BMJ Open is committed to open peer review. As part of this … · Cumming School of Medicine, University of Calgary Alberta Children’s Hospital, 2888 Shaganappi Trail NW T3B6A8

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For peer review onlyProtocol for Creation of An Enhanced Recovery After

Surgery (ERAS®) Guideline for Neonatal Abdominal Surgery Patients: A Knowledge Synthesis and Consensus Generation

Approach

Journal: BMJ Open

Manuscript ID bmjopen-2018-023651

Article Type: Protocol

Date Submitted by the Author: 20-Apr-2018

Complete List of Authors: Gibb, Ashleigh; University of Calgary Cumming School of MedicineCrosby, Megan; University of Alberta, MedicineMcDiarmid, Caraline; University of Calgary Cumming School of MedicineUrban, Denisa; University of Calgary, SurgeryLam, Jennifer; University of Calgary Cumming School of Medicine, SurgeryWales, Paul W.; Hosp Sick ChildrenBrockel, Megan ; University of Colorado Hospital, AnesthesiaRaval, Mehul; Northwestern University - Chicago, SurgeryOffringa, Martin; The Hospital for Sick Children, Child Health Evaluation SciencesSkarsgard, Erik; University of British Columbia Faculty of Medicine, Pediatric SurgeryWester, Tomas; Karolinska Universitetssjukhuset, SurgeryWong, Kenneth; University of Hong Kong Li Ka Shing Faculty of Medicine, Pediatric Surgeryde Beer, David; Great Ormond Street Hospital For Children NHS Foundation Trust, AnaesthesiaNelson, Gregg; University of Calgary Cumming School of Medicine, Obstetrics and GynecologyBrindle, Mary E; University of Calgary, Surgery

Keywords:Protocols & guidelines < HEALTH SERVICES ADMINISTRATION & MANAGEMENT, Paediatric surgery < SURGERY, Neonatal intensive & critical care < INTENSIVE & CRITICAL CARE

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

BMJ Open on January 7, 2021 by guest. P

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For peer review only

Protocol for Creation of An Enhanced Recovery After Surgery (ERAS®) Guideline for

Neonatal Abdominal Surgery Patients: A Knowledge Synthesis and Consensus Generation

Approach

Ashleigh CN Gibb1, Megan A Crosby

2, Caraline McDiarmid

1, Denisa Urban

1, Jennifer YK

Lam1, Paul W Wales

3, Megan Brockel

4, Mehul Raval

5, Martin Offringa

6, Erik Skarsgard

7,

Tomas Wester8, Kenneth Wong

9, David de Beer

10, Gregg Nelson

11, Mary E Brindle

1

Corresponding Author:

Mary Brindle MD MPH

Associate Professor of Surgery

Cumming School of Medicine, University of Calgary

Alberta Children’s Hospital, 2888 Shaganappi Trail NW

T3B6A8 403-955-2848

Email [email protected]

1. Department of Surgery, Alberta Children’s Hospital, Cumming School of Medicine, University of

Calgary, AB, Canada

2. Department of Medicine, University of Alberta, Edmonton, AB, Canada

3. Department of Pediatric Surgery, Hospital for Sick Children, University of Toronto, Toronto, ON,

Canada

4. Department of Pediatric Anesthesia, University of Colorado, Denver, CO, United States of America

5. Department of Pediatric Surgery, Northwestern University, Chicago, IL, United States of America

6. Department of Neonatology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

7. Department of Pediatric Surgery, British Columbia Children’s Hospital, Vancouver, BC, Canada

8. Department of Pediatric Surgery, Karolinska University, Stockholm, Sweden

9. Department of Pediatric Surgery, Li Ka Shing, University of Hong Kong, Hong Kong, China

10. Department of Pediatric Anesthesia, Great Ormond Street, London, United Kingdom

11. Department of Obstetrics and Gynecology, Cumming School of Medicine, University of Calgary, AB,

Canada

Word Count: 3056

Key Words: guideline development, health systems research, pediatric surgery, neonatology, Enhanced Recovery

After Surgery (ERAS)

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Approach

Authors: Ashleigh CN Gibb, Megan A Crosby, Caraline McDiarmid, Denisa Urban, Jennifer YK

Lam, Paul W Wales, Megan Brockel, Mehul Raval, Martin Offringa, Erik Skarsgard, Tomas

Wester, Kenneth Wong, David de Beer, Gregg Nelson, Mary E Brindle

ABSTRACT

Introduction: Enhanced Recovery After Surgery (ERAS®) guidelines integrate evidence-based

practices into multimodal care pathways designed to optimize patient recovery following surgery. The

objective of this project is to create an ERAS® protocol for neonatal abdominal surgery. The protocol

will identify and attempt to bridge the gaps between current practices and best evidence. Our study is

the first pediatric ERAS® protocol endorsed by the International ERAS® Society. Methods: A

research team consisting of international clinical and family stakeholders as well as methodologic

experts have iteratively defined the scope of the protocol in addition to individual topic areas. A

modified Delphi method was used to reach consensus. The second phase will include a series of

knowledge syntheses involving a rapid review coupled with expert opinion. Potential protocol

elements supported by synthesized evidence will be identified. The GRADE system will be used to

determine strength of recommendations and the quality of evidence. The third phase will involve

creation of the protocol using a modified RAND/UCLA Appropriateness Method. Group consensus

will be used to rate each element in relation to the quality of evidence supporting the recommendation

and the appropriateness for guideline inclusion. This protocol will form the basis of a future

implementation study. Ethics and dissemination: This study has been registered with the ERAS®

Society. Human ethics approval has also been sought in order to engage patient families within

protocol development. This research is to be published in peer-reviewed journals and will form the

care standard for neonatal abdominal surgery.

ARTICLE SUMMARY

Strengths and limitations of this study

• The great variability in neonatal surgical care practices provides an opportunity for practice

improvement; however, recommendations must be informed by valid empirical studies

• This protocol outlines the development of the first pediatric ERAS® with unique areas of

topic development, e.g., parental involvement

• This research is developed by an international panel of experts and stakeholders including

parents. The methods used are an expansion of those applied in the development of

previous ERAS® protocols and are informed by robust methodology

• Several care-pathway elements will have little evidence or evidence of low quality

• This study is endorsed by the International ERAS® Society which provides excellent

opportunity for knowledge translation.

INTRODUCTION

Background

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The care of children undergoing surgery presents physiologic and sociologic challenges that are

different from those encountered in the care of adults. Neonates constitute a particularly complex

patient population due to small blood volume, temperature instability, immature immune

systems, nutritional needs for growth and healing and the inability to verbally communicate

among others.1 Furthermore, there is considerable variability in perioperative care in neonatal

surgery, which is believed to contribute to adverse outcomes.2,3

ERAS® guidelines are innovative tools differing from other evidence-based guidelines as they

encompass multiple aspects of patient care in the preoperative, intraoperative and postoperative

periods, are used by a multidisciplinary care team, and have strong implementation frameworks.

The holistic approach of ERAS® protocols in multiple subspecialties such as colorectal and

other intra-abdominal surgical specialties have been shown to improve health outcomes by

decreasing complications and length of stay (LOS), translating to a reduction in health care

costs.1,4-8

There have been few attempts to introduce ERAS® into the pediatric surgical setting, none of

which have been designed for the neonatal population.9,10

Audit is an important component of any ERAS® program. Using a tailored database (eg

RedCap) or the ERAS® Interactive Audit System (EIAS), teams review their compliance to the

ERAS® guideline recommendations during the pre-implementation phase and then iterate

towards improved compliance. This iterative cycle translates to improved clinical outcomes.11

The ERAS® Society adopts evidence based practices by integrating perioperative interventions

for optimal patient recovery following a surgical procedure. We have developed our approach in

partnership with the ERAS® Society as well as family and clinician stakeholders.

Objectives This project aims to create an ERAS® guideline to reduce adverse events, enhance quality of

care, increase parent satisfaction and reduce health-related expenses.

Relevance

Intestinal obstruction in a newborn is a frequent indication for surgical intervention with an

estimated incidence of neonatal intestinal obstruction of 1:1500 live births. Neonatal patients

undergoing surgery are at high risk of surgical site infections (SSIs), with an observed SSI

incidence rate of 4% in clean surgeries, and a rate as high as 19% in dirty surgeries.12

Complications such as SSIs lead to increased length of stay and impairment of growth and

development.13

In addition, two thirds of neonatal patients undergoing intestinal resection are

likely to require unanticipated reoperation within a year of their initial surgery.14

Our team has

recognized that these adverse outcomes likely represent a knowledge-to-action gap in the

surgical care of these newborns. This study aims to address the gap by synthesizing the current

evidence on best practices surrounding neonatal abdominal surgery, and devising a

comprehensive ERAS® guideline aimed at reducing the need for reoperation, and enhancing the

overall quality, efficiency, and safety of care for this fragile patient population.

Anticipated Impact

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The evidence-based framework resulting from this research will be implemented in a pilot study

in the care of neonatal patients undergoing abdominal surgery at the Alberta Children’s Hospital

(ACH) in Calgary, Alberta, Canada. With more than 57,000 live births a year in Alberta, an

estimated 38 neonates experience intestinal obstruction requiring surgery in the province every

year.15,16

Roughly 10% of neonatal surgical patients suffer at least one postoperative adverse

event in Canada.17

Compliance with ERAS® guideline elements will be measured prospectively

and attitudes and acceptability of the guideline will be measured through clinician and parent

surveys and interviews. Secondary measures will include clinical outcomes, such as nutritional

outcomes, complication rates and length of stay, that will be compared within a time series

analysis during ERAS® guideline implementation. Data derived from the pilot study will be

used to refine the neonatal ERAS® guideline and develop an international trial to evaluate the

impact of this guideline on clinical outcomes and measures of resource utilization.

The following outcomes will be targeted by the ERAS® guideline and anticipated to be

improved: length of stay, weight gain (neonatal z-scores), blood glucose levels/insulin resistance,

complication rates and adverse outcomes (surgical site infection, postoperative ileus, mortality,

sepsis, postoperative vomiting, intraventricular hemorrhage), perceived care quality, and parent

and staff satisfaction.

METHODS AND ANALYSIS

Establishment of a Multidisciplinary Team

This research represents a collaborative effort between a core research team, an international

guideline committee, and a group of subject matter experts. Dr. Mary Brindle, director of the

Efficiency, Quality, Innovation and Safety (EQuIS) research platform, supports this project in

partnership with Dr. Gregg Nelson, Secretary of the International ERAS® society. The EQuIS

research group is dedicated to improving the quality of care delivered to pediatric surgical

patients in Calgary, in Canada, and internationally.

The international guideline committee consists of a multidisciplinary international panel of

individuals involved in the surgical care of neonates, with representation from Canada, United

States, Sweden, United Kingdom, and China. Panel selections were based on clinical expertise,

expertise in knowledge synthesis and expertise in ERAS® methods. The international guideline

committee is comprised of the following: Megan A. Brockel, MD, Pediatric Anesthesiologist, USA;

David DeBeer, Consultant Pediatric Anaesthetist, UK; Martin Offringa, MD, PhD, Neonatologist,

Canada; Mehul V. Raval, MD, MS, Pediatric Surgeon, USA; Erik Skarsgard, MD, MSc, Pediatric

Surgeon, Canada; Paul Wales, MD, MSc, Pediatric Surgeon, Canada; Tomas Wester, MD, PhD,

Pediatric Surgeon, Sweden; Kenneth Wong, MD, PhD, Pediatric Surgeon, China. Subject matter

experts represent the areas of nutritional care, physiotherapy/occupational therapy, and nursing.

Parent representatives will be involved in the framing of recommendations, and the design of

implementation strategies post tool development.

Study Design

This study involves knowledge synthesis, quality assessment and expert consensus to generate an

international ERAS® guideline. Knowledge synthesis will be performed using rapid literature

review and snowballing to synthesize the current evidence base supporting various elements of

neonatal perioperative care. The most relevant research evidence will be summarized and the

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quality of the evidence will be evaluated. The resulting synthesis will be used to generate

evidence-supported recommendations. These recommendations will be assessed for ERAS®

guideline inclusion through group consensus including broad stakeholder involvement and

following clearly-established principles. These final recommendations will take the form of an

ERAS® guideline. This ERAS® guideline and its implementation strategy will be assessed for

clinical effectiveness within a future pilot trial at ACH. The results from this trial will be used to

further adapt the care pathway and implementation strategy for an ERAS® Society supported

international trial.

Scope Determination

The international panel was invited to attend as many as three International ERAS® Neonatal

Teleconferences to define the scope and topics for the guideline. All members attended at least

one teleconference. Two of these teleconferences occurred in June of 2017 and one in July of

2017. Teleconferences were moderated by the senior leader (MEB). The opinion of all

participants was obtained. The three areas for discussion included the scope of the target

population, the scope of the conditions for inclusion and the general list of topics for

consideration as ERAS® elements. Final decisions on scope and topics were made in an iterative

fashion based on majority consensus and total group agreement. Detailed field notes were

compiled for each session.

A modified Delphi method was used to reach consensus for topic inclusion within each area of

inquiry. Each panelist was sent an email survey regarding target population, conditions and

topics, and was asked to rate the “Agreement of Inclusion into Guideline” based on a 9-point

scale where 9 was completely agree and 1 was completely disagree. ERAS® topics that had an

overall panel score of greater or equal to 7 were included. Topics with a score of 1 to 3 were

excluded. Topics with a score between 4 and 6 were discussed within the group and decision for

inclusion was based on group consensus.

The final target population determined was the term neonate defined as an infant born at or after

37 weeks without major comorbidity undergoing intestinal surgery within the first four weeks of

life. All ten panelists agreed upon this definition (eight rating 9/9, one rating 8/9 and one rating

7/9). Residual areas for further consideration included the definition of major comorbidity. The

final decision of the group was that intestinal resections including stomas in term neonates would

be considered for inclusion. All ten panelists agreed upon this (seven rating 9/9, two rating 8/9

and one rating 7/9).

Based on previous ERAS® literature supplemented with expert opinion, a working list of

perioperative elements was generated for consideration of inclusion within the guidelines. Topics

were emailed to the international panel who were asked to mark each topic as either “include”,

“exclude”, or “for discussion”. Panel members were also invited to provide other topics that

could be included. Additional topics for discussion that were added included antenatal

management, postoperative infections, postoperative skin care, postoperative stoma care, use of

transfusions, postoperative assessment, surgical techniques and ethics. An environmental scan of

the evidence surrounding each topic was provided to all participants to supplement discussion

about the necessity of each topic. Areas of agreement for inclusion and exclusion were identified.

Group discussion occurred around each area that did not have agreement. Each panelist

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discussed their perspective on the relevance of the topic for inclusion and the list of topics were

once again sent to panelists for review to achieve consensus.

The final topics identified for inclusion were: parental involvement (especially discharge planning),

antimicrobial prophylaxis and skin preparation, perioperative communication and team structure,

standard anesthetic protocol and perioperative fluid management, postoperative vomiting/nasogastric

intubation, preventing intraoperative hypothermia/temperature control, urinary drainage,

postoperative nutritional care, the role of physiotherapy/occupational therapy, surgical practices,

optimal hemoglobin levels, postoperative analgesia, management of transitional circulation, and

postoperative skin care/stoma care.

Literature Search

Depending on expertise and preference, each topic was assigned to one or two members to

perform a literature search. Within each topic, potential ERAS® elements or target questions

were selected following a predetermined (deductive) consensus, as well as a literature screen

(inductive) to identify unanticipated areas of inquiry. A targeted search strategy for each topic

was developed in collaboration with a research librarian. Target databases included MEDLINE,

and CINAHL for select topics. The structured search will be supplemented by a review of

personal archives and citations, as well as contacting experts to obtain important published and

unpublished information. We project that each topic will require screening of approximately 50-

200 abstracts. Titles will be catalogued using EndNote software. Planned limits have not been

defined, in order to capture all relevant data. The search strategies aim to obtain the most

relevant and important studies but not necessarily generate a completely comprehensive review

of the literature. Table 1 provides a sample of the root terms and topics used to create a specific

search for nutritional care.

Table 1: Planned search strategy for post-operative nutritional care topic of inquiry

Population Procedure Topic Neonatal Neonate Neonates Neonatology/ Infant/ Infants Newborn/ Newborns Infant, Newborn/ 37 weeks Term Birth/ Gestational Age/

Intestinal resection surgery Intestinal resections Colon resection Bowel resection Laparoscopic resection Small bowel resection Colectomy/ Partial colectomy Anastomoses, Surgical/ Intestinal repair Digestive System Surgical Procedures/ Ileostomy/ Bowel Surgery Surgical Stoma/ Stoma Ostomy/

Reinitiating Feeds Introduction of Feeds Advancing Feeds Feed progression Feeding Methods/ Enteral Nutrition/ Enteral feeding Oral feeding vs. tube feeding Elemental formula vs. Semi-elemental Continuous feeds Bolus feeds Nutrition Assessment/ Optimal growth Optimal nutrition Adequate nutrition Nutritional intake

Study selection

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Titles and abstracts will be screened using Rayyan QCRI, a web-based systematic review

application,18

for each topic by international guideline committee members and their respective

teams to identify potentially relevant articles. Discrepancies in judgement will be resolved by a

third reviewer. Meta-analyses, systematic reviews, randomized controlled studies, non-

randomized controlled studies, reviews, and case series are considered for each individual topic

(Eligibility criteria outlined in Table 2). Studies will be primarily restricted to those in the

English language, however, important papers written in a language understood by other members

of the team will also be considered.

Elements will be identified deductively and inductively within each topic by each team and will

be catalogued along with a summary of the evidence supporting the ERAS® recommendation.

For the topic area of prevention of intraoperative hypothermia, pre-determined areas for inquiry

included: Target temperature range for neonates undergoing surgery, recommended

environmental interventions to reduce hypothermia, and recommended direct and indirect

therapies to maintain normothermia.

Table 2: Eligibility Criteria

Inclusion Criteria

Study

Design

Meta-analyses, OR systematic reviews, OR published guidelines or

protocols, OR Randomized control studies, OR non-randomized control

studies OR reviews, OR case series.

Population Neonate patients ≥ 37 weeks; Term neonates OR gestational age;

Population without any major multi-comorbidities.

Excluded are: Population with abdominal wall defects (gastroschisis,

omphalocele); Population with necrotizing enterocolitis.

Type of

Surgery

Surgery performed in the first four weeks of life. For appropriate subtopics

(e.g., nutrition) studies will be restricted to intestinal resection procedures

(intestinal repair, colon resection, bowel resection, laparoscopic resection,

small bowel resection, colectomy, partial colectomy), OR stoma/ostomy,

OR anastomoses.

Intervention Satisfies the following ERAS® elements

• An action/intervention that can be performed in the preoperative,

intraoperative or post-operative period prior to discharge from hospital.

• An action/intervention that has an evidence-supported link to a

measurable improvement in clinical outcome or system efficiency.

• An action/intervention that, despite good evidence of benefit, is

inconsistently performed

• An action/intervention that is simply defined and applied.

• An action/intervention that is easily measured as having been

completed.

Quality assessment and data analyses

Responsibility for grading of evidence for each topic will rest with the respective guideline

committee member and their team. Quality of data will be assessed to determine the strength of

the recommendations. The GRADE system will be used, and evidence rated as either “high”,

“moderate”, “low”, or “very low” (Table 3a) 16

. The ERAS® team will decide upon the strength

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of the recommendations. Any accompanying recommendations will be given a value of “strong”

or “weak” based on the interpretation of results and consensus of the ERAS® team (Table 3b).

Table 3a: GRADE system for rating quality of evidence

Quality Definition

High Further research unlikely to change confidence in estimate of effect

Moderate Further research likely to have important impact on confidence in

estimate of effect and may change the estimate

Low Further research very likely to have important impact on confidence in

estimate of effect and likely to change the estimate

Very low Any estimate of effect is very uncertain

Table 3b: GRADE system for rating strength of recommendations

Strength Definition

Strong When desirable effects of intervention clearly outweigh the undesirable

effects, or clearly do not

Weak When the trade-offs are less certain – either because of low quality

evidence or because evidence suggests desirable and undesirable effects are

closely balanced

Consensus of evidence

The study will be performed according to the RAND/UCLA Appropriateness Method by

conducting a two-round consensus process.19

In round one, panel members will be asked to

consider each statement on its own merits using the corresponding summarized evidence as well

as their own experience and knowledge. We will ask panelists to rate the clarity or lack of

ambiguity of each statement, as well as the necessity of including it in the ERAS® guideline.

Round two will consist of a full-day workshop in August 2018, moderated by the senior

investigator as well as a representative from the ERAS® Society leadership. Panelists will first

discuss each statement as a group, followed by a re-evaluation of items on individual rating

sheets. The latter will include anonymized ratings from the first consensus round, the ratings

distribution, as well as their median. The creation of the finalized guideline will occur in

September 2018, with publication sought.

Patient and Public Involvement

Parents’ expectation of engagement in pediatric surgical and neonatal care pathways is

demonstrated in systematic reviews of the literature and qualitative studies of parents’ attitudes

in the neonatal intensive care unit20-23

. Our approach has been informed by this published data.

We engaged parent stakeholders in identifying neonatal surgical care as a key priority for an

ERAS® guideline. Once topics were selected for development by our ERAS® guideline

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committee, we formally reviewed each of these topics with our ERAS® parent advisor to

identify subtopics for exploration and key areas that required parental involvement. Discharge

planning was identified as a major theme to address within many key ERAS® topics. In

addition, parental psychological support was identified as a priority within the topic of parental

involvement.

Two parent focus groups will be engaged in this project. The first focus group will meet before

final refinement of the ERAS® tool and will discuss proposed ERAS® recommendations,

highlighting areas where parental needs have not been adequately met. The second group will

engage with the ERAS® committee to aid in the development of feasible and acceptable

implementation strategies for the completed guideline.

Guideline Implementation

Guidelines are to be implemented in a multistep process. Initially, the guidelines will be piloted

in a large tertiary pediatric center in Canada for three months. A focused assessment of

acceptability and compliance will be performed through audits as well as surveys and targeted

interviews. Further revisions of the guideline will be performed.

The results of the implementation pilot will be reviewed by the international panel as well as the

ERAS® Society and an international implementation study will be designed. Both clinical and

process measure outcomes will be measured before and during implementation. Outcomes of

interest that have potential to be improved by the ERAS® guideline are: length of stay, surgical

site infection incidence, mortality, sepsis, postoperative vomiting, weight gain, and parent and

staff satisfaction. As per ERAS® Society regulations, the guideline is to be considered for

revision by the Scientific and Executive ERAS® committee every three years, or earlier if

deemed appropriate.

Ethics and dissemination: This study has been registered with the ERAS® Society. Human

ethics approval has also been sought in order to engage patient families within guideline

development. This research will contribute to a consistent standard of care for neonatal

abdominal surgery. This ERAS® guideline development represents the first phase of a larger

quality improvement project aimed at improving neonatal abdominal surgery.

Author Contributions: The Senior author, Dr. Brindle, is a pediatric surgeon and health systems

researcher with experience in leading international collaborative work in pediatric surgical safety

and expertise in systematic reviews. Dr. Nelson is an international leader in ERAS® with

expertise in ERAS® guideline development and study. Dr. Brockel is an anesthesiologist with

considerable practical experience in adapting adult ERAS® guidelines to the care of pediatric

patients. Dr. de Beer is an anesthesiologist with special expertise in human factors and anesthetic

emergencies. Dr. Offringa brings national leadership in neonatal surgical collaboration and

guideline development. Dr. Raval has considerable expertise in the application of ERAS®

guidelines in children. Dr. Skarsgard is the president of the Canadian Association of Pediatric

Surgery and an international leader in pediatric surgery quality and safety. Dr. Wales is a

pediatric surgeon and internationally-recognized researcher in neonatal nutrition. Dr. Wester has

considerable experience in neonatal surgery and epidemiology. Dr. Wong is a leader in Pediatric

surgery in Hong Kong with a strong history of international surgical leadership.

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Authors are involved to ensure search strategies are relevant to each topic area, responsible for

screening abstracts and full text articles in adherence with the project timeline, and the creation

of catalogue of areas of importance. In addition, collaborators will be involved in the full text

extraction and quality assessment processes.

Funding Statement: The work in this study is supported by the Brian and Brenda MacNeill

Chair in Pediatric Surgery. This research received no specific grant from any funding agency in

the public, commercial or not-for-profit sectors.

Competing Interest Statement: No authors have competing interests.

Acknowledgements: The authors would like to thank the members of the EQuIS Research

Platform especially Ali MacRobie for assistance in data collection. In addition, the authors

would like to thank Beth Haliburton who provided input on topics for development in neonatal

nutrition and Ashley Jones, our parent advisor, who has provided input on implementation,

usability and priorities from a parent’s perspective. We would also like to thank Diane

Lorenzetti, research librarian, who provided input on search strategy development. Lastly, we

thank the ERAS® Society for their advice and endorsement.

Data Statement: The search strategies, screening results and extracted information will be

available in the Dryad repository and/or within supplementary materials published alongside the

final guideline.

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2. Le Compte AJ, Chase JG, Lynn A, Hann CE, Shaw GM, Lin J. Development of blood glucose control

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3. Varadhan KK, Neal KR, Dejong CH, Fearon KC, Ljungqvist O, Lobo DN. The enhanced recovery

after surgery (ERAS) pathway for patients undergoing major elective open colorectal surgery: a meta-

analysis of randomized controlled trials. Clinical nutrition 2010; 29(4): 434-40.

4. Cerantola Y, Valerio M, Persson B, et al. Guidelines for perioperative care after radical

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Clinical nutrition 2013; 32(6): 879-87.

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Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery 2016; 41(2): 118-26.

6. Tracy ET, Mears SE, Smith PB, et al. Protocolized approach to the management of congenital

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1343-8.

7. Ljungqvist O, Scott M, Fearon KC. Enhanced Recovery After Surgery: A Review. JAMA Surg 2017;

152(3): 292-8.

8. Ljungqvist O, Thanh NX, Nelson G. ERAS-Value based surgery. J Surg Oncol 2017; 116(5): 608-12.

9. Leeds IL, Boss EF, George JA, Strockbine V, Wick EC, Jelin EB. Preparing enhanced recovery after

surgery for implementation in pediatric populations. Journal of pediatric surgery 2016; 51(12): 2126-9.

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10. Short HL, Heiss KF, Burch K, et al. Implementation of an enhanced recovery protocol in pediatric

colorectal surgery. Journal of pediatric surgery 2017.

11. Group EC. The Impact of Enhanced Recovery Protocol Compliance on Elective Colorectal Cancer

Resection: Results From an International Registry. Ann Surg 2015; 261(6): 1153-9.

12. Segal I, Kang C, Albersheim SG, Skarsgard ED, Lavoie PM. Surgical site infections in infants

admitted to the neonatal intensive care unit. Journal of pediatric surgery 2014; 49(3): 381-4.

13. Stoll BJ, Hansen NI, Adams-Chapman I, et al. Neurodevelopmental and growth impairment

among extremely low-birth-weight infants with neonatal infection. Jama 2004; 292(19): 2357-65.

14. Young JY, Kim DS, Muratore CS, Kurkchubasche AG, Tracy TF, Jr., Luks FI. High incidence of

postoperative bowel obstruction in newborns and infants. Journal of pediatric surgery 2007; 42(6): 962-

5; discussion 5.

15. Kliegman R, Nelson WE. Nelson textbook of pediatrics. 18th ed. Philadelphia: Saunders; 2007.

16. Statistics Canada. Births, estimates, by province and territory.2017.

http://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/demo04a-eng.htm (accessed 2018-

01-02).

17. Matlow AG, Baker GR, Flintoft V, et al. Adverse events among children in Canadian hospitals: the

Canadian Paediatric Adverse Events Study. CMAJ : Canadian Medical Association journal = journal de

l'Association medicale canadienne 2012; 184(13): E709-18.

18. Olofsson H, Brolund A, Hellberg C, et al. Can abstract screening workload be reduced using text

mining? User experiences of the tool Rayyan. Res Synth Methods 2017; 8(3): 275-80.

19. Fitch K, European Commission. Directorate-General XII Science Research and Development.,

Rand Corporation. The Rand/UCLA appropriateness method user's manual. Santa Monica: Rand; 2001.

20. Obeidat HM, Bond EA, Callister LC. The parental experience of having an infant in the newborn

intensive care unit. The Journal of Perinatal Education 2009; 18(3): 23.

21. Reis MD, Rempel GR, Scott SD, Brady‐Fryer BA, Van Aerde J. Developing nurse/parent

relationships in the NICU through negotiated partnership. Journal of Obstetric, Gynecologic, & Neonatal

Nursing 2010; 39(6): 675-83.

22. Ward K. Perceived needs of parents of critically ill infants in a neonatal intensive care unit

(NICU). Pediatric nursing 2001; 27(3): 281.

23. Lagoo J, Lopushinsky SR, Haynes AB, et al. Effectiveness and meaningful use of paediatric

surgical safety checklists and their implementation strategies: a systematic review with narrative

synthesis. BMJ Open 2017; 7(10): e016298.

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Approach

Journal: BMJ Open

Manuscript ID bmjopen-2018-023651.R1


Date Submitted by the Author: 25-Aug-2018


<b>Primary Subject Heading</b>: Health services research

Secondary Subject Heading: Surgery, Paediatrics, Anaesthesia

Keywords:Protocols & guidelines < HEALTH SERVICES ADMINISTRATION & MANAGEMENT, Paediatric surgery < SURGERY, Neonatal intensive & critical care < INTENSIVE & CRITICAL CARE, ERAS




jopen.bmj.com

/B

MJ O


ecember 2018. D

ownloaded from



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Approach



1, Denisa Urban

1, Jennifer YK

Lam1, Paul W Wales

3, Megan Brockel

4, Mehul Raval

5, Martin Offringa

6, Erik Skarsgard

7,


9, David de Beer

10, Gregg Nelson

11, Mary E Brindle

1


Mary Brindle MD MPH




T3B6A8 403-955-2848



Calgary, AB, Canada



Canada

4. Department of Pediatric Anesthesia, University of Colorado, Aurora, CO, United States of America





9. Department of Surgery, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China



Canada

Word Count: 3056



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Approach


Lam, Paul W Wales, Megan Brockel, Mehul V. Raval, Martin Offringa, Erik Skarsgard, Tomas


ABSTRACT
















Society. Human ethics approval has also been sought in order to engage patient families within

protocol development. This research is to be published in peer-reviewed journals and will form the

care standard for neonatal intestinal surgery.

ARTICLE SUMMARY


• The great variability in neonatal surgical care practices provides an opportunity for practice

improvement; however, recommendations must be informed by valid empirical studies

• This protocol outlines the development of the first pediatric ERAS® with unique areas of

topic development, e.g., parental involvement

• This research is developed by an international panel of experts and stakeholders including

parents. The methods used are an expansion of those applied in the development of

previous ERAS® guidelines, but include systematic literature reviews and evaluation. This

approach offers a potential standard for future ERAS® guideline generation informed by

robust methodology


• This study is endorsed by the International ERAS® Society which provides excellent

opportunity for knowledge translation.

INTRODUCTION

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Background













costs.1,4-8










Relevance






development.13



Our team has


surgical care of these newborns. This study will address the gap by synthesizing the current

evidence on best practices surrounding neonatal abdominal surgery, and devise a comprehensive

ERAS® guideline that is designed to reduce the need for reoperation, and enhance the overall

quality, efficiency, and safety of care for this fragile patient population while increasing parent

satisfaction.

Anticipated Impact

The development of an ERAS guideline has the potential to translate the benefits of protocolized

care seen in the adult population to the vulnerable neonatal population as well as identify key

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knowledge gaps that must be addressed to further improve care. The evidence-based guideline

resulting from this research will be implemented in a pilot study in the care of neonatal patients

undergoing abdominal surgery at the Alberta Children’s Hospital in Calgary, Alberta, Canada

and the Hospital for Sick Children in Toronto, Ontario, Canada. Roughly 10% of neonatal

surgical patients suffer at least one postoperative adverse event in Canada.15

Compliance with

ERAS® guideline elements will be measured prospectively and attitudes and acceptability of the

guideline will be measured through clinician and parent surveys and interviews. Secondary

measures will include clinical outcomes, such as nutritional outcomes, complication rates and

length of stay, that will be compared within a time series analysis during ERAS® guideline

implementation. Data derived from the pilot study will be used to refine the neonatal ERAS®

guideline and develop an international trial to evaluate the impact of this guideline on clinical

outcomes and measures of resource utilization.

Objectives This project aims to create an ERAS® guideline that will reduce adverse events, enhance quality

of care, increase parent satisfaction and improve the efficiency of neonatal surgical health care

delivery.





















Study Design






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Scope Determination











inquiry by ten panelists. Each panelist was sent an email survey regarding target population,

conditions and topics, and was asked to rate the “Agreement of Inclusion into Guideline” based

on a 9-point scale where 9 was completely agree and 1 was completely disagree. ERAS® topics

that had an overall median panel score of greater or equal to 7 were included. Topics with a score

of 1 to 3 were excluded. Topics with a score between 4 and 6 were further discussed within the

group and decision for inclusion was based on group consensus.









perioperative topics was generated. Topics were selected that could generate potential

recommendations for inclusion within the guidelines. Proposed topics were emailed to the

international panel. Panel members were also invited to provide other topics that could be

included. An environmental scan of the evidence surrounding each topic was provided to all

participants to supplement discussion about the necessity of each topic. Each panelist discussed

their perspective on the relevance of the topic for inclusion and the list of topics were once again

sent to panelists for review to achieve consensus. Each rater provided a rating of necessity for

inclusion for each topic on a nine-point scale.

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The final topics identified for recommendation development were: parental involvement

(especially discharge planning), antimicrobial prophylaxis and skin preparation, perioperative

communication and team structure, standard anesthetic protocol and perioperative fluid

management, postoperative vomiting/nasogastric intubation, preventing intraoperative

hypothermia/temperature control, urinary drainage, postoperative nutritional care, the role of

physiotherapy/occupational therapy, surgical practices, optimal hemoglobin levels, postoperative

analgesia, management of transitional circulation, and postoperative skin care/stoma care. The

topics that were eliminated were those of antenatal management and location of surgery. Overall,

interrater reliability across topics was excellent for absolute agreement with an interclass

correlation of 0.95 (95%CI 0.91, 0.98)

Literature Search

Evidence searching within each topic area was performed using a modification of the systematic

review process described within PRISMA (PRISMA-P checklist showing modifications to the

process included in supplementary material). Depending on expertise and preference, each topic

was assigned to one or two members to perform a literature search. Within each topic, potential

ERAS® elements or target questions were selected following a predetermined (deductive)

consensus, as well as a literature screen (inductive) to identify unanticipated areas of inquiry. A

targeted search strategy for each topic was developed in collaboration with a research librarian.

Target databases included MEDLINE, and CINAHL for select topics. The structured search was

supplemented by the members pursuing each topic with further focused literature searches,

citation searching, a review of personal archives, as well through contact with experts to obtain

important published and unpublished information. Each topic produced between 200 to 500

abstracts. Titles were catalogued using EndNote software. The search strategies aimed to obtain

the most relevant and important studies but not necessarily generate a completely comprehensive

review of the literature. Table 1 provides a sample of the root terms and topics used to create a

specific search for nutritional care.

Table 1: Planned search strategy for post-operative nutritional care topic




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Study selection The library of titles and abstracts for each topic were screened using Rayyan QCRI, a web-based

systematic review application,16

by international guideline committee members and their

respective teams to identify potentially relevant articles. Discrepancies in judgement were

resolved by a third reviewer. Meta-analyses, systematic reviews, randomized controlled studies,

non-randomized controlled studies, reviews, and case series were all considered for each

individual topic (Eligibility criteria outlined in Table 2). Studies were primarily restricted to

those in the English language, however, important papers written in a language understood by

other members of the team were also considered.

Subtopics were identified deductively and inductively within each topic by each team and were

catalogued along with a summary of the evidence supporting proposed ERAS®

recommendations. For example, within the topic area of prevention of intraoperative

hypothermia, pre-determined areas for inquiry included: Target temperature range for neonates

undergoing surgery, recommended environmental interventions to reduce hypothermia, and

recommended direct and indirect therapies to maintain normothermia.

Initial systematic searches of MEDLINE and CINAHL were performed on December 17th

, 2017.

Subsequent targeted searches of the peer-reviewed literature were performed within each topic

based on the development of subtopics. Additional searches of the grey literature were also

performed. The dates of these subsequent searches will accompany the search strategies for all

recommendation when the ERAS® guideline is published. Screening of titles and abstracts and

full texts was performed by each group exploring each topic (paired screening was not required).

An example of the screening flow diagram for the perioperative antibiotics topic is provided in

Figure 1.


Inclusion Criteria

Study Design Meta-analyses, OR systematic reviews, OR published guidelines or







Type of Surgery Surgery performed in the first four weeks of life. For appropriate subtopics




OR anastomoses.

Intervention

(for ERAS®

Recommendation)

Satisfies the following ERAS® elements




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completed.

Study quality assessment and data synthesis

Within each topic, one or more recommendation was developed meeting the criteria for

intervention (Table 2). For each recommendation, teams created tables summarizing the

supporting studies (supplementary Table S1) and the level of evidence for each study according

to the Oxford Level of Evidence Guidelines.17




Round one was completed through electronic

surveys. In this round, panel members were asked to consider each recommendation on its own

merits using the corresponding summarized evidence tables as well as their own experience and

knowledge. Our panel included an expanded working group of 17 members including additional

experts across specialties (surgery, neonatology, anesthesiology).

We asked panelists to rate the clarity or lack of ambiguity of each recommendation statement, as

well as the necessity of including it in the ERAS® guideline. These ratings were performed on a

9-point rating scale. In addition, panelists were asked to provide comments or suggestions

regarding the wording, the necessity of the recommendation or general comments.

Round two consisted of a full-day workshop in August 2018, moderated by the senior

investigator. Attendees were, once again, provided with a summary of the peer-reviewed

evidence including the level of evidence for each study as well as relevant guidelines. Each

working group presented their recommendations to the panel and reviewed the screening flow

chart, a table of the evidence, and the results of the ratings including distribution and median,

and comments from round one. Each recommendation was discussed in terms of potential

measurable outcomes resulting from implementation of the recommendation. Recommendations

were revised through group discussion or identified for further development. Recommendations

were voted upon for necessity for inclusion using the 9-point scale. Those recommendations with

consensus for inclusion (a median panel score greater or equal to 7), were assessed for aggregate

data quality and strength of recommendation (see below). Those recommendations that required

further development will be reviewed after revision for consensus on necessity for inclusion,

group assessment of aggregate quality and strength of recommendation.

The ratings for the recommendations at each stage will be reported including an interclass

correlation to provide a measure of rater agreement.


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Quality Definition

High We are very confident that the true effect lies close to that of the estimate

of the effect

Moderate We are moderately confident in the effect of the estimate: The true effect

is likely to be close to the estimate of the effect, but there is a possibility

that it is substantially different

Low Our confidence in the effect estimate is limited: The true effect may be

substantially different from the estimate of the effect

Very low We have very little confidence in the effect estimate


Strength Definition





closely balanced

Assessment of aggregate data quality and strength of recommendations:

The aggregate quality of evidence for each topic will be rated by the respective guideline

committee member and their team and discussed and voted upon by the ERAS® team. The

GRADE system will be used, and evidence rated as either “high”, “moderate”, “low”, or “very

low” (Table 3a).19

The ERAS® team will decide upon the strength of the recommendations

based on the quality of data and the balance of potential desirable/undesirable effects through

discussion and consensus. Any accompanying recommendations will be given a value of

“strong” or “weak” (Table 3b).20

The creation of the finalized guideline will occur in October 2018 in partnership with the

ERAS® Society, with publication sought.











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involvement.

The initial proposal was developed with feedback from parent advocates. Two additional parent

focus groups are engaged in this project. The first focus group provided input to the stakeholder

group at the time of the face-to-face workshop to review recommendations. This group will meet

again before the final refinement of the ERAS® tool to discuss proposed ERAS®

recommendations, highlighting areas where and how parental needs can be better addressed. The

second group will engage with the ERAS® committee to aid in the development of feasible and

acceptable implementation strategies for the completed guideline.

Future Work: Guideline Implementation

Guidelines are to be implemented in a multistep process and evaluated within two separate

studies. Stakeholder involvement in developing an implementation strategy will ensure

appropriate engagement and context-sensitive adaption. The ERAS® guideline will be integrated

with existing surgical safety tools such as the Surgical Safety Checklist- a tool that performs

optimally within larger quality and safety initiatives.25

Integration will occur in a manner that

will avoid duplication, assist in appropriate tailoring and strengthen the implementation around

both the surgical safety tool (i.e., the checklist) and the ERAS® guideline through a common

protocol.

Implementation fidelity and impact on outcomes will both be assessed in this multimodal

approach. Implementation fidelity will be determined through measures of compliance with

ERAS® elements and with other integrated surgical safety tools. Guidelines will be piloted in a

large tertiary pediatric center in Canada for three months. A focused assessment of acceptability

and compliance will be performed through audits as well as surveys and targeted interviews. The

content of these surveys and interviews will depend on the final elements included within the

guideline but will be developed using survey-creation methods including team item generation,

question development, piloting and revision. We will use previously published surveys

reviewing acceptability of clinical guidelines as a starting point. Based on this feedback further

revisions of the guideline will be performed.

The results of the initial implementation pilot will be reviewed by the international panel as well

as the ERAS® Society and an international multi-center implementation study for clinical

effectiveness will be designed. Clinical and process measure outcomes will be measured before

and during implementation. Outcomes of interest will be determined by the eventual ERAS®

recommendations and may include: length of stay, surgical site infection incidence, mortality,

sepsis, postoperative vomiting, weight gain, and parent and staff satisfaction. As per ERAS®

Society regulations, the guideline is to be considered for revision by the Scientific and Executive

ERAS® committee every three years, or earlier if deemed appropriate.


ethics approval has also been sought in order to engage patient families for guideline

implementation development. This research will contribute to a consistent standard of care for

neonatal abdominal surgery. This ERAS® guideline development represents the first phase of a

larger quality improvement project aimed at improving neonatal abdominal surgery.

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Author Consensus Contributions: The Senior author, Dr. Brindle, is a pediatric surgeon and

health systems researcher with experience in leading international collaborative work in pediatric

surgical safety and expertise in systematic reviews. Dr. Nelson is an international leader in

ERAS® with expertise in ERAS® guideline development and study. Dr. Brockel is an

anesthesiologist with considerable practical experience in adapting adult ERAS® guidelines to

the care of pediatric patients. Dr. de Beer is an anesthesiologist with special expertise in human

factors and anesthetic emergencies. Dr. Offringa brings national leadership in neonatal surgical

collaboration and guideline development. Dr. Raval has considerable expertise in the application

of ERAS® guidelines in children. Dr. Skarsgard is the president of the Canadian Association of

Pediatric Surgeons and an international leader in pediatric surgery quality and safety. Dr. Wales

is a pediatric surgeon and internationally-recognized researcher in neonatal nutrition. Dr. Wester

has considerable experience in neonatal surgery and epidemiology. Dr. Wong is a leader in

Pediatric surgery in Hong Kong with a strong history of international surgical leadership.

Author Protocol Contributions:

Ashleigh CN Gibb- created tools, performed surveys, developed initial searches, analyzed data

and completed the first draft of the paper as well as critically revising the paper. She approves

the final version

Megan A Crosby- performed surveys, aided in searches, aided in analysis, as well as critically

revising the paper. She approves the final version

Caraline McDiarmid- created tools, performed additional searches and surveys, aided in

screening, consolidated and analyzed data, developed summary tables as well as critically


Denisa Urban- aided in creating timeline and tools performed searches and screening, as well as

critically revising the paper. She approves the final version

Jennifer YK Lam, Paul w. Wales, Megan Brockel, Mehul V. Raval, Martin Offiringa, Erik

Skarsgard, Tomas Wester, Ken Wong and David de Beer- Helped determine initial scope and

population as well as topics, performed screening, developed evidence tables, provided feedback

on approach as well as critically revising the paper. They all approve the final version.

Gregg Nelson- Aided in concept development with ERAS, provided feedback on approach as

well as critically revising the paper. He approves the final version.

Mary E Brindle- Developed the initial concept and approach. Lead the development of research

methods, organized consensus development. Provided final review of data and performed and

reviewed analyses. Provided first critical revision of draft and subsequent revision. She approves

the final version









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final guideline.

Legends:

Figure 1: Flow Diagram for Study Screening (Perioperative Antibiotics)

References


surgery 2002; 183(6): 630-41.














1343-8.


152(3): 292-8.














5; discussion 5.

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17. OCEBM Table of Evidence Working Group. The Oxford 2011 Levels of Evidence. 2011.

http://www.cebm.net/index.aspx?o=5653.



19. Balshem H, Helfand M, Schunemann HJ, et al. GRADE guidelines: 3. Rating the quality of

evidence. J Clin Epidemiol 2011; 64(4): 401-6.

20. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of

evidence and strength of recommendations. BMJ 2008; 336(7650): 924-6.



22. Reis MD, Rempel GR, Scott SD, Brady-Fryer BA, Van Aerde J. Developing nurse/parent


Nursing 2010; 39(6): 675-83.






25. Brindle ME, Henrich N, Foster A, et al. Implementation of surgical debriefing programs in large

health systems: an exploratory qualitative analysis. BMC Health Serv Res 2018; 18(1): 210.

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875x492mm (72 x 72 DPI)

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Table S1: Neonatal Operative Skin Preparation Solution Evidence Summary with Level of Evidence (2011 Oxford Level of Evidence)

CLABSI =Central Line Associated Blood Stream Infection; RCT=Randomized Controlled Trial; GA= Gestational Age ; BW= Birth Weight; CHG=Chlorhexidine Gluconate; NICU=Neonatal Intensive Care Unit

Study Type of Study Population Intervention Outcomes Key findings Level of Evidence/Quality

Kieran et al. Arch Dis Child Fetal Neonatal Ed 2018

RCT (2 center) Ireland

NICU infants (n-304) <31 weeks having CVCs inserted

Skin disinfection with either 2% CHG w 70% isopropyl alcohol vs 10% poviodine iodine

CLABSI Skin reactions Thyroid dysfunction

No difference in CLABSI (# or rate per 1000 catheter days). Skin reaction rates <1%, and not different between groups More infants in PI group req’d thyroxine

LOE 2 Quality Moderate (underpowered)

Sinha et al. Cochrane Library, 2015

Cochrane Review 12 studies: 7 hospital, 5 community based

Term, Late preterm/ Hospitals Term, Late preterm/Community care

Chlorhexidine vs dry cord care or total body cleansing vs usual care (0.25%-4% CHG)

Neonatal mortality Omphalitis occurrence

Hospitals: skin or cord cleaning=no difference in mortality, reduced omphalitis Community care: CHG cord cleansing vs no care may reduce omphalitis, no effect on mortality

LOE 1 Quality Variable (low, moderate, high)

Abdeyazdan et al. Educ Health Promot 2014

Single blinded clinical trial with “within subjects” design

NICU infants >28 weeks and 1000g (n=98).

Half of body (random determination) disinfected with 10% poviodine/iodine, other half with 2% CHG

Differences in skin culture rates before, immediately after, 2h later

Significant difference in skin culture positivity Immediately following skin decontamination (3.1% vs 17.3%: favoring povidine/iodine)

LOE 2 Quality Moderate

Linder et al. Acta Paediatr (2004)

Retrospective Comparative cohort study (Israel)

Single institution NICU Skin disinfection study

1992-93-10% poviodine-iodine 1996-96-0.5% CHG/70% isopropanol

Positive blood cultures and sepsis symptoms (“true infection”) and “contamination”

CHG group lower GA and BW No difference in rates of “true infection” or “contamination”

LOE 3 Qulality Moderate

Chapman et al. J Perinatol (2012)

Review article (summarizing 11 cohort studies)

>1200 NICU infants <32 weeks GA

Variety of CHG (0.5-4%, some with alcohol) exposures. Indications: whole body bathing, cord care, PICC placement, “invasive procedures” (not surgery)

Skin changes (contact dermatitis, severe skin irritation). Detectable levels of CHG in blood

Of papers reporting adverse outcome, these included contact dermatitis, severe skin irritation (n=23). Of 3 studies reporting detection of CHG (total 58 pts, 22 had detectable levels of CHG)

Review (not included but identified for citation searching)

Garland et al. Pediatr Infect Dis J (1995)

Non-randomized, multicenter, sequential comparative cohort study (US)

254 NICU term infants (GA 35.7 w)

PIV catheter site cleansing with either 10% poviodine iodine or 0.5% CHG/70% isopropyl alcohol

Catheter colonization; and Catheter-related bacteremia (+ blood culture and catheter colonization with same org)

Catheter colonization rate lower in CHG patients (4.7 vs 9.3%). In poviodine/iodine site cleanses, rate is correlated with duration of IV access. No difference in rates of catheter related bacteremia


Darmstadt et al. Pediatr Infect Dis 2007

RCT, single center (India)

344 NICU patients >1000g

Randomized to placebo or 0.44% CHG body wipe

Skin cultures taken at various time points after wipe Skin related adverse effects

Skin culture positive rates 35-55% lower in CHG group. No difference in skin condition between groups


Nuntnarumit, et al. Inf Contr Hosp Epidiol 2013

RCT single center (Thailand)

212 late preterm infants >1500 g

Randomized to 1%CHG vs10% Poviodine Iodine After skin allowed to dry, prep wiped off with normal saline

Blood culture positive rates Skin related adverse effects

No positive cultures in CHG group. 2.9% positive cultures in PI group. No skin erythema, burn or contact dermatitis or evidence of systemic effect?


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PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols) 2015 checklist: recommended items to

address in a systematic review protocol*

Section and topic Item No Checklist item

ADMINISTRATIVE INFORMATION

Title:

Identification 1a Identify the report as a protocol of a systematic review

Update 1b If the protocol is for an update of a previous systematic review, identify as such

Registration 2 If registered, provide the name of the registry (such as PROSPERO) and registration number

Authors:

Contact 3a Provide name, institutional affiliation, e-mail address of all protocol authors; provide physical mailing address of

corresponding author

Contributions 3b Describe contributions of protocol authors and identify the guarantor of the review

Amendments 4 If the protocol represents an amendment of a previously completed or published protocol, identify as such and list changes;

otherwise, state plan for documenting important protocol amendments

Support:

Sources 5a Indicate sources of financial or other support for the review

Sponsor 5b Provide name for the review funder and/or sponsor

Role of sponsor or funder 5c Describe roles of funder(s), sponsor(s), and/or institution(s), if any, in developing the protocol

INTRODUCTION

Rationale 6 Describe the rationale for the review in the context of what is already known

Objectives 7 Provide an explicit statement of the question(s) the review will address with reference to participants, interventions,

comparators, and outcomes (PICO)

METHODS

Eligibility criteria 8 Specify the study characteristics (such as PICO, study design, setting, time frame) and report characteristics (such as years

considered, language, publication status) to be used as criteria for eligibility for the review

Information sources 9 Describe all intended information sources (such as electronic databases, contact with study authors, trial registers or other

grey literature sources) with planned dates of coverage

Search strategy 10 Present draft of search strategy to be used for at least one electronic database, including planned limits, such that it could be

repeated

Study records:

Data management 11a Describe the mechanism(s) that will be used to manage records and data throughout the review

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(Protocol of guideline generation. Identification of protocol knowledge synthesis elements)



Selection process 11b State the process that will be used for selecting studies (such as two independent reviewers) through each phase of the

review (that is, screening, eligibility and inclusion in meta-analysis)

Data collection process 11c Describe planned method of extracting data from reports (such as piloting forms, done independently, in duplicate), any

processes for obtaining and confirming data from investigators

Data items 12 List and define all variables for which data will be sought (such as PICO items, funding sources), any pre-planned data

assumptions and simplifications

Outcomes and prioritization 13 List and define all outcomes for which data will be sought, including prioritization of main and additional outcomes, with

rationale

Risk of bias in individual studies 14 Describe anticipated methods for assessing risk of bias of individual studies, including whether this will be done at the

outcome or study level, or both; state how this information will be used in data synthesis

Data synthesis 15a Describe criteria under which study data will be quantitatively synthesised

15b If data are appropriate for quantitative synthesis, describe planned summary measures, methods of handling data and

methods of combining data from studies, including any planned exploration of consistency (such as I2, Kendall’s τ)

15c Describe any proposed additional analyses (such as sensitivity or subgroup analyses, meta-regression)

15d If quantitative synthesis is not appropriate, describe the type of summary planned

Meta-bias(es) 16 Specify any planned assessment of meta-bias(es) (such as publication bias across studies, selective reporting within studies)

Confidence in cumulative evidence 17 Describe how the strength of the body of evidence will be assessed (such as GRADE)

* It is strongly recommended that this checklist be read in conjunction with the PRISMA-P Explanation and Elaboration (cite when available) for important

clarification on the items. Amendments to a review protocol should be tracked and dated. The copyright for PRISMA-P (including checklist) is held by the

PRISMA-P Group and is distributed under a Creative Commons Attribution Licence 4.0.

From: Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart L, PRISMA-P Group. Preferred reporting items for systematic review and

meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015 Jan 2;349(jan02 1):g7647.

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Recommendation According to GRADE guidelines




Approach

Journal: BMJ Open

Manuscript ID bmjopen-2018-023651.R2


Date Submitted by the Author: 02-Oct-2018


<b>Primary Subject Heading</b>: Health services research

Secondary Subject Heading: Surgery, Paediatrics, Anaesthesia

Keywords:Protocols & guidelines < HEALTH SERVICES ADMINISTRATION & MANAGEMENT, Paediatric surgery < SURGERY, Neonatal intensive & critical care < INTENSIVE & CRITICAL CARE, ERAS




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Approach



1, Denisa Urban

1, Jennifer YK

Lam1, Paul W Wales

3, Megan Brockel

4, Mehul Raval

5, Martin Offringa

6, Erik Skarsgard

7,


9, David de Beer

10, Gregg Nelson

11, Mary E Brindle

1


Mary Brindle MD MPH




T3B6A8 403-955-2848



Calgary, AB, Canada



Canada

4. Department of Pediatric Anesthesia, University of Colorado, Aurora, CO, United States of America





9. Department of Surgery, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China



Canada

Word Count: 3056



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Approach


Lam, Paul W Wales, Megan Brockel, Mehul V. Raval, Martin Offringa, Erik Skarsgard, Tomas


ABSTRACT
















Society. Human ethics approval (REB 18-0579) is in place to engage patient families within protocol

development. This research is to be published in peer-reviewed journals and will form the care

standard for neonatal intestinal surgery.

ARTICLE SUMMARY


• This protocol outlines the development of the first pediatric ERAS® guideline with unique

areas of topic development, e.g., parental involvement

• The aims and targets of this study were developed by an international panel of experts and

stakeholders including parents.

• The methods include systematic literature reviews and evaluation, offering a potential

standard for future ERAS® guideline generation informed by robust methodology

• This study has integrated knowledge translation through endorsement and ongoing

engagement with the International ERAS® Society.


INTRODUCTION

Background



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costs.1,4-8










Relevance






development.13



Our team has


surgical care of these newborns. This study will address the gap by synthesizing the current

evidence on best practices surrounding neonatal abdominal surgery, and devise a comprehensive

ERAS® guideline that is designed to reduce the need for reoperation, and enhance the overall

quality, efficiency, and safety of care for this fragile patient population while increasing parent

satisfaction.

Anticipated Impact

The development of an ERAS guideline has the potential to translate the benefits of protocolized

care seen in the adult population to the vulnerable neonatal population as well as identify key

knowledge gaps that must be addressed to further improve care. The evidence-based guideline

resulting from this research will be implemented in a pilot study in the care of neonatal patients

undergoing abdominal surgery at the Alberta Children’s Hospital in Calgary, Alberta, Canada

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and the Hospital for Sick Children in Toronto, Ontario, Canada. Roughly 10% of neonatal

surgical patients suffer at least one postoperative adverse event in Canada.15

Compliance with

ERAS® guideline elements will be measured prospectively and attitudes and acceptability of the

guideline will be measured through clinician and parent surveys and interviews. Secondary

measures will include clinical outcomes, such as nutritional outcomes, complication rates and

length of stay, that will be compared within a time series analysis during ERAS® guideline

implementation. Data derived from the pilot study will be used to refine the neonatal ERAS®

guideline and develop an international trial to evaluate the impact of this guideline on clinical

outcomes and measures of resource utilization.

Objectives This project aims to create an ERAS® guideline that will reduce adverse events, enhance quality

of care, increase parent satisfaction and improve the efficiency of neonatal surgical health care

delivery.





















Study Design









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Scope Determination











inquiry by ten panelists. Each panelist was sent an email survey regarding target population,

conditions and topics, and was asked to rate the “Agreement of Inclusion into Guideline” based

on a 9-point scale where 9 was completely agree and 1 was completely disagree. ERAS® topics

that had an overall median panel score of greater or equal to 7 were included. Topics with a score

of 1 to 3 were excluded. Topics with a score between 4 and 6 were further discussed within the

group and decision for inclusion was based on group consensus.









perioperative topics was generated. Topics were selected that could generate potential

recommendations for inclusion within the guidelines. Proposed topics were emailed to the

international panel. Panel members were also invited to provide other topics that could be

included. An environmental scan of the evidence surrounding each topic was provided to all

participants to supplement discussion about the necessity of each topic. Each panelist discussed

their perspective on the relevance of the topic for inclusion and the list of topics were once again

sent to panelists for review to achieve consensus. Each rater provided a rating of necessity for

inclusion for each topic on a nine-point scale.

The final topics identified for recommendation development were: parental involvement

(especially discharge planning), antimicrobial prophylaxis and skin preparation, perioperative

communication and team structure, standard anesthetic protocol and perioperative fluid

management, postoperative vomiting/nasogastric intubation, preventing intraoperative

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hypothermia/temperature control, urinary drainage, postoperative nutritional care, the role of

physiotherapy/occupational therapy, surgical practices, optimal hemoglobin levels, postoperative

analgesia, management of transitional circulation, and postoperative skin care/stoma care. The

topics that were eliminated were those of antenatal management and location of surgery. Overall,

interrater reliability across topics was excellent for absolute agreement with an interclass

correlation of 0.95 (95%CI 0.91, 0.98)

Literature Search

Evidence searching within each topic area was performed using a modification of the systematic

review process described within PRISMA (PRISMA-P checklist showing modifications to the

process included in supplementary material). Depending on expertise and preference, each topic

was assigned to one or two members to perform a literature search. Within each topic, potential

ERAS® elements or target questions were selected following a predetermined (deductive)

consensus, as well as a literature screen (inductive) to identify unanticipated areas of inquiry. A

targeted search strategy for each topic was developed in collaboration with a research librarian.

Target databases included MEDLINE, and CINAHL for select topics. The structured search was

supplemented by the members pursuing each topic with further focused literature searches,

citation searching, a review of personal archives, as well through contact with experts to obtain

important published and unpublished information. Each topic produced between 200 to 500

abstracts. Titles were catalogued using EndNote software. The search strategies aimed to obtain

the most relevant and important studies but not necessarily generate a completely comprehensive

review of the literature. Table 1 provides a sample of the root terms and topics used to create a

specific search for nutritional care.

Table 1: Planned search strategy for post-operative nutritional care topic




Study selection The library of titles and abstracts for each topic were screened using Rayyan QCRI, a web-based

systematic review application,16

by international guideline committee members and their

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respective teams to identify potentially relevant articles. Discrepancies in judgement were

resolved by a third reviewer. Meta-analyses, systematic reviews, randomized controlled studies,

non-randomized controlled studies, reviews, and case series were all considered for each

individual topic (Eligibility criteria outlined in Table 2). Studies were primarily restricted to

those in the English language, however, important papers written in a language understood by

other members of the team were also considered.

Subtopics were identified deductively and inductively within each topic by each team and were

catalogued along with a summary of the evidence supporting proposed ERAS®

recommendations. For example, within the topic area of prevention of intraoperative

hypothermia, pre-determined areas for inquiry included: Target temperature range for neonates

undergoing surgery, recommended environmental interventions to reduce hypothermia, and

recommended direct and indirect therapies to maintain normothermia.

Initial systematic searches of MEDLINE and CINAHL were performed on December 17th

, 2017.

Subsequent targeted searches of the peer-reviewed literature were performed within each topic

based on the development of subtopics. Additional searches of the grey literature were also

performed. The dates of these subsequent searches will accompany the search strategies for all

recommendation when the ERAS® guideline is published. Screening of titles and abstracts and

full texts was performed by each group exploring each topic (paired screening was not required).

An example of the screening flow diagram for the perioperative antibiotics topic is provided in

Figure 1.


Inclusion Criteria

Study Design Meta-analyses, OR systematic reviews, OR published guidelines or







Type of Surgery Surgery performed in the first four weeks of life. For appropriate subtopics




OR anastomoses.

Intervention

(for ERAS®

Recommendation)

Satisfies the following ERAS® elements








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completed.

Study quality assessment and data synthesis

Within each topic, one or more recommendation was developed meeting the criteria for

intervention (Table 2). For each recommendation, teams created tables summarizing the

supporting studies (supplementary Table S1) and the level of evidence for each study according

to the Oxford Level of Evidence Guidelines.17




Round one was completed through electronic

surveys. In this round, panel members were asked to consider each recommendation on its own

merits using the corresponding summarized evidence tables as well as their own experience and

knowledge. Our panel included an expanded working group of 17 members including additional

experts across specialties (surgery, neonatology, anesthesiology).

We asked panelists to rate the clarity or lack of ambiguity of each recommendation statement, as

well as the necessity of including it in the ERAS® guideline. These ratings were performed on a

9-point rating scale. In addition, panelists were asked to provide comments or suggestions

regarding the wording, the necessity of the recommendation or general comments.

Round two consisted of a full-day workshop in August 2018, moderated by the senior

investigator. Attendees were, once again, provided with a summary of the peer-reviewed

evidence including the level of evidence for each study as well as relevant guidelines. Each

working group presented their recommendations to the panel and reviewed the screening flow

chart, a table of the evidence, and the results of the ratings including distribution and median,

and comments from round one. Each recommendation was discussed in terms of potential

measurable outcomes resulting from implementation of the recommendation. Recommendations

were revised through group discussion or identified for further development. Recommendations

were voted upon for necessity for inclusion using the 9-point scale. Those recommendations with

consensus for inclusion (a median panel score greater or equal to 7), were assessed for aggregate

data quality and strength of recommendation (see below). Those recommendations that required

further development will be reviewed after revision for consensus on necessity for inclusion,

group assessment of aggregate quality and strength of recommendation.

The ratings for the recommendations at each stage will be reported including an interclass

correlation to provide a measure of rater agreement.


Quality Definition

High We are very confident that the true effect lies close to that of the estimate

of the effect

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Moderate We are moderately confident in the effect of the estimate: The true effect

is likely to be close to the estimate of the effect, but there is a possibility

that it is substantially different

Low Our confidence in the effect estimate is limited: The true effect may be

substantially different from the estimate of the effect

Very low We have very little confidence in the effect estimate


Strength Definition





closely balanced

Assessment of aggregate data quality and strength of recommendations:

The aggregate quality of evidence for each topic will be rated by the respective guideline

committee member and their team and discussed and voted upon by the ERAS® team. The

GRADE system will be used, and evidence rated as either “high”, “moderate”, “low”, or “very

low” (Table 3a).19

The ERAS® team will decide upon the strength of the recommendations

based on the quality of data and the balance of potential desirable/undesirable effects through

discussion and consensus. Any accompanying recommendations will be given a value of

“strong” or “weak” (Table 3b).20

The creation of the finalized guideline will occur in October 2018 in partnership with the

ERAS® Society, with publication sought.












involvement.

The initial proposal was developed with feedback from parent advocates. Two additional parent

focus groups are engaged in this project. The first focus group provided input to the stakeholder

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group at the time of the face-to-face workshop to review recommendations. This group will meet

again before the final refinement of the ERAS® tool to discuss proposed ERAS®

recommendations, highlighting areas where and how parental needs can be better addressed. The

second group will engage with the ERAS® committee to aid in the development of feasible and

acceptable implementation strategies for the completed guideline.

Future Work: Guideline Implementation

Guidelines are to be implemented in a multistep process and evaluated within two separate

studies. Stakeholder involvement in developing an implementation strategy will ensure

appropriate engagement and context-sensitive adaption. The ERAS® guideline will be integrated

with existing surgical safety tools such as the Surgical Safety Checklist- a tool that performs

optimally within larger quality and safety initiatives.25

Integration will occur in a manner that

will avoid duplication, assist in appropriate tailoring and strengthen the implementation around

both the surgical safety tool (i.e., the checklist) and the ERAS® guideline through a common

protocol.

Implementation fidelity and impact on outcomes will both be assessed in this multimodal

approach. Implementation fidelity will be determined through measures of compliance with

ERAS® elements and with other integrated surgical safety tools. Guidelines will be piloted in a

large tertiary pediatric center in Canada for three months. A focused assessment of acceptability

and compliance will be performed through audits as well as surveys and targeted interviews. The

content of these surveys and interviews will depend on the final elements included within the

guideline but will be developed using survey-creation methods including team item generation,

question development, piloting and revision. We will use previously published surveys

reviewing acceptability of clinical guidelines as a starting point. Based on this feedback further

revisions of the guideline will be performed.

The results of the initial implementation pilot will be reviewed by the international panel as well

as the ERAS® Society and an international multi-center implementation study for clinical

effectiveness will be designed. Clinical and process measure outcomes will be measured before

and during implementation. Outcomes of interest will be determined by the eventual ERAS®

recommendations and may include: length of stay, surgical site infection incidence, mortality,

sepsis, postoperative vomiting, weight gain, and parent and staff satisfaction. As per ERAS®

Society regulations, the guideline is to be considered for revision by the Scientific and Executive

ERAS® committee every three years, or earlier if deemed appropriate.


ethics approval (REB 18-0579) is in place to engage patient families for guideline

implementation development. This research will contribute to a consistent standard of care for

neonatal abdominal surgery. This ERAS® guideline development represents the first phase of a

larger quality improvement project aimed at improving neonatal abdominal surgery.

Author Consensus Contributions: The Senior author, Dr. Brindle, is a pediatric surgeon and

health systems researcher with experience in leading international collaborative work in pediatric

surgical safety and expertise in systematic reviews. Dr. Nelson is an international leader in

ERAS® with expertise in ERAS® guideline development and study. Dr. Brockel is an

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anesthesiologist with considerable practical experience in adapting adult ERAS® guidelines to

the care of pediatric patients. Dr. de Beer is an anesthesiologist with special expertise in human

factors and anesthetic emergencies. Dr. Offringa brings national leadership in neonatal surgical

collaboration and guideline development. Dr. Raval has considerable expertise in the application

of ERAS® guidelines in children. Dr. Skarsgard is the president of the Canadian Association of

Pediatric Surgeons and an international leader in pediatric surgery quality and safety. Dr. Wales

is a pediatric surgeon and internationally-recognized researcher in neonatal nutrition. Dr. Wester

has considerable experience in neonatal surgery and epidemiology. Dr. Wong is a leader in

Pediatric surgery in Hong Kong with a strong history of international surgical leadership.

Author Protocol Contributions:

Ashleigh CN Gibb- created tools, performed surveys, developed initial searches, analyzed data

and completed the first draft of the paper as well as critically revising the paper. She approves

the final version

Megan A Crosby- performed surveys, aided in searches, aided in analysis, as well as critically


Caraline McDiarmid- created tools, performed additional searches and surveys, aided in

screening, consolidated and analyzed data, developed summary tables as well as critically


Denisa Urban- aided in creating timeline and tools performed searches and screening, as well as

critically revising the paper. She approves the final version

Jennifer YK Lam, Paul w. Wales, Megan Brockel, Mehul V. Raval, Martin Offiringa, Erik

Skarsgard, Tomas Wester, Ken Wong and David de Beer- Helped determine initial scope and

population as well as topics, performed screening, developed evidence tables, provided feedback

on approach as well as critically revising the paper. They all approve the final version.

Gregg Nelson- Aided in concept development with ERAS, provided feedback on approach as

well as critically revising the paper. He approves the final version.

Mary E Brindle- Developed the initial concept and approach. Lead the development of research

methods, organized consensus development. Provided final review of data and performed and

reviewed analyses. Provided first critical revision of draft and subsequent revision. She approves

the final version












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final guideline.

Legends:


References


surgery 2002; 183(6): 630-41.














1343-8.


152(3): 292-8.














5; discussion 5.






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17. OCEBM Table of Evidence Working Group. The Oxford 2011 Levels of Evidence. 2011.

http://www.cebm.net/index.aspx?o=5653.



19. Balshem H, Helfand M, Schunemann HJ, et al. GRADE guidelines: 3. Rating the quality of

evidence. J Clin Epidemiol 2011; 64(4): 401-6.

20. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of

evidence and strength of recommendations. BMJ 2008; 336(7650): 924-6.



22. Reis MD, Rempel GR, Scott SD, Brady-Fryer BA, Van Aerde J. Developing nurse/parent


Nursing 2010; 39(6): 675-83.






25. Brindle ME, Henrich N, Foster A, et al. Implementation of surgical debriefing programs in large

health systems: an exploratory qualitative analysis. BMC Health Serv Res 2018; 18(1): 210.

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210x118mm (300 x 300 DPI)

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Table S1: Neonatal Operative Skin Preparation Solution Evidence Summary with Level of Evidence (2011 Oxford Level of Evidence)

CLABSI =Central Line Associated Blood Stream Infection; RCT=Randomized Controlled Trial; GA= Gestational Age ; BW= Birth Weight; CHG=Chlorhexidine Gluconate; NICU=Neonatal Intensive Care Unit

Study Type of Study Population Intervention Outcomes Key findings Level of Evidence/Quality

Kieran et al. Arch Dis Child Fetal Neonatal Ed 2018

RCT (2 center) Ireland

NICU infants (n-304) <31 weeks having CVCs inserted

Skin disinfection with either 2% CHG w 70% isopropyl alcohol vs 10% poviodine iodine

CLABSI Skin reactions Thyroid dysfunction

No difference in CLABSI (# or rate per 1000 catheter days). Skin reaction rates <1%, and not different between groups More infants in PI group req’d thyroxine

LOE 2 Quality Moderate (underpowered)

Sinha et al. Cochrane Library, 2015

Cochrane Review 12 studies: 7 hospital, 5 community based

Term, Late preterm/ Hospitals Term, Late preterm/Community care

Chlorhexidine vs dry cord care or total body cleansing vs usual care (0.25%-4% CHG)

Neonatal mortality Omphalitis occurrence

Hospitals: skin or cord cleaning=no difference in mortality, reduced omphalitis Community care: CHG cord cleansing vs no care may reduce omphalitis, no effect on mortality

LOE 1 Quality Variable (low, moderate, high)

Abdeyazdan et al. Educ Health Promot 2014

Single blinded clinical trial with “within subjects” design

NICU infants >28 weeks and 1000g (n=98).

Half of body (random determination) disinfected with 10% poviodine/iodine, other half with 2% CHG

Differences in skin culture rates before, immediately after, 2h later

Significant difference in skin culture positivity Immediately following skin decontamination (3.1% vs 17.3%: favoring povidine/iodine)


Linder et al. Acta Paediatr (2004)

Retrospective Comparative cohort study (Israel)

Single institution NICU Skin disinfection study

1992-93-10% poviodine-iodine 1996-96-0.5% CHG/70% isopropanol

Positive blood cultures and sepsis symptoms (“true infection”) and “contamination”

CHG group lower GA and BW No difference in rates of “true infection” or “contamination”

LOE 3 Qulality Moderate

Chapman et al. J Perinatol (2012)

Review article (summarizing 11 cohort studies)

>1200 NICU infants <32 weeks GA

Variety of CHG (0.5-4%, some with alcohol) exposures. Indications: whole body bathing, cord care, PICC placement, “invasive procedures” (not surgery)

Skin changes (contact dermatitis, severe skin irritation). Detectable levels of CHG in blood

Of papers reporting adverse outcome, these included contact dermatitis, severe skin irritation (n=23). Of 3 studies reporting detection of CHG (total 58 pts, 22 had detectable levels of CHG)

Review (not included but identified for citation searching)

Garland et al. Pediatr Infect Dis J (1995)

Non-randomized, multicenter, sequential comparative cohort study (US)

254 NICU term infants (GA 35.7 w)

PIV catheter site cleansing with either 10% poviodine iodine or 0.5% CHG/70% isopropyl alcohol

Catheter colonization; and Catheter-related bacteremia (+ blood culture and catheter colonization with same org)

Catheter colonization rate lower in CHG patients (4.7 vs 9.3%). In poviodine/iodine site cleanses, rate is correlated with duration of IV access. No difference in rates of catheter related bacteremia


Darmstadt et al. Pediatr Infect Dis 2007

RCT, single center (India)

344 NICU patients >1000g

Randomized to placebo or 0.44% CHG body wipe

Skin cultures taken at various time points after wipe Skin related adverse effects

Skin culture positive rates 35-55% lower in CHG group. No difference in skin condition between groups


Nuntnarumit, et al. Inf Contr Hosp Epidiol 2013

RCT single center (Thailand)

212 late preterm infants >1500 g

Randomized to 1%CHG vs10% Poviodine Iodine After skin allowed to dry, prep wiped off with normal saline

Blood culture positive rates Skin related adverse effects

No positive cultures in CHG group. 2.9% positive cultures in PI group. No skin erythema, burn or contact dermatitis or evidence of systemic effect?


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PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols) 2015 checklist: recommended items to

address in a systematic review protocol*

Section and topic Item No Checklist item

ADMINISTRATIVE INFORMATION

Title:

Identification 1a Identify the report as a protocol of a systematic review

Update 1b If the protocol is for an update of a previous systematic review, identify as such

Registration 2 If registered, provide the name of the registry (such as PROSPERO) and registration number

Authors:

Contact 3a Provide name, institutional affiliation, e-mail address of all protocol authors; provide physical mailing address of

corresponding author

Contributions 3b Describe contributions of protocol authors and identify the guarantor of the review

Amendments 4 If the protocol represents an amendment of a previously completed or published protocol, identify as such and list changes;

otherwise, state plan for documenting important protocol amendments

Support:

Sources 5a Indicate sources of financial or other support for the review

Sponsor 5b Provide name for the review funder and/or sponsor

Role of sponsor or funder 5c Describe roles of funder(s), sponsor(s), and/or institution(s), if any, in developing the protocol

INTRODUCTION

Rationale 6 Describe the rationale for the review in the context of what is already known

Objectives 7 Provide an explicit statement of the question(s) the review will address with reference to participants, interventions,

comparators, and outcomes (PICO)

METHODS

Eligibility criteria 8 Specify the study characteristics (such as PICO, study design, setting, time frame) and report characteristics (such as years

considered, language, publication status) to be used as criteria for eligibility for the review

Information sources 9 Describe all intended information sources (such as electronic databases, contact with study authors, trial registers or other

grey literature sources) with planned dates of coverage

Search strategy 10 Present draft of search strategy to be used for at least one electronic database, including planned limits, such that it could be

repeated

Study records:

Data management 11a Describe the mechanism(s) that will be used to manage records and data throughout the review

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-

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Title page

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Throughout the methods

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Funding Statement included

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No role

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Funding Statement

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Background

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Determination of the PICO elements is a crucial aspect of the review. How these elements are developed are outlined thoughout.

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Table 1

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Described throughout

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(Protocol of guideline generation. Identification of protocol knowledge synthesis elements)



Selection process 11b State the process that will be used for selecting studies (such as two independent reviewers) through each phase of the

review (that is, screening, eligibility and inclusion in meta-analysis)

Data collection process 11c Describe planned method of extracting data from reports (such as piloting forms, done independently, in duplicate), any

processes for obtaining and confirming data from investigators

Data items 12 List and define all variables for which data will be sought (such as PICO items, funding sources), any pre-planned data

assumptions and simplifications

Outcomes and prioritization 13 List and define all outcomes for which data will be sought, including prioritization of main and additional outcomes, with

rationale

Risk of bias in individual studies 14 Describe anticipated methods for assessing risk of bias of individual studies, including whether this will be done at the

outcome or study level, or both; state how this information will be used in data synthesis

Data synthesis 15a Describe criteria under which study data will be quantitatively synthesised

15b If data are appropriate for quantitative synthesis, describe planned summary measures, methods of handling data and

methods of combining data from studies, including any planned exploration of consistency (such as I2, Kendall’s τ)

15c Describe any proposed additional analyses (such as sensitivity or subgroup analyses, meta-regression)

15d If quantitative synthesis is not appropriate, describe the type of summary planned

Meta-bias(es) 16 Specify any planned assessment of meta-bias(es) (such as publication bias across studies, selective reporting within studies)

Confidence in cumulative evidence 17 Describe how the strength of the body of evidence will be assessed (such as GRADE)

* It is strongly recommended that this checklist be read in conjunction with the PRISMA-P Explanation and Elaboration (cite when available) for important

clarification on the items. Amendments to a review protocol should be tracked and dated. The copyright for PRISMA-P (including checklist) is held by the

PRISMA-P Group and is distributed under a Creative Commons Attribution Licence 4.0.

From: Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart L, PRISMA-P Group. Preferred reporting items for systematic review and

meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015 Jan 2;349(jan02 1):g7647.

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Described in literature review

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Recommendation development process described

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Developed iteratively throughout the process.

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To be determined throughout the process

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Done at the study level

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Quantitative synthesis N/A

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Table summaries

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Descriptive

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GRADE of evidence. Strength of

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Recommendation According to GRADE guidelines


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