The CRAC study showed that in a selected cohort of Italian hospitals, in March and April 2020, the number of appendectomies has drastically dropped and that during the first wave of the COVID-19 pandemic, patients undergoing surgery were more frequently affected by more severe forms of appendicitis compared to the same timeframe of the previous year. This is the outcome of data analysis of over 1,300 individual patients undergoing appendectomy for acute appendicitis, a much more comprehensive dataset than previous international and national surveys [8, 19, 20] and multicenter retrospective studies [21, 22] had suggested or highlighted.
How this is to be interpreted is questionable. The reduction in the overall number of appendectomies performed may have several explanations. First, individuals affected by acute appendicitis may have renounced to approach emergency rooms in hospitals for fear of SARS-CoV-2 contagion. Simultaneously, we cannot exclude that surgeons restricted the indications for surgery to more severe cases, offering milder clinical cases the opportunity of conservative medical therapy at home. The vast majority of patients with uncomplicated appendicitis can safely be managed by active observation and pain control , and this is what might have happened during the first wave of the pandemic.
Since the outbreak of the COVID-19 pandemic in Europe and the U.S., several recommendations issued by surgical societies and institutional bodies have supported surgery's decision-making processes, including emergency scenarios. Although the overall level of evidence of such recommendations was low, there has been a significant impact of these documents on surgeons' daily clinical practice. Globally, during the first wave of the COVID-19 pandemic, recommendations on the treatment of acute appendicitis suggested the use of appropriate non-operative treatments whenever possible in order to avoid overloading hospitals, already heavily burdened by SARS-CoV-2 patients. Our findings are in line with the ACIE Appy international survey on the global attitudes in managing acute appendicitis during the pandemic, which showed a statically significant decrease in the number of acute appendicitis patients referred to the hospitals, with only 10% of surgical units reporting > 20 referrals per month . According to 34% of respondents to the survey, patients had more advanced disease features at a presentation during the COVID-19 pandemic. Results from the CRAC study confirmed this change in behavior by considering real-patient data and assessing a reduction of more than 30% in the number of appendectomies compared to 2019.
Whatever the reason, our study demonstrates that the severity of appendicitis during appendectomy significantly increased during the first wave of the pandemic, bringing together an increase of complication rate including the severity of complications, but not mortality. The impression that appendectomies could have been delayed after admission to the emergency room does not correspond to the truth. This is a promising finding, as it is known that the rate of complications increases in delayed surgery cases. This means that despite the apparent difficulties in the emergency area organization in hospitals, this did not affect the efficiency of the surgical activity. Nevertheless, complications observed were significantly more in 2020 as well as their severity.
Perforated appendicitis occurs in up to 15% of cases . We found a relative increase of surgical referrals for complicated acute appendicitis with phlegmon, abscess, or diffuse peritonitis, as defined by the grades 4–5 of the American Association for the Surgery of Trauma (ASST) classification. In our study, 20% of patients in 2019 presented to observation with perforated appendicitis according to the ASST classification, whereas the rate increased to 27% in 2020, with a statistically significant difference. The CRAC study found that patients undergoing surgery > 24 hours from the hospitalization were more prone to experience post-operative complications following appendectomy than those who underwent surgery within the first 24 hours. The United Kingdom National Surgical Research Collaborative found that in a cohort of more than 2,500 patients with acute appendicitis, of whom 32% had complex findings, delaying appendectomy for over 48 hours was related to a statically significant increased risk of surgical site infection and 30-day adverse events . Our study reached similar results, as surgical delay > 24 hours was a risk factor for post-operative complications both at the univariate and multivariate analyses. Our results are in line with those published by Alore et al., who found that appendectomies performed on hospital day three had significantly worse outcomes, as demonstrated by increased 30-day mortality and all major post-operative complications compared to operations taking place on hospital day one . Since in our study, the rate of complicated appendicitis reported during the pandemic period of 2020 was higher than that usually found during 2019, and generally, in the contemporary literature, we argue that it may be reasonable to prioritize patients reporting symptoms lasting for over 24 hours for operative management.
The technique adopted during the pandemic did not differ from the previous habit. Open appendectomy for patients with intra-abdominal sepsis of appendiceal origin or those with the non-resolving disease following antibiotic treatment was initially recommended [27–29]. Recommendations that claimed to avoid the use of laparoscopy were based on previous findings that activated corynebacterium, papillomavirus, HBV, and HIV had been detected in surgical smoke and the assumption that SARS-CoV-2 infection aerosol should not have been any exception . Such recommendations need to be contextualized within the scenario in which European surgeons had been facing the viral spread during the first wave of the pandemic, characterized by the lack of availability of ultrafiltration systems, the paucity of personal protective equipment, the shortage of surgical workforce, and the impossibility of routine testing of all patients. However, a year after the first case of SARS-CoV-2 infection was identified in China, the virus has not been isolated so far from the laparoscopic plumes within the peritoneal cavity of infected subjects.
Consequently, the potential of viral spreading during laparoscopy is not known. In circumstances where operating theatre resources are available and based on surgeon judgment, laparoscopic appendectomy should continue to be performed, as the safe performance of laparoscopic appendectomy allows short hospitalization. Data from the CRAC study showed that, in Italy, the rate of laparoscopic appendectomy performed in March-April 2020 was comparable to that in the same two months in 2019 (90.1% vs. 90.3%). The reason for this finding, which is in contrast with the trend in favor of open appendectomy reported in other countries , might be found in the enormous effort made by surgeons in Italy to equip operating rooms with systems for the safe evacuation of laparoscopic plumes, first with home-made systems, and then with the certified ones introduced on the market by companies .
The CRAC results have also highlighted Italian surgeons' attitudes on the use of antibiotic therapy after appendectomy. It is well known that a single dose of broad-spectrum antibiotics given preoperatively is highly effective in decreasing wound infection and post-operative intra-abdominal abscess following appendectomy . So that, guidelines recommend against post-operative antibiotics for patients with uncomplicated appendicitis . In patients with complicated acute appendicitis, conversely, post-operative broad-spectrum antibiotics are recommended. For those who had undergone an adequate surgical source control through an appendectomy, the outcomes after fixed-duration antibiotic therapy (approximately 3–5 days) are similar to those after a long course of antibiotics . The results of our study, which have confirmed the attitude towards the prolonged use of post-operative antibiotics for more than five days, both in the pre-pandemic (49%) and in the pandemic (53%), poses serious concerns, as we are currently experiencing a worldwide increase in infections caused by multi-drug resistant organisms as a result of widespread antibiotic use and excessive antimicrobial prescribing practice.
Our study results must be interpreted within the context of some limitations. First, due to the urgent need for evidence on appendicitis management during the first wave of the COVID-19 pandemic, data collection was limited to short-term follow-up. The study design did not allow us to assess post-operative visits after 30 days from the surgical intervention. As a consequence, longer-term complications, such as post-operative adhesions and incisional hernia, might be missed. Second, due to the ambispective design, the quality of data collected depended on the quality of medical records and the researcher's interpretation of charted notes. Third, there is a considerable variation in the organization of the emergency surgical departments across the country, and the most relevant source of bias is probably the heterogeneity of the diagnostic pathways adopted in the various centers involved. Ultimately, the study has a non-randomized nature, associated with any extensive database. Conclusions from non-randomized studies can be misleading because there is always a chance for selection bias, leading to underestimating or overestimating the real intervention effect. On the other hand, our study's strength lies in the fact that we demonstrated, through the analysis of individual patients' data, that during the lock-down due to the COVID-19 pandemic, fewer patients sought medical attention for acute appendicitis in Italy. In this context, the rate of complicated appendicitis increased, leading to a relatively higher incidence of post-operative complications than in the past.