Current Management of Children with Appendicitis CIPESUR Meeting November 18, 2011

Current Management of Children with Appendicitis

CIPESUR MeetingNovember 18, 2011

George W. Holcomb, III, M.D., MBA

Surgeon-in-ChiefChildren’s Mercy Hospital

Kansas City, Missouri

Three Presentations

• Acute appendicitis 60 - 65%

• Perforated appendicitis 25 - 30%

• Perforated appendicitis with well-defined abscess (5-7 day history)

5 - 10%

Surgical History for Appendicitis (U.S.)

1990 – 2000

• Slow adoption for laparoscopic approach

• Why – Relatively small open incision (c/w

splenectomy, fundoplication, cholecystectomy)

Many cases done middle of night – OR crews not used to laparoscopy

Benefits were not well appreciated

Surgical History for Appendicitis (U.S.)

2000 – 2010• Laparoscopic approach now favored

(exclusively used at many centers including CMH) for all conditions: acute, perforated, abscess

• Why Operative times improved – closure faster Significantly fewer wound infections (almost

none) Improved cosmesis, esp if infection develops

Laparoscopic AppendectomyPersonnel/Port Positions

Laparoscopic AppendectomyTechnique

• Window in mesoappendix

• Vascular stapler across mesoappendix

Postoperative Appearance3 Port Laparoscopic Appendectomy

Acute Appendicitis(No Perforation)

• April 2003 – Nov 2006

• 609 Pts – laparoscopic appendectomy

• 3 post-op abscesses (0.49%)

Acute Appendicitis Appendiceal Perforation

• Perforated appendicitis (3 - 5 day hx) Evacuation/irrigation of purulent material Wound problems minimized 20% post-op abscess rate

Laparoscopic Appendectomy

Please use this link if you experience problems viewing the video above.

http://youtu.be/ikRWNOKGpaE

Laparoscopic vs Open AppendectomyPerforated Appendicitis

• Far fewer (almost none) wound infection with laparoscopic approach

• Allows surgeon to suction/irrigate under direct visualization

• Less postoperative SBO

Adhesive Small Bowel Obstruction After Appendectomy in Children: Comparison

Between the Laparoscopic and Open Approach

Jan 98-June 05: 1105 Appendectomies-447 Open, 628 Lap.

AAP 2006AAP 2006J Pediatr Surg 42:939-942, 2007J Pediatr Surg 42:939-942, 2007

Laparoscopic versus Open Appendectomy(1105 Patients)

Laparoscopic (n = 628) Open (n = 477) P Value

Age (years) 11.0 +/- 3.7 9.2 +/- 5.1 p > 0.05

Gender (M/F) 355/273 301/176 p > 0.05

SBO 1 (0.2%) 7 (1.5%) p = 0.01

Perforated appendicitis 186 192

Mean time to SBO 8 days 58 days

Median follow-up (years) 3.5 (0.8 – 6.5) 4.9 (0.9 – 8.3)


SBO After Perforated Appendicitis(378 Patients)

Laparoscopic Open p value

Perforated appendicitis 186 192

SBO 1 (0.5%) 6 (3.1%) p = 0.03


2000 – 2010 Questions

1) Do we operate in the middle of the night?

2) Is there an optimal antibiotic regimen for perforated appendicitis?

3) How do we define perforated appendicitis?

4) How do we manage the patient presenting with an abscess?

5) Which is better: SSULS or 3 port appendectomy?

1. When to Operate?Current Practice at CMH

• Patients identified with appendicitis are booked for laparoscopic appendectomy

• All receive a dose of rocephin (50mg/kg) and flagyl (30mg/kg)

• This antibiotic regimen was shown to be most cost effective in PRT

• If patients present at night, the operations are scheduled for the ‘surgeon of the week’ the next day (8 am or 1 pm start)

• Appendectomies rarely occur after 10 PM at night

Antibiotics Only vs Appendectomy For Non-Perforated Appendicitis

Liu K, Ahanchi S, Pisaneschi M, et al. Can acute appendicitis be treated by Liu K, Ahanchi S, Pisaneschi M, et al. Can acute appendicitis be treated by antibiotics alone? Am Surg 73:1161-1165, 2007antibiotics alone? Am Surg 73:1161-1165, 2007

• Retrospective comparative study (Level 3 study) in adults found no differences in complications between appendectomy at presentation or antibiotic therapy alone

• 5% recurrence rate

Early Operation Versus Delayed OperationAbou-Nukta F, Bakhos C, Arroyo K, et al. Effects of delaying Abou-Nukta F, Bakhos C, Arroyo K, et al. Effects of delaying appendectomy for acute appendicitis for 12 to 24 hours. Arch Surg appendectomy for acute appendicitis for 12 to 24 hours. Arch Surg 141:504-506, 2006141:504-506, 2006

• Retrospective comparison in adults (Level 3 study) between operation < 12 hrs or > 12 hours after presentation

• 308 patients

• No differences in OR time, complications, % with advanced appendicitis, or length of stay

Operation At Presentation Versus The Following Day

Yardeni D, Hirschl RB, Drongowski RA, et al: Delayed versus immediate Yardeni D, Hirschl RB, Drongowski RA, et al: Delayed versus immediate surgery in acute appendicitis: Do we need to operate during the night? J surgery in acute appendicitis: Do we need to operate during the night? J Pediatr Surg 39:464–469, 2004.Pediatr Surg 39:464–469, 2004.

• Retrospective comparison in children (Level 3 study) between operation < 6 hrs after presentation or the following day

• 126 patients (38 early vs 88 late)

• No differences in operating time, perforation rate, or complications

The remaining four questions can be answered from studies

at Children’s Mercy

5 – Expert opinion, or applied principles from physiology, basic science, or other conditions

4 – Case series or poor quality case control and cohort studies

3 – Case control studies

2 – Review of case control or cohort studies with agreement or poor quality randomized trial

1 – Prospective, randomized controlled trials

Levels Of Evidence

2. Is There an Optimal Antibiotic Management for Perforated

Appendicitis?

• Prior to 2000, most pediatric centers in the U.S. were treating patients with intraabdominal infections with Ampicillin, Gentamicin and Clindamycin (Triple Antibiotic Therapy)

• Triple antibx provide good coverage; inexpensive

But• Gentamicin known to be toxic to hearing and

renal function

• Serum levels recommended for Gentamicin use

• Same broad spectrum coverage as triples

• The duo of Ceftriaxone and Metronidazole require no serum levels

• Ceftriaxone and Metronidazole has been shown to be safe and effective in once/day dosing

• Daily dosing allows easy transition to outpatient IV therapy, if needed

Why Not Use Ceftriaxone/Metronidazole?

Advantages

Retrospective ReviewRetrospective Review

• 250 patients w/perforated appendicitis - 1998 - 2004

• Those treated with Ceftriaxone/Metronidazole were compared to those treated with triple antibiotic coverage (Ampicillin, Gentamicin, Clindamycin)

• Retrospective Study (Level 3 study)

• Parameters included temperature curves for the first 5 post-operative days, abscess rate, length of hospitalization, length of intravenous antibiotic treatment and medication charges

CAPS, 2005CAPS, 2005J Pediatr Surg 41: 1020-1024, 2006J Pediatr Surg 41: 1020-1024, 2006

Retrospective ResultsRetrospective Results

Outcomes

WBC (x103) 9.8 +/- 0.5 11.6 +/- 0.4 0.10

LOS (Days) 6.8 +/- 0.4 7.9 +/- 0.2 0.03

IV Tx (Days) 7.2 +/- 0.5 8.6 +/- 0.4 0.05

Abscess (%) 8.8% 14.2% 0.37

C/MC/M A/G/CA/G/C P ValueP Value


ResultsResultsTemperature Curves

36.5

37

37.5

38

38.5

Admission 1 2 3 4 5

Post-Operative Days 1 - 5

Tm

ax (

Deg

rees

Cel

siu

s)

C/M

A/G/C*

**

**

* P < 0.001


ResultsResultsMedication Charges

Expense of dose ($ dose) = (drug price + dispensing charge )

Expense of course = ($ dose) x (# doses/day) x (days of treatment)



Ceftriaxone Dose Charge = ( Ceftriaxone Dose Charge = ( $19.48$19.48 + $28.13 ) + $28.13 )

Expense of Course = ($47.51) x (1 dose/day) x (7 days) = Expense of Course = ($47.51) x (1 dose/day) x (7 days) = $332$332

Ampicillin Dose Charge = ( Ampicillin Dose Charge = ( $0.38$0.38 + $28.13 ) + $28.13 )

Expense of Course = ($28.51) x (4 doses/day) x (7 days) = Expense of Course = ($28.51) x (4 doses/day) x (7 days) = $798$798

Impact Of Nursing ChargesImpact Of Nursing Charges


ResultsMedication Charges

$ of Course

C/M A/G/C

P Value < 0.0001

$546.01 +/- $29.34$546.01 +/- $29.34 $2494.06 +/- $78.44$2494.06 +/- $78.44

CAPS, 2005CAPS, 2005

J Pediatr Surg J Pediatr Surg 41:1020-1024, 2006. 41:1020-1024, 2006.

With this information, is there any reason

to perform a prospective randomized trial

comparing Ceftriaxone/Metronidazole to

Triple Antibiotic Therapy (Ampicillin,

Gentamicin, Clindamycin) for perforated

appendicitis?

Why A Prospective, Randomized Trial?Why A Prospective, Randomized Trial?

Weaknesses• Retrospective

• Uneven numbers between groups

• Postoperative care not standardized

• Recent experience vs historical experience creates bias

Far more laparoscopy in recent cohort (C/M)

(47% in C/M group vs 2% in A/G/C group)

Experience w/laparoscopy improved

Pressures to discharge sooner in recent cohort independent of medication regimen?

Prospective Randomized TrialProspective Randomized Trial• Ceftriaxone/Metronidazole or A/G/C

• Perforated appendicitis at the time of appendectomy Hole in the appendix Visible appendicolith in the abdomen

• Power 0.8; alpha 0.05; sample size 100

Exclusion Criteria• Known allergy to one of the medications

Standardized Management

• All patients receive 5 days IV antibiotics

• Diet begins after flatus

• WBC drawn on POD 5

• Nl WBC count and tolerating PO’s w/o fever meets discharge criteria

• If elevated, draw again on POD 7, then if elevated, draw on POD 10 and obtain CT

• No antibiotics on discharge

ResultsResultsOutcomes

WBC (x103) 9.4 +/- 3.9 9.9 +/- 4.4 0.56

LOS (Days) 6.27 +/- 2.5 6.20 +/- 3.2 0.850.85

IV Tx (Days) 6.0 +/- 1.5 6.2 +/- 1.1 0.480.48

Abscess (%) 20.4% 16.3% 0.79

C/MC/M A/G/C P ValueP Value

AAP, 2007AAP, 2007J Pediatr Surg 43:79-82, 2007J Pediatr Surg 43:79-82, 2007


Total Meds $3370 $3817 0.20

% of Med Charges 4.5% 6.1% <0.001

C/MC/M A/G/CA/G/C P ValueP Value

IV Abx $1412 $1940 <0.001


Triples

C/M

36.5

37

37.5

38

38.5

39

Admission 1 2 3 4 5

Post-Operative Day

Max

Tem

eper

atu

re (

Deg

rees

Cel

siu

s)

ResultsTemperature Curves


Conclusions

• There is no difference in infectious complications, recovery or defervescence after perforated appendicitis between Ceftriaxone/Metronidazole and Triples (A/G/C)

• Ceftriaxone/Metronidazole is more cost-effective than standard triple antibiotic therapy


• The literature is replete with retrospective studies regarding perforated appendicitis

• All of these studies fail to strictly define perforation

Dependent on surgeon’s definition

“Gangrenous”, “suppurative”, “perforated”

• Therefore, the conclusions from these retrospective reports must be approached cautiously

3. How Do We Define Perforated Appendicitis?

J Pediatr Surg 43:2242-2245, 2008J Pediatr Surg 43:2242-2245, 2008

Post-operative Antibiotic Regimen For Post-operative Antibiotic Regimen For Perforated Appendicitis In Children: A Perforated Appendicitis In Children: A

Prospective Randomized TrialProspective Randomized Trial

• April 2005 - November 2006

• 100 patients

• To ensure accurate data, the two groups had to be equal and a definition had to be created

Visible appendicolithHole in appendix

Definition of Perforation Used in Prospective Randomized Trial

HypothesisHypothesis• A correct definition of perforation (DOP) is important

because Provides us with the information to safely and efficiently treat

patients Allows us to better identify which patients are at risk for

developing postoperative complications

• If our definition of perforation was correct There should be no increase in abscess rate in the cohort of

patients treated as non-perforated appendicitis after the definition was used

• If our definition of perforation was incorrect There should be an increase in abscess rate in the cohort of

patients treated as non-perforated appendicitis after the definition was used (b/c of under-treatment)

ResultsResults OutcomesOutcomes

NON-Perforated

Prior DOP(n=292)

After DOP(n=388)

Abscess rate 1.7% 0.8%

LOS (days) 1.9 +/- 1.3 1.5 +/- 1.5

Perforated Prior DOP(n=131)

After DOP(n=161)

Abscess rate 14.0% 18%

LOS (days) 9.4 +/- 4.2 7.4 +/- 8.8

PAPS 2008PAPS 2008 J Pediatr Surg 43:2242-2245, 2008J Pediatr Surg 43:2242-2245, 2008

ConclusionsConclusions

• Our strict DOP (either a visible hole in the appendix or appendicolith in the abdomen) has been shown to be safe No increase in abscess rate for non-perforated patients No detectable risk of under treating patients defined as non-

perforated

• This DOP will improve overall care for children with appendicitis Eliminate unnecessary antibiotic treatment Improve cost management Simplify treatment protocols Improve the integrity of clinical data Allow for ongoing clinical research

PAPS 2008PAPS 2008J Pediatr Surg 43:2242-2245, 2008J Pediatr Surg 43:2242-2245, 2008

4. How do we manage the child presenting with an abscess due to

ruptured appendicitis?

Perforated AppendicitisPerforated AppendicitisPresenting With AbscessPresenting With Abscess

• Open operation for abscess is difficult

• Percutaneous drainage has been described and applied

• Laparoscopy is being used to treat perforated appendicitis and abscess

• Which is better?

HistoryHistory

Perforated Appendicitis with Abscess

1) 5 - 7 day history

2) Dehydrated – needs IVF

3) Percutaneous drainage (interventional radiology)

4) PICC line - antibiotics

5) Discharge day 3-5 if stable

6) Antibiotics con’t 10 - 14 days at home

7) Return 8-10 wk. for interval appendectomy (to prevent recurrent appendicitis) - overnight hospitalization

Retrospective Experience with Interval Appendectomy

• 52 patients – 2000-2006

• Total hospital days = 7.0 +/- 3.9

• Total healthcare visits = 7.6 +/- 2.8

• Total number of CT scans = 3.5 +/- 2.0

• Recurrent Abscess = 10 pts (19.2%)

AAP, 2007AAP, 2007JJ Pediatr Surg 43:981-985, 2008Pediatr Surg 43:981-985, 2008

Perforated Appendicitis with Perforated Appendicitis with Abscess Abscess

Prospective Trial• Drainable abscess

• OR for laparoscopic appendectomy vs percutaneous drainage as initial management

• Drain groups undergoes laparoscopic appendectomy at 10 weeks.

• Quality of life surveys at admission, at 2 weeks and at 12 weeks

• Pilot study – 40 patients

APSA 2009APSA 2009J Pediatr Surg 45:236-240, 2010J Pediatr Surg 45:236-240, 2010

Initial Non-Op Mgmt vs Lap Appendectomy in Children Presenting

with an Abscess


Patient Characteristics at the Time of Admission

Initial operation (n=20)

Initial nonoperative management (n=20)

P

Age (y) 10.1 ± 4.2 8.8 ± 4.2 .31

Weight (kg) 37.0 ± 16.2 37.1 ± 20.8 .98

Body mass index (kg/cm2) 18.0 ± 4.5 19.5 ± 5.5 .39

White blood cell count 17.4 ± 6.6 16.9 ± 6.8 .84

Maximum temperature 37.8 ± 1.0 37.7 ± 0.9 .95

Maximum axial area of abscess (cm2)

29.2 ± 29.7 26.2 ± 21.1 .75

Values are expressed as mean ± SD

Initial Non-Op Mgmt vs Lap Appendectomy in Children Presenting with

an Abscess


Outcomes Comparing Initial Operation and Initial Abscess Drainage Followed by Interval Appendectomy

Initial operation (n = 20)

Initial nonoperative management (n = 20)

P

Operation time (min) 62.1 ± 38.7 42.0 ± 45.5 .06

Total length of hospitalization (d) 6.5 ± 3.8 6.7 ± 6.6 .92

Recurrent abscess after initial treatment (%)

20% 25% 1.0

Doses of narcotics 9.7 ± 4.0 7.1 ± 15.8 .47

Total health care visits 2.8 ± 1.1 4.1 ± 1.0 <.001

No. of CT scans 1.5 ± 0.7 2.1 ± 1.1 .04

Total charges $44,195 ± $19,384 $41,687 ± $18,483 .68

Values are expressed as mean ± SD, unless otherwise indicated

Prospective Randomized Trial

• Conclusion – There is no difference b/w initial laparoscopic operation vs initial non-operative management followed by laparoscopic interval appendectomy

• Management can be determined by the surgeon’s preference and experience

APSA 2009J Pediatr Surg 45:236-240, 2010

5. Is there an advantage

performing the laparoscopic

appendectomy through a single

umbilical incision?

SSULS Appendectomy

SSULS Appendectomy

Please use this link if you experience problems viewing the video above.

http://youtu.be/syhyhGBv0-M

Postoperative Appearance

Prospective Randomized Trial

• 360 total patients

• Acute non-perforated appendicitis

• August 09 – November 10

• Primary outcome variable – postoperative wound infection

• Standardized pre and postoperative management

• Quality of life surveys at 6 weeks and 6 months

Single Umbilical Incision vs 3-PortLaparoscopic Appendectomy

Patient Characteristics at Operation

Single Incision (N=180)

3-Port (N=180)

P-value

Age (yrs) 11.05 ± 3.47 11.04 ± 3.41 0.98

Weight (kg) 42.7 ± 18.5 42.5 ± 17.4 0.90

Gender (% male) 54.4% 51.1% 0.53

Leukocyte count 14.7 ± 5.2 14.6 ± 5.4 0.89

American Surgical Assn – 2011American Surgical Assn – 2011Ann Surg 254:586-590, 2011Ann Surg 254:586-590, 2011

Outcome Data

Single Incision (N=180)

3-Port (N=180)

P-value

Wound Infection 3.3% 1.7% 0.50

Operative Time (mins) 35.2 ± 14.5 29.8 ± 11.6 <0.001

Postoperative Length of Stay (hours)

22.7 ± 6.2 22.2 ± 6.8 0.44

Hospital Charges ($) 17.6K ± 4.0K 16.5 ± 3.8K 0.005

American Surgical Assn – 2011American Surgical Assn – 2011Ann Surg 254:586-590, 2011Ann Surg 254:586-590, 2011

Summary

• There have been significant changes in the surgical management of appendicitis

• These changes have revolved around timing of surgery and the almost exclusive use of the laparoscopic approach

• Unclear if appendicitis will be a surgical disease in the future

QUESTIONS

www.cmhclinicaltrials.com

www.cmhmis.com

http://www.centerforprospectiveclinicaltrials.com/

http://www.cmhmis.com/

Documents

Current Management of Children with Appendicitis CIPESUR Meeting November 18, 2011