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Bowel Preparation in Elective Pediatric Colorectal Surgery

Not Applicable
Conditions
Hirschsprung Disease - Pull Through
Necrotizing Enterocolitis
Inflammatory Bowel Diseases
Bowel Obstruction
Elective Surgery
Colostomy
Meconium Ileus
Interventions
Registration Number
NCT03593252
Lead Sponsor
McMaster University
Brief Summary

Infections after elective intestinal surgery remain a significant burden for patients and for the health care system. The cost of treating a single surgical site infection is estimated at approximately $27,000. In adult patients, there is good evidence that the combination of oral antibiotics and mechanical bowel preparation is effective at reducing infections after intestinal surgery. In children, the body of evidence is much weaker. In this population, little evidence exists for oral antibiotics reducing infections and no data exists as to the effect of combining antibiotics with mechanical bowel preparation (such as polyethylene glycol (PEG)). The goal of the proposed study is to examine the effects of oral antibiotics with and without the combined use of mechanical bowel preparation on the rate of post-operative infectious complications in children aged 6 months to 18 years. This will be compared to the institution's current standard of care, which is to abstain from any type of mechanical bowel preparations or oral antibiotic administration before intestinal surgery.

Detailed Description

Background:

A Cochrane review of randomized controlled trials of MBP use in adults showed no difference in the rate of wound infection or anastomotic leak in colon or rectal procedures with MBP compared to no preparation (Guenaga, Matos, \& Wille-Jorgensen, 2011). Two recent systematic reviews and meta-analyses support those findings. Lok and colleagues (2018) identified two randomized controlled trials and four retrospective reviews for patient \<21 years, looking at preoperative MBP and its effect on the incidence postoperative complications, including anastomotic leak, wound infection, and intra-abdominal infection (Janssen Lok M 2018). Overall, MBP before colorectal surgery did not significantly decrease the incidence of post-operative outcomes. This was consistent with findings from a systematic review in mechanical bowel preparation in pediatric population. The review showed that the risk of developing a post-operative infection was 10.1% in patients who received MBP compared to 9.1% in patients who did not receive MBP, resulting in no statistically significant difference difference (risk difference of -0.03% (95% CI, -0.09% - 0.03%)) (Zwart 2018).

With regards to OA alone, the adult literature showed promising results in favour of the OA. In a Cochrane review on antimicrobial prophylaxis in colorectal surgery, the addition of OA to the intravenous antibiotics was found to reduce surgical wound infection (RR 0.56, 95% CI 0.43 to 0.74) (Nelson, Gladman, \& Barbateskovic, 2014).

There are fewer studies in the pediatric population on the subject, they contain fewer patients and are mainly retrospective in nature. In a multi-center retrospective study, Serrurier et al. (2012), reviewed outcomes in children who underwent colostomy closure, and found higher rates of wound infection (14% vs. 6%, p=0.04) and a longer hospital length of stay in children who received MBP. In a retrospective cohort study including 1581 pediatric patients from PHIS database, post-operative complications were found to be highest in the no preparation group compared to combination prep and OA alone (23.3%, 15.9%, and 14.2% respectively; p=0.002) (Ares 2018). One study compared MBP alone versus MBP with OA in children undergoing colostomy closure post anorectal malformation repair and found no difference in overall SSI rates (MBP+OA: 13% (7/53) versus MBP alone: 17% (7/12) p=0.64) (Breckler, Rescorla, \& Billmire, 2010). The authors found that the use of MBP alone was associated with a greater risk of wound infection (14% vs. 6%, p=0.04) and a longer hospital stay. Evidence to support the sole use of oral antibiotics versus in combination with MBP is lacking, particularly in the pediatric literature, with more studies being required to address this question.

One recent meta-analysis including adults assessed 8458 adult patients (38 clinical trials), comparing 4 groups of different bowel preparation: MBP with OA, OA only, MBP only, and no preparation. The primary outcome was the total rate of incisional and organ/space SSIs. Results showed that only MBP with OA versus MBP alone was associated with a statistically significant reduction in SSI rates. The use of OA without MBP was not associated with a statistically significant reduction in SSI rates when compared to any other group. The authors concluded that MBP with OA was associated with the lowest risk of SSI, followed by OA only (Toh et al., 2018).

It remains unclear whether the addition of MBP to OA in pediatric population affects the rate of post-operative infectious complications positively or negatively. The current study is therefore needed to build on the work conducted in the adult literature to determine best practices for the pediatric population.

Purpose:

This is a pilot study to check the feasibility of conducting a randomized controlled trial to assess the efficacy of oral nonabsorbable antibiotics, with or without mechanical bowel preparation, in reducing the rate of post-operative infectious complications occurring within 30 days post-operatively in children and adolescents (aged 6 months to 18 years) undergoing elective colon or rectal surgery.

Post-operative complications include: surgical site infections (incisional, organ-space, and anatomic leak), length of hospital stay, readmission, post-operative use of therapeutic antibiotics, re-operation, occurrence of electrolyte disturbances (in case MBP was used), and occurrence of C. difficile infection.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
81
Inclusion Criteria
  1. Pediatric patients aged three months to eighteen years being treated by the Pediatric General Surgery service at McMaster Children's Hospital.
  2. Undergoing elective colorectal surgery.
  3. Parents or legal guardian able to give free and informed consent.
Exclusion Criteria
  1. Non-elective surgery

  2. Procedures that would not require mechanical bowel preparation:

    1. Colorectal resection with an existing diverting small bowel ostomy.
    2. Completion proctectomy - Ileal Pouch Anal Anasotmosis (IPAA)
    3. Closure of small bowel ostomy (e.g. ileostomy)
  3. Mechanical bowel obstruction

  4. Known hypersensitivity to laxatives or oral antibiotics (neomycin and metronidazole)

  5. Contraindication to oral antibiotics

  6. Patients on long-term antibiotics for other reasons

  7. Congestive heart failure

  8. Renal insufficiency

  9. Other medical conditions precluding the use of either oral antibiotics or mechanical bowel preparation

  10. Co-enrolment in another intervention trial

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Oral antibioticsMetronidazole OralThe patients will receive prophylactic oral antibiotics (3 doses, 1 day before surgery)as well as standard care (NPO for anesthesia and intravenous antibiotics on induction).
Combination bowel prepClear fluids the day before surgeryPatients will received mechanical bowel preparation (age appropriate dose, starting 2 days before surgery) and prophylactic oral antibiotics (3 doses, 1 day before surgery). Clear fluids (or breast milk if applicable) will be given starting day before surgery. The standard care will also be delivered (NPO for anesthesia and intravenous antibiotics on induction) Patients/parents will be provided with stool diary to document the adequacy of preparation. This will include frequency and character of stool according to Bristol grade. The treating surgeon will rate the adequacy of the preparation intra-operatively.
No prepNil per osPatients will receive no pre-operative bowel prep. The will receive the standard care only.
Combination bowel prepMetronidazole OralPatients will received mechanical bowel preparation (age appropriate dose, starting 2 days before surgery) and prophylactic oral antibiotics (3 doses, 1 day before surgery). Clear fluids (or breast milk if applicable) will be given starting day before surgery. The standard care will also be delivered (NPO for anesthesia and intravenous antibiotics on induction) Patients/parents will be provided with stool diary to document the adequacy of preparation. This will include frequency and character of stool according to Bristol grade. The treating surgeon will rate the adequacy of the preparation intra-operatively.
Combination bowel prepNil per osPatients will received mechanical bowel preparation (age appropriate dose, starting 2 days before surgery) and prophylactic oral antibiotics (3 doses, 1 day before surgery). Clear fluids (or breast milk if applicable) will be given starting day before surgery. The standard care will also be delivered (NPO for anesthesia and intravenous antibiotics on induction) Patients/parents will be provided with stool diary to document the adequacy of preparation. This will include frequency and character of stool according to Bristol grade. The treating surgeon will rate the adequacy of the preparation intra-operatively.
Combination bowel prepSodium Picosulfate, Magnesium Oxide and Citric AcidPatients will received mechanical bowel preparation (age appropriate dose, starting 2 days before surgery) and prophylactic oral antibiotics (3 doses, 1 day before surgery). Clear fluids (or breast milk if applicable) will be given starting day before surgery. The standard care will also be delivered (NPO for anesthesia and intravenous antibiotics on induction) Patients/parents will be provided with stool diary to document the adequacy of preparation. This will include frequency and character of stool according to Bristol grade. The treating surgeon will rate the adequacy of the preparation intra-operatively.
Oral antibioticsNil per osThe patients will receive prophylactic oral antibiotics (3 doses, 1 day before surgery)as well as standard care (NPO for anesthesia and intravenous antibiotics on induction).
Combination bowel prepNeomycinPatients will received mechanical bowel preparation (age appropriate dose, starting 2 days before surgery) and prophylactic oral antibiotics (3 doses, 1 day before surgery). Clear fluids (or breast milk if applicable) will be given starting day before surgery. The standard care will also be delivered (NPO for anesthesia and intravenous antibiotics on induction) Patients/parents will be provided with stool diary to document the adequacy of preparation. This will include frequency and character of stool according to Bristol grade. The treating surgeon will rate the adequacy of the preparation intra-operatively.
Combination bowel prepCefazolinPatients will received mechanical bowel preparation (age appropriate dose, starting 2 days before surgery) and prophylactic oral antibiotics (3 doses, 1 day before surgery). Clear fluids (or breast milk if applicable) will be given starting day before surgery. The standard care will also be delivered (NPO for anesthesia and intravenous antibiotics on induction) Patients/parents will be provided with stool diary to document the adequacy of preparation. This will include frequency and character of stool according to Bristol grade. The treating surgeon will rate the adequacy of the preparation intra-operatively.
Combination bowel prepMetronidazolePatients will received mechanical bowel preparation (age appropriate dose, starting 2 days before surgery) and prophylactic oral antibiotics (3 doses, 1 day before surgery). Clear fluids (or breast milk if applicable) will be given starting day before surgery. The standard care will also be delivered (NPO for anesthesia and intravenous antibiotics on induction) Patients/parents will be provided with stool diary to document the adequacy of preparation. This will include frequency and character of stool according to Bristol grade. The treating surgeon will rate the adequacy of the preparation intra-operatively.
Oral antibioticsCefazolinThe patients will receive prophylactic oral antibiotics (3 doses, 1 day before surgery)as well as standard care (NPO for anesthesia and intravenous antibiotics on induction).
Oral antibioticsNeomycinThe patients will receive prophylactic oral antibiotics (3 doses, 1 day before surgery)as well as standard care (NPO for anesthesia and intravenous antibiotics on induction).
No prepMetronidazolePatients will receive no pre-operative bowel prep. The will receive the standard care only.
Oral antibioticsMetronidazoleThe patients will receive prophylactic oral antibiotics (3 doses, 1 day before surgery)as well as standard care (NPO for anesthesia and intravenous antibiotics on induction).
No prepCefazolinPatients will receive no pre-operative bowel prep. The will receive the standard care only.
Combination bowel prepSennaPatients will received mechanical bowel preparation (age appropriate dose, starting 2 days before surgery) and prophylactic oral antibiotics (3 doses, 1 day before surgery). Clear fluids (or breast milk if applicable) will be given starting day before surgery. The standard care will also be delivered (NPO for anesthesia and intravenous antibiotics on induction) Patients/parents will be provided with stool diary to document the adequacy of preparation. This will include frequency and character of stool according to Bristol grade. The treating surgeon will rate the adequacy of the preparation intra-operatively.
Primary Outcome Measures
NameTimeMethod
Adverse eventsFrom randomization to 30 days post-operatively

Any expected and unexpected adverse event, with grade of adverse event

Protocol deviationsFrom randomization to 30 days post-operatively

Number of protocol deviations

Feasibility (no. enrolled)From randomization to 30 days post-operatively

recruitment rate (percentage of eligible patients enrolled and retained to the end of study).

Incomplete follow-upFrom randomization to 30 days post-operatively

Number missing follow-up appointments at 2 week mark

rate of post-randomization exclusionsFrom randomization to 30 days post-operatively

Patients excluded after being randomized

Secondary Outcome Measures
NameTimeMethod
Time to full enteric feed.30 days post-operatively.

Post-operative return to full feed/diet in days

Anastomotic leak - Surgical site infection (SSI)30 days post-operatively.

Rate of anastomotic leak (verified by a contrast study or intra-operatively) (number of patients who developed OS-SSI per group/subgroup).

Re-operation30 days post-operatively.

Yes/No. Note:operation indication is directly related to the surgery

Electrolyte disturbanceOn day of surgery

If abnormal levels were detected, whether this was associate by clinical signs (Yes/No)

Superficial Incisional surgical site infection (SSI)30 days post-operatively.

Rate of SI-SSI (superficial or deep, number of patients who developed SSI per group/subgroup).

Length of hospital stay30 days post-operatively.

Post-operative hospitalization on primary admission in days

Re-admission30 days post-operatively.

admission in post-operative period for a reason related to the surgery (yes/No)

Deep incisional surgical site infection (SSI)30 days post-operatively.

Rate of DI-SSI (number of patients who developed SSI per group/subgroup).

Organ space - Surgical site infection (SSI)30 days post-operatively.

Rate of OS- SSI (number of patients who developed OS-SSI per group/subgroup).

Clostridium difficile infection30 days post-operatively.

Occurrence of C. difficile infection post-operatively (Yes/No)

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