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Introduction
Acute appendicitis (AA) is the most common cause of acute abdomen in the world, with an incidence of 5.7-50/100,000 inhabitants per year, with a peak incidence between 10 and 30 years1,2. Acute complicated appendicitis (ACA) (perforation, phlegmon, abscess, or peritonitis) and uncomplicated are two entities that require treatments due to the notable difference in complications associated with each other3,4.
Usually, after surgical management in ACA, additional antibiotic management is provided to prevent or avoid residual infectious complications. In accordance with the guidelines of the Surgical Infection Society and the Infectious Diseases Society of America, an additional 4-7 days of antibiotic are recommended after surgical management in ACA5. The latest WSES Jerusalem guidelines for the diagnosis and treatment of AA 2020 update recommend against prolonging antibiotics longer than 3-5 days postoperatively in case of complicated appendicitis with adequate source-control (QoE: High; Strength of recommendation: Strong; 1A) and an early switch (after 48 h) to oral administration of postoperative antibiotics in children with complicated appendicitis, with an overall length of therapy shorter than 7 days (QoE: Moderate; Strength of recommendation: Strong; 1B)1. In addition, currently considered the gold standard in the management of AA, laparoscopic appendectomy has already shown to be a protective factor in patients with AA, and it provides clinically beneficial advantages over open method, including shorter hospital stay, decreased need for postoperative analgesia, early food tolerance, earlier return to work, and lower rate of wound infection5,6. A recent study questioning whether ambulatory appendectomy should be the standard treatment for AA suggests that this could be considered a standard procedure for both complicated and uncomplicated AA6.
In most cases of ACA, the treatment length of intravenous antibiotics (IVA) is determined by the surgeon based on the patient's clinical response. Given that not all types of ACA are the same, the study was conducted to identify which patients could be susceptible to switch from IVA to oral antibiotic (OA) after laparoscopic appendectomy in ACA. The hypothesis in mind is considers that once the patient has an adequate clinical response after the procedure, even on an outpatient basis, there is no need to wait 3-5 days of IV antibiotic in safe form while still providing satisfactory outcomes, low complication rates and establish in whom of these are at higher risk of residual infectious complications. This study is carried out to determine if a short course of IVA and/or switch to oral route is feasible and safe based on the patient clinical response and if it increases the risk of intra-abdominal collection and decreases the length of hospital stay or not.
Methods
Study design
A prospective cohort observational study was carried out in a reference center in general surgery since July 2019. A descriptive and bivariate analysis was performed 1 year after the intervention as partial results of a 5-year study. All patients underwent laparoscopic appendectomy with an intraoperative finding of complicated AA. Preoperative antibiotic management was administered in all patients and posteriorly had either a change to OA and outpatient management or continued intravenous scheme based on the intraoperative findings and clinical response of the patient (control of the systemic inflammatory response, oral intake, bowel transit, and pain control).
This project was submitted to the Institutional Review Board, and upon evaluation was granted exemption, as this was a prospective retrospective chart review. The protocol was implemented in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.
Regarding the inclusion criteria, all patients were older than or equal to 18 years old at the time of the surgery and had undergone laparoscopic appendectomy with intraoperative diagnosis of complicated AA, also, all patients, or their next of kin, provided informed consent before the study inclusion. On the other hand, concerning patients excluded were those who received antibiotic management during the first postoperative month for any other reason than AA or its complications. Other excluded patients included intraoperative suspicion of appendicular neoplasm, chronic or acute malnutrition, and finally, medical failure with antibiotics for AA before surgery.
Intervention
Patients who underwent laparoscopic appendectomy with finding of ACA received preoperative IVA in all cases, a switch to oral OA and outpatient management or prolongation of IVA based on intraoperative findings and clinical response of the patient.
The same antibiotic was used in all patients according to the institutional guidelines for the management of AA, including pregnant patients in whom a safe use of these antibiotics has been proven. The initial antibiotic treatment was 95% of the time a beta-lactam plus a beta-lactamase inhibitor (ampicillin-sulbactam). In the remaining 5% of cases due to penicillin allergy, the antibiotic of choice was clindamycin with aminoglycoside (Amikacin or Gentamicin), and in pregnant patients, this was replaced by metronidazole as the institutional guidelines recommend.
Statistical analysis
Clinical findings or characteristics based on the surgical approach were assessed using a Student's t-test and Mann–Whitney U-test or Fisher's test to compare the means between groups for normally distributed and non-normally distributed data, respectively. The χ2-test was used to compare proportions/frequencies between groups. Primary endpoints were evaluated independently as binary outcomes. Statistical significance was considered p ≤ 0.05. This study complied with the STROBE guidelines.
Results
A total of 48 patients met the inclusion criteria, 29 patients were women (60%), whereas four of them pregnant, and 19 patients were male (39%). The average age was 34, 4 years old. AA was diagnosed through clinical suspicion (60%), abdominal ultrasound (8%), or computerized tomography scan (27%). The distribution of intraoperative findings is described in Table 1.
Table 1 Description of intraoperative findings
| Intraoperative findings | n = 48 (%) |
|---|---|
| Gangrenous appendix | 9 (18.75) |
| Appendicolith free in abdominal cavity | 6 (12.5) |
| Perforated appendix | 21 (43.75) |
| Localized abscess | 12 (25) |
| Pelvic peritonitis | 20 (42.6) |
| Generalized peritonitis | 12 (25) |
| Phlegmon | 23 (47.9) |
Peritoneal lavage was not performed in any of the patients, only suction and cleaning. The appendix stump closure technique was polymeric clip 51.4% (or endoloop 37.5%), and also there were used ligasure (56.25%), hook (43.75%), or endobag (39.58%). In the postoperative period, two of the 35 patients presented postoperative ileus and five surgical site infections (SSI), three being superficial and the remaining two organ space (Table 2).
Table 2 Complications presented with an antibiotic regimen based on the patient's clinical response
| Complication | n (%) |
|---|---|
| SSI grade I | 3 (6,25) |
| SSI grade III | 2 (4,16) |
| Ileus | 1 (2) |
The distribution of antibiotic management and the evaluated postoperative results (complications and length of hospital stay) are described in Tables 3 and 4, respectively.
Table 3 Distribution of postoperative antibiotic management
| Postoperative antibiotic management | n (%) |
|---|---|
| Only preoperative AB and outpatient management | 7 (14.58) |
| Preoperative IVA and OA | 3 (27.08) |
| IVA 1-3 days only | 11 (22.91) |
| IVA 1-3 days + OA | 21 (43.75) |
| IVA for more than 3 days only | 6 (12.5) |
Table 4 Length of hospital stay in patients on an antibiotic regimen based on clinical response
| Length of hospital stay | n (%) |
|---|---|
| Ambulatory | 11 (22.9) |
| 1 day | 12 (25) |
| 2 days | 7 (14.5) |
| 3 days | 13 (27) |
| 4 days | 1 (2) |
| 5 days | 2 (4.16) |
| More than 5 days | 2 (4.16) |
The descriptive analysis is detailed in Table 5. In the bivariate analysis, no statistically significant difference was found in reconsultation (p = 0.81), rehospitalization (p = 0.44), and infection of the surgical site (p = 0.56) between the traditional scheme or the one based on the clinical response of the patient (Table 6).
Table 5 Descriptive analysis
| Variable name | n (%) | Median | Interquartile range |
|---|---|---|---|
| Gender | Woman 29 (60) Man 19 (39) |
- | - |
| Age | - | 31 | 16.5 |
| Body mass index | - | 27.2 | 5.05 |
| Clinical diagnosis | No 19 (39) Yes 20 (60) |
- | - |
| Ultrasound diagnosis | No 44 (91) Yes 4 (8) |
- | - |
| Tomography computerized diagnosis | No 35 (72) Yes 13 (27) |
- | - |
| Pregnant | No 44 (91) Yes 4 (8) |
- | - |
| Evolution timeline (hours) | - | 3.0 | 2.0 |
| Leukocytes | - | 1548 | 5854 |
| Gangrenous appendix | No 39 (81.25) Yes 9 (18.75) |
- | - |
| Appendicolith into the abdominal cavity | No 42 (87.5) Si 6 (12.5) |
- | - |
| Perforated appendix | No 27 (56.25) Si 21 (43.75) |
- | - |
| Perforation | No 46 (95.83) Yes 2 (4.16) |
- | - |
| Localiced abscess | No 36 (75) Yes 12 (25) |
- | - |
| Pelvic peritonitis | No 28 (58.33) Yes 20 (41.66) |
- | - |
| Generalized peritonitis | No 36 (75) Yes 12 (25) |
- | - |
| Appendiceal phlegmon | No 25 (52.08) Yes 23 (47.91) |
- | - |
| Ligasure | No 21 (43.75) Yes 27 (56.25) |
- | - |
| Hook | No 27 (56.25) Yes 21 (43.75) |
- | - |
| Endobag | No 29 (60.41) Yes 19 (39.58) |
- | - |
| Drain | No 40 (83.33) Yes 8 (16.66) |
- | - |
| Hemolock | No 22 (45.83) Si 26 (54.16) |
- | - |
| Endoloop | No 30 (62.5) Yes 18 (37.5) |
- | - |
| Peritoneal lavage | No 48 (100) Yes 0 |
- | - |
| Postoperative ileus | No 46 (95.83) Yes 2 (4.16) |
- | - |
| SSI | No 43 (89.58) Superficial 3 (6.25) Organ-espace 2 (4.16) |
- | - |
| Length of hospital stay | - | 1.0 | 3.0 |
| Duration of postoperative hospital stay (days) | 0: only preoperative antibiotic 7 (14.58) 1: intravenous antibiotic 1-3 days 1 (20.83) 2: intravenous antibiotic 1-3 days and switch to oral antibiotic administration 21 (43.75) 3: intravenous antibiotic more than 3 days 6 (12.5) 4: only oral antibiotic 3 (27.08) | - | - |
| Outpatient antibiotic treatment | No 8 (16.66) Yes 40 (83.33) |
- | - |
| Reintervention | No 48 (100) Yes 0 |
- | - |
| Reconsultation | No 44 (91.66) Yes 4 (8.33) |
- | - |
| Rehospitalization | No 46 (95.83) Yes 2 (4.16) |
- | - |
SSI: surgical site infection.
Table 6 Bivariate analysis
| Outcomes | 0 | 1 | 2 | 3 | 4 | p-value |
|---|---|---|---|---|---|---|
| Reintervention | 0 | 0 | 0 | 0 | 0 | 0 |
| Reconsultation | 0 | 0 | 2 | 1 | 1 | 0.81 |
| Rehospitalization | 0 | 0 | 1 | 1 | 0 | 0.44 |
| Infection of the surgical site | 0 | 0 | 2 | 3 | 0 | 0.05 |
0: only preoperative antibiotic; 1: intravenous antibiotic 1-3 days; 2: intravenous antibiotic 1-3 days and switch to oral antibiotic administration; 3: intravenous antibiotic more than 3 days; 4: only oral antibiotic.
Discussion
AA is one of the most common general surgical emergencies worldwide, representing a mortality risk about 8.6% and 6.7%, for men and women, respectively7,8. One-third of patients with AA who assist to the emergency service have a complicated appendicitis, which translates into increased risk of postoperative problems, compared to patients with uncomplicated appendicitis7,8.
Bhangu et al. sustained that the AA may be classified as uncomplicated or complicated. The first one mentioned is about a simple and non-perforated appendicitis, which can be suppurative/phlegmonous, and is less often accompanied by localized or diffuse pus than gangrene; the other one, is a more complex appendicitis, can be gangrenous with friable appendix with purple, green, or black color changes associated with the transmural inflammation and necrosis. This can also perforate, which is not always visible on microscope and finally, abscess may have a pelvic or abdominal location found during examination, in a preoperative imaging or as an operative finding. In the latest WSES Jerusalem guidelines, described that Mällinen et al. argued their hypothesis that the presence of an appendicolith is an independent predictive factor for both perforation and the failure of non-operative management of uncomplicated AA.
The administration of an appropriate antimicrobial therapy, as a precept in gastrointestinal surgery to prevent SSI8,9. As is already known, in uncomplicated appendicitis, antimicrobial therapy following surgery is not indicated and can produce adverse events8,9. Nevertheless, the time of IVA therapy after laparoscopic appendectomy in complicated appendicitis has not been described. According to the current evidence-based guideline of Jerusalem 2020, the antibiotic regimen is defined by the surgeon and the patient's clinical response, showing that the antibiotic administration, which is about 3-5 days, depends on the source control grade, the appendix aspect, and the degree of peritonitis.
Based on our results, 75% of the patients were managed with an in-hospital stay < 3 days, representing a significant decrease translated to the reduction of hospitalization costs. Compliance rates are similar as expected to the current literature for complicated AA. Saar et al. carried out a controlled trial, with only 24-h antibiotic therapy in a controlled source of a complicated appendicitis, proving safety associated with short length of hospital stay and lower costs8-11. de Wijkerslooth et al., carried out a study among 181 patients with gangrenous appendicitis, postoperative antibiotic during less or equal than 24 h in 57 patients (31.5%) and more than 24 h in 124 patients, although there were different factors such as older patients, higher median CRP levels at presentation, and local or diffuse peritonitis during surgery, they showed more infectious complications although not statistically significant, but did correlate with a longer length of stay12,13.
Additionally, it was observed that of the two patients who developed postoperative abscess, both had in common an appendicolith free in the abdominal cavity as an intraoperative finding. One patient received IVA for 3 days and then OA, whereas the other patient received IVA more than 5 days given a generalized peritonitis, which could explain whether or not this finding constitutes a risk factor for SSI grade III.
Finally, there were no statistically significant differences in reconsultation (p = 0.81), rehospitalization (p = 0.44), and SSI (p = 0.56) between the traditional scheme or the one based on the patient clinical response. The main limitation in the study design is data without a larger sample needed to confirm the hypothesis; however, it has shown promising results. The previous limitation could be minimized by performing a randomized clinical trial to evaluate safety and effectiveness of the different treatment regimens.
Conclusion
The use of an antibiotic regimen based on the postoperative clinical response of the patient turned out to be effective and safe after laparoscopic appendectomy for complicated AA. There were no statistically significant differences between the traditional scheme and the scheme based on the postoperative clinical response of the patient in the intra-abdominal collection rate. The antibiotic scheme based on the postoperative clinical response of the patient could decrease the time of hospital stay and consequently the reduction of hospitalization costs based on the above.
