The relative importance or values of the main outcomes of interest: Outcome. Survival to Hospital Discharge

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1 Problem Is there a problem priority? Yes The existing evidence, though observational, indirect, imprecise, and thus very low quality, shows a consistent association between hypotension and adverse outcome. Given the available evidence, there is a high priority to avoid and where present mitigate the exposure (hypotension). It is important to te that the research evidence does t directly assess the intervention of interest as defined in our PICO question. The research evidence does t directly assess the intervention of interest. Benefits & harms of the s What is the overall certainty of this evidence? Is there important uncertainty about how much people value the main outcomes? included studies Very low Low Moderate High Important uncertainty or Possibly important uncertainty or The relative importance or values of the main outcomes of interest: Outcome Survival to Hospital Discharge Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year Patient Satisfaction Relative importance IMPORTANT CRITICAL CRITICAL Certainty of the evidence (GRADE) VERY LOW VERY LOW Confounding by indication is a serious methodological concern when considering the effects of an exposure like hypotension post ROSC following cardiac arrest. The Topjian et al. paper did include measurement of a number of important confounders and thus was able to statistically control for these in the analyses presented in that manuscript.

2 desirable anticipated effects large? important uncertainty of important uncertainty of kwn undesirable Harm to Patient Summary of findings: intervention Outcome Survival to Hospital Discharge Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year Without the use of parenteral fluids and itropes vasopressors to maintain targeted measures of perfusion such as blood pressure 338 per per 1000 IMPORTANT With the use of parenteral fluids and itropes vasopressors to maintain targeted measures of perfusion such as blood pressure Difference (95% CI) t t Relative effect (RR) (95% CI) t t undesirable anticipated effects small? Patient Satisfaction Harm to Patient t t t t

3 desirable effects large relative to undesirable effects? Resource use resources required small? None The intervention under consideration involves use of resuscitation fluids medications that are commonly available and commonly used in settings capable of providing paediatric advanced life support.

4 Is the incremental cost small relative to the net benefits? None The incremental cost of the intervention relative to the net benefits has t been specifically assessed. Equity What would be the impact on health inequities? Increased increased reduced Reduced None The impact of the intervention on health inequities has t been specifically assessed. Acceptability Is the acceptable to key stakeholders? The included studies report use of fluids and vasoactive medications in this population as part of their management post ROSC. Acceptability was t specifically assessed, however the available data suggests that this intervention is probably acceptable to stakeholders. The intervention under consideration involves use of resuscitation fluids medications that are commonly available

5 and commonly used in settings capable of providing paediatric advanced life support. Feasibility Is the feasible to implement? The included studies report use of fluids and vasoactive medications in this population as part of their management post ROSC. Feasibility were t specifically assessed, however the available data suggests that this intervention can be implemented in settings capable of providing paediatric advanced life support. The intervention under consideration involves use of resuscitation fluids medications that are commonly available and commonly used in settings capable of providing paediatric advanced life support.

6 Recommendation Should the use of parenteral fluids and itropes vasopressors to maintain targeted measures of perfusion such as blood pressure vs. intervention be used for children post ROSC after cardiac arrest? Balance of consequences Undesirable consequences clearly outweigh desirable consequences in most settings Undesirable consequences probably outweigh desirable consequences in most settings The balance between desirable and undesirable consequences is closely balanced or uncertain Desirable consequences probably outweigh undesirable consequences in most settings Desirable consequences clearly outweigh undesirable consequences in most settings Type of recommendation We recommend against offering this We suggest t offering this We suggest offering this We recommend offering this Recommendation Data is t available to provide a recommendation regarding the use of fluids and itropes vasopressors to maintain targeted measures of perfusion such as blood pressure in children post ROSC after cardiac arrest. Based on the available evidence, we do suggest to avoid hypotension in the period immediately following ROSC for paediatric survivors of in-hospital cardiac arrest (IHCA) and out of hospital cardiac arrest (OHCA). The quality of evidence was determined to be very low based on the number of relevant studies identified (3), study design (observational studies), risk of bias (very serious), inconsistency (serious), indirectness (serious), and imprecision (very serious). None of the studies directly assessed the intervention of interest as defined in our PICO question. Justification In the three observational studies identified, the proportion of children surviving to hospital discharge was lower among children who experienced hypotension versus hypotension following IHCA or OHCA. As an exposure, hypotension post ROSC following cardiac arrest is subject to serious confounding by indication. In other words, the very factors (kwn and unkwn) that place a child as risk for hypotension post ROSC may be linked with identified important outcomes including survival and neurological/functional outcome. Recognizing this limitation, hypotension post ROSC was associated with adverse outcome in all the three identified studies and we therefore suggest that this should be avoided. The critical period in which hypotension should be avoided post ROSC is unclear. In the available studies, hypotension was variably defined and ascertained over differing time periods ranging from 1 to 6 hours post ROSC. Only one observational study (Topjian et al) provided data with respect to favourable neurologic outcome versus unfavourable neurologic outcome according to post ROSC exposure to hypotension versus hypotension. While the authors of this study did

7 assess and statistically control for multiple potential confounders, the overall quality of evidence remains very low. Based on the available evidence, we are able to state that exposure to hypotension post ROSC following cardiac arrest was associated with adverse outcome across the three studies identified. We therefore suggest the avoidance of hypotension immediately following ROSC in children following IHCA or OHCA based on the available data. Subgroup No subgroup can be offered at this moment. Implementation No implementation can be made at this moment. Monitoring and evaluation No recommendations can be made at this moment. Research possibilities High quality research is needed to assess the intervention as defined in our PICO to avoid hypotension post ROSC following cardiac arrest. The optimal strategy i.e. the relative use of parenteral fluids versus itropes vasopressors for avoidance of hypotension post ROSC following cardiac arrest in children is also currently unclear. The optimal perfusion endpoints to target have yet to be defined. Such endpoints could include systolic blood pressure, mean blood pressure, measures of cardiac output, markers of perfusion such as serum lactate. The optimal time period during which targeted measures of perfusion should be considered remains unclear. It is unclear whether any harm to the patient or adverse effects may arise as a result of use of parenteral fluids and itropes vasopressors to maintain targeted measures of perfusion. It is also unkwn if there are subgroups of children who respond differently to components of the intervention, such as cardiac patients or trauma patients who may be particularly sensitive to preload status or changes in afterload.