Authors: Shuo-Lun Lai, Chin-Hao Chang, Po-Chu Lee, Cheng-Maw Ho, Jin-Ming Wu, Hong-Shiee Lai, Been-Ren Lin
Categories: Research, Appendectomy, Appendicitis, Complications, Delay, Timing
Source: Perioperative Medicine
Authors: Shuo-Lun Lai, Chin-Hao Chang, Po-Chu Lee, Cheng-Maw Ho, Jin-Ming Wu, Hong-Shiee Lai, Been-Ren Lin
Several factors are associated with increased postoperative complications after appendectomies. However, few studies combined these potential factors for comprehensive prediction of surgical outcomes. Whether high-risk patients benefit from a shorter waiting time for surgery remains unclear. This study aimed to explore the impact of surgical waiting time and potential risk factors on postoperative complications.
A total of 1343 patients diagnosed with acute appendicitis requiring an emergent appendectomy were included from 2013 to 2018. The preoperative risk factors associated with postoperative complications were selected and the probability of postoperative complications was calculated by multivariate logistic regression model. Patients were divided into four groups based on the risk (high & low) and time to surgery (> 12 & ≤12 hours). The odds ratios for complications were evaluated between groups.
The selected risk factors included age, neutrophil-lymphocyte ratio, systemic inflammatory response syndrome and abdominal pain duration. Compared with low-risk patients with time to surgery ≤12 hours, high-risk patients with time to surgery > 12 hours had significant increased overall postoperative complication rate (16.85% vs. 8.16%, p = 0.002) and a trend toward increased surgical site infection rate (10.99% vs. 6.46%, p = 0.058). When operated within 12 hours, there was no difference in outcomes between high- and low-risk patients. On the other hand, time to surgery > 12 hours did not increase complication rate in low-risk patients.
The surgical outcome may be affected by preoperative factors and time to surgery. It is suggested that high-risk patients receive appendectomy within 12 hours to avoid increased postoperative complications.
The online version contains supplementary material available at 10.1186/s13741-024-00365-z.
Acute appendicitis is one of the most common causes of an acute abdomen and usually requires emergent surgery. Although antibiotic treatment may be effective in select patients, appendectomy is still the only way to prevent recurrent appendicitis. Several factors (i.e., age, obesity, leukocytosis, symptom duration) have been proposed to be associated with an increased risk of postoperative complications (Andert et al. 2017; Kim et al. 2018b; Schlottmann et al. 2017). However, few studies combined these potential factors to predict the risk of surgical outcomes comprehensively.
Furthermore, there has been a dispute over the impact of surgical delay on outcomes for years. Some studies claimed that a prolonged waiting time for surgery increased the risk of complications (Ditillo et al. 2006; Giraudo et al. 2013) or surgical site infection (Teixeira et al. 2012), while others disagreed (Almstrom et al. 2017; Boomer et al. 2016; Boomer et al. 2014; van Dijk et al. 2018). If those patients at high risk for complication benefit from a shorter waiting time for appendectomies remains unclear. Since the coronavirus disease 2019 (COVID-19) became a pandemic and created challenges in managing surgical emergencies, optimizing the time to the operating room (OR) for select vulnerable patients has become an important issue. In this study, we aimed to develop a risk model for postoperative complications and identify patients who might be affected by surgical delay.
We retrospectively analyzed the surgical outcomes of patients diagnosed with acute appendicitis at a single tertiary medical center from 2013 to 2018. The Research Ethics Committee Office at National Taiwan University Hospital, Taipei, Taiwan approved this study (Institutional Review Board 202010066RINB). Patients who had visited our emergency room (ER) and underwent an emergent appendectomy were included in this study. Those who received conservative treatment first or had an elective appendectomy were excluded. Patients accidentally found appendicitis mixed with neoplastic lesions (i.e., adenocarcinoma, carcinoid, pseudomyxoma) or other conditions requiring combined surgery with other specialists (i.e., urologists, obstetricians, gynecologists) were excluded. Patients with incomplete emergency room records or an unclear history were also excluded.
Emergency room records included basic arrival information, clinical history, laboratory values, and imaging reports. Arrival information included the time of ER arrival, body temperature, pulse rate, respiratory rate, and blood pressure upon arrival at the ER. Perioperative data included surgery starting time, operative time, operative method (laparoscopic or open), operative findings, pathology reports, hospital stay, and postoperative complications. Abdominal pain duration, as an essential indicator in the study, was defined as the time from symptom onset to ER arrival. To minimize recall bias, we reviewed the historical record from the ER note, admission note, and nursing note. Cases with discordant descriptions were excluded. Time to surgery was defined as the time from ER arrival to surgery start.
Empiric intravenous antibiotics were administered to all patients as soon as they were diagnosed with acute appendicitis by clinical or imaging findings. Unless contraindicated, the preferred image study is computed tomography (CT) because of its reduced waiting time in recent years. The CT images helped surgeons evaluate disease severity and accessibility of surgery. The decision for surgery was based on the surgeon’s opinion and consensus with the patients. Patients who agreed to appendectomy were placed on the emergent operation waiting list. At our institution, the emergent operations are continuously executed regardless of day/night shift, but the operation room usage is reduced at night. The order of emergent surgery is affected by the degree of urgency.
Disease severity was classified as perforation and non-perforation based on intraoperative and pathological findings. An abscessed or ruptured appendix were defined as perforation. The gangrenous change was defined as non-perforation because the appendiceal wall remained intact. There was evidence that treating gangrenous appendicitis as a non-perforated disease did not affect surgical outcome (Nordin et al. 2019). The correlation of disease severity and postoperative complications were evaluated using the Chi-square test.
Postoperative complications included surgical site infection, intra-abdominal abscess formation, ileus, and internal bleeding. Surgical site infection referred to an incisional wound infection, and intra-abdominal abscess referred to a deep infection from the appendectomy area. Patients with surgical site infections required incision and drainage, wet dressings, or a special sterile dressing on their wounds with oral or intra-venous antibiotic administration. An intra-abdominal abscess was confirmed on computed tomography when patients reappeared to the ER complaining of a fever or abdominal pain after discharge. Ileus was diagnosed if the patient required short-term nasogastric tube decompression or prokinetic drugs during recovery. Postoperative internal bleeding requires emergent surgical intervention or transarterial embolization. Inpatient and outpatient records of all patients were followed, and patients with adverse events after surgery were graded with Clavien-Dindo Classification.
The clinical characteristics of patients with complications and without complications were compared using a Chi-square or Fisher’s exact test for categorical variables and an independent Student’s t-test for continuous variables. The preoperative factors were analyzed by univariate logistic regression. Afterward, the significant factors (p < 0.05) were included in the multivariate model. The probability of postoperative complications for all patients was calculated by the multivariate model. Patients with probability higher than the median were classified as high risk, and patients with probability lower than the median were classified as low risk.
An interim guideline for timing of emergent surgery was proposed by the Timing of Acute Care Surgery Classification (TACS) study group. Although the guideline recommended appendectomy within 12 hours, expert opinion and literature reviews varied on the timing of appendectomy (Kluger et al. 2013). Patients were further divided into four 1) low-risk patients with time to surgery ≤12 hours, 2) high-risk patients with time to surgery ≤12 hours, 3) low-risk patients with time to surgery > 12 hours, and 4) high-risk patients with time to surgery > 12 hours. The odds ratios for postoperative complications between four groups were estimated using the logistic regression.
In addition, for continuous variables that were significantly related with postoperative complications, a cut-off point was obtained by Youden index using receiver operating characteristic (ROC) curve. The results were shown in supplementary data. All statistical analysis was performed with SAS version 9.4 (SAS Institute Inc., Cary, NC). Statistical significance was defined as p < 0.05.
From 2013 to 2018, a total of 1558 patients diagnosed with acute appendicitis were cared for at our institution, of whom 1343 were included in this study. The study flowchart is shown in Fig. 1.Fig. 1Study flow chart
Overall, complications occurred in 130 patients after surgery (Table 1). Among them, 88 (6.55%) patients had surgical site infections, 20 (1.49%) had an intraabdominal abscess, 32 (2.38%) had ileus, and 1 (0.07%) had internal bleeding. In the Clavien-Dindo classification, Grade I, Grade II, and Grade III were 16 (12.3%), 108 (83.08%), and 6 (4.62%), respectively. No complication was graded as Grade IV. Table 1Patients with postoperative complications (n, %)Overall complications130 (9.68%)Surgical site infection88 (6.55%)Intra-abdominal abscess20 (1.49%)Ileus32 (2.38%)Internal bleeding1 (0.07%)Clavien-Dindo Classification Grade I16 (12.3%) Grade II108 (83.08%) Grade III6 (4.62%) Grade IV0 (0%)
The baseline demographic and clinical characteristics of patients with or without postoperative complications are shown in Table 2. The complication rate was 9.68%, which was similar to other studies (Andert et al. 2017; Kim et al. 2018b). The average diagnostic time was 3.86 hours, indicating that patients were administered empiric antibiotics within 4 hours. There were significant differences in age, abdominal pain duration, operative time, systemic inflammatory response syndrome (SIRS), hospital stay, and disease severity between groups. Perforation rate was higher in complication group (52.31% vs. 27.45%, p < 0.001) in terms of disease severity. There was a trend toward a higher neutrophil-lymphocyte ratio (NLR) in the complication group (11.94 vs. 10.32), but it did not reach statistical significance (p = 0.055). Table 2Baseline demographics and clinical characteristicsAll Patients(n = 1343)Without complications(n = 1213)With complications(n = 130)p-valueAge (Mean, SD)38.25 (19.33)37.7 (19.28)43.45 (19.05)0.001^a^Sex (n, %)0.212^b^ Female638 (47.51%)583 (48.06%)55 (42.31%) Male705 (52.49%)630 (51.94%)75 (57.69%)Body Mass Index (Mean, SD)22.86 (4.59)22.82 (4.66)23.19 (3.89)0.315^a^Body temperature at triage (n, %)0.235^b^ 36–38 °C1095 (81.53%)994 (81.95%)101 (77.69%) < 36 or > 38 °C248 (18.47%)219 (18.05%)29 (22.31%)Heart rate at triage (n, %)0.121^b^ ≤ 90 bpm655 (48.77%)600 (49.46%)55 (42.31%) > 90 bpm688 (51.23%)613 (50.54%)75 (57.69%)Respiratory rate at triage (n, %)0.299^b^ ≤ 20 /min1216 (90.54%)1095 (90.27%)121 (93.08%) > 20 /min127 (9.46%)118 (9.73%)9 (6.92%)Systolic blood pressure at triage (Mean, SD)124.2 (20.32)124.12 (20.25)124.98 (21.08)0.645^a^Diastolic blood pressure at triage (Mean, SD)75.4 (22.02)75.51 (22.68)74.4 (14.47)0.437^a^Pain score (VAS) (Mean, SD)5.98 (1.81)5.98 (1.76)6 (2.21)0.928^a^Abdominal pain duration (n, %)0.001^b^ < 24 h708 (52.72%)659 (54.33%)49 (37.69%) 24-48 h273 (20.33%)241 (19.87%)32 (24.62%) > 48 h362 (26.95%)313 (25.8%)49 (37.69%)Diagnostic tool1.000^c^ Physical examination2 (0.15%)2 (0.17%)0 (0%) CT1315 (98.95%)1187 (98.92%)128 (99.22%) Ultrasound10 (0.75%)9 (0.75%)1 (0.78%) MRI2 (0.15%)2 (0.17%)0 (0%)Diagnostic time (ER- > Exam) (h) (Mean, SD)3.86 (2.79)3.88 (2.8)3.68 (2.68)0.443^a^Time to surgery (ER- > OR) (h) (n, %)0.536^b^ ≤ 12 h593 (51.84%)534 (52.15%)59 (49.17%) > 12 h551 (48.16%)490 (47.85%)61 (50.83%)Operative time (min) (Mean, SD)70.99 (32.46)70.18 (32.58)77.85 (30.68)0.014^a^Operative method (n, %)0.074^c^ Laparoscopic1324 (98.73%)1198 (98.93%)126 (96.92%) Open17 (1.27%)13 (1.07%)4 (3.08%)White blood cell count (n, %)0.677^b^ 4000-12,000456 (33.95%)414 (34.13%)42 (32.31%) < 4000 or > 12,000887 (66.05%)799 (65.87%)88 (67.69%)Neutrophil-Lymphocyte Ratio (Mean, SD)10.47 (7.85)10.32 (7.69)11.94 (9.12)0.055^a^Platelet-Lymphocyte Ratio (Mean, SD)27.87 (21.39)27.64 (21.45)30.04 (20.73)0.229^a^Systemic inflammatory response syndrome0.037^b^ No716 (53.31%)658 (54.25%)58 (44.62%) Yes627 (46.69%)555 (45.75%)72 (55.38%)Hospital stay in days (Mean, SD)3.7 (3.45)3.35 (2.09)7 (8.4)< 0.001^a^Disease severity< 0.001^b^Non-perforation942 (70.14%)880 (72.55%)62 (47.69%)Perforation401 (29.86%)333 (27.45%)68 (52.31%)^a^Estimated by independent t test^b^Estimated by chi-square test^c^Estimated by Fisher’s exact test (Non-parameter statistic)
Of the clinical characteristics listed in Table 2, potential risk factors for postoperative complications were selected. On univariate analysis, age, NLR, SIRS, and abdominal pain duration 24-48 hr. and > 48 hr. had a statistically significant relationship with postoperative complications. On multivariate analysis, age and abdominal pain > 48 h reached statistical significance (Table 3). Table 3Association of preoperative factors and postoperative complicationsUnivariate modelMultivariate modelOR (95% CL)p-valueOR (95% CL)p-valueAge1.0152 (1.0059,1.0247)0.0011.0153 (1.0059,1.0249)0.001Sex1.2619 (0.8754,1.8191)0.213Body Mass Index1.0162 (0.9803,1.0534)0.382Body temperature at triage 36–38 °Cref < 36 or > 38 °C1.3034 (0.8411,2.0199)0.236Heart rate at triage ≤ 90 bpmref > 90 bpm1.3347 (0.9259,1.924)0.122Respiratory rate at triage ≤ 20 /minref > 20 /min0.6902 (0.3416,1.3945)0.302Systolic blood pressure at triage1.0021 (0.9933,1.011)0.645Diastolic blood pressure at triage0.9964 (0.9843,1.0088)0.570Pain score (VAS)1.0056 (0.9096,1.1117)0.914Diagnostic time (ER- > Exam) (h)0.9704 (0.8985,1.048)0.444Time to surgery (ER- > OR) (h) ≤ 12 href > 12 h1.1267 (0.7718,1.6448)0.536White blood cell count 4000-12,000ref < 4000 or > 12,0001.0856 (0.7378,1.5975)0.677Neutrophil-Lymphocyte Ratio1.0232 (1.0025,1.0444)0.0281.0192 (0.9976,1.0413)0.082Platelet-Lymphocyte Ratio1.0046 (0.9971,1.0121)0.231Systemic inflammatory response syndrome1.4718 (1.0229,2.1175)0.0371.4499 (0.9791,2.1472)0.064Abdominal pain duration < 24 hrefref 24-48 h1.7858 (1.1169,2.8551)0.0151.6047 (0.9928,2.5937)0.054 > 48 h2.1054 (1.3859,3.1986)0.0011.9907 (1.2955,3.0588)0.002
Age, NLR, SIRS, and abdominal pain duration 24-48 hr. and > 48 hr. were selected as parameters of a preoperative probability calculation. Based on the multivariate logistic regression model, the probability was calculated as \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ Score=\left(-3.5807\right)+ Age\times 0.0152+ NLR\times 0.0190+ SIRS\times 0.3715+ Duration\left(24-48 hr\right)\times 0.4729+ Duration\left(>48 hr\right)\times 0.6685
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