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Society of Asian Academic Surgeons

Nonoperative Management Is Cost-Effective in

Patients With Perforated Appendicitis With Longer
Days of Symptoms

Mubina A. Isani, MD,​a​,​1​ Jeremy Jackson, MD,​a​,​1​ Wesley E. Barry, MD,​a​,​1​ Michael U.
Mallicote, MD,​a​,​1​ David Rosenberg, BS, a​​ James E. Stein, MD, MS,​a​,​b​ Aaron R. Jensen,
MD, MEd,​a​,​b​ and Eugene S. Kim, MD​a​,​b​,​*
a Division of Pediatric Surgery, Children’s Hospital Los Angeles, Los Angeles, California

bDepartment of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California

article info abstract

Background: Management of perforated appendicitis in children remains

Article history: controversial. Nonoperative (NO) and immediate operative (IO) strategies
Received 26 October 2018 are used with varying out-comes. We hypothesized that IO intervention for
patients with perforated appendicitis would be more cost-effective than NO
Received in revised form
management.
15 January 2019
Methods: A retrospective chart review of all patients with appendicitis from
Accepted 21 February 2019 2012 to 2015 was performed. Patients with perforated appendicitis were
Available online xxx defined by evidence of perfo-ration on imaging. We excluded patients who
presented with sepsis, organ failure, and ventriculoperitoneal shunts. NO

Keywords: management was determined by surgeon preference. Univariate and

multivariate analyses were performed.
Perforated appendicitis Nonoperative Cost
Results: IO was performed on 145 patients with perforated appendicitis,
Immediate operative whereas 83 were treated with NO management. Compared to IO patients,
NO patients incurred higher overall costs, greater length of stay, more
readmissions, complications, peripherally inserted central venous catheter
lines, interventional radiology drains, and unplanned clinic and emergency
department visits (P ​< 0.0001 for all). Multivariate analysis adjusting for
age, days of symptoms, admission C-reactive protein and white blood cell than 6.3 d of symptoms, after which point, NO management is more
count revealed that NO management was independently associated with cost-effective.
increased costs (OR 1.35, 1.12-1.62, 95% CI). Cost curves demonstrated
Level of Evidence: IV.
that total cost for IO surpasses that of NO management when patients
present with greater than 6.3 d of symptoms (P ​¼​ 0.01). ª ​2019 Elsevier Inc. All rights reserved.

Conclusions: Our data suggest that IO is more cost-effective than NO

management for pa-tients with perforated appendicitis who present with less

To be presented at the Society of Asian Academic Surgeons third Annual Meeting September 27-28th Milwaukee, WI.

* Corresponding author. Children’s Hospital Los Angeles, 4650 Sunset Blvd, MS 100, Los Angeles, CA 90027. Tel.: ​þ​1 (323) 361-8332; fax: ​þ​1 (323)
361-3534.

E-mail address: ​eugeneskim@chla.usc.edu​ ​(E.S. Kim).

1​
Co-first authors, both authors contributed equally.

0022-4804/$ ​e​ see front matter ​ª​ 2019 Elsevier Inc. All rights reserved.

https://doi.org/10.1016/j.jss.2019.02.033
 
 isanietal managementofperforatedappendicitis 71

bowel obstruction), ED visits, and unplanned clinic visits. Potentially

Introduction confounding covariates were also evaluated which included days of
symptoms, C-reactive pro-tein (CRP), white blood cell count (WBC), age,
Appendicitis is the most common urgent pediatric surgical disease, and presence of
traditionally treated by operative intervention. It is estimated that up to
30%-50% of children with appendicitis present with advanced, perforated
disease.​1,2 While operative management represents the current standard of
care for acute, nonperforated appendicitis in children, there exists a high
variability in practice in the management of patients with perforated
appendicitis.​3-5 Some surgeons perform im-mediate operative (IO)
management, whereas others support nonoperative (NO) management,
which includes initial fluid resuscitation, intravenous antibiotics, source
control, fol-lowed by delayed interval appendectomy 6-8 wk later.​3,6-9
Moreover, variability in practice exists regarding the neces-sity and
timing of performing appendectomy altogether for patients with
appendicitis.​10-13

Many institutions in the United States have created clinical pathways

for managing children with perforated appendicitis. These pathways are
often inconsistently followed, and vari-ability in management is
widespread. Some institutions treat perforated appendicitis nonoperatively
if the patient presents with more than 3 d of pain, whereas others use 5-7 d
as a threshold for NO management.​3,14,15

To date, two randomized controlled trials (RCTs) have been

performed to address the best management for perfo-rated appendicitis,
but they show conflicting results. One study involved a small number of
patients with unclear superiority of either treatment modality, whereas the
other study did not evaluate the costs of the two management
strategies.​14,16,17 As such, a definitive consensus with regard to the
optimal management is still lacking. We sought to evaluate differences in
cost for the management of all pa-tients at our institution who presented
with perforated appendicitis. We hypothesized that IO intervention for
pa-tients with perforated appendicitis would be more cost-effective than
NO management.

Methods

We analyzed a retrospective cohort of pediatric patients (1-18 y) with

perforated appendicitis. Data were abstracted from medical records from
patients treated at a single freestanding quaternary care children’s
hospital. We compared patients who underwent operative or NO
management of perforated appendicitis, and the primary outcome measure
in this study was overall cost. Overall cost was determined by direct
patient cost of emergency department (ED) visits, initial hospitaliza-tion,
procedures, any readmissions, and clinic visits not included in the global
postoperative billing package. Second-ary outcomes included length of
stay (LOS), placement of peripherally inserted central venous catheters
(PICCs), inter-ventional radiology (IR) placement of drains, readmissions,
complications (recurrent appendicitis, intra-abdominal ab-scess, partial
abscess on imaging. This study was approved by the Chil-dren’s Hospital  
Los Angeles Institutional Review Board and appropriate waiver of
consent was obtained with permission of the institutional review board
(#15-00324).

Patient selection and definitions

Patients admitted to Children’s Hospital Los Angeles and who underwent

an appendectomy between 2012 and 2015 with an index admission for
appendectomy (defined per All Patients Refined Diagnosis Related
Groups, code 225) were screened for inclusion in the study. Patients were
excluded if they had no evidence of perforation on imaging (free fluid,
abscess, or phlegmon on computed tomography [CT] or ul-trasound) or
found to have simple acute appendicitis in the operating room. In addition,
two patients who presented with ruptured appendicitis with signs of sepsis
and admitted to the intensive care unit were excluded. One presented in
acute renal failure and the other was hypotensive and tachycardic on
arrival. One patient requiring externalization of a ventriculoperitoneal
shunt was also excluded.

Patients were defined as IO if they underwent appendec-tomy within

24 h of admission or primary NO if they were initially intentionally
managed nonoperatively by the admit-ting surgeon and subsequently
underwent an interval ap-pendectomy. At our institution, patients undergo
immediate operation versus NO management largely based on surgeon
preference. Our protocol recommends that patients with suspected
perforation and 4 d of pain should be given IO treatment. For patients with
>​4 d of pain, a CT scan of the abdomen and pelvis is initially performed to
identify a fluid collection or phlegmon. Patients with a drainable abscess
should first undergo percutaneous drainage of the abscess by IR, followed
by NO management. Patients without an abscess should be given IO
treatment.

Immediate operative management group

Patients with perforated appendicitis who underwent IO management were

defined as perforated by the surgeon’s operative findings and histological
confirmation of perfora-tion (gross or microperforation). We intentionally
defined these patients by concordance of both surgeon and pathologic
diagnosis to minimize treatment bias. By using this definition, we
eliminated overtreatment of nonperforated appendicitis in patients with
surgeon-defined perforation without pathologic confirmation, which
would have biased the study toward su-periority of operative
management. In turn, we minimized the number of patients who may have
been undertreated with pathology-defined perforation without surgeon
concordance, and thus may not have been clinically treated as a
perforation postoperatively.

Postoperative management of IO patients consisted of 3 d of

intravenous antibiotics (piperacillin/tazobactam (100 mg/kg/dose TID) or
clindamycin (40 mg/kg/day) plus gentamicin (2.5 mg/kg/TID) for
penicillin-allergic patients) followed by a complete blood count on
postoperative day 3
72 journalofsurgicalresearch a u g u s t 2 0 1 9 ( 2 4 0 ) 7 0 ​e​7 9

APR-DRG Coded

Pts. w/Appendectomy

2012-2015 Excluded
(n=718)
No evidence of perforation

on imaging (FF, abscess,

phlegmon on US or CT)
Organ failure
VP shunts
Perforated

Appendicitis Patients

(n=228)

Non-Operative Excluded
(n= 83) patients
Immediate without
surgery and
Operative
(surgery perf and pathology
≤4 days of
pathology perf)
> 4 days of perf
symptoms symptoms
(n= 40) (n=145)
(n= 43)

Fig. 1 e Flow diagram of analysis of patients with perforated appendicitis.

the initial hospitalization; these patients were also included in the NO

group. Failure of NO management was defined as patients who despite
if clinically well. If the patient was clinically well and the WBC ​<​12,000, antibiotic therapy remained febrile, had abdominal pain, and/or clinical
they were sent home with 5 additional days of oral antibiotics. Patients deterioration at the time of initial admission. All NO patients included in
with a leukocytosis ​>​12,000 and ​<​15,000 were discharged home on oral our study underwent interval appendectomy.
antibiotics for 7 ​additional days. Patients who had a WBC ​>​15,000 were
kept as inpatients for additional intravenous antibiotics. Imaging was
performed on patients who had a persistent WBC ​>​15,000 or were febrile
7 d postoperatively to identify an​ ​abscess.

Nonoperative management group

Patients with documented perforated appendicitis by imag-ing, who are

managed nonoperatively, are treated with 10 d of antibiotics, preferably
piperacillin/tazobactam (Zosyn 100 mg/kg/dose TID), starting with the
day of source control, as defined as interventional drain placement or last
day of fever. The patients are kept in the hospital until they are clinically
well without fever, tolerating a regular diet, and having a WBC ​<​12,000.
After 10 d of antibiotics, a complete blood count is obtained, and if the
WBC ​<​12,000, antibiotics, and the PICC line are discontinued. If WBC
>​12,000 on day 10, antibiotics are continued for another week and a
repeat WBC is drawn at the end of the week. These patients follow up in
the outpatient clinic and undergo a readmission for interval appendectomy
6-8 wk after discharge. Of note, in this study, there were 5 NO patients
who failed NO man-agement and underwent urgent appendectomy during
Statistical analysis

Descriptive statistics were used to summarize and describe the distribution

of continuous variables (expressed as mean standard deviation for
normally distributed variables and median with interquartile range for the
non-normally distributed variables) and categorical variables (expressed
as percentages and frequencies). In the univariate analysis, dif-ferences in
the selected clinical characteristics between the immediate and NO
management groups were examined. The two-sample t-test was used for
comparing means between two groups, and the Wilcoxon rank-sum test
was used for comparing the non-normally distributed variables.
Chi-square tests were used when the expected frequency of categorical
variables was five or more, and Fisher’s exact test was used when an
expected frequency of categorical variable was less

Table 1 ​e​ Demographics and patient characteristics.

Patient Nonoperative Immediate P-value

characteristics operative
Number of 83 (36.4%) 145(63.6%) -
patients, n
Age (mean SD) 8.0 ( 4.7) 9.3 ( 4.1) 0.0283
Gender
Male 48.2% 51.0%
Female 51.8% 49.0%
CRP (median, IQR) 20.0 (9-28.7) 8.5 (5.9-21.3) 0.0001
WBC (mean SD) 18.5 ( 6.6) 17.1 ( 6.1) 0.1070
Days of symptoms 5 (3-7) 2 (1-3) <​0.0001
(median, IQR)

 
isanietal managementofperforatedappendicitis 73

Table 2 ​e​ Univariate analysis of clinical parameters.

Clinical parameters Nonoperative (n ​¼​ 83) Immediate operative (n ​¼​ 145) P-value
Total costs (median, IQR) $15,450 ($11,410.97-$21,820) $10,358 ($8760-$13,792) <​0.0001
No. of hospital readmissions <​0.0001
0 5 (6.0%)​ * 134(92.4%)
1 61 (73.5%) 11 (7.6%)
2 16 (19.3%) 0 (0%)
3 1 (1.2%) 0 (0%)
Hospital readmission 78 (94.0%) 11 (7.6%) <​0.0001
Unplanned clinic visits <​0.0001
0 67 (80.7%) 142(97.9%)
1 13 (15.7%) 2 (1.4%)
2 3 (3.6%) 1 (0.7%)
ED visits <​0.0001
0 51 (61.5%) 131(90.3%)
1 23 (27.7%) 11 (7.6%)
2 8 (9.6%) 2 (1.4%)
3 1 (1.2%) 1 (0.7%)
Initial hospital stay (d) 7 (5-10) 6 (5-7) 0.0005
Total length of stay (d) 10 (8-15) 6 (5-8) <​0.0001
Total number of ultrasound <​0.0001
0 24 (28.9%) 31 (21.4%)
1 37 (44.6%) 102(70.3%)
2 22 (26.5%) 12 (8.3%)
Total number of CT scan <​0.0001
0 5 (6.0%) 64 (44.1%)
1 58 (69.9%) 66 (45.5%)
2 20 (24.1%) 15 (10.3%)
Any complications 38 (45.8%) 27 (18.6%) <​0.0001
PICC line 62 (74.7%) 22 (15.2%) <​0.0001
IR drain 45 (54.2%) 13 (9.0%) <​0.0001
Days of symptoms 5 (3-7) 2 (1-3) <​0.0001
Days of symptoms group <​0.0001
4 40 (48.2%) 136(94.4%)
>​4 43 (51.8%) 8 (5.6%)

* Patients who failed nonoperative management and underwent appendectomy during the initial hospitalization subsequently did not require readmission.

Initial perforated
appendicitis management
Operative management 1.00 - -
(reference)
Nonoperative management 1.35 (1.12-1.62) 0.002
Table 3 ​e​ Multivariate analysis on total costs based on Days of symptoms 1.00 (0.97-1.02) 0.823
initial management of perforated appendicitis.
CRP 1.01 (1.00-1.02) 0.078
Initial WBC 0.99 (0.98-1.01) 0.361
Age 1.00 (0.98-1.02) 0.811
Covariates Odds 95% CI P-value
ratio
than five. In the multivariate analysis, a generalized linear model with a
gamma distribution was fitted to the log of the cost to analyze difference
in cost between the NO and IO treatment groups based on complete
observations as well as adjusted for possible confounding variables. The
results were summarized as relative cost with 95% confidence intervals
and P-values. Statistical significance was set at the 5% level and was
two-sided throughout the analysis (Stata/IC 13.1, Stata-Corp, College
Station, Texas and R program version 3.4.3).

Results

From 2012 to 2015, 718 patients were admitted with an All Patient
Refined Diagnosis Related Group code 225 for
 
74 journalofsurgicalresearch a u g u s t 2 0 1 9 ( 2 4 0 ) 7 0 ​e​7 9

$260,000 in total hospital costs would be saved, not to mention the lost
time, wages and
appendectomy at our institution. Of these, 490 patients were excluded
based on the criteria outlined in the ​methods ​section​, ​which included
patients without evidence of perfo-ration on imaging, simple acute
appendicitis, those with complicated hospital courses due to organ failure,
and those with ventriculoperitoneal shunts. The remaining 228 patients
were divided into IO (n ​¼ 145) and NO cohorts (n ​¼ 83, includes NO and
failed NO patients; ​Fig. 1​).

The IO group was slightly older than the NO group. Although the NO
patients had a greater CRP on admission, there was no difference in the
WBC between the two groups. Patients undergoing NO management
presented with a greater number of days of symptoms, defined as
abdominal pain and/or fevers compared with the IO patients (​Table 1​).

By univariate analysis, nonoperatively managed patients with

perforated appendicitis incurred significantly higher total costs, more
appendicitis-related hospital readmissions (which includes the additional
admission for interval appendectomy), more ED visits after the index
admission, more unplanned urgent clinic visits and significantly longer
initial hospital LOS, and total LOS (TLOS) for all admissions (all P ​<
0.0001, ​Table 2​). Nonoperatively managed patients were also found to
undergo more imaging studies sustain more complications (recurrent
abscess, prolonged ileus, recurrent appendicitis, bowel obstruction, and
postsurgical abscess) and had a greater number of PICC lines and IR
drains (all P ​<​ 0.0001, ​Table 2​).

A multivariate regression analysis was performed with log of the cost

as the primary outcome. After adjusting for cova-riates such as number of
days of symptoms, admission CRP, WBC, and age, we found that NO
management of perforated appendicitis was independently associated with
increased costs (​Table 3​).

Although our institutional guidelines for NO management of

perforated appendicitis is targeted toward patients who present with
symptoms of 4 d or greater, we noted a number of patients with 4 d of
symptoms who were managed non-operatively (21.6%). We sought to
determine if nonoperatively managed patients who presented with ​>​4 d of
symptoms were comparable to those who presented with 4 d. By
uni-variate analysis, we found that patients with ​>​4 d of symp-toms have a
slightly higher CRP than patients with 4 d. Interestingly, there are no
statistically significant differences in cost, readmission rate, number of
unplanned clinic and ED visits, length of hospital stay, imaging studies
performed, abscess rates, or complications between these two groups
(​Table 4​). This analysis suggests that the NO groups are clin-ically
comparable despite the number of days of symptoms before admission.

To better match our patient cohorts, we compared non-operatively

managed patients with 4 d of symptoms, who should have undergone
immediate operation by our guide-lines, to those patients who underwent
immediate operation. Similar to our previous findings, we found that
nonoperatively managed patients incurred significantly higher costs, more
hospital readmissions, more unplanned clinic and ED visits, greater LOS
and TLOS, more complications, imaging studies, PICC lines, and IR
drains (P ​< 0.0001 for all) (​Table 5​). Specific to our study, if these 40
nonoperatively managed patients had undergone immediate operation,
 management results in an increase in the total cost of care by $1216 per
day of symptoms. Conversely, over time, NO management results in a
Table 4 ​e Univariate analysis of nonoperatively managed
decrease
patients with perforated appendicitis based on number of
 

days of symptoms.

Variates Nonoperative
Days of Days of
symptoms symptoms
4 (n ​¼​ 40) > ​4 (n​ ¼ 4​ 3)
Total costs (median, IQR) $16,913.21 $15,251.25
($11,228.50- ($11,410.97-
$22,708.93) $20,880.00)
No. of hospital readmissions

0 4 (10.0%) 1 (2.4%)
1 29 (72.5%) 32 (74.4%)
2 6 (15.0%) 10 (23.3%)
3 1 (2.5%) 0 (0.0%)
Hospital readmission 36 (90.0%) 42 (97.7%)
Unplanned clinic visits

0 32 (80.0%) 35 (81.4%)
1 6 (15.0%) 7 (16.3%)
2 2 (5.0%) 1 (2.3%)
3
ED visits

0 25 (62.5%) 26 (60.5%)
1 10 (25.0%) 13 (30.2%)
2 5 (12.5%) 3 (7.0%)
3 0 (0.0%) 1 (2.3%)
Initial hospital stay (d) 8 (5.5-11) 6 (5-10)
Total length of stay (d) 10 (8-15.5) 10 (7-14)
Total number of ultrasound

0 13 (32.5%) 11 (25.6%)
1 16 (40.0%) 21 (48.8%)
2 11 (27.5%) 11 (25.58%)
Total number of CT scans
0 1 (2.5%) 4 (9.3%)
1 28 (70.0%) 40 (69.8%)
2 11 (27.5%) 9 (20.9%)
Any complications 20 (50.0%) 18 (40.5%)
PICC line 27 (67.5%) 35 (81.4%)
IR drains 21 (52.5%) 24 (55.8%)
Initial WBC 17.8 ( 5.8) 19.1 ( 7.2)
CRP 18.5 (7.7-22.9) 20.8 (18.3-34.1)

schooling attributable to the readmissions, ED visits, un-planned clinic

visits, and PICC lines.

Using multivariate analysis and comparing NO patients with 4 d of

symptoms to immediate operation patients, we found NO management to
be independently associated with higher overall costs when we accounted
for potentially con-founding factors such as initial CRP, WBC, and age at
diag-nosis (​Table 6​).

We next examined the cost of operative management over the course

of time, and we discovered that with increasing days of symptoms, IO
 isanietal managementofperforatedappendicitis 75

Table 5 e Univariate analysis comparing nonoperatively managed patients with £ 4 d of symptoms to patients who
underwent immediate operation for perforated appendicitis.
Variates Nonoperative days of symptoms 4 (n ​¼​ 40) Immediate operative (n ​¼​ 145) P-value
Total cost (median, IQR) $16,913.21($11,228.50-$22,708.93) $10,358.00($8760.15-$13,792.00) <​0.0001
Age at diagnosis 8.2 ( 4.9) 9.3 ( 4.1) 0.1557

Days of symptoms 3 (2-4) 2 (1-3) 0.0429

No. of hospital readmissions <​0.0001

0 4 (10.0%) 134(92.4%)
1 29 (72.5%) 11 (7.6%)
2 6 (15.0%) 0 (0.0%)
3 1 (2.5%) 0 (0.0%)
Hospital readmission 36 (90.0%) 11 (7.6%) <​0.0001
Unplanned clinic visits <​0.0001

0 32 (80.0%) 142(97.9%)
1 6 (15.0%) 2 (1.4%)
2 2 (5.0%) 1 (0.7%)
3 - -
ED visits <​0.0001
0 25 (62.5%) 131(90.3%)
1 10 (25.0%) 11 (7.6%)
2 5 (12.5%) 2 (1.4%)
3 0 (0.0%) 1 (0.7%)
Initial hospital stay (d) 8 (5.5-11) 6 (5-7) 0.0011

Total length of stay (d) 10 (8-15.5) 6 (5-8) <​0.0001

Total number of ultrasound <​0.0001

0 13 (32.5%) 31 (21.4%)
1 16 (40.0%) 102(70.3%)
2 11 (27.5%) 12 (8.3%)
Total number of CT scans <​0.0001
0 1 (2.5%) 64 (44.1%)
1 28 (70.0%) 66 (45.5%)
2 11 (27.5%) 15 (10.3%)
Any complications 20 (50.0%) 27 (18.6%) <​0.0001
PICC line 27 (67.5%) 22 (15.2%) <​0.0001
IR drains 21 (52.5%) 13 (9.0%) <​0.0001

Initial WBC 17.8 ( 5.8) 17.1 ( 6.2) 0.5045

CRP 18.5 (7.7-22.9) 8.6 (5.9-21.4) 0.1013

management with less than or equal to 6.3 d of symptoms and decreased

in the total cost of care by $121 per day of symptoms. Using the best-fit TLOS for patients
multivariate linear regression coefficients comparing the two management
plans, we found that it is more cost-effective to manage patients with 6.3
or less days of symp-toms with immediate operation, whereas it is more
cost-effective to manage patients with greater than 6.3 d of symptoms
nonoperatively (P ​¼ 0.012) (​Fig. 2​). Similarly, perhaps relatedly, we
found a similar interaction among the operative strategy, number of days
of symptoms, and patient TLOS (P ​< 0.005). With increasing days of
symptoms, imme-diate operation results in greater total length of
hospitaliza-tion. However, with NO management, increasing days of
symptoms results in decreased total hospital stay after 6.28 d of symptoms
(​Fig. 3​). Overall, we predict lower total costs for patients undergoing IO
undergoing operative management with less than or equal to 6.28 d of
symptoms. To apply these data in a practical manner, we found that in
patients with 6 d of symptoms, the cost difference is $403.37 and an
expected LOS difference of 0.32 d, favoring operative management. For 7
d of symptoms, the cost difference is $934.35 and the expected LOS
difference is 0.80 d, favoring NO management. Therefore, from our
analysis, pa-tients with 7 d of symptoms should undergo NO management.

Discussion

Practice variability exists with regard to the management of perforated

appendicitis in the pediatric population.​8,10,11,16,18 Chen’s survey of
pediatric surgeons in the United States
 
76 journalofsurgicalresearch a u g u s t 2 0 1 9 ( 2 4 0 ) 7 0 ​e​7 9

To date, two RCTs have compared initial NO to IO man-agement for

Table 6 ​e​ Multivariate analysis examining overall total costs perforated appendicitis. In 2011, St. Peter et al. published the first RCT to
study IO versus NO management in children with perforated appendicitis
when comparing non-operative management of patients with ​£​4
and a defined abscess.​16 Interestingly, the study found no significant
d of symptoms compared to immediate operation of patients. differences be-tween the groups in terms of total length of hospitalization,
recurrent abscess rate, or total charges. But, the NO patients had a
significantly increased number of total health care visits and CT scans. In
Covariates Odds 95% CI P-value
ratio addition, significant higher costs were noted in patients with a defined
abscess regardless of operative strategy. However, the study numbers
Initial perforated appendicitis
were low with only 20 patients enrolled in each arm, thus making it
management
difficult to draw any definitive conclusions.​16
Operative management 1.00 - -
(reference)
Nonoperative management 1.43 (1.18-1.73) <​0.0001 Blakely et al. conducted an RCT from 2006 to 2009 on 131 pediatric
with days of symptoms 4 patients with perforated appendicitis, 64 random-ized to early
CRP 1.01 (1.00-1.02) 0.099 appendectomy, and 67 to interval appendec-tomy.​14 The study found
Initial WBC 0.99 (0.98-1.00) 0.227 higher rates of adverse events (defined as intra-abdominal abscess, small
Age at diagnosis 1.01 (0.99-1.03) 0.321 bowel obstruc-tion, wound infection, unplanned readmissions, central
venous line​e​related complications, IR complications, and recurrent
appendicitis) in patients undergoing interval ap-pendectomy. Moreover,
patients who underwent early ap-pendectomy had a significantly
highlights the differences in management strategies of perforated
decreased total length of hospitalization. The primary outcome evaluated
appendicitis.​3 Although some groups only offer early operation if the
in this study was time away from normal activities influenced by adverse
patient presents with peritonitis, others offer surgery within 24 h if
events, whereas cost of care was not specifically evaluated.​14 To
patients present with ​<​3 or ​<​5 d of pain​11,13​. Some practitioners prefer
summarize, the St. Peter study suggests
NO management for perforated appendicitis based on the assumption that
there is decreased intraoperative visceral inflammation and adhe-sions and
because of the relative ease of interval appendec-tomy after
intra-abdominal infection has abated.​19

Fig. 2 e Linear
regression model of
interaction between management strategy, costs, and number of days of symptoms.

After 6.30 d of symptoms, it is more cost-effective to manage patients with perforated appendicitis nonoperatively.
 
isanietal managementofperforatedappendicitis 77

Fig. 3 e Linear regression model of interaction between management strategy, total length of stay, and number of days of symptoms. After
6.28 d of symptoms, nonoperative management results in decreased total length of hospital stay.

days of symptoms, CRP, WBC, and age, NO management of perfo-rated

appendicitis was independently associated with increased costs.

similar costs and outcomes between the immediate opera-tion and NO

patients, whereas the Blakely study shows higher adverse events for At our institution, the decision for operative versus NO management is
patients undergoing NO manage-ment followed by interval ultimately based on surgeon preference; however, our group’s protocol for
appendectomy. NO management was spe-cifically designed for patients with ​>​4 d of
symptoms.
In the present study, we sought to determine the effect of intent of
initial treatment for patients with perforated appendicitis on overall costs.
By univariate analysis, we found that the decision to nonoperatively treat
a patient with perforated appendicitis leads to an increase in total costs of
nearly 50% compared to patients treated with im-mediate appendectomy.
In addition, we discovered that NO management of perforated appendicitis
was significantly associated with increased hospital readmissions,
un-planned urgent clinic visits, emergency room visits, greater TLOS,
greater number of CT scans, more postoperative complications, more
PICC lines, and more IR drains compared with immediate operation
patients. By multi-variate analysis and adjusting for covariates such as
Therefore, we compared the nonoperatively managed pa-tients with 4 d of
pain to those who presented with ​>​4 d. Overall, we found no clinically
significant difference in costs, readmission rates, number of urgent clinic
and ED visits, length of hospital stay, imaging studies performed, abscess
rates, or complications between these groups. Therefore, the NO patients
with 4 d and ​>​4 d of symptoms were clinically comparable.

To better match the patients who underwent immediate operation, we

performed an analysis to compare the NO pa-tients with 4 d of pain (those
who should have undergone an immediate operation) to those who
underwent immediate operation. Similar to our previous analysis, the NO
patients with 4 d of symptoms incurred 63% higher costs than the IO
group, in addition to significantly more readmissions, un-planned clinic
visits, ED visits, greater TLOS, complications, imaging studies, PICC
lines, and IR drains. Multivariate anal-ysis confirmed that NO
management of patients with 4 d of symptoms was independently
associated with higher overall costs.

Moreover, we found that NO patients underwent 38% more CT scans

than the IO patients. Abdominal and pelvic CT scans confer a radiation
risk equivalent of 25.7 mo of natural back-ground radiation exposure, and
multiple CT scans in children may affect the life-time radiation risk of
malignancy.​20​ In an
 
78 journalofsurgicalresearch a u g u s t 2 0 1 9 ( 2 4 0 ) 7 0 ​e​7 9

Author contributions: E.S.K., J.E.S, and A.R.J. contributed to study

conception and design; J.J., M.A.I., J.B., W.E.B., M.U.M.,
era of promoting less ionizing radiation studies in children, this finding
becomes all the more important.

Furthermore, we found that it is more cost-effective to immediately

operate on patients who present with less than or equal to 6.3 d of
symptoms, which results in a shorter LOS.

There are several limitations to this study including the retrospective

nature and a data source derived from a single institution. Another
limitation is that it is difficult to ensure that all nonoperatively managed
patients were perforated. To address this point, we limited our NO patients
in this study to those patients who demonstrated evidence of perforation
based on imaging findings including free fluid, abscess, or phlegmon. In
addition, operative patients may have been undertreated if a perforated
appendix was not appreciated by the surgeon. Conversely, IO patients
may have been overtreated if the surgeon incorrectly thought there was a
perforation; however, on pathology, the appen-dix was intact. Therefore,
to address this possible bias, IO patients were included in the study only if
both surgeon and pathology were concordant with perforation. These
criteria were used to minimize treatment bias and eliminate pa-tients who
would be overtreated or undertreated. A number of patients undergoing
immediate operation did not have preoperative imaging as many of them
went straight to the operating room. As such, many of these patients do
not compare well to the NO group, who all underwent imaging, and, thus
were excluded from the study. In addition, a granular breakdown of costs
for each patient may also pro-vide insight into where opportunities may lie
to make future therapies more cost-effective.

In our study, NO management of perforated appendicitis is associated

with higher overall costs, more complications, greater exposure to
radiation, longer hospital stays, addi-tional procedures, and complications
compared to IO man-agement. Whether NO patients presented with 4 d or
>​4 d of pain, IO management was superior with regard to overall costs
and clinical outcomes. Furthermore, we found that it was more
cost-effective and resulted in shorter LOS to operate on patients
presenting with less than 7 d of symptoms.

Based on our institutional data, patients with perforated appendicitis

who present with less than 7 d of symptoms should undergo IO
management, as it is more cost-effective and results in decreased total
length of hospitalization. Conversely, patients with greater than or equal
to 7 d of symptoms and are clinically stable should undergo NO
man-agement as it is more cost-effective and results in decreased total
length of hospitalization.

Acknowledgment
The authors would like to acknowledge Dr. Jordan Bowling, Grace
Asuelime, and Alberto Chiccone for their help in data collection. In
addition, the authors would like to thank Choo Phei Wee who helped them
with data analysis as part of the Biostatistics Core at Children’s Hospital
Los Angeles.
 15. Agrawal V, Acharya H, Chanchlani R, Sharma D. Early​ ​laparoscopic
G.A., and A.C. contributed to data acquisition; C.P.W, E.S.K., J.E.S., management of appendicular mass in children:​ ​still a taboo, or time for a
A.R.J., and D.R. contributed to analysis and data inter-pretation; M.A.I. change in surgical philosophy? J​ ​Minim Access Surg. 2016;12:98​e​101​.
contributed to drafting of the manuscript; M.A.I. and W.E.B. contributed
16. St Peter SD, Aguayo P, Fraser JD, et al. Initial laparoscopic
to editing; E.S.K. contributed to critical revision.
appendectomy versus initial nonoperative management and​ ​interval
appendectomy for perforated appendicitis with
 

Disclosure
This study was not funded and the authors have no conflict of interest.

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