Appraisal of Australian and New Zealand paediatric sepsis guidelines

Clinical practice guidelines (CPGs) are an important tool for the management of children with sepsis. The quality, consistency and concordance of Australian and New Zealand (ANZ) childhood sepsis CPGs with the Australian Commission on Safety and Quality in Healthcare (ACSQHC) sepsis clinical care standards and international sepsis guidelines is unclear.

territories through Paediatric Research in Emergency Departments International Collaborative members.The guidelines were assessed for quality using the AGREE-II instrument.Consistency between CPG treatment recommendations was assessed, as was concordance with the ACSQHC sepsis clinical care standards and international sepsis guidelines.Results: Overall, eight CPGs were identified and assessed.CPGs used a narrative and pathway format, with those using both having the highest quality overall.CPG quality was highest for description of scope and clarity of presentation, and lowest for editorial independence.Consistency between guidelines for initial treatment recommendations was poor, with substantial variation in the choice and urgency of empiric antimicrobial administration; the choice, volume and urgency of fluid resuscitation; and the choice of first-line vasoactive agent.Most CPGs were concordant with time-critical components of the ACSQHC sepsis clinical care standard, although few addressed post-acute

Introduction
Clinical practice guidelines (CPGs) are systematically developed recommendations for healthcare providers to assist in making healthcare decisions for specific clinical circumstances. 1 They are based on the best available evidence, expert opinion and patient values and preferences; and they provide guidance on diagnostic tests, treatments and management strategies. 2PGs are important because they provide evidence-based recommendations to healthcare providers, and can improve the quality and consistency of care for patients. 3By following guidelines, healthcare providers can reduce unnecessary variation in clinical practice, audit care, promote best practices and improve patient outcomes.Guidelines can also help to reduce healthcare costs by reducing unnecessary tests and treatments. 4However, high-quality CPGs are generally time consuming and expensive to develop, may be limited in applicability to individual patients and require frequent updating as new evidence emerges. 4n Australia and New Zealand (ANZ), CPGs for the management of paediatric sepsis have been developed independently by multiple states and hospitals.Guidelines have also been produced by major international organisations such as the Surviving Sepsis Campaign. 5Consistency between key treatment recommendations across ANZ guidelines is unclear, as is concordance between ANZ CPGs and international key treatment recommendations.In addition, the Australian Commission on Safety and Quality in Healthcare (ACSQHC) released a clinical care standard for sepsis in June 2022 that aims to support a national coordinated approach and limit unwarranted variation in practice by providing seven quality statements to improve early recognition, treatment, outcomes and post-discharge support. 6It also provides a set of indicators to support monitoring and quality improvement in sepsis management (Appendix S1).It is unclear whether the ANZ CPGs currently address the ACSQHC quality statements.
The present study evaluates the quality of existing ANZ paediatric sepsis guidelines using the Appraisal of Guidelines for REseach and Evaluation (AGREE)-II tool. 7We report the consistency of treatment recommendations between guidelines, compare local guidelines to international treatment recommendations 5 and assess concordance of Australian paediatric sepsis guidelines with the ACSQHC Sepsis Clinical Care Standard.

Study design
The study was designed to appraise multiple CPGs for paediatric sepsis in ANZ.The study was approved by the lead site institutional review board (The Royal Children's Hospital Human Research Ethics Committee, approval number 88085).

Guideline assessment
The AGREE-II tool was selected as an evidence-based instrument to assess the quality of CPGs, 10 as it was developed and validated internationally for this purpose 11,12 and is widely used.Overall there was found to be one guideline for each state of Australia, excepting ACT, and one guideline for New Zealand, and as such this has been used for classification of guidelines throughout this paper.
Guideline format was narrative, pathway-based or a combination of both.The narrative format, used in Victoria, Tasmania, Western Australia and New Zealand, included a wider overview of the topic, including both theoretical and clinical aspects.A pathway format, used in NSW, was more focused, providing the steps to be taken as part of  1).The two domains in which all CPGs were strongest were domain 1: scope and purpose, and domain 4: clarity of presentation, while the weakest domain was domain 6: editorial independence.
Guidelines were consistent in the use of a third-generation cephalosporin for initial antimicrobial management (Table 2).There was variation in the recommendation to administer specific anti-staphylococcal cover, and whether this should target methicillinsensitive or methicillin-resistant Staphylococcus aureus (MSSA and MRSA, respectively).Recommended timing of antimicrobial administration varied between 15 min and <3 h from sepsis recognition.Recommended fluid type for bolus administration was most commonly 0.9% saline, with variable recommended volume (10-20 mL/kg).The total volume of bolus fluid prior to consideration of vasoactive infusion was most commonly 40 mL/kg, and the most commonly recommended initial vasoactive was adrenaline.
The majority of CPGs addressed ACSQHC quality statements regarding recognition, initial management and initial antimicrobial therapy (Table 3).Ongoing aspects of care, including antimicrobial rationalisation, care coordination, patient and carer education, transitions of care and post-acute care, were addressed infrequently.

Discussion
Narrative formats in CPGs were noted to score higher than CPGs using the sepsis pathway format.The AGREE-II tool best lends itself to scoring narrative formats, which include more detail and background to the CPG development process and condition (sepsis).While narrative CPGs offer comprehensive recommendations and principles for managing sepsis based on evidence and expert consensus, pathway CPGs are more focused and time-bound plans that operationalise the guidelines into practical steps to be taken in a coordinated manner.Both tools aim to improve the care and outcomes of sepsis patients while serving slightly different roles in the clinical setting.This does not necessarily mean that the pathway format is inferior; however, as its purpose is to provide a direct and streamlined approach to managing sepsis which is easy to implement, and the lack of detail is, in this context, intentional.However, it was noted that the three CPGs that use both narrative and pathway formats (Queensland, Northern Territory and South Australia) scored higher than any CPG using only a single format.As such, a combination of both formats should be considered where possible, to provide recommendations that are clear, easily understood and appropriately detailed.In practice, the narrative format may be of greater utility as background and rationale for treatment recommendations, while the pathway format may be of greater utility in guideline implementation.
The areas in which all CPGs demonstrated weakness included description of methodology, use of references and listing of authors.Additionally, target audience and editorial independence were not well described.While the majority of the CPGs did include a list references, and many of them referenced other CPGs included in the present study, no clear methodology was provided for collecting or assessing these, or for the choice of what recommendations were included or not included.Target audiences were rarely specified, and while it may be assumed that those seeking out this information are likely to be healthcare professionals, this presumption should be formally documented in order to prevent inappropriate use.Additionally, there was an absence of information provided regarding authors and their affiliations, which allows the possibility for conflict of interest or potential bias.While such influences would not be expected in this setting, they are not unknown in practice 7,15 and as such, a statement of authorship, affiliations, contributions and real or perceived conflicts of interest would be advisable.
There was variable concordance between CPGs with key treatment recommendations, particularly regarding haemodynamic support.This is likely a reflection of the limited evidence upon which treatment recommendations are based.The Surviving Sepsis Campaign international guideline for the management of sepsis in children states that most aspects of care have relatively low quality of evidence, resulting in the frequent provision of weak treatment recommendations. 16Evidence is required in order to issue more robust treatment recommendations.
CPG quality assessments for other common paediatric conditions are highly disease specific.Bronchiolitis guidelines are highly consistent for most treatment recommendations. 17igh-quality evidence underpins the majority of these treatment recommendations, with areas of guideline discordance reflecting evidence gaps.On the other hand, appraisal of paediatric prehospital head injury guidelines identifies areas of inconsistency in multiple treatment recommendations. 18Low-quality or non-existent evidence for these treatment recommendations may be a substantial contributor.
Concordance of CPGs with the ACSQHC sepsis care standards was highest for initial time-critical management, but variable or absent with standards for de-escalation of care, ongoing management including care coordination, communication with patients and families and post-acute care including sepsis survivorship.The sepsis clinical care standard was released in June 2022, and sepsis CPGs may not have had time to be updated (see Table 2).Many sepsis guidelines target initial resuscitation and stabilisationthe acute and timecritical areas which most impact patient outcomesand do not aim to address ongoing care.Indeed, some elements of the ACSQHC Sepsis Standard may be aspirational, with resource limitations restricting delivery in some settings.Lastly, the evidence for improved outcomes, including cost and patient-centred outcomes, from care coordination and standardised post-acute care, while present for adults, [19][20][21][22] is lacking for childhood sepsis survivors.
The existence of multiple sepsis CPGs throughout ANZ health regions is suboptimal, although not unique to sepsis.Creating independent CPGs for each state and territory results in the duplication of effort, and as demonstrated in the current study does not result in highquality CPGs across all ANZ health regions.While some aspects of care, such as antimicrobial choice, depend on local pathogen prevalence and resistance patterns, the vast majority of care is universal and could be included in a high-quality ANZ CPG.Such bi-national CPGs have been developed for bronchiolitis and more recently, paediatric head injury, both underpinned by goodquality evidence. 23,24While the provision of a high-quality CPG alone does not necessarily translate into improved care and should be supported by a targeted effective implementation plan, the use of both a CPG and implementation plan has led to improved bronchiolitis care in ANZ. 25,26This scoping exercise forms the foundation for the development of a bi-national sepsis guideline for children, as prioritised and supported by paediatric EDs. 16

Limitations
Although efforts were made to identify every sepsis guideline in current use in ANZ through the PREDICT network, it is possible that not all CPGs were identified.The AGREE-II tool may be biased towards certain types or formats of CPGs, yielding higher scores for these guidelines.The AGREE-II tool can assess quality of guidelines, but not their content.

Conclusions
In this assessment of sepsis CPGs in current use in ANZ, the best performing CPGs used a combination of narrative and pathway formats, focused on background and implementation, respectively.Treatment recommendations were variable in their consistency.The majority of CPGs agreed with the ACSQHC sepsis clinical care standard quality statements for time-critical management, but did not address post-acute care.Concordance between ANZ and international sepsis CPGs was poor.A bi-national sepsis CPG would reduce duplication in the effort of CPG development, reduce variation in clinical practice, facilitate quality improvement and allow healthcare teams to respond rapidly and consistently to children with sepsis.

TABLE 1 .
Appraisal of Guidelines for REseach and Evaluation-II domain scores by guideline • Unnecessary variation in sepsis care may be reduced by a bi-national guideline.

TABLE 2 .
Australian, New Zealand and international sepsis guideline treatment recommendations 13,14The AGREE-II tool assessed CPGs via 23 questions in six domains:

TABLE 3 .
Do sepsis guidelines address ACSQHC Sepsis Clinical Care Standard Quality statement?