Acute Appendicitis in the Twenty-First Century: Should We Modify the Management Protocol?

ORIGINAL ARTICLE

Acute Appendicitis in the Twenty-First Century:Should We Modify the Management Protocol?

Eran Sadot & Nir Wasserberg & Ron Shapiro &

Andrei Keidar & Bernice Oberman & Siegal Sadetzki

Received: 16 February 2013 /Accepted: 7 May 2013 /Published online: 24 May 2013# 2013 The Society for Surgery of the Alimentary Tract

AbstractBackground Recent data challenge the traditional management of acute appendicitis with early surgical intervention. Thisstudy evaluated the impact of timing of appendectomy and other potential risk factors on progression of acute appendicitis.Study Design A search of the relevant databases of a tertiary medical center identified 1,604 patients with verified acuteappendicitis who underwent appendectomy in 2004–2007. Demographic and clinical data and time from symptom onset toemergency room admission (“patient interval”) and from emergency room admission to surgery (“hospital interval”) and theircombination were analyzed by pathological grade.Results On multivariate analyses, independent risk factors for appendiceal perforation were age <20 years (OR=1.58, 95 %CI 1.07–2.35) or >50 years (OR=2.84, 95 % CI 1.82–4.45) (relative to 20–50 years), white cell count >10×103/mm3 (OR=4.45, 95 % CI 2.05–9.67), body temperature >37.8 °C (OR=2.23, 95 % CI 1.45–3.41), hospital interval >24 h (OR=2.84,95 % CI 1.49–5.4), patient interval >48 h (OR=3.84, 95 % CI 2.35–6.29), and combined interval >48 h (OR=4.29, 95 % CI2.2–8.36). No association with perforation was found for the hour of emergency room arrival, hour of operation, surgicalapproach, or the performance of preoperative imaging.Conclusions In the general population, the risk of advanced pathological grade of appendicitis increases with time. Thus,prompt appendectomy is warranted. Prospective studies of subgroups of perforated and nonperforated appendicitis areneeded.

Keywords Appendicitis . Appendectomy . Time . Delay .

Timing . Outcomes . PerforationIntroduction

Appendectomy for acute appendicitis is the most commonnonelective operation performed by general surgeons.1 Fitz,2

in 1886, was the first to identify an inflammation of the appen-dix. He recommended early appendectomy to reduce mortalityrates on the assumption that untreated acute appendicitisevolves to perforation. This pathophysiologic hypothesis hasnever been proven.2 Despite 120 years of experience, thetreating surgeons still weigh the risks and benefits of earlyappendectomy. Immediate operation could lower the perfora-tion rate but could also increase the negative appendectomy rate(removal of a normal appendix). The accepted negative appen-dectomy rate in the literature is 10–20 %.3,4 Flum andKoepsell5 found that in the USA, patients after negative appen-dectomy had longer hospitalization, more complications, andhigher mortality rates than patients with appendicitis. Further-more, more recent evidence suggests that delaying surgery doesnot impact perforation rate6

–11 and can be fairly tolerated.12

These findings may be explained by the introduction of new

This study was presented at the American College of Surgeons 96thAnnual Clinical Congress, Washington, DC, October 3–7, 2010.

E. Sadot (*) :N. Wasserberg :A. KeidarDepartment of Surgery, Rabin Medical Center, Beilinson Campus,Petach-Tiqva 49100, Israele-mail: [email protected]

R. ShapiroDepartment of Surgery, Chaim Sheba Medical Center,Tel Hashomer, Israel

E. Sadot :N. Wasserberg : R. Shapiro :A. Keidar :B. Oberman :S. SadetzkiSackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

B. Oberman : S. SadetzkiCancer and Radiation Epidemiology Unit, Gertner Institute,Chaim Sheba Medical Center, Tel Hashomer, Israel

J Gastrointest Surg (2013) 17:1462–1470DOI 10.1007/s11605-013-2232-3

antibiotics that halt disease progression, much like whatoccurred in acute cholecystitis and acute diverticulitis.13,14

Moreover, a recent randomized controlled study demonstratedthat antibiotics appear to be a safe first-line therapy in unselect-ed patients with acute appendicitis.15 The potential benefits ofdelaying surgery are enhanced clinical performance outcomeassociated with a lower negative appendectomy rate, improvedpreoperative preparation, and a refreshed surgical staff, in ad-dition to better hospital resource management.16

–18

The aims of this study were twofold: (1) to evaluate therelationship of time from onset of symptoms to emergencyroom admission and to surgery with progression of appen-dicitis as defined by a high-resolution pathological gradingsystem, and (2) to identify clinical factors that may affectdisease progression.

Methods

Study Design and Setting

The study was approved by the local Institutional ReviewBoard. The target population included all patients whounderwent appendectomy between January 2004 and De-cember 2007 at a tertiary university-affiliated medicalcenter and had a pathologically confirmed diagnosis ofacute appendicitis. A search of the hospital’s administra-tive database using appendectomy procedural codesyielded 1,910 consecutive patients (all ages) treated sur-gically for presumed appendicitis. Of these, 306 wereexcluded from the study because of a pathology reportof normal appendix (n=294), history of periappendicularphlegmon/abscess (n=9), and elective operation for inter-val appendectomy (n=3). Patients who were preopera-tively diagnosed with periappendicular phlegmon/abscesswere not included because it is our hospital policy thatthese patients are initially treated nonoperatively (antibi-otics, percutaneous drainage). Moreover, no other patientin our cohort underwent initial nonoperative treatment.The final study population consisted of 1,604 patients.All received a nil per os regimen of intravenous hydra-tion with crystalloid fluid and intravenous antibiotics(ceftriaxone and metronidazole) at diagnosis. Imagingstudies and the operative intervention were performed atthe discretion of the individual attending surgeon.

For the present study, the following data were abstractedfrom the medical records of the relevant hospital depart-ments (emergency room, surgery and anesthesia; adult andpediatric) and outpatient clinics: patient age and sex, bodytemperature at admission, white blood cell count (WBC),findings on imaging studies (computed tomography, ultra-sound), time from symptom onset to emergency room ad-mission (“patient interval”), and time from emergency room

admission to onset of surgery (“hospital interval”). Thepatient interval was determined by self-report as docu-mented in the history taken in the emergency room; thehospital interval was abstracted from computerized docu-mentation. Time from symptom onset to surgery (“com-bined interval”) was calculated by adding the patientinterval to the hospital interval. To determine diseaseprogression, we analyzed the patients’ pathology reportsusing a grading system (with uniform definitions used atour institution between the pathologists and the sur-geons), described in Table 1.4 In addition, we reviewed theoperative reports for macroscopic pathological findings ofappendiceal perforation, phlegmon, and periappendicular ab-scess. We defined G1 as acute appendicitis, G2 as gangrenousappendicitis, G3 as perforated appendicitis or a phlegmon, andG4 as periappendicular abscess. Patients were divided intofour groups accordingly. Operative time was recorded, as wellas postoperative length of hospital stay, surgical site infec-tions, and other postoperative complications.

Data Analysis

Chi-squared tests were used to assess difference in thefrequencies between the groups for categorical variables,and t tests and analysis of variance for continuous vari-ables. Odds ratios for appendiceal grade with correspond-ing 95 % confidence intervals (CI) were calculated as theprimary measure of effect size of the different explana-tory variables using standard unconditional logistic re-gression. Variables that were significant on univariateanalysis were entered into a multivariate analysis (uncon-ditional logistic regression), where the outcome variablewas appendiceal perforation. We utilized two differentmultivariate logistic regression models: the first includedpatient interval and hospital interval and the other includ-ed the combination of both intervals. In order to includethe whole study population in the multivariate analysis, amissing category was set up for variables with largequantities of missing data (temperature (n=350) and pa-tient interval (n=207)). We utilized graphs to illustratethe interquartile range and medians for each pathologygrade for the relevant variables. P for trend was calcu-lated using linear regression.

Table 1 Pathology grading system for acute appendicitis4

Grade Explanation

G1 Acute appendicitis

G2 Gangrenous appendicitis

G3 Perforated appendicitis or a phlegmon

G4 Periappendicular abscess

J Gastrointest Surg (2013) 17:1462–1470 1463

Table 2 Description of demographic and clinical variables of the study population by pathology grade

Variable type Pathology gradea

Total (n=1,604) G1 (n=1,284) G2 (n=133) G3 (n=122) G4 (n=65) P value

Demographic Age (years), (mean±SD) 29.0±18.2 28.4±17.0 29.8±20.2 30.0±22.4 36.9±25.2 0.003

Sex n (%) 0.19

Male 927 (57.9) 735 (57.2) 84 (63.2) 76 (62.3) 32 (49.2)

Female 677 (42.1) 549 (42.8) 49 (36.8) 46 (37.7) 33 (50.8)

Hour of arrivalb n (%) 0.5

7 a.m. to 3 p.m. 608 (38) 475 (37) 52 (39.1) 53 (43.4) 28 (43.1)

3 p.m. to 11 p.m. 714 (45) 573 (44.7) 64 (48.1) 49 (40.2) 28 (43.1)

11 p.m. to 7 a.m. 282 (18) 236 (18.9) 17 (12.8) 20 (16.4) 9 (13.9)

Time interval Patient intervalc (h), <0.001

(mean±SD) 31±34.5 27.4±29.5 34.5±28.2 41±35.1 74.5±77.3

Hospital intervald (h), <0.001

(mean±SD) 11.9±10.5 11.7±10.2 11.2±7.3 13.5±11.7 16.6±16.9

Combined intervale (h), <0.001

(mean±SD) 42.9±36.5 39.1±31.5 45.4±30.4 54±36.6 91.3±78.6

Preoperative WBCf n (%) <0.001

≤10×103/mm3 216 (14) 200 (15.7) 5 (3.8) 7 (5.8) 4 (6.2)

>10×103/mm3 1,374 (86) 1,073 (84.3) 127 (96.2) 113 (94.2) 61 (93.9)

Feverg n (%) <0.001

≤37.8 °C 920 (73) 799 (79.3) 48 (48) 53 (54.1) 20 (40.8)

37.8–38.5 °C 201 (16) 136 (13.5) 26 (26) 22 (22.5) 17 (34.7)

≥38.5 °C 133 (11) 72 (7.2) 26 (26) 23 (23.5) 12 (24.5)

Preoperative CT n (%) 0.002

No 1,260 (79.0) 1,017 (79.2) 110 (82.7) 94 (77.0) 39 (60.0)

Yes 344 (21.0) 267 (20.8) 23 (17.3) 28 (23.0) 26 (40.0)

Preoperative US n (%) 0.55

No 1,323 (82.0) 1,062 (82.7) 112 (84.2) 95 (77.9) 54 (83.1)

Yes 281 (18.0) 222 (17.3) 21 (15.8) 27 (22.1) 11 (16.9)

Operative Operative time (h), (mean±SD) <0.001

Open 1.08±0.4 1.01±0.4 1.16±0.4 1.23±0.5 1.6±0.72

Laparoscopic 1.18±0.4 1.12±0.4 1.3±0.4 1.54±0.5 1.5±0.75

Postoperative Length of stayh (days), <0.001

(mean±SD) 3.4±3.1 2.7±1.8 4.1±3.0 7.7±4.9 7.6±6.5

Wound infection n (%) <0.001

No 1,542 (96.1) 1,252 (97.5) 128 (96.2) 102 (83.6) 60 (92.3)

Yes 62 (3.9) 32 (2.5) 5 (3.8) 20 (16.4) 5 (7.7)

Intra-abdominal abscess n (%) <0.001

No 1,549 (96.6) 1,253 (97.6) 123 (92.5) 115 (94.2) 58 (89)

Yes 55 (3.4) 31 (2.4) 10 (7.5) 7 (5.7) 7 (10.7)

NA nonapplicablea G1—acute appendicitis, G2—gangrenous appendicitis, G3—perforated appendicitis or a phlegmon, G4—periappendicular abscessb Hour of arrival to the emergency roomc Time from onset of symptoms to the emergency room admission. For 207 persons, data regarding patient interval were missingd Time from the emergency room admission to the operating roome Time interval from onset of symptoms to the operating room. For 207 persons, data regarding combined interval were missingf There were only 1,590 complete observations for WBCg For 350 persons, data regarding fever were missingh Complete information regarding length of stay was available for 1,580 persons

1464 J Gastrointest Surg (2013) 17:1462–1470

Results

Demographics

Table 2 summarizes the demographic and clinical variables ofthe study population by pathology grade (G1–G4, Table 1).Mean age of the whole population was 29 years; the mean agewas highest in the G4 group (36.9 years, P=0.003). The male-to-female ratio for the whole population was 1.4:1. The meanpatient interval was 31 h (range 0.75–504 h), and the meanhospital interval was 11.9 h (range, 1.3–201.6 h). The meancombined interval was 42.9 h (range, 2.05–705.6 h). Forty-four percent of patients underwent open surgery, and theremaining patients were treated laparoscopically. The conver-sion rate from the laparoscopic to the open approach was0.01 %. The mean length of hospital stay for the wholepopulation was 3.4 days (range, 1–39 days). The woundinfection rate was 3.9 % and the intra-abdominal abscess rate,3.4%. The pathology report indicated that 80% of the patients(n=1284) had G1 disease at surgery. The overall perforationrate (defined as G3 or G4 pathology) was 9.9 %.

Table 3 lists the postoperative complications other thansurgical site infections, wound infection, or intra-abdominalabscess, which are described in Table 2. Only complicationsthat occurred within 30 days after appendectomy were con-sidered, with the exception of small bowel obstruction, whichwas taken into account indefinitely. Three patients requiredreoperation for leakage from the cecum resection line, smallbowel obstruction, and intractable abdominal pain.

Relationship between Time Intervals and Pathology Grade

We examined the continuous effect of time on the pathologygrade. Figures 1, 2, and 3 describe the median time interval(combined, patient, and hospital interval, respectively) foreach pathology grade. For each of these time intervals, ahigher pathology grade was associated with a longer timeinterval. However, it is interesting to note that while thepatient interval rose dramatically from 24 h in G1 to 28 h inG2 to 48 h in G4 (2-fold), the hospital interval was almostconstant for all pathology grades.

Factors Associated with Appendiceal Perforation(G3 and G4)

Potential risk factors for appendiceal perforation are shownin Table 4, demonstrating the role of very young age (≤19years, increased risk by 1.7-fold) and older age (>50 years,increased risk by 3-fold) compared to the age range between20 and 50 years, leukocytosis (≥10×103/mm3, increasedrisk by 2.8 fold), elevated body temperature (>37.8 °C,increased risk by 2.7-fold), a hospital interval of at least24 h (increased risk by 2.6-fold), a patient interval of at least

48 h (increased risk by 4.7-fold), and a combined interval ofat least 48 h (increased risk by 5.9-fold). These are all theunivariate results. Adjustment of these variables for eachother in two different models (each including different timevariables which are highly correlated with each other)showed similar results. Compared to patients between theages of 20 and 50 years, those under 20 years had about 1.5-fold risk of perforation, and those over 50 years had analmost 3-fold risk. In the first model, a hospital interval ofmore than 24 h increased the risk for perforation by 2.9-fold,and a patient interval of 48–72 h increased the risk by 4.2-fold, whilst in the second model, a combined interval in-creased the risk by 5.4-fold and 7.1-fold for intervals of 48to 72 h and more than 72 h, respectively. Of note, the hour

Table 3 Postoperative complications

Type Number Percentage

Mortality 1 0.06

Readmission 52 3.24

Ileus 15 0.94

Postoperative fever 14 0.87

Small bowel obstruction 7 0.44

Drug hypersensitivity reaction 4 0.25

Atrial fibrillation 3 0.19

Pneumonia 3 0.19

Urinary tract infection 3 0.19

Reoperation 3 0.19

Phlebitis 2 0.12

Wound hematoma 2 0.12

Bacteremia 2 0.12

Pulmonary edema 2 0.12

Hypo/hyperkalemia 2 0.12

Septic shock 1 0.06

Macrohematuria 1 0.06

Duodenal ulcer and duodenitis 1 0.06

Leg hypoesthesia 1 0.06

Diarrhea 1 0.06

Lower gastrointestinal bleeding 1 0.06

Elevated liver enzymes 1 0.06

Incisional hernia 1 0.06

Chest pain 1 0.06

Acute myocardial infarction 1 0.06

ARDS 1 0.06

Extra pyramidal symptomsa 1 0.06

Upper gastrointestinal bleeding 1 0.06

Syncope 1 0.06

Colitis 1 0.06

Acute gastroenteritis 1 0.06

ARDS acute respiratory distress syndromea Secondary to metoclopramide


of arrival to the emergency room, hour of operation, surgicalapproach (laparoscopic vs. open), and performance of pre-operative CT scan or US did not demonstrate an associationwith perforation rate in the logistic regression model (datanot shown). These variables, however, did not enter to themultivariate model because they are not related to the pa-tient’s condition at admission.

Discussion

Appendiceal perforation is one of the most important con-siderations when timing surgery for presumed acute appen-dicitis. In our group of 1,604 unselected consecutivepatients with pathologically proven appendicitis, the overallperforation rate was 9.9 %. This value is in line with thehospital-based studies of Bickell et al.19 (16 %) and

Musunuru et al.20 (13 %). However, it is considerably lowerthan that reported in population-based series (20–30 %),21,22

perhaps because they defined perforation rate according tothe ICD-9 codes which do not differentiate gangrenous fromperforated appendicitis.

An intention-to-treat analysis would have also includedpatients found to have a pathologically normal appendixafter appendectomy. However, the primary goal of the pres-ent study was to evaluate the impact of timing of appendec-tomy on disease progression among individuals with acuteappendicitis. Therefore, including patients with negativeappendectomy would have diluted this effect, if present.Future studies assessing the patients who underwent nega-tive appendectomy, their complication rates, and the relationto imaging are currently being performed.

The combined interval is the time interval that demon-strates more comprehensively the relation between time and

Fig. 1 Relationship betweencombined interval (data notavailable for 207 patients) andpathology grade. P for trend,from linear regression, is lessthan 0.001. Data are expressedas medians with barsrepresenting 25th and 75thpercentiles. G1–G4 pathologygrades as defined in the“Methods” section

G1 G2 G3 G4

Pathology Grade

2040

6080

Pat

ient

Inte

rval

2424

28

4848 48

96

10

16.75

24 2424

Fig. 2 Relationship betweenpatient interval (data notavailable for 207 patients) andpathology grade. P for trend,from linear regression, is lessthan 0.001. Data are expressedas medians with barsrepresenting 25th and 75thpercentiles. G1–G4 pathologygrades as defined in the“Methods” section


appendiceal pathology grade. This time interval is subject torecall errors, mainly because pain is a very subjective.Moreover, the components of the combined interval mighthave different effects on disease progression due to the anti-biotic treatment that might slow disease progression duringthe hospital interval. Thus, we decided to analyze separatelythe combined interval, the hospital interval, and the patientinterval. Our results demonstrate a positive association be-tween time and pathology grade. The longer the time intervalin the patient interval, in the hospital interval, and in thecombined interval, the higher grade of appendiceal pathologyeach revealed (Figs. 1, 2, and 3).

As can be seen in Fig. 3, the difference in median hospitalinterval between pathology grade 1 (G1) and pathology grade 4(G4) is less than an hour (0.9 h). Given that appendiceal pathol-ogy is unlikely to advance so dramatically in so short a time andthe retrospective design of this research, causality could only bespeculated. Therefore, this difference, though statistically signif-icant, may simply reflect the relatively large sample size, with noapparent clinical implication. On the other hand, the 24-h differ-ence seen in the patient interval (Fig. 2) between pathologygrades G1 and G4 is likely to be the cause of the advancedpathology. Thus, perforation rate at surgery might be influencedmore by the patient interval (an interval that we can barelyinfluence) and less by the hospital interval. This observationhas been similarly described in the literature.23,24 Ditillo et al.25

concluded on this basis that delaying appendectomy isunconditionally unsafe. According to the above paragraph, wepoint out the importance of acquiring an accurate history whichincludes the exact time since the onset of symptoms for everypatient with presumed acute appendicitis at admission. Ourdata add to their findings by the multivariate logisticregression models which identified independent risk factors

for appendiceal perforation: young age and older age,leukocytosis, elevated body temperature, a hospital interval ofat least 24 h, patient interval of at least 48 h, and combinedinterval of at least 48 h. Although recent publications26

–29

report on the safety of antibiotics as first-line treatment forappendicitis, we cannot assume on the basis of the presentstudy that it is safe to delay surgery for up to 24 h (hospitalinterval) or 48 h (patient and combined intervals), as suggestedby others,6,30

–32 because several selection biases might haveinfluenced the results. The major biases are the antibiotictreatment which was initiated without an exact timingprotocol and might have halted pathology progression. Aswell, the fact that we evaluated a single institution cohortposes an inherent selection bias which narrows thegeneralizability of the findings. An additional bias wasdescribed earlier and relates to the exclusion of the patientswith negative appendectomy which is another important factorwhile considering appendectomy for presumed appendicitis. Afurther potential bias might have resulted from the fact thatpatients who presented to the ER with advanced pathologyhave been worked up more extensively (e.g., ultrasound, CT)which resulted in longer time intervals. Another importantselection bias was described by Livingston et al.33 andAndersson34 who reported a dissociation between the rates ofperforated and nonperforated appendicitis which theyexplained by the presence of undiagnosed resolvingappendicitis which appears after longer time intervals.Thus, we believe that the results from trials suggestingnonoperative treatment for appendicitis are complementaryto our results, and future research will specify the safety ofnonoperative treatment for different subgroups of appendicitisdepending on patient interval and pathology grading asindicated by imaging at the emergency room. Therefore, to

G1 G2 G3 G4

Pathology Grade

810

1214

1618

Hos

pita

l Int

erva

l

9.6

14.2

6.5

13.5

9.5

6.95

14.8

10

6.7

18.1

10.4

8.2

Fig. 3 Relationship betweenhospital interval and pathologygrade. P for trend, from linearregression, is less than 0.001.Data are expressed as medianswith bars representing 25th and75th percentiles. G1–G4pathology grades as defined inthe “Methods” section


fully evaluate the outcome of delayed appendectomy,prospective randomized controlled studies are needed.

Another limitation to this study is the missing data for thetemperature. At the same time, this study presents the largestsingle institution series correlating time intervals withappendiceal pathology. Unlike other studies, which assessedthe effect of time on the risk of appendiceal perforation bycomparing groups with perforated and nonperforatedappendicitis,35

–40 we used a high-resolution pathology grad-ing system and multivariate analysis to examine risk factorsfor advanced disease. In addition, besides patient interval,all data were collected from objective sources (e.g., pathol-ogy and operating room reports).

In conclusion, in the general population, the longer thetime to appendectomy, the higher the risk of advancedpathology. Thus, until prospective studies of subgroups ofappendicitis (perforated and nonperforated) are conducted toclarify the relationship between different time intervals,perforation rate, and other postoperative complications,prompt appendectomy is warranted in cases of suspectedappendicitis. Special attention should be addressed to pa-tients who arrive at the emergency room 24 h or more aftersymptom onset or to the operating room 48 h or more aftersymptom onset, to patients who are younger (<20 years) andolder (>50 years), and to patients with leukocytosis orelevated temperature.

Table 4 Risk factors forappendiceal perforation(G1 and G2 vs. G3 and G4)

G1—acute appendicitis,G2—gangrenous appendicitis,G3—perforated appendicitis or aphlegmon,G4—periappendicular abscess

WBC white blood cell countaMultivariate logistic regression(unconditional)bA group of 350 patients whosetemperature data were missingcTime from the emergency roomadmission to the operating roomdTime from onset of symptoms tothe emergency room admissioneA group of 207 patients for whompatient interval was missingfTime interval from onset ofsymptoms to the operating room

Univariate logistic regression Model 1a Model 2a

OR 95 % CI OR 95 % CI OR 95 % CI

Age (years)

≤19 1.73 1.22–2.47 1.58 1.07–2.35 1.52 1.04–2.24

20–50 1.00 1.00 1.00

>50 3.00 2.00–4.52 2.83 1.81–4.43 2.69 1.73–4.17

WBC (×103/mm3)

≤10 1.00 1.00 1.00

10–15 2.85 1.39–5.88 4.47 2.06–9.72 4.31 2.00–9.29

15–20 2.71 1.3–5.62 3.99 1.81–8.79 3.94 1.80–8.61

≥20 6.13 2.86–13.13 8.72 3.79–20.1 8.3 3.62–19.00

Temp1

≤37.8 1.00 1.00 1.00

37.8–38.5 2.72 1.84–4.04 2.20 1.43–3.37 2.25 1.47–3.43

≥38.5 4.75 2.96–7.61 2.75 1.63–4.65 2.78 1.65–4.69

Missingb 1.71 1.12–2.63 1.63 1.02–2.61 1.73 1.09–2.76

Hospital intervalc (h)

≤6 1.00 1.00 NA

6–12 1.19 0.78–1.82 1.28 0.8–2.04

12–24 0.97 0.61–1.57 0.94 0.55–1.6

≥24 2.64 1.5–4.65 2.87 1.51–5.46

Patient intervald (h)

≤12 1.00 1.00 NA

12–24 1.08 0.53–2.2 1.01 0.48–2.12

24–48 1.41 0.84–2.37 1.32 0.77–2.27

48–72 4.68 2.77–7.92 4.19 2.39–7.35

≥72 5.3 3.12–9.00 5.27 2.99–9.29

Missinge 1.42 0.75–2.66 1.25 0.64–2.44

Combined intervalf (h)

≤12 1.00 NA 1.00

12–≤24 1.17 0.35–3.93 1.12 0.32–3.95

24–≤48 1.9 0.6–6.07 1.66 0.49–5.55

48–≤72 5.93 1.84–19.06 5.37 1.58–18.29

72+ 7.19 2.25–23.02 7.06 2.08–23.99

Missinge 1.96 0.58–6.65 1.59 0.44–5.72


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Acute Appendicitis in the Twenty-First Century: Should We Modify the Management Protocol?

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