Abstract
Background:
Left ventricular systolic dysfunction in children with suspected infection can worsen outcomes and complicate early management of sepsis. Cardiac ultrasound enables bedside assessment of ventricular function, but it remains unclear which bedside markers are associated with an increased risk of myocardial dysfunction.
Objective:
To identify which bedside markers commonly incorporated into pediatric sepsis assessment are associated with reduced left ventricular systolic function on cardiac ultrasound in children with suspected infection.
Methods:
In this retrospective cohort study, we included patients aged 1 month to 21 years with suspected infection who had documented heart rate and blood pressure within 6 hours of emergency department presentation and underwent cardiac ultrasound assessment (CUS), defined as either cardiac point of care ultrasound (POCUS) or transthoracic echocardiography (TTE), within 24 hours (N = 2,046). Patients whose CUS was performed after initiation of vasoactive therapy were excluded. Reduced left ventricular systolic function was defined as either qualitative assessment of reduced function on expert reviewed cardiac POCUS or a left ventricular ejection fraction <50% on TTE. A multivariable logistic regression model assessed associations between bedside markers included in commonly used pediatric sepsis assessment tools (tachycardia, systolic hypotension, altered mental status, capillary refill time [CRT], and a high risk condition) and reduced left ventricular systolic function. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated.
Results:
Among 2,046 eligible patients undergoing CUS, 89 (4.3%) had reduced left ventricular systolic function. In multivariable analysis, systolic hypotension (aOR 2.16, 95% CI 1.00 to 4.65) and prolonged capillary refill time (CRT 3 seconds, aOR 1.84, 95% CI 1.03 to 3.28; CRT ≥4 seconds, aOR 2.22, 95% CI 0.98 to 5.03) were associated with reduced left ventricular systolic function. Tachycardia (aOR 0.79, 95% CI 0.50 to 1.26), altered mental status (aOR 1.18, 95% CI 0.63 to 2.21), and a high risk condition (aOR 1.19, 95% CI 0.69 to 2.05) were not associated with reduced function.
Conclusions:
Reduced left ventricular systolic function on cardiac ultrasound among children with suspected infection was uncommon but associated with systolic hypotension and prolonged capillary refill time. Notably, it was not associated with tachycardia alone. These findings suggest that systolic hypotension and prolonged capillary refill are bedside markers associated with an increased risk of myocardial dysfunction and may help inform the selective use of cardiac ultrasound during the early evaluation of children with suspected infection. Prospective studies are needed to validate these findings.
Introduction:
Cardiac dysfunction in pediatric patients with suspected infection is associated with increased illness severity and mortality.1,2 Early recognition of myocardial impairment is therefore central to guiding initial resuscitation decisions in pediatric sepsis. Septic shock management has emphasized early fluid resuscitation; however, in children with sepsis-associated myocardial dysfunction, this approach may contribute to fluid overload and subsequent morbidity, including secondary organ injury and increased mortality.3 These concerns highlight the importance of identifying impaired cardiac function early in the course of illness.
Recent evidence has questioned the reliability of clinical assessment alone for characterizing pediatric septic shock physiology.4,5 Earlier guidelines recommended categorizing shock as “warm” or “cold” based on physical examination findings to guide therapy, but observational studies have demonstrated poor correlation between these bedside signs and objective measures of cardiac output and vascular resistance.4,6 Notably, myocardial dysfunction has been observed even in children who clinically appear to have preserved cardiac output.6 As a result, contemporary pediatric sepsis guidelines advise against reliance on bedside clinical assessment in isolation, citing limited and low-quality supporting evidence.7
Echocardiography offers a more direct assessment of hemodynamic status and has been shown to identify myocardial dysfunction and hypovolemia not apparent on clinical examination. In pediatric populations, echocardiography-guided assessment has been associated with earlier shock reversal, reduced fluid administration, and improved clinical outcomes.8-10
An alternative to detect myocardial dysfunction is cardiac point-of-care ultrasound (POCUS) as it has emerged as a practical bedside modality for rapid, non-invasive evaluation of global cardiac function in children.11-14 When performed by clinical providers, cardiac POCUS can be integrated early in the patient’s clinical course and has been shown to alter hemodynamic assessment and management decisions in children with suspected septic shock.15 With this in mind, the Society of Critical Care Medicine and the European Society of Intensive Care Medicine now recommend the use of cardiac POCUS to guide resuscitation in pediatric sepsis.16 Nevertheless, the evidence remains limited, and further studies are needed to define the optimal role of cardiac POCUS in pediatric sepsis. Several bedside clinical markers, including heart rate, blood pressure, capillary refill time, and mental status, are routinely incorporated into pediatric sepsis recognition tools such as the Children's Hospital of Philadelphia (CHOP) sepsis screen and qPS4. These bedside markers are widely used during the initial evaluation of children with suspected infection and represent readily available measures of cardiovascular status.17-19
Despite recognized concern for myocardial dysfunction in children with suspected infection, it remains unclear which clinical features should prompt concern for underlying cardiac dysfunction prior to vasoactive therapy. Specifically, understanding which commonly used bedside markers of pediatric sepsis are associated with left ventricular systolic dysfunction may help identify children at increased risk for myocardial dysfunction and inform the selective use of cardiac ultrasound during the early evaluation of suspected infection..18,19 The primary objective of this study was to determine which bedside markers included in widely used pediatric sepsis screening tools are associated with reduced left ventricular systolic function on either cardiology-performed echocardiography or cardiac POCUS in children presenting with suspected infection.
Methods
Study Design and Setting
We conducted a retrospective cohort study of pediatric patients aged 1 month to 21 years who presented to a tertiary pediatric emergency department (PED) between January 1, 2015, and August 1, 2024. The PED evaluates approximately 65,000 annual visits and maintains a departmental quality assurance (QA) process for all POCUS examinations. Transthoracic echocardiography (TTE) is available 24 hours per day when clinically indicated. The study was approved by the Institutional Review Board with a waiver of informed consent.
Study Population
Patients were eligible for inclusion if they were evaluated or treated for suspected infection. In addition, they had to undergo a cardiac ultrasound assessment of left ventricular function within 24 hours of presentation. Cardiac ultrasound was defined as a cardiac POCUS examination or transthoracic echocardiogram (TTE). To be included, patients were required to meet the following criteria:
Documentation of both heart rate and blood pressure within 6 hours of PED arrival.
Evaluation or treatment consistent with suspected infection defined as either fever or hypothermia, administration of systemic (either oral or intravenous) antimicrobial therapy, or microbiologic testing other than routine surveillance cultures, occurring within 6 hours of PED arrival (Supplemental Table 1 and 2).20
Cardiac POCUS or TTE performed within 24 hours of presentation.
If cardiac POCUS was performed a corresponding POCUS QA record with expert interpretation.
Study inclusion was based on the predefined study definition of suspected infection and did not require activation or confirmation of an institutional sepsis alert.
Patients were excluded if the first cardiac POCUS or TTE was performed after initiation of intravenous vasoactive therapy, as vasoactive medications may alter left ventricular function on cardiac ultrasound. Studies that were classified as a technically limited study (TLS) on expert review were also excluded. Additionally, patients were excluded if they had decreased cardiac function on their most recent prior TTE, when available, as this was considered evidence of pre-existing persistent left ventricular dysfunction. Finally, the TTE was not included if no left ventricular ejection fraction (LVEF) was documented on that TTE. At our institution, reporting of LVEF is standard practice unless technical limitations are encountered or specific congenital heart lesions are present (e.g., hypoplastic left heart syndrome, tricuspid atresia, or congenitally corrected transposition of the great arteries), in which assessment and reporting of LVEF are less common.21
Cardiac POCUS Acquisition and Interpretation
Cardiac POCUS examinations were performed by residents, advanced practice providers, fellows, and attending physicians and were supervised by attending physicians credentialed in cardiac POCUS. Credentialing required a structured educational training pathway and completion of a minimum number of technically adequate cardiac examinations, with ongoing maintenance of competency through continued performance and departmental review.11,12
All studies received real-time bedside interpretation, followed by formal expert review as part of routine QA. Expert reviewers, consisting of fellowship trained POCUS faculty or PEM physicians with RDMS certification, assessed the interpretability and accuracy of each study and classified studies as technically limited if minimum criteria for image interpretation were not met. The QA assessment was used to determine qualitative left ventricular systolic function on POCUS. Left ventricular systolic function was qualitatively categorized as normal, hyperdynamic, reduced, or severely reduced. Consistent with the study objective of identifying the presence or absence of left ventricular dysfunction, reduced and severely reduced function were grouped as reduced, whereas normal and hyperdynamic function were grouped as not reduced. This grouping strategy was specified a priori before analysis.
Transthoracic Echocardiography
Left ventricular systolic function was described by echocardiography as quantitative ejection fraction and categorized as non-reduced when the left ventricular ejection fraction was ≥50%.22 TTE was considered positive for left ventricular systolic dysfunction if the ejection fraction was <50%.11
Clinical Variables and Bedside Markers
Study data were extracted directly from the electronic health record without manual chart review. Extracted variables included demographic characteristics, vital signs, mental status, triage and nursing assessments (including capillary refill time), and high-risk comorbidities. Mental status was determined from documented level of consciousness or Glasgow Coma Scale scores. Electronic health record time stamps were used for time-based variables. The predictors evaluated in the multivariable model were selected a priori based on components of the Children's Hospital of Philadelphia (CHOP) pediatric sepsis screen and the qPS4 (quick Pediatric Septic Shock Screening Score), which include tachycardia, systolic hypotension, altered mental status, capillary refill time (≤2 seconds, approximately 3 seconds, and >4 seconds), and the presence of a high-risk comorbidity (Table 1).18,20 Capillary refill time was categorized as ≤2s, 3s, and ≥4s because nursing documentation recorded values as "2 seconds or less, 3 seconds or equal and greater to 4 seconds” precluding more granular categorization. The most abnormal value of a predictor observed prior to cardiac ultrasound examination or 6 hours (whichever came first) was used to determine whether the predictor was abnormal or not. When mental status or capillary refill time data were missing, values were considered within normal limits.20
Table 1:
Definition of bedside markers
| Cutoff values | |||
|---|---|---|---|
| Age | Heart rate (bpm) | Systolic blood pressure (in mmHg) | |
| 1 mo – 2 mo | >180 | <50 | |
| 3 mo – 11 mo | >170 | <70 | |
| 1 yr – 3 yr | >150 | <75 | |
| 4 yr – 11 yr | >130 | <80 | |
| 12 yr – 17 yr | >120 | <85 | |
| Upper extremity capillary refill | ≤ 2 seconds ~ 3 seconds ≥4 seconds |
||
| Level of consciousness | Glasgow Coma Scale ≤ 14 | ||
| High risk condition | < 56 days old Asplenia or sickle cell disease Bone marrow or solid organ transplant Central line Malignancy Significant CNS/Functional tech dependence Other immunocompromise |
||
Outcome
The primary outcome was left ventricular systolic dysfunction on cardiac POCUS based on PEM POCUS expert interpretation or LVEF function < 50% on TTE. Septic shock was defined as receipt of both intravenous antibiotics and intravenous vasoactive therapy.
Statistical Analysis
Continuous variables were summarized as medians with interquartile ranges and compared across cardiac function groups using the Wilcoxon rank-sum test. Categorical variables were expressed as counts and percentages and compared using chi-squared testing. A multivariable logistic regression model was constructed to assess the association between CHOP sepsis screen components and left ventricular systolic dysfunction. All CHOP screen variables were included a priori based on clinical relevance. Adjusted odds ratios and corresponding 95 percent confidence intervals were calculated. Because missing mental status and capillary refill time values were classified as normal in the primary analysis, a sensitivity analysis was performed excluding patients with missing values for either variable.
We assessed inter-rater agreement between bedside providers and PEM POCUS experts for the presence of left ventricular systolic dysfunction using Cohen’s kappa statistics.
Statistical significance was established at a two-sided alpha of 0.05. Analyses were performed using Python version 3.11 and Stata version 18.
Results:
A total of 2,046 patients were included in the final cohort (Figure 1). Left ventricular systolic dysfunction was identified in 89 patients (4.3%; Table 2). Patients with reduced function were older (median age 9.2 vs 7.2 years) and more frequently had elevated lactate levels (24.7% vs 6.5%), systolic hypotension (11.2% vs 4.1%), and abnormal capillary refill time (29.2% vs 15.7%) than patients without reduced function. Tachycardia, altered mental status, and high-risk comorbidities were similar between groups. Left ventricular systolic dysfunction was associated with higher rates of hospital admission (95.5% vs 75.6%), ICU admission (56.2% vs 18.6%), septic shock (27.0% vs 2.5%), and 30-day mortality (6.7% vs 0.6%), as well as fewer hospital-free days within 30 days (median 20.9 vs 27.3 days). Initial cardiac imaging modality did not differ between groups. Tachycardia was not significantly different between those with and without left ventricular systolic dysfunction (33.7% vs 34.9%). Furthermore, among the 516 patients with tachycardia but without delayed capillary refill or hypotension, 16 (3.1%) had left ventricular systolic dysfunction. Among the 1154 patients without tachycardia, delayed capillary refill, or hypotension, 40 (3.5%) had reduced LV function (chi-squared p=0.70).
Figure 1.
Flow diagram
Table 2.
Patient characteristics and outcomes (N=2046). Values are n (%) unless specified. The qualitative cardiac function is based on TTE or POCUS expert interpretation.
| Overall, N=2046 |
Reduced function, N=89 |
Not-reduced function, N=1957 |
|
|---|---|---|---|
| Cardiac ultrasound (first modality) | |||
| POCUS | 1017 (49.7%) | 43 (48.3%) | 974 (49.8%) |
| TTE | 1029 (50.3%) | 46 (51.7%) | 983 (50.2%) |
| Covariates | |||
| Age (yr), median (IQR) | 7.3 (3.2 – 14.2) | 9.2 (3.6 – 16.4)* | 7.2 (3.2 – 14.0)* |
| Female sex | 874 (42.7%) | 34 (38.2%) | 840 (42.9%) |
| Lactic acid > 2.2 mmol/L1 | 149 (7.3%) | 22 (24.7%)* | 127 (6.5%)* |
| Bedside Markers based on CHOP1 and qPS42 screens | |||
| Tachycardia | 712 (34.8%) | 30 (33.7%) | 682 (34.9%) |
| Systolic hypotension | 91 (4.5%) | 10 (11.2%)* | 81 (4.1%)* |
| Altered mental status1 (GCS ≤ 14 or not alert) | 229 (11.2%) | 15 (16.9%) | 214 (10.9%) |
| Capillary refill time1 | |||
| <= 2 s | 1712 (83.7%) | 63 (70.8%)* | 1649 (84.3%)* |
| ~ 3 s | 242 (11.8%) | 17 (19.1%)* | 225 (11.5%)* |
| >= 4 s | 92 (4.5%) | 9 (10.1%)* | 83 (4.2%)* |
| High-risk comorbidity | 328 (16.0%) | 17 (19.1%) | 311 (15.9%) |
| Outcomes | |||
| Hospital admission | 1564 (76.4%) | 85 (95.5%)* | 1479 (75.6%)* |
| Hospital free days (in 30), median (IQR) | 27.2 (23.3 – 29.1) | 20.9 (1.9 – 26.1)* | 27.3 (24.1 – 29.2)* |
| ICU admission | 413 (20.2%) | 50 (56.2%)* | 363 (18.6%)* |
| ICU free days (in 30), median (IQR) | 30 (30 – 30) | 28.5 (21.2 – 30) | 30 (30 – 30) |
| Septic shock (IV vasoactive and antibiotics) | 73 (3.6%) | 24 (27.0%)* | 49 (2.5%)* |
| 30-day mortality | 17 (0.8%) | 6 (6.7%)* | 11 (0.6%)* |
CHOP refers to the sepsis screen and its components from the Children’s Hospital of Philadelphia
qPS4 refers to quick Pediatric Septic Shock Screening Score
Missing values were assumed normal
P<0.05 by Chi-squared test (for dichotomous variable) or Wilcoxon rank sum test (for continuous variables)
In multivariable analysis, systolic hypotension remained independently associated with left ventricular systolic dysfunction (Figure 2; adjusted OR 2.16, 95% CI 1.00 – 4.65). Compared with a capillary refill time ≤2 seconds, a capillary refill time of 3 seconds was independently associated with left ventricular systolic dysfunction (adjusted OR 1.84, 95% CI 1.03–3.28). The adjusted OR for a capillary refill time ≥4 seconds was 2.22 (95% CI 0.98–5.03). Tachycardia, altered mental status, and high-risk comorbidities were not significantly associated with left ventricular systolic dysfunction.
Figure 2.
Adjusted odds ratios for the outcome of left ventricular systolic dysfunction on cardiac ultrasound (cardiac POCUS or echocardiography). The dots indicate point estimate and the lines indicate the 95% confidence intervals.
Findings were similar in an exploratory analysis in which capillary refill time was dichotomized as ≤2 seconds versus ≥3 seconds (Figure 3). Prolonged capillary refill time remained independently associated with left ventricular systolic dysfunction (adjusted OR 1.94, 95% CI 1.15–3.25), as did systolic hypotension (adjusted OR 2.23, 95% CI 1.05 – 4.71). In a sensitivity analysis restricted to patients with documented mental status and capillary refill time assessments (1,765/2,046, 86.3%), findings were similar (Supplemental Table 3). Systolic hypotension remained independently associated with left ventricular systolic dysfunction (adjusted OR 2.18, 95% CI 1.09–5.16), while capillary refill times of 3 seconds (adjusted OR 1.81, 95% CI 0.99–3.29) and ≥4 seconds (adjusted OR 2.33, 95% CI 1.01–5.35) demonstrated associations of similar magnitude to the primary analysis.
Figure 3.
Multivariable logistic regression using dichotomized capillary refill time (≥3 seconds vs ≤2 seconds) for prediction of reduced left ventricular systolic function.
Agreement between bedside providers and PEM POCUS experts for assessment of left ventricular systolic function was 97.4%, with a Cohen’s kappa of 0.87 (95% CI 0.82–0.91). Among 149 patients who underwent both cardiac POCUS and TTE within the study-defined time window, overall agreement for the presence of left ventricular systolic dysfunction was 90.6%. Left ventricular systolic dysfunction was identified by both modalities in 13 patients and by neither modality in 122 patients, while discordant findings were observed in 14 patients. Agreement between cardiac POCUS expert interpretation and TTE was moderate (κ=0.60, p<0.001).
Discussion:
Myocardial dysfunction is increasingly recognized as an important component of pediatric sepsis and may influence hemodynamic management and outcomes. However, it remains unclear which clinical findings should prompt clinicians to evaluate cardiac function during the early assessment of children with suspected infection. In this study of more than 2,000 children with suspected infection who underwent cardiac ultrasound assessment, systolic hypotension and prolonged capillary refill time were independently associated with reduced ventricular systolic function identified on either cardiac POCUS or echocardiography, whereas tachycardia was not. These findings suggest that specific bedside markers commonly incorporated into pediatric sepsis screening tools are associated with myocardial dysfunction and may help identify children at increased risk who could benefit from cardiac ultrasound during the early evaluation of suspected infection.
Cardiac dysfunction is increasingly recognized as an important contributor to morbidity in sepsis, yet early identification remains challenging, particularly in pediatric patients.1,6,23 Children often maintain blood pressure until later stages of shock, and tachycardia is common across a wide range of infectious and noninfectious conditions, limiting its specificity as a marker of circulatory compromise.7,24 In this context, our finding that hypotension and abnormal capillary refill were associated left ventricular systolic dysfunction is physiologically plausible and highlights the potential value of perfusion-based clinical signs in identifying children at risk for myocardial dysfunction. In contrast, no difference was observed between children with and without tachycardia, independent of the presence of abnormal capillary refill or hypotension, suggesting that tachycardia alone may not be a reliable indicator of cardiac dysfunction in children with suspected infection. These findings further suggest that commonly used sepsis screening elements differ in their ability to reflect underlying cardiovascular dysfunction.
The observed association between abnormal capillary refill and reduced left ventricular function aligns with emerging evidence from adult sepsis literature emphasizing the clinical relevance of peripheral perfusion assessment. In the ANDROMEDA-SHOCK randomized trial, a resuscitation strategy targeting normalization of capillary refill time resulted in faster resolution of organ dysfunction and reduced fluid administration compared with a lactate-guided approach.25 Subsequent data from ANDROMEDA-SHOCK-2 further demonstrated that a capillary refill–anchored, physiologically informed resuscitation strategy improved a hierarchical composite outcome in patients with early septic shock.26 Notably, the ANDROMEDA-SHOCK-2 protocol incorporated bedside echocardiography as part of a structured hemodynamic assessment to identify cardiovascular phenotypes and tailor resuscitative interventions. Although these trials were conducted in adult ICU populations, they support the concept that capillary refill reflects clinically meaningful hypoperfusion and may be more closely linked to underlying cardiovascular dysfunction than other markers.27 Capillary refill may represent a focused and actionable bedside marker of perfusion, compared with the broader warm versus cold shock paradigm, which can be difficult to interpret and may not reflect underlying physiology.
Assessment of cardiac function by ultrasound is increasingly incorporated into the evaluation of patients with sepsis, reflecting growing recognition of the heterogeneity of septic shock and the importance of identifying underlying cardiovascular physiology. A prior study has shown that vasoactive strategies misaligned with underlying cardiovascular physiology may be associated with harm, whereas management tailored to identified pathophysiology is associated with improved outcomes.10 These findings highlight the limitations of a one-size-fits-all resuscitation approach in pediatric sepsis.28 Our results suggest that systolic hypotension and prolonged capillary refill are bedside markers associated with an increased risk of myocardial dysfunction rather than standalone screening tests. Although these findings were independently associated with reduced left ventricular systolic function, many children with myocardial dysfunction did not have either abnormality. Accordingly, these bedside markers may help identify children in whom cardiac ultrasound is most likely to provide additional physiologic information, but they should not be used in isolation to rule in or rule out myocardial dysfunction. More broadly, our findings suggest that individual bedside markers may provide insight into underlying cardiovascular physiology and support a more targeted use of cardiac ultrasound during the evaluation of children with suspected infection.
This study has several limitations. Its retrospective, single-center design introduces potential selection bias, as both cardiac POCUS and TTE examinations were obtained at clinician discretion rather than through a standardized protocol. Although patients with previously documented reduced ventricular function on echocardiography were excluded, baseline cardiac function data were not universally available and some patients with unrecognized pre-existing dysfunction may have been included. analysis. In addition, information on specific pre-existing cardiac conditions and prior cardiac surgery was not available, precluding disease-specific subgroup analyses. Because the study focused on children with suspected infection, infectious etiology was not uniformly established, and data on vaccination status and immunocompromising conditions were not sufficiently complete to permit subgroup analyses. Cardiac ultrasound was not performed at a uniform time point during illness, and treatment prior to imaging may have influenced ventricular function. Because resuscitation is a dynamic process, ventricular function may have evolved between emergency department presentation and ultrasound assessment. Some clinical variables were treated as normal when undocumented, which may have resulted in misclassification; however, sensitivity analyses yielded similar results. In addition, left ventricular systolic dysfunction was determined using either cardiac POCUS expert interpretation or TTE, which may have resulted in outcome misclassification. This is supported by the moderate agreement observed between cardiac POCUS and TTE, potentially reflecting temporal changes in left ventricular systolic function between examinations, response to treatment, or challenges in classifying borderline abnormalities using qualitative assessments. Agreement between bedside providers and PEM POCUS experts on the other hand was high. However, POCUS expert reviewers were not blinded to the bedside interpretation because image review was performed as part of routine clinical quality assurance, which may have increased agreement estimates. Lastly, findings from this single tertiary pediatric emergency department may not be generalizable to other settings with different patient populations or clinical practice patterns.
Conclusion:
Among children presenting to the emergency department with suspected infection and concern for myocardial dysfunction, left ventricular systolic dysfunction identified on cardiac ultrasound, including either cardiac point-of-care POCUS or echocardiography, was uncommon but was independently associated with systolic hypotension and prolonged capillary refill time, whereas tachycardia was not. These findings suggest that systolic hypotension and prolonged capillary refill are bedside markers associated with an increased risk of left ventricular systolic dysfunction and may help inform the selective use of cardiac ultrasound during the early evaluation of children with suspected infection. Prospective, multicenter studies are needed to validate these findings, further define the role of cardiac ultrasound in the evaluation of children with suspected infection, and determine whether this approach can improve risk stratification and inform hemodynamic management in pediatric sepsis.
Supplementary Material
Footnotes
Declaration of interests
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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