

Propensity Score Adjusted Comparison of Pelviperineal Morbidity with and Without Omentoplasty Following Abdominoperineal Resection for Primary Rectal Cancer

BACKGROUND: Abdominoperineal resection is associated with a high incidence of perineal complications, and whether this is reduced by an omentoplasty is still unclear. OBJECTIVE: This study aimed to investigate the impact of omentoplasty on pelviperineal morbidity in patients undergoing abdominoperineal resection for rectal cancer. DESIGN: This was a retrospective comparative cohort study using propensity score analyses to reduce potential confounding. SETTING: The study was undertaken in 2 teaching hospitals and 1 university hospital. PATIENTS: Patients who underwent abdominoperineal resection for primary rectal cancer between 2000 and 2017 were included. MAIN OUTCOME MEASURES: The main end points were primary perineal wound healing at 30 days and overall and specific pelviperineal morbidity until the end of the study period. RESULTS: Among 254 included patients, 106 had an omentoplasty. The primary perineal wound healing rate at 30 days was similar for omentoplasty and no omentoplasty (65% vs 60%; p = 0.422), also after adjusting for potential confounding by propensity score analysis (OR, 0.89; 95% CI, 0.45-1.75). Being free from any pelviperineal complication at 6 months (75% vs 79%; p = 0.492), absence of any pelviperineal morbidity until 1 year (54% vs 49%; p = 0.484), and incidence of persistent perineal sinus (6% vs 10%; p = 0.256) were also similar in both groups. The unadjusted higher perineal hernia rate after omentoplasty (18% vs 7%; p = 0.011) did not remain statistically significant after regression analysis including the propensity score (OR, 1.34; 95% CI, 0.46-3.88). Complications related to the omentoplasty itself were observed in 8 patients, of whom 6 required reoperation. LIMITATIONS: This study was limited by the retrospective and nonrandomized design causing some heterogeneity between the 2 cohorts. CONCLUSION: In this multicenter study using propensity score analyses, the use of omentoplasty did not lower the incidence or the duration of pelviperineal morbidity in patients undergoing abdominoperineal resection for rectal cancer, and omentoplasty itself was associated with a risk of reoperation. See Video Abstract at http://links.lww.com/DCR/A918

Daytime versus Nighttime in Acute Appendicitis

Background: Little is known about patients with appendicitis presenting at nighttime. It is hypothesized that patients presented at night more frequently have a complicated (gangrenous or perforated) appendicitis and therefore develop more postoperative complications. Methods: In this study data were used from the nationwide, prospective SNAPSHOT study appendicitis, including 1975 patients undergoing surgery for suspected appendicitis. This study included only adults. Two primary outcomes were defined: (A) The proportion of patients with complicated appendicitis and (B) the proportion of patients with a complication postoperatively presenting during daytime versus nighttime period. Analysis for both complicated and uncomplicated appendicitis was performed, and a multivariate model was used to correct for baseline characteristics and time to surgery. Results: In total, 1361 adult patients with appendicitis were analyzed. Both at nighttime and at daytime, 34% had complicated appendicitis. In patients presenting in the daytime, 12.1% developed a postoperative complication versus 18.6% for presentation at night (p = 0.008). In a multivariate analysis, the risk for a postoperative complication when presenting at night was significantly increased (adjusted OR 1.74; 95% CI 1.14&ndash;2.66, p = 0.01). Surgery within eight hours after presentation does not lower this risk (adjusted OR 1.37; 95% CI 0.97&ndash;1.95, p = 0.078). Conclusion: Complicated appendicitis is seen as frequently during the day as at nighttime. For patients who present at nighttime with acute appendicitis, the risk of a postoperative complication is higher compared with a presentation at daytime. In multivariate analysis, nighttime presentation but not surgery within 8 h after presentation is independently associated with postoperative complication risk

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

Abstract 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

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

Abstract 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

Discrepancies between Intraoperative and Histological Evaluation of the Appendix in Acute Appendicitis

Purpose: To identify discrepancies between intraoperative and histological evaluations of the appendix in acute appendicitis and to evaluate the effect on surgical outcome. Methods: Data was used from our previous multicentre, prospective, cohort study of patients with suspected acute appendicitis. Appendices were scored during intraoperative and histological evaluation as uncomplicated or complicated appendicitis. Primary outcome was percentage of concordance between intraoperative and histological evaluation. Secondary outcomes were (infectious) postoperative complications, length of hospital stay, hospital re-admission and re-intervention rate, all within 30 days of surgery. Results: A total of 1850 patients were included. In 65.7% (1215/1850) of the appendices, the intraoperative evaluation was uncomplicated and in 34.3% (635/1850), complicated appendicitis. Patients with uncomplicated appendicitis had a postoperative course with significantly less postoperative complications (7.2% vs 24.3%), a shorter length of hospital stay (2 vs 5 days) and a lower re-admission (4.2% vs 9.6%) and re-intervention rate (1.1% vs 4.3%) than intraoperative complicated appendicitis (p < 0.001). In 93.5% (1136/1215) of the intraoperative uncomplicated patients and in 46.6% (296/635) of the intraoperative complicated patients, there was an agreement with pathology (Kappa 0.45). In 23.9% (81/339) of patients with intraoperative complicated and histological uncomplicated appendicitis, a postoperative complication was observed, which was similar to the postoperative complication rate of complicated appendicitis both on intraoperative and histological evaluation (24.7% (73/296)). Conclusions: There is a moderate agreement between a surgeon and pathologist in diagnosing patients with complicated appendicitis. However, the intraoperative diagnosis of complicated appendicitis was significantly associated with postoperative complications. Routine histological evaluation should be preserved for excluding malignancies in suspect appendices

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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