Cardiovascular Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference

Abstract

Context:

Cardiovascular dysfunction is associated with poor outcomes in critically ill children.

Objective:

To derive an evidence-informed, consensus-based definition of cardiovascular dysfunction in critically ill children.

Data Sources:

Electronic searches of PubMed and EMBASE were conducted from January 1992 to January 2020, using medical subject heading terms and text words to define concepts of cardiovascular dysfunction, pediatric critical illness, and outcomes of interest.

Study Selection:

Studies were included if they evaluated critically ill children with cardiovascular dysfunction, assessment/scoring tools to screen for cardiovascular dysfunction, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies of adults or premature infants (≤36 weeks gestational age), animal studies, reviews/commentaries, case series with sample size ≤10, and non-English language studies were excluded. Studies of children with cyanotic congenital heart disease or cardiovascular dysfunction after cardiopulmonary bypass were excluded.

Data Extraction:

Data were abstracted from each eligible study into a standard data extraction form along with risk of bias assessment by a task force member.

Results:

Cardiovascular dysfunction was defined by nine elements, including four which indicate severe cardiovascular dysfunction. Cardiopulmonary arrest (> five minutes) or mechanical circulatory support independently define severe cardiovascular dysfunction, while tachycardia, hypotension, vasoactive-inotropic score, lactate, troponin I, central venous oxygen saturation, and echocardiographic estimation of left ventricular ejection fraction were included in any combination. There was expert agreement (>80%) on the resulting definition.

Limitations:

All included studies were observational and many were retrospective.

Conclusions:

The PODIUM panel propose this evidence-informed definition of cardiovascular dysfunction.

Summary:

This manuscript reports a systematic review on cardiovascular dysfunction scoring tools and proposes evidence-based criteria for cardiovascular dysfunction in critically ill children.

INTRODUCTION

Cardiovascular dysfunction is common during childhood critical illness due to the complex interplay between myocardial and endothelial function. This dysfunction may manifest as vasoplegia, left ventricular (LV), right ventricular (RV) or bi-ventricular systolic and/or diastolic dysfunction.(1) Independent of etiology, cardiovascular dysfunction during critical illness may result in inadequate delivery of oxygen (DO₂) to tissues. Reduced DO₂ is associated with increased risk of morbidity, mortality, and need for high resource therapies such as extracorporeal life support (ECLS) and/or mechanical circulatory support (MCS).(2) While there are no randomized clinical trials to support this, it is likely that early recognition and appropriate management of cardiovascular dysfunction would reduce morbidity and mortality in critically ill children. Physical exam, vital signs, laboratory tests, and imaging studies can assist in the diagnosis of cardiovascular dysfunction, however utilization of these diagnostic tools is variable.(3) There is a lack of consensus on how to investigate and ultimately define life-threatening cardiovascular dysfunction in pediatric critical care.

Critically ill children with cardiovascular dysfunction can be broadly separated into two populations – those who develop cardiovascular dysfunction associated with critical illness, and those who develop critical illness in the setting of pre-existing primary structural or functional cardiac abnormalities. Here, we used existing scientific evidence and an expert consensus panel to define cardiovascular dysfunction in critically ill children that can be applied broadly in clinical practice, as well as for scientific inquiry. We have targeted this definition to patients without underlying cyanotic congenital heart disease (CHD) who have cardiovascular dysfunction in the setting of critical illness. This definition is not intended to assess or grade post-cardiopulmonary bypass (CPB) impaired cardiac output or inflammatory state. Thus, we have also excluded consideration of children who underwent CPB during ICU admission, prior to developing cardiovascular dysfunction.

METHODS

The PODIUM collaborative sought to develop evidence-based criteria for organ dysfunction in critically ill children. The present manuscript reports on the systematic review on acute cardiovascular dysfunction scoring tools performed as part of PODIUM, provides a critical evaluation of the available literature, proposes evidence-based criteria for acute cardiovascular dysfunction in critically ill children, as well as recommendations for future research. The PODIUM Executive Summary details Population, Interventions, Comparators, and Outcomes (PICO) questions, search strategies, study inclusion and exclusion criteria, and processes for risk of bias assessment, data abstraction and synthesis, and for drafting and developing agreement for criteria indicating acute cardiovascular dysfunction (4).

RESULTS

Of 6,737 unique citations published between 1992 and 2020, 175 studies were eligible for inclusion, as shown in the PRISMA flowchart (Fig. 1). Data tables (Supplemental Tables 1 and 2), supplemental references (Supplemental Tables 3–6) and risk of bias assessment summaries (Supplemental Fig. 1) are detailed in the Data Supplement.

Figure 1.

Study flow diagram according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols recommendations.

The criteria incorporated into the definition of cardiovascular dysfunction in critically ill children are shown in Table 1. As noted above, these criteria were informed by medical literature excluding children with underlying cyanotic CHD and those who underwent CPB during the ICU admission. Elements not incorporated into the current definition of cardiovascular dysfunction, because they did not reach expert panel agreement, are shown in Table 2. These data elements, however, represent important criteria for further investigation.

Table 1.

PODIUM: Criteria for Cardiovascular Dysfunction in Critically Ill Children

Criteria for cardiovascular dysfunction in patients who have cardiovascular dysfunction in the setting of critical illness Excluding patients: with underlying cyanotic congenital heart disease and those who underwent cardiopulmonary bypass (CPB) during the ICU admission, prior to cardiovascular dysfunction. These criteria are not intended to assess or grade post-CPB impaired cardiac output or inflammatory state.
Organ system	Criterion for organ dysfunction	Suggested thresholds	Conditions	Severity
CV	Cardiac Arrest	NA	Cardiac arrest for >5 mins from any etiology. Even if the cardiopulmonary arrest occurred from dislodged ETT, or hypoxic respiratory failure precipitating cardiac failure, if the cardiac arrest is not reversible then some element of cardiovascular dysfunction should be presumed to be present.	Severe
CV	Venoarterial ECLS, temporary or durable LVAD or RVAD support	NA	None	Severe
CV	Heart rate (HR)	>2 SD above normal for age 0–7 days: HR>180 >1 week – 1 month: HR>180 >1 month – <1 year: HR>180 >1 year – <6 years: HR>160 6 years – <13 years: HR>150 13 – <18 years: HR>130	*confirmed sinus rhythm, when present at the same time as any of the other criteria for CV organ dysfunction	Not graded
CV	Systolic blood pressure (SBP)	More than 2 SD below normal for age 0–7 days: SBP<50 >1 week – 1 month: SBP<70 >1 month – <1 year: SBP<75 >1 year – <6 years: SBP<75 6 years – <13 years: SBP<80 13 years – <18 years: SBP<80	*when present at the same time as any of the other criteria for CV organ dysfunction	Not graded
CV	Vasoactive Inotropic Scorea	≥ 5	*when present at the same time as any of the other criteria for CV organ dysfunction	Not graded
CV	Serum lactate	≥3 – <5 mmol/L	*when present at the same time as any of the other criteria for CV organ dysfunction	Non-severe
		≥5 mmol/L	*when present at the same time as any of the other criteria for CV organ dysfunction	Severe
CV	Serum troponin I	0.6 – 2.0 ng/mL	*when present at the same time as any of the other criteria for CV organ dysfunction	Non-severe
		>2.0 ng/mL	*when present at the same time as any of the other criteria for CV organ dysfunction	Severe
CV	Central venous oxygen saturation	<70%	*when present at the same time as any of the other criteria for CV organ dysfunction In patients without cyanotic congenital heart disease Ideally sampled from right atrium or pulmonary artery in a patient without intracardiac abnormalities, but proximal SVC and IVC acceptable. Whole blood laboratory assay as standard, but consider validated continuous invasive monitoring	Not graded
CV	Echocardiographic estimation of left ventricular ejection fraction	30% – <50%	*when present at the same time as any of the other criteria for CV organ dysfunction	Non-severe
		<30%	*when present at the same time as any of the other criteria for CV organ dysfunction	Severe

SD, standard deviation; SVC, superior vena cava; IVC, inferior vena cava; ECLS, extracorporeal life support; LVAD, left ventricular assist device; RVAD, right ventricular assist device

^aVasoactive Inotropic Score = dopamine dose (µg/kg/min) + dobutamine dose (µg/kg/min) + 100 x epinephrine dose (µg/kg/min) + 10 x milrinone dose (µg/kg/min) + 10,000 x vasopressin dose (U/kg/min) + 100 x norepinephrine dose (µg/kg/min)

Table 2.

Clinical Criteria for Further Study in Cardiovascular Dysfunction in Pediatric Critical Illness

Criteria	No. of Studies	Types of Studies	Setting	Patient Population	Outcomes Studied
Capillary refill time	5	Retrospective, prospective, case-control, cross-sectional, case series, observational	PICU, Newborns, in hospital patients (CHEWS score assessment), sepsis	Neonates, pediatric inpatients	Correlation with blood pressure; Not independently associated with mortality, may form part of a composite score predicting need for escalation of care
Composite prediction scores of adverse event (e.g. PEWS)	8	Retrospective, prospective, case-control, cross-sectional, case series, observational	Inpatients on floor, PICU, PICU-Transport System	Inpatients on floor, Bone marrow transplant, meningococcal sepsis, Acute heart failure patients with MCS.	Respiratory or Cardiac Arrest, death, or unexpected admission to the PICU
Lactate clearance	5	Retrospective, prospective, case-control, cross-sectional, case series, observational	PICU NICU	PICU, NICU, sepsis, meningococcal sepsis, birth asphyxia,	Mortality
NIRS Cerebral	2	Retrospective, prospective, case-control, cross-sectional, case series, observational	NICU admitted ECMO	CDH	Cannulated to ECMO
NIRS Somatic <70%	3	Retrospective, prospective, case-control, cross-sectional, case series, observational	PICU, mixed PICU	All patients	Combined outcome of resuscitation requirement (mortality, ECMO, volume resuscitation, NIV);
BNP or NT-pro BNP	21	Retrospective, prospective, case-control, cross-sectional, case series, observational	PICU, NICU, mixed PICUs, inpatient ward, ER	PICU, NICU, sepsis, meningococcal sepsis, enterovirus, birth asphyxia, DCM, Myocarditis, Acute decompensated heart failure, malaria	Mortality, ventricular dysfunction by echo, severe heart failure, composite adverse event outcomes

NICU, neonatal intensive care unit; PICU, pediatric intensive care unit; BNP, brain natriuretic peptide; CHEWS, Children’s Hospital Early Warning System; DCM, dilated cardiomyopathy; ECMO, extracorporeal membrane oxygenation; MCS, mechanical circulatory support; PEWS, Pediatric Early Warning System; NIRS, near infrared spectroscopy

Clinical Criteria Included in Definition

Cardiovascular dysfunction in critically ill children is defined as presence of (1) cardiac arrest for more than 5 minutes; and/or (2) mechanical circulatory support; or (3) at least 2 abnormal criteria of heart rate, systolic blood pressure, vasoactive-inotrope score, lactate, central venous oxygen saturation, troponin I, or echocardiographic estimation of left ventricular ejection fraction (Table 1).

Cardiac Arrest

Rationale - Any patient with cardiac arrest for more than five minutes, under any circumstances, will be considered to have severe cardiovascular dysfunction. Post cardiac arrest myocardial dysfunction occurs even in the absence of an underlying cardiac cause for the arrest and is associated with early mortality (5–7). This pragmatic approach reflects the underlying cardiovascular dysfunction inherent when return of circulation is not rapidly achieved with administration of advanced life support therapies, as well as the resulting cardiovascular dysfunction from prolonged cardiopulmonary resuscitation.

Mechanical Circulatory Support

Rationale - Any patient supported with MCS including veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or temporary or durable ventricular assistance device (VAD) will be considered to have severe cardiovascular dysfunction. In neonates and children managed on ECMO for cardiac indications, survival to hospital discharge remains low (45% and 57% respectively). (8) Heart-transplant free-survival for children managed with durable VADs remains less than 10% at 12 months. (9) The pragmatic approach of defining severe cardiovascular dysfunction due to the presence of MCS alone reflects the underlying cardiovascular dysfunction inherent with the requirement for this support.

Heart Rate and Systolic Blood Pressure

Rationale - Heart rate (HR) is an element of many combination ‘early warning’ scores, as well as descriptive and predictive models for mortality in critical illness, contributing to the explanatory power of the multivariable models.(10–12) During critical illness HR has been shown to be associated with cardiovascular dysfunction and is used an indirect indicator of severity of illness or response to therapies: 1) in diverse settings including consideration for escalation of care (transport to a specialist center or admission to ICU), classification of severity of injury, and indications for and response to blood transfusions; 2) in diverse populations including inpatients on general wards, in the emergency department (ED), cardiac catheterization laboratory and pediatric ICU (PICU); and 3) in diverse diagnoses such as trauma, bone marrow transplant, sepsis, acute heart failure, pulmonary hypertension and requirement for MCS. (12, 13) When we consider blood pressure (BP), hypotension is included in predictive models of mortality in critical illness, descriptive and prognostic tools and ‘early warning’ scores.(10–12) A low systolic BP has similarly been shown to be associated with cardiovascular dysfunction and outcomes including referral to transport teams for escalation of care, severity of injury, blood transfusion, PICU admission, cardiopulmonary arrest and mortality within populations including inpatient hospital wards and PICUs, as well as patients with specific diagnoses including trauma, bone marrow transplantation, sepsis, myocarditis, acute heart failure and need for MCS.(11)

In order to estimate age-appropriate cut-offs for abnormal HR and BP, we elected to cohort patients into ages with similar normative ranges, informed by previous guidelines and scores (Table 1).(11) The HR and BP cutoffs incorporated into the definition were estimated as two standard deviations outside observed range for age cohorts in a critically ill pediatric population.(14) Elevated HR and low systolic BP will contribute, in combination with at least one other abnormal criterion, to the criteria for cardiovascular dysfunction in critically ill children.

Vasoactive-Inotropic Score

Rationale - Supportive care, such as tracheal intubation, ventilation, sedation, neuromuscular blockade, vasoactive-inotropic infusions and mechanical circulatory support, have the potential to modulate vital signs and end-organ findings associated with cardiovascular dysfunction in critical illness. Of these, only vasoactive-inotropic infusions and MCS are specific to the cardiovascular system and so are included in the definition criteria. Higher vasoactive-inotropic doses administered in the post-cardiopulmonary bypass period have been associated with adverse outcomes in infants and children with CHD.(15, 16) The vasoactive-inotropic score (VIS) was initially established in this population as a dose-dependent marker associated with morbidity and mortality.(16) VIS is calculated using the formula: dopamine dose (mcg/kg/min) + dobutamine dose (mcg/kg/min) + 100 x epinephrine dose (mcg/kg/min) + 10 x milrinone dose (mcg/kg/min) + 10,000 x vasopressin dose (U/kg/min) + 100 x norepinephrine dose (mcg/kg/min).(16) Vasoactive-inotropic infusion doses were incorporated into studies of patients with cardiomyopathy, myocarditis, as well as some assessments of general critical illness. (17, 18) Subsequently VIS has been specifically assessed in critically ill children without CHD and has been shown to be associated with cardiovascular dysfunction and cortisol levels, as well as outcomes including duration of ventilation, ICU length of stay, cardiopulmonary arrest, use of ECLS and mortality prior to hospital discharge among general PICU patients and those with sepsis.(18) For every unit increase in VIS at 12 hours, there was a 14% increased odds of having the composite outcome of cardiopulmonary arrest, ECLS, or mortality prior to hospital discharge.(18) At 48 hours VIS showed the strongest correlation with ICU length of stay and ventilator days. For every unit increase in VIS at 48 hours, there was a 13% increase in ICU length of stay and 8% increase in ventilator days. In systemic illness associated with sepsis, the median VIS was 5–6 which is much lower than in the post-cardiopulmonary bypass population (16); hence we included an informed cutoff VIS of ≥5 to contribute, in combination with other abnormal criteria, to the definition of cardiovascular dysfunction in critically ill children.

Biomarkers of Cardiovascular Dysfunction

Rationale - Laboratory derived markers of cardiac injury, congestive heart failure, inadequate systemic oxygen delivery (or increased oxygen extraction to compensate for low cardiac output) and secondary organ dysfunction such as acute kidney and hepatic injury, are often assessed in critical illness. We excluded assessment of secondary organ dysfunction from our definition elements, as these will be captured within alternative organ-specific elements. Elevated lactate, elevated troponin I and low mixed (central) venous oxygen saturation are included in combination with at least one other abnormal criterion in the definition of cardiovascular dysfunction in critically ill children.

Lactate

Rationale - Lactate, resulting from inadequate oxygen delivery to tissues and anaerobic metabolism, is incorporated into pediatric sepsis guidelines, PELOD-2 score, and has been combined with the PRISM-III score to improve explanatory power for the outcome of mortality associated with critical illness.(11, 19) Lactate levels during critical illness have been associated with cardiovascular dysfunction and outcomes of septic shock, hospital length of stay greater than ten days, mortality prior to ICU or hospital discharge, and 18–24 month neurodevelopmental outcomes, within specific populations including inpatients, ED, NICU and mixed PICUs, as well as those with specific diagnoses including suspected sepsis, sepsis, malaria, birth asphyxia, acute heart failure, out of hospital cardiac arrest and respiratory disease managed with MCS.(11, 19–23) Measurements were variably taken at specified timepoints related to admission (19, 20, 22–24), reported as maximum during a given timeframe (21), or expressed as clearance of lactate burden over time.(20) Studies have consistently shown lactate <2 mmol/L to be an important negative predictor of mortality, while higher lactates (>3 mmol/L, >4 mmol/L, >5 mmol/L, >5.5 mmol/L, >10 mmol/L, >25 mmol/L) were associated with mortality with a relatively linear relationship when multiple cutoffs were assessed in the same analysis.(11, 19, 21, 24) In children with suspected sepsis, lactate measurements >3 mmol/L and >4 mmol/L at PICU admission, respectively, were associated with septic shock diagnosis and hospital length of stay greater than ten days.(25) In newborn infants with perinatal hypoxia, lactate levels >8.7 mmol/L were associated with hypoxic ischemic encephalopathy (HIE) of greater or equal to Grade 2.(21) In a prospectively followed cohort of patients with neonatal respiratory disease supported with ECLS, peak lactate >15 mmol/L was associated with the composite adverse outcome: death from any cause before 18–24 month follow-up or evidence of neurological disability at 18–24 months.(23) Informed by studies demonstrating gradation of association with poor outcomes, we included lactate 3–5 mmol/L (non-severe), and lactate >5 mmol/L (severe) in association with another abnormal criteria for the definition of cardiovascular dysfunction in critically ill children.

Troponin I

Rationale - Troponin I is released from damaged myocardium in the setting of ischemia, injury or illness. Troponin I levels during critical illness have been associated with cardiovascular dysfunction evaluated by echocardiogram and outcomes of adverse neurodevelopmental status, respiratory failure and mortality prior to hospital discharge, within populations in the ED, NICU, and unselected patients in mixed PICUs, as well as those with specific diagnoses of myocarditis, sepsis, birth asphyxia, enterovirus infection, RSV bronchiolitis, scorpion envenomation, trauma and cardiopulmonary arrest after submersion.(1, 26) Measurements were variably taken at specified timepoints related to birth or admission. Detectable troponin I levels at PICU admission in unselected patients were associated with mortality.(26) Troponin I levels correlated with impaired ventricular systolic function in studies of patients with sepsis, birth asphyxia and scorpion envenomation. In patients with sepsis, higher troponin I levels were predictive of LVEF <50% by echocardiographic criteria. In babies with HIE, cord blood troponin I level was associated with mortality and neurodevelopmental outcome at 18–24 months.(27) In children presenting with RSV bronchiolitis, troponin I level was positively associated with requirement for intubation and ventilation.(28) Informed by studies demonstrating gradation of association with poor outcomes, we included troponin I 0.6 −2.0 ng/mL (non-severe), and troponin I >2.0 ng/mL (severe) in association with another abnormal criteria for definition of cardiovascular dysfunction in critically ill children.

Central Venous Oxygen Saturation

Rationale – Central (or mixed) venous oxygen saturation (ScvO₂), when compared to arterial oxygen saturation (or the arteriovenous oxygen saturation difference), reflects the degree of oxygen extraction by the tissues. Under circumstances of impaired or inadequate cardiac output, critically ill patients partially compensate for reduced oxygen delivery with increased tissue oxygen extraction, reflected by lower ScvO₂. Ideally sampled from right atrium or pulmonary artery (proximal superior and inferior vena cava acceptable) in patients without intracardiac abnormalities, whole blood co-oximetry is considered standard. Validated continuous invasive monitoring via central venous catheters are acceptable surrogates. During critical illness ScvO₂ has been shown to be associated with cardiovascular dysfunction and in-hospital mortality in a general population of critically ill children and in patients with a diagnosis of sepsis. (29) Children with sepsis who did not achieve ScvO₂ >70% after six hours of resuscitation were more likely to die during hospital admission.(29) We included an informed cutoff ScvO₂ <70% to contribute to the definition of cardiovascular dysfunction in critically ill children in combination with another abnormal criteria.

Echocardiographic Assessment of Left Ventricular Ejection Fraction

Rationale - Echocardiographic assessment of cardiac structure and function remains a mainstay of assessment of the critically ill patient. Left ventricular systolic dysfunction as evidenced by reduced ejection fraction (LVEF) during critical illness has been associated with outcomes of heart transplantation, mechanical circulatory support (MCS), and in-hospital mortality within populations including hospital inpatients, ED, NICU, mixed PICUs, and those with diagnoses of myocarditis, sepsis, enterovirus, RSV bronchiolitis, birth asphyxia, scorpion envenomation and trauma.(17) In patients with meningococcal sepsis, LVEF <30% was associated with mortality. There was significant variability in the studies assessed; studies in children with myocarditis, sepsis and birth asphyxia informed suggested thresholds. In studies of patients with myocarditis, survivors had higher LVEF than non-survivors, with odds of survival increasing per 10% in LVEF > 30%.(17) Informed by studies demonstrating gradation of association with poor outcomes, we included LVEF 30–50% (non-severe), and LVEF <30% (severe) in association with another abnormal criteria for definition of cardiovascular dysfunction in critically ill children.

Incorporating Multiple Criteria for the Definition of Cardiovascular Dysfunction

Rationale - Cardiovascular dysfunction in critical illness includes both myocardial and endothelial components. If the primary insult is related to systolic or diastolic myocardial dysfunction, then functional assessment with echocardiography may be ideal. However continuous monitoring is not feasible, so the clinician is unable to readily trend responses to treatment such as vasodilation or diuresis.(17) The majority of criteria included in the definition of cardiovascular dysfunction in critically ill children reflect pathophysiologic responses to some perturbation in either myocardial or endothelial function. Unlike other organs, there is limited data for any individual criterion that capture the clinical state. As such the pre-existing multi-organ dysfunction definitions have included a requirement for more than one criterion to be present in order to meet the definition of cardiovascular dysfunction.(30, 31) We have thus incorporated similar recommendations to include at least two of the following to meet the definition of cardiovascular dysfunction: elevated heart rate, low systolic blood pressure, elevated VIS, elevated lactate, elevated troponin, low central venous oxygen saturation or reduced left ventricular ejection fraction.

Limitations

All included studies were observational, and many were retrospective. Studies included populations from international centers, inpatients on general wards, in Emergency Departments, cardiac catheterization laboratory and PICU; and representing patients with diverse diagnoses such as trauma, bone marrow transplant, sepsis, acute heart failure, pulmonary hypertension and requirement for MCS. The international burden of disease associated with severe sepsis in the critically ill pediatric population, and prioritization of research targeting this diagnosis, may have resulted in over-representation in this population informing the cardiovascular dysfunction definition.

CONCLUSION

We propose an evidence-informed consensus definition for cardiovascular dysfunction in critically ill children (without underlying CHD or recent CPB) that considers the vital signs, vasoactive-inotropic support, biomarkers, measures of oxygen extraction and echocardiography. Cardiopulmonary arrest (of longer than five minutes) and use of MCS independently define severe cardiovascular dysfunction, while the other criteria define cardiovascular dysfunction when two or more abnormal elements are identified. Cardiopulmonary arrest, use of MCS, elevated troponin I (>2 ng/mL), elevated lactate (>5 mmol/L) and severely impaired LVEF measured by 2-D echocardiography (<30%) indicate severe cardiovascular dysfunction.

Supplementary Material

Data Supplement

Supplemental Figure 1. Risk of Bias Assessment Summary for Studies Included in the PODIUM Cardiovascular Dysfunction Systematic Review (n=162 studies)

Supplemental Table 1. Studies Included in the PODIUM Cardiovascular Dysfunction Systematic Review (n=162 studies)

Supplemental Table 2. Performance Characteristics for Assessment Tools and Scores for Cardiovascular Dysfunction in Critically Ill Children (n=162 studies)

Supplemental Table 3. Complete References for Heart Rate and Systolic Blood Pressure

Supplemental Table 4. Complete References for Vasoactive-Inotropic Score

Supplemental Table 5. Complete References for Biomarkers of Cardiovascular Dysfunction

Supplemental Table 6. Complete References for Echocardiographic Assessment of Left Ventricular Ejection Fraction

Abbreviations:

MODS

Multiple organ dysfunction syndrome

PELOD

Pediatric Logistic Organ Dysfunction Score

PODIUM

Pediatric Organ Dysfunction Information Update Mandate

PRISM

Pediatric Risk of Mortality