Evidence Based Medicine and Level 1 Outcomes Research in Pediatric Surgery

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Evidence Based Medicine and Level 1 Outcomes
Research in Pediatric Surgery

• George W. Holcomb, III, M.D., MBA
• Childrens Mercy Hospital
• Kansas City, Missouri
• Center for Prospective Clinical Trials
• www.centerforprospectiveclinicaltrials.com

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The Right People
Good to Great
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Evidence Based Medicine

• Integration of best research evidence with
  clinical expertise and patient values
• Treating patients based on data, not feeling
  (gestalt), or ones own experience

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Levels of EvidenceQuestion

• A clinical surgeon publishes a retrospective
  review of 350 patients over 20 years undergoing
  an endorectal pull-through (Soave procedure) for
  Hirschsprungs Disease. This is felt to be a
  seminal paper on this disease in infants and
  children. What is the level of evidence for this
  paper?
• Level 1 (A)
• Level 2 (B)
• Level 3 (C)
• Level 4 (D)
• Level 5 (E)

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Levels Of Evidence
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
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Levels of Evidence

• Expert opinion, or applied principles from
  physiology, basic science, or other conditions
• Example
• Leave patient intubated and paralyzed for 3-5
  days following an esophageal resection to take
  tension off esophageal anastomosis
• No data no study to show intubated/paralyzed
  patient has less esophageal tension
• Transverse incision is used for abdominal
  exploration in baby b/c better exposure
• No data to support this practice

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Levels of Evidence

• Case series or poor quality case control and
  cohort studies
• Example
• Paper reviewing results from one approach to a
  disease
• Large retrospective review of Soave operation for
  Hirschsprungs Disease

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Levels of Evidence

• Case control studies
• Example
• Paper showing different management
  strategies/operative technique for one disease
  process
• Single center (or multicenter) retrospective
  review of Duhamel vs Soave operation for
  Hirschsprungs Disease

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Levels of Evidence

• Review of case control or cohort (followed
  long-term) studies with agreement or a poorly
  performed prospective randomized trial
• Example
• Review of two or three large series describing
  one management strategy (Soave procedure)
  compared to two or three large series describing
  another management strategy (Duhamel procedure)

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Levels of Evidence

• Prospective randomized trials

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Childrens Mercy Hospital

• Focus on common conditions which are
  controversial
• Pyloric stenosis
• Perforated appendicitis
• Pectus excavatum
• Fundoplication for reflux
• Empyema
• Non-palpable intra-abdominal testis

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Complicated cases (relatively rare) best suited
for multi-institutional trials

• Choledochal cyst
• Esophageal atresia
• Pulmonary lobectomy
• Pull-through for high imperforate anus

But, need good infrastructure at each institution
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Remember

• There is a lot more to an MIS operation than just
  technique
• Postoperative care is also important and open for
  study (antibiotics?, pain management?, etc.)

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Open vs Lap Pyloromyotomy

• Lap vs Open 2003 - controversial around the
  world and in our hospital
• Different feeding regimens used in our hospital
  (2 hours, 4 hours, 6 hours)
• Different postoperative pain management
  strategies utilized
• Differences between staff made it difficult for
  residents, NPs, floor nurses
• Benefits single protocol for feeding, pain
  management, discharge used in study still used
  currently (6 years later)
• No level 1 data

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ResultsOutcomes
OPEN (n 100)
LAP (n 100)
P value
(Mean /- S.E.)
(Mean /- S.E.)
0.93 0.05 0.43 0.12 0.01
Ann Surg 244363-370, 2006
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ResultsCosmetic Outcome
Open
Lap
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2. Thoracoscopy vs Fibrinolysis for Empyema
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Treatment Of Empyema

• Fibrinolysis had been shown to be better than
  chest tube drainage alone in several
  retrospective studies
• Primary thoracoscopic debridement had been shown
  to better that tube drainage alone in several
  retrospective studies
• At the initiation of this study, there were no
  comparative data between primary thoracoscopic
  debridement and fibrinolysis as initial treatment
  for empyema in children

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Study Population Inclusion Criteria

• Under 18 years of age
• Septation or loculation seen on ultrasound or
  computed tomography
• Greater than 10,000 white blood cells identified
  on pleural tap

Exclusion Criteria

• Immunodeficiency process
• Secondary condition that would limit discharge

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Sample Size

• Using our own institutions retrospective data on
  length of hospitalization after intervention
  between thoracoscopic debridement and
  fibrinolysis with an alpha 0.05 and power of 0.8
• Sample size of 36 with 18 in each arm

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Empyema Study ProtocolFibrinolysis

• 12 Fr tube placed by IR or surgery in procedure
  room
• 4mg tPA in 40ml NS given into tube on insertion
  and each day for 3 doses

Thoracoscopy

• Thoracoscopic debridement with chest tube left
  behind on 20 cm H20 suction

APSA, 2008 J Pediatr Surg 44106-111, 2008
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Empyema Study Protocol Primary Outcome Measure

• Length of hospitalization after intervention (tPA
  or thoracoscopic debridement) until discharge
  criteria met (chest tube removed, afebrile oral
  analgesics)

APSA, 2008 J Pediatr Surg 44106-111, 2008
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Empyema Study ProtocolSecondary Outcome Measure

• Days of Tmax gt 38?CDays of tube drainage
• Doses of analgesia
• Days of oxygen requirement
• Hospital charges after intervention
• Procedure charges

APSA, 2008 J Pediatr Surg 44106-111, 2008
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Study Results
Patient Variables at Consultation
VATS
tPA
P value
Age (Years) 4.8 5.2 0.77
Weight (kg) 24.6 20.7 0.52
WBC 20.8 19.7 0.71
O2 support (L/min) 0.81 0.79 0.96
Days of Symptoms 9.0 10.6 0.32
ER/PCP visits 2.9 2.7 0.69
J Pediatr Surg 44106-111, 2008
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Study Results
Outcomes
VATS
tPA
P value
16.6 failure rate for fibrinolysis
J Pediatr Surg 44106-111, 2008
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London Prospective Trial
VATS v Fibrinolysis w/Urokinase

• No difference in LOS (6 v 6 days)
• No difference in 6 month CXR
• VATS more expensive (11.3K v 9.1K)
• 16 failure rate for fibrinolysis

Am J Respir Crit Care Med 174221-227, 2006
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CONCLUSIONS

• There appears to be no therapeutic or recovery
  advantages to thoracoscopic debridement compared
  to fibrinolysis as the primary treatment for
  empyema
• Thoracoscopy results in significantly higher
  patient charges

J Pediatr Surg 44106-111, 2008
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3. Complete esophageal mobilization vs minimal
mobilization during laparoscopic fundoplication
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Prospective Randomized TrialPrimary Outcome
Measure

• Transmigration of fundoplication wrap
• 2 centers participating
• Powered at 360 patients (12vs 5)
• All patients get upper GI study at 1 yr
• Study closed at interim analysis (177 pts)
• Presentation at APSA, 2010

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PRCTs Now Enrolling

• Epidural vs PCA for pain control after MIS pectus
  repair (Nuss procedure)
• Sample size of 110 Patients (now at 109)
• APSA, 2011

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PRCTs Now Enrolling

• Burn study SSD vs collagenase
• One stage vs 2 stage laparoscopic orchiopexy for
  intra-abdominal testis
• Standardized feeding protocol vs ad lib feedings
  following laparoscopic pyloromyotomy
• Esophago-crural sutures vs no sutures at
  laparoscopic fundoplication (both groups receive
  minimal esophageal dissection)
• SSULS appendectomy vs 3 port lap appendectomy
• SSULS cholecystectomy vs 4 port lap
  cholecystectomy
• Irrigation/suction vs suction alone in patients
  with perforated appendicitis

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Why Do This?

• Manage patient according to evidence
• Evidence based medicine allows us to treat
  patients on objective data rather than our own
  opinions which are fraught with anecdotal
  experience and may not represent the best care
  for the patient

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QUESTIONS
www.centerforprospectiveclinicaltrials.com