Outpatient management of acute uncomplicated appendicitis after laparoscopic appendectomy – A Randomized Controlled Trial

Abstract

Objective: To confirm the safety and efficacy of outpatient management of laparoscopic appendectomy, with an Enhanced Recovery After Surgery (ERAS) protocol, in adult patients with uncomplicated acute appendicitis. Summary Background Data: Outpatient laparoscopic appendectomy is feasible and secure in selected patients in observational studies. The benefits include reduced length of stay (LOS) and post-operative complications. This is the first Randomized Controlled Trial (RCT) of outpatient management following ERAS protocol. 

Methods: Patients admitted from the emergency department with acute appendicitis randomized into one of two groups. Standard care within the hospital (HG) or the outpatient group (OG). An ERAS protocol was followed for both groups. Patients in the HG were admitted to the surgical ward. Patients in the OG were referred to the day-surgery unit. The primary endpoint was length of stay. 

Results: Ninety-seven patients were included, 49 in the OG and 48 in the HG. LOS was significantly shorter in the OG (mean 8.82h) than the HG (mean 43.53h), p<0.001. There was no difference in readmission rates (p = 0.320), we observed only one readmission in the OG.  No further emergency consultations or complications were observed. The cost saving was $516.52/patient as a result of the intervention. 

Conclusion: Outpatient management of appendectomy is safe and feasible procedure in selected patients. This approach could become the standard of care for patients with uncomplicated appendicitis, showing fewer complications, lower LOS and cost. Trial registration: Clinical Trial ID: NCT05401188 Keywords: Appendicitis, Acute Appendicitis, uncomplicated Acute Appendicitis, outpatient management, laparoscopic appendectomy, ERAS protocol

Backgrounds And Aim

Acute appendicitis (AA) is one of the most performed surgical procedures in emergency surgery(1). The treatment is traditionally with laparoscopic appendectomy (LA)(1). AA has a hazard rate of 1.17 to 1.9 per 1,000 habitants/year, and a lifetime risk of 8.6% for men and 6.7% for women. The most common age range is between 25 and 35(2). Open appendectomy was first described by George Thomas Martin in 1887 and then by Charles McBurney in 1889. The first laparoscopic appendectomy (LA) was not performed until 1983 by Kurt Semm(3).

Nechay et al.(4) published a modified Enhanced Recovery after Surgery (ERAS) protocol based on the well-known ERAS program for elective (colorectal) surgery(5). The choice of modified ERAS protocol components was determined by how well they could be adapted to the emergency setting(4, 6). The behind publications showed that the management of outpatient appendectomy(7) was safe and feasible. This evidence was validated for patients with uncomplicated AA(8).

The first time an appendectomy was performed as outpatient surgery was in 1994(9). However, an increase in complications and hospital readmissions was observed. Since then, many systematic reviews have been published(10, 11). Data reported in 17 studies (mainly retrospective) suggested that outpatient appendectomy might be feasible. Several observational studies have shown that outpatient surgery is not associated with increased readmissions, increased morbidity rates, or reoperation(9, 11–13). In 2019 de Wijkerslooth(1) published a systemic review and meta-analysis of comparative studies. However, significant clinical heterogeneity was observed and therefore no recommendations could be given. Currently available data(11, 14–16) suggest that in selected patients with uncomplicated AA, patients can be managed via an outpatient route, but there is no good-quality evidence for this. To date, no RCTs have been published.

This is the first RCT of outpatient management of AA following ERAS protocol. The aim of this study is to evaluate the efficacy and safety of this management in patients with uncomplicated AA.

METHODS

Study design and participants

This is a single center randomized controlled trial consisting of two treatment groups (NCT05401188). This study was designed in accordance with the Declaration of Helsinki guidelines and approved by the Ethics Committee of Pere Virgili Institute (CEIm 081/2019). Patients were recruited at University Hospital of Tarragona Joan XXIII in Spain from the June 1st 2019 to June 1st 2021.

All patients admitted in the emergency department with AA diagnosis were recruited for the study. Saint Antoine’s criteria were evaluated in all patients(17). These criteria were the following: Leukocytosis lower than 15.000; C-reactive protein lower than 30mg; Body mass index lower than 30kg/m2; appendicular diameter lower than 10 mm and no radiological sign of complication(17). The radiological diagnosis could be made by ultrasonography (US) or Computed Tomography (CT) scan.

Eligible patients were approached, and informed consent was taken. After LA had been performed and a non-complicated AA was confirmed, the patients were randomly assigned to the hospitalization group (HG) or outpatient group (OG).

The inclusion criteria were the following: patients over 18 years old with diagnosis of AA, who met at least 4 out of 5 Saint Antoine criteria, ASA less than or equal to 3, patients who did not live alone at a maximum distance of 30 minutes from the hospital with an adequate cognitive capacity.

The exclusion criteria were the following: pregnancy or breastfeeding, complicated AA, or a surgical time longer than 90 minutes.

If the criteria were not met or presenting any exclusion criteria, the patient was excluded from the study and followed the usual clinical management according to our center protocol.

Anesthetic and surgical protocol

To ensure consistency, an anesthetic and surgical protocol were established for both groups. A modified ERAS protocol(4) was followed in both groups.

During preadmission, the ERAS protocol is not available in the emergency setting. The patient was fasted before surgery. The abdomen was prepared using clippers to remove hair from the incision area. The patient was asked to void the bladder before surgery.

The ERAS protocol for anesthetic management was preoperative evaluation. Intraoperative monitoring included: non-invasive blood pressure, EKG, oxygen saturation, heart rate, Bispectral Index(BIS™) and train of four(TOF™). Pre-oxygenation was performed. Rapid sequence induction was achieved using propofol at a dose of 2mg/kg, remifentanil in continuous infusion starting at 0.2picograms/kg/min and rocuronium at a dose of 1 mg/kg/min. One minute after induction, intubation was carried out using direct Mackintosh laryngoscopy. Intravenous fluid with balanced crystalloids was started at a rate of 5 ml/kg/h as a replacement for potential losses. Anesthetic status was maintained with Remifentanil TIVA(Total Intravenous Anesthesia) between 0.1–0.2 picograms/kg/min continuous infusion, and propofol at a dose of 10mg/kg/min in the first 10 minutes and at 8mg/kg/min during the next 10 minutes, and finally between 5-7mg/kg/min for the rest of the surgery according to BIS™. Nausea prophylaxis of dexamethasone 4mg after induction, and Ondansetron 4mg 20 minutes prior to completion was completed. Multimodal analgesia preformed with infiltration at the surgical site prior to incision of 10ml of 2% lidocaine, with an additional subfascial infiltration before aponeurotic closure with 10ml of 0.2% of Ropivacaine. Intraoperative analgesia is administered with Dexketoprofen 50mg and Metamizole 2gr. Reversal of neuromuscular blockade with Suggamadex^→ is achieved according to TOF at the end of the procedure. Finally, the patient is extubated and transferred to the recovery unit.

For the surgical protocol, the patient is positioned supine. Laparoscopic approach begins with pneumoperitoneum performed through a Hasson’s Trocar placed in an umbilical incision after infiltration with local anesthesia. A slow and progressive insufflation is performed. Low-pressure (8–9mmHg) pneumoperitoneum is established. A 5mm trocar is inserted in the hypogastric area and a 5/10mm trocar in the left iliac fossa, after infiltration with local anesthesia. The meso-appendix is dissected either using diathermy or by diving the vessels with endoscopic clips. The closure of the appendix stump is commonly carried out with Endoscopic loop. The specimen is retrieved through an Endoscopic bag. Right iliac fossa and the Douglas cul-de-sac are flushed with saline solution. The trocars are removed under direct vision, the residual pneumoperitoneum is eliminated through them. Finally, the closure of umbilical fascia is conducted with long-term monofilament resorbable material nd staples are placed in the skin.

Following the postoperative ERAS care protocol, postoperative pain intensity was measured at rest on the visual analog scale (VAS) immediately after the patients regained responsiveness and then after 2, 6, 12 and 24 h following the surgical intervention. Analgesia was provided on demand for patients with pain intensity > 5 cm (VAS). Those who developed postoperative nausea and vomiting (PONV) received antiemetics. No intravenous infusions were given postoperatively to any of the patients.

The patients were discharged home if they had no complications, and they accomplished a ALDRETE score

A telephone survey was conducted on days 2 and 30 after discharge from hospital. The patients were asked about the presence of pain, the episodes of fever and indigestion, any complications and readmissions.

Randomization and intervention

Randomization was performed using a computer-generated program. Surgeons on-call were responsible for enrollment and treatment allocation, according to sequentially numbered envelops. Enrollment was unblinded for patients and physicians, due to the type of intervention. To reduce biases, the investigators assessing the outcome did not participate in the follow-up or discharge of patients. All patients received detailed written information about their diagnosis and study treatment plan.

After obtaining the informed consent of the study, the patients were admitted and operated following the same anesthetic technique and the same surgical technique by all the members of the on-call team. Once the patient was operated and an uncomplicated appendicitis was confirmed, the patient was randomized to one of the two branches: the HG or the OG.

Patients in the HG, once the surgical intervention was finished, were transferred to the postoperative recovery unit, and later they were discharged to the usual hospital ward. Patients received adequate intravenous fluid resuscitation, based on their individual hemodynamic parameter and fluid balance, and they received analgesia according to personal requirement. In the hospital ward, the usual patient management protocols were followed until a complete recovery, and consequently discharged according to the conventional criteria.

Patients in the OG, once operated, were transferred to the surgery-day unit and were later discharged home if they met the ALDRETE criteria (18), in less than 23 hours after the intervention(19) (following the same day surgery criteria). If the patient was operated during the night shift, following the advice of major outpatient surgery (19, 20) where overnight stays are allowed, the patient was admitted to the post-anesthetic recovery unit and discharged the next day, always in less than 23 hours. In case of being discharged after 23 hours or not meeting ALDRETE criteria, it was considered a failure of the outpatient treatment.

Study Endpoints

We consider the length of stay (LOS) the best indicator to confirm the safety and efficacy of outpatient management of laparoscopic appendectomy.

The primary endpoint was the LOS. The LOS was calculated from the time of admission in the surgical area to the time of discharge. The secondary endpoints included the failure of outpatient management, complications, readmission, unplanned hospital appointments within 30 days and cost.

Data Collection

The anthropomorphic, radiologic characteristics and blood samples were collected in the emergency department. Quantitative data were obtained from the blood results and from the appendicular diameter. Categorical data were obtained from radiological features. The postoperative complications were evaluated according to the Clavien-Dindo(21) and Comprehensive Complication Index scores(22). The day and time of admission to the surgical unit and time of discharge, were collected as a time variable. Follow-up after discharge, consultations to the emergency department and its reason were assessed. Outpatient follow-up was carried out up to 6 months. The cost analysis study was also conducted.

Data on each patient were collected in a standard form by the research coordinator ensuring the anonymity of the patients. Data was monitored and included in a database using Access© Microsoft 2013 and the statistical study was performed with Stata® inc. 16 version.

Sample size and Statistical analysis

In the hospital reference population, the median of LOS was 2.75 days (SE 0.42), according to a previous review of cases of AA, admitted to the hospital between 2015 and 2018. The population sample was calculated using Stata®, based on a 5%-α and 10% β-risks. A dropout rate of approximately 30% was assumed. Based on this, to detect a reduction in hospital stay which meets the requirements for surgery without admission (contemplated up to a maximum of 23h, or what is the same as 0.95 days), a total of 60 patients per group was assigned (a total of 120 patients). An analysis was conducted, with the exclusion of patients in whom AA diagnosis was incorrect or in whom no exclusion criteria was met (it was decided before any analysis by the data monitoring committee whose members did not know the treatment assignments).

Differences between groups were analyzed using Fisher exact test for categorical variables and t-test or ANOVA test for quantitative variables. P-values < 0.05 were considered significant. If after performing the Shapiro-wilk test the variable did not follow a normal distribution, the p-values were obtained through a permutation test. Multiple comparison was conducted using Wilcoxon nonparametric test for the categorical variables. Fisher and McNemar test were used to analyze the results of contingency tables. Valid variables were considered if they presented a maximum of 10% of missing values, choosing a multiple imputation with a matrix of 20 values to solve it. All analyses were performed by a statistician.

Results

Discussion

AA is one of the most common general surgical emergencies worldwide. The reported life-time risk of appendicitis in the United States is 8.6% in men and 6.7% in women, with an annual incidence of 9.38 per 100.000 persons. In Spain, according to the registry of the Ministry of Health, 44.168 patients were treated for acute AA in 2017(24).

Several systematic reviews of RCTs compared LA with open appendectomy. They reported that LA is often associated with longer operative times and higher operative costs, but leads to less postoperative pain, shorter stay, lower incidence of surgical site infection, earlier return to work and physical activity, and better outcomes. Quality of life scores(1, 28). Thus, in most hospitals in Western countries, LA has become the preferred approach.

The first experience of ambulatory care in the management of AA was published in 2015 by Lefrancois(17) as a prospective descriptive study. Multivariate analysis was performed to create a predictive score of same-day discharge. It allowed to select patients eligible for ambulatorization with a success rate of 97%. However, this study did not assess the severity of appendicitis based on the intraoperative findings. This type of care needs to be validated on a largest cohort.

Trejo-Avila demonstrated in 2019 that implementation of ERAS for appendectomy is associated with a significantly shorter LOS, allowing for outpatient management. The authors concluded that outpatient LA is safe and feasible with similar morbidity and readmission rates compared to conventional care (29).

Recently, Saverio in a 2020 update to the WSES Jerusalem(1) guidelines, and Wijkerslooth in a systematic review, established that outpatient LA for uncomplicated AA is feasible and safe with no difference in morbidity and readmission rates. These results are associated with the potential benefits of earlier recovery after surgery and lower hospital and social costs. However, the quality of the evidence was moderate and the strength of recommendation weak (2B).

To date, only four comparative studies have been published in adult patients, using a prospective protocol of a historical control cohort(9, 12, 17, 30). In addition, two other non-RCT multicenter studies(9, 31) and only one systematic review (11) with significant heterogeneity were published. As a result of this lack of evidence, we decided to design this randomized clinical trial.

LOS was our primary endpoint. LOS was significantly lower in the OG, 8.82h (SD 0.83), while in the HG it was 45.43h (SD 0.96). Coinciding with the literature, where the mean LOS ranged between 3.1h and 9.6h (11, 16, 33).

One readmission was observed in the OG for adynamic intestinal ileus. No readmissions were observed in the HG (p = 0.320). Based on similar studies, we have shown that following an ERAS protocol and outpatient management of uncomplicated AA in adult patients is a safe procedure, with low complications and readmission rates ranging from 0–4.6%(9, 12, 17, 30)

We observe a lower percentage of complications especially Clavien-Dindo 1 (all related to the presence of postoperative abdominal pain) in the OG than the HG. For these remarkable and significant findings, there is no clear clinical or pathophysiological explanation despite having evaluated inflammatory parameters, such as C-reactive protein and leukocyte levels, and surgical findings. It would be interesting to carry out other studies to try to explain these findings.

In terms of costs, AA is associated with a considerable financial burden due to its high incidence and the cost of hospitalization. The effective use of resources by minimizing costs and maintaining quality is the goal of health care. In 2009, the estimated cost of hospitalization for patients with AA was estimated to be $1,900 in the US(7). In our study, health savings were €493.43($516.52) per patient. In the literature, various prospective studies with same-day surgery reported a median reduction in hospital costs ranging from $323 to $4111 per patient(11, 16, 30)

Assessing the possible limitations of this study, the fact that the study design is not blind can be considered a limitation, but the nature of the interventions performed (OG vs HG) made it clear to patients and physicians which group was assigned treatment. Furthermore, the main variables are objective measures, so they are unlikely to be affected by this fact.

Another possible limitation of the study is that the COVID-19 pandemic occurred during the patient recruitment period, which spanned 2020–2021. During the first stage of the COVID-19 pandemic, there was a significant increase in the rate of complicated appendicitis (34). In addition, a PCR test was added to the protocol, which could increase the hours of stay. However, outpatient management during the pandemic allowed a greater availability of hospital beds to care for patients with medical conditions. Thus, outpatient appendectomy allows better optimization of resources.

Our results agree with those reported in most studies (9, 11, 12, 15–17, 35, 36). We can conclude that in our experience it is possible to start an ERAS protocol and an outpatient appendectomy program with an experienced team. Although several studies (9, 11, 15)had shown, before ours, a reduction in LOS in patients selected for outpatient treatment, it had not been possible to draw solid recommendations due to the significant clinical and methodological heterogeneity between the different studies. Along the same lines, the international guidelines(1) could not give strong recommendations due to the lack of scientific evidence from randomized clinical trials. This is the first RCT on the subject. We have shown that ambulatory appendectomy with the ERAS protocol is safe in selected patients, due to the improvement in terms of quality of care, clinical and economic benefits.

Conclusion

The emergency outpatient appendectomy with an ERAS protocol is a safe and feasible procedure in selected patients with non-complicated appendectomy. It can be achieved with low morbidity, few readmissions, high patient satisfaction and cost reduction. This approach will become the standard of care for patients with uncomplicated AA in the future.

Declarations

The study was not funded by any grant.

All the authors report no conflicts of interest.

Registration: www.clinicaltrials.gov (NCT05401188) 

Author contributions: Jordi Elvira Lopez, Rosa Jorba Martin

All the phases of the study were participated with the help of other authors in the different parts

Conception and design: Jordi Elvira Lopez, Rosa Jorba Martin.

Administrative, technical, or logistic support: Jordi Elvira Lopez, Rosa Jorba Martin, Ricard Sales Mallafré, Joan Ferreres Serafini, Erlinda Daniela Padilla, Robert Memba Ikuga.

Collection and assembly of data: Jordi Elvira Lopez

Data Access Statement: The data were collected in a protected database ensuring the anonymity of the patients. The data access statement was protected.

Draft of the article: Jordi Elvira Lopez, Rosa Jorba Martin, Robert Memba Ikuga, Roisin Tully.

Economical Study: Elisabet Romero Alvarez
 Critical revision of the article for important intellectual content: Jordi Elvira Lopez, Rosa Jorba Martin, Ricard Sales Mallafré, Joan Ferreres Serafini, Erlinda Daniela Padilla, Robert Memba Ikuga, Roisin Tully

 All authors read and approved the final manuscript.

Acknowledgements

We would like to thank Esther Torregrosa at the participating for translating this article and Roisin Tully (RCSI, Ireland) for providing a critical review and translating.

Ethical Approval and Consent to participate

This Randomized Clinical Trial received ethical approval from the Ethics Committee of Pere Virgili Institute (CEIm 081/2019). This study was designed in accordance with the Declaration of Helsinki guidelines and approved by the Clinical Trial (NCT05401188). All participants provided written informed consent.

Consent for publication

Obtained

Availability of data and materials

The full de-identified database will be made available for independent analysis on reasonable request to the corresponding author or as an appendix in the publishing journal.

Competing interests

The authors declare that they have no competing interests.

Funding

The study was not funded by any grant.

Authors' contributions

All the phases of the study were participated with the help of other authors in the different parts:

Conception and design: Jordi Elvira Lopez

References

1. di Saverio S, Podda M, de Simone B, Ceresoli M, Augustin G, Gori A, et al. Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines. World Journal of Emergency Surgery. 2020 Dec 15;15(1):27.
2. Trejo-Avila M, Cárdenas-Lailson E, Valenzuela-Salazar C, Herrera-Esquivel J, Moreno-Portillo M. Ambulatory versus conventional laparoscopic appendectomy: a systematic review and meta-analysis. Int J Colorectal Dis. 2019;34(8):1359–68.
3. Semm K. Endoscopic appendectomy. Endoscopy. 1983 Mar;15(2):59–64.
4. Nechay T, Sazhin A, Titkova S, Tyagunov A, Anurov M, Melnikov-Makarchuk K, et al. Evaluation of enhanced recovery after surgery program components implemented in laparoscopic appendectomy: prospective randomized clinical study. Sci Rep. 2020;10(1):10749.
5. Varadhan KK, Neal KR, Dejong CHC, Fearon KCH, Ljungqvist O, Lobo DN. The enhanced recovery after surgery (ERAS) pathway for patients undergoing major elective open colorectal surgery: a meta-analysis of randomized controlled trials. Clin Nutr. 2010 Aug;29(4):434–40.
6. Paduraru M, Ponchietti L, Casas IM, Svenningsen P, Zago M. Enhanced Recovery after Emergency Surgery: A Systematic Review. Bull Emerg Trauma. 2017 Apr;5(2):70–8.
7. Frazee R. Can Surgery for Appendicitis Be Performed as an Outpatient Procedure? Adv Surg [Internet]. 2017;51(1):101–11. Available from: http://dx.doi.org/10.1016/j.yasu.2017.03.008
8. Aubry A, Saget A, Manceau G, Faron M, Wagner M, Tresallet C, et al. Outpatient Appendectomy in an Emergency Outpatient Surgery Unit 24 h a Day: An Intention-to-Treat Analysis of 194 Patients. World J Surg. 2017;41(10):2471–9.
9. Rosen DR, Inaba K, Oh PJ, Gutierrez AC, Strumwasser AM, Biswas S, et al. Outpatient Laparoscopic Appendectomy: Feasible in a Public County Hospital? In: Journal of the American College of Surgeons. Elsevier Inc.; 2017. p. 862–7.
10. Cosse C, Sabbagh C, Grelpois G, Brehant O, Regimbeau JM. Day case appendectomy in adults: a review. Int J Surg [Internet]. 2014;12(7):640–4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24887358
11. de Wijkerslooth EML, Bakas JM, van Rosmalen J, van den Boom AL, Wijnhoven BPL. Same-day discharge after appendectomy for acute appendicitis: a systematic review and meta-analysis. Int J Colorectal Dis. 2021 Jun;36(6):1297–309.
12. Cash CL, Frazee RC, Abernathy SW, Childs EW, Davis ML, Hendricks JC, et al. A prospective treatment protocol for outpatient laparoscopic appendectomy for acute appendicitis. J Am Coll Surg. 2012 Jul;215(1):101–5.
13. Salam IM, Fallouji MA, el Ashaal YI, Chandran VP, Asham NN, Galala KH, et al. Early patient discharge following appendicectomy: safety and feasibility. J R Coll Surg Edinb. 1995 Oct;40(5):300–2.
14. Trejo-Avila M, Cárdenas-Lailson E, Valenzuela-Salazar C, Herrera-Esquivel J, Moreno-Portillo M. Ambulatory versus conventional laparoscopic appendectomy: a systematic review and meta-analysis. Vol. 34, International Journal of Colorectal Disease. Springer Verlag; 2019. p. 1359–68.
15. Frazee R. Can Surgery for Appendicitis Be Performed as an Outpatient Procedure? Vol. 51, Advances in Surgery. Academic Press Inc.; 2017. p. 101–11.
16. Farach SM, Danielson PD, Walford NE, Harmel RP, Chandler NM. Same-day discharge after appendectomy results in cost savings and improved efficiency. Am Surg. 2014 Aug;80(8):787–91.
17. Lefrancois M, Lefevre JH, Chafai N, Pitel S, Kerger L, Agostini J, et al. Management of acute appendicitis in ambulatory surgery: Is it possible? How to select patients? Ann Surg. 2015;261(6):1167–72.
18. Aldrete JA KD. A postanesthetic recovery score. An&h Analg. 1970;9:924–34.
19. Terol García E, Palanca Sánchez I. Manual de Unidad de Cirugía Mayor Ambulatoria: Estándares y recomendaciones. Informes estudios e investigación Ministerio de Sanidad y Consumo [Internet]. 2008;150. Available from: http://www.msc.es/organizacion/sns/planCalidadSNS/docs/guiaCMA.pdf
20. Viñoles J, Argente P. Criterios de alta en cirugía ambulatoria. Cirugía mayor ambulatoria [Internet]. 2013;18(3):125–32. Available from: www.asecma.org
21. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The clavien-dindo classification of surgical complications: Five-year experience. Ann Surg. 2009;250(2):187–96.
22. Clavien PA, Vetter D, Staiger RD, Slankamenac K, Mehra T, Graf R, et al. The comprehensive complication index (CCI ®): Added value and clinical perspectives 3 years “down the line.” Ann Surg. 2017;265(6):1045–50.
23. Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340.
24. Prieto M, Ielpo B, Jiménez Fuertes M, González Sánchez M del C, Martín Antona E, Balibrea JM, et al. National survey on the treatment of acute appendicitis in Spain during the initial period of the COVID-19 pandemic. Cir Esp. 2021;99(6):450–6.
25. Gomes CA, Sartelli M, di Saverio S, Ansaloni L, Catena F, Coccolini F, et al. Acute appendicitis: proposal of a new comprehensive grading system based on clinical, imaging and laparoscopic findings. World Journal of Emergency Surgery. 2015 Dec 3;10(1):60.
26. Sallinen V, Akl EA, You JJ, Agarwal A, Shoucair S, Vandvik PO, et al. Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis. Br J Surg. 2016 May;103(6):656–67.
27. O’Leary DP, Walsh SM, Bolger J, Baban C, Humphreys H, O’Grady S, et al. A Randomized Clinical Trial Evaluating the Efficacy and Quality of Life of Antibiotic-only Treatment of Acute Uncomplicated Appendicitis: Results of the COMMA Trial. Ann Surg. 2021;274(2):240–7.
28. Li X, Zhang J, Sang L, Zhang W, Chu Z, Li X, et al. Laparoscopic versus conventional appendectomy–a meta-analysis of randomized controlled trials. BMC Gastroenterol. 2010 Nov 3;10:129.
29. Trejo-Ávila ME, Romero-Loera S, Cárdenas-Lailson E, Blas-Franco M, Delano-Alonso R, Valenzuela-Salazar C, et al. Enhanced recovery after surgery protocol allows ambulatory laparoscopic appendectomy in uncomplicated acute appendicitis: a prospective, randomized trial. Surg Endosc. 2019 Feb 9;33(2):429–36.
30. Dubois L, Vogt KN, Davies W, Schlachta CM. Impact of an outpatient appendectomy protocol on clinical outcomes and cost: a case-control study. J Am Coll Surg. 2010 Dec;211(6):731–7.
31. Grigorian A, Kuza CM, Schubl SD, Nguyen NT, de Virgilio C, Kim D, et al. Same-Day Discharge after Non-Perforated Laparoscopic Appendectomy Is Safe. Journal of Investigative Surgery. 2021 Mar 16;34(3):270–5.
32. James E. Davis M.D. The Future of Major Ambulatory Surgery. Surgical Clinics of North America. 1987 Aug;67(4):893–901.
33. Hussain A, Singh S, Singh Ahi K, Singh M. Status of Day Care Laparoscopic Appendectomy in Developing Countries. Int Sch Res Notices. 2014;2014:502786.
34. Abramov R, Neymark M, Harbi A, Gilshtein H. Laparoscopic Appendectomy in the Days of COVID-19. Surg Laparosc Endosc Percutan Tech. 2021 May 27;31(5):599–602.
35. Aubry A, Saget A, Manceau G, Faron M, Wagner M, Tresallet C, et al. Outpatient Appendectomy in an Emergency Outpatient Surgery Unit 24 h a Day: An Intention-to-Treat Analysis of 194 Patients. World J Surg. 2017 Oct 1;41(10):2471–9.
36. Litz CN, Stone L, Alessi R, Walford NE, Danielson PD, Chandler NM. Impact of outpatient management following appendectomy for acute appendicitis: An ACS NSQIP-P analysis. J Pediatr Surg. 2018 Apr 1;53(4):625–8.