Abstract
Introduction
Hypotension burden measured using continuous high-resolution blood pressures (BPs) is associated with outcome following pediatric cardiac arrest. It is unclear whether this holds when using EHR-documented blood pressures, which are more available but measured differently. Our objective was to determine the association of hypotension burden calculated using EHR-documented BPs with outcome after pediatric cardiac arrest. Secondarily, we compared hypotension burden calculated using EHR-documented BPs vs. continuous high-resolution BPs.
Methods
In this single-center retrospective study, we quantified hypotension burden using EHR-documented BPs for 24 hours following return of spontaneous circulation. We determined association of hypotension burden below the 10th percentile for age with unfavorable outcome (Pediatric Cerebral Performance Category Score ≥3 with change from pre-arrest) using logistic regression controlling for age, sex, arrest location, and lactate. Hypotension burden using EHR-documented BPs vs. continuous high-resolution BPs was compared with Bland-Altman analysis.
Results
139 patients were analyzed (median age 54 months, 60.7% male); 63% had unfavorable outcome. Using EHR-documented BPs, increasing burden of hypotension below 10th percentile-for-age was associated with greater odds of unfavorable outcome (odds ratio 4.64, 95% CI [1.21,17.6], p=0.025). Hypotension burden was similar when calculated using EHR-documented BPs vs. continuous high-resolution BPs (0.03 [0,0.26] vs 0.04 [0,0.38] mmHg-hrs, p=0.165). There was no significant bias toward either measurement modality on Bland-Altman analysis (mean difference 0.22±0.95, p= 0.096).
Conclusions
Hypotension burden calculated using EHR-documented BPs was associated with unfavorable outcome after pediatric cardiac arrest and closely approximated hypotension burden from continuous high-resolution BPs.
Keywords: Post-arrest care, Hypotension, hypotension burden, Pediatrics
Introduction
Hypotension following pediatric cardiac arrest is associated with unfavorable outcome.(1–8) Historically, post-arrest hypotension was defined using singular blood pressures (BPs) below a pre-defined threshold.(6–8) More recent studies have determined the proportion of BPs below specific thresholds or used regression analyses to define BPs associated with an inflection point in outcome.(9–11) Based on these studies, multiple guidelines recommend maintaining mean arterial pressure (MAP) >10th percentile-for-age during post-cardiac arrest care.(12–14)
We previously used continuous high-resolution BPs to measure the duration and magnitude of individual hypotensive episodes and determined that an area-under-the-curve measurement (“hypotension burden”) was dose-dependently associated with outcome.(15) However, continuous high-resolution BPs are not universally available, limiting widespread adoption of the hypotension burden concept in clinical care and research. Intermittent measurements from non-invasive cuff measurements and invasive arterial lines can also be abstracted from the electronic health record (EHR-documented BPs). These are a more accessible alternative, but it is unclear whether hypotension burden calculated from these EHR-documented BPs is associated with outcome or approximates hypotension burden calculated using continuous data.
Our objective was to quantify the duration, magnitude, and burden of hypotension using EHR-documented BPs following pediatric cardiac arrest and determine their association with neurologic outcome, and to determine whether hypotension burden calculated from EHR-documented BPs approximated hypotension burden calculated using continuous high-resolution BPs.
Materials and Methods
Study Design
This was a single-center retrospective observational study of patients ≤18 years old with return of spontaneous circulation (ROSC) after cardiac arrest admitted to a quaternary PICU from November 2018 until May 2023. We previously reported the association between hypotension burden calculated with continuous high-resolution BPs and outcome in this cohort.(15) Patients were eligible if they had continuous high-resolution BPs recorded via an arterial catheter using a multimodal neuromonitoring device (Natus Medical, Middleton, WI, USA) and EHR-documented BPs available in the EHR. Patients were excluded if they had poor-quality data, defined as >50% of data identified as artifact by an unbiased detection algorithm. Only index arrests for each patient were analyzed.
BP Data Acquisition
For each patient, we abstracted EHR-documented and continuous high-resolution BPs in the first 24 hours after ROSC:
EHR-documented BPs: All BPs available in EHR flowsheets were abstracted, including values from both arterial lines and noninvasive blood pressure cuffs. When simultaneous invasive and noninvasive measurements were available, the invasive value was used.
Continuous high-resolution BPs: Arterial waveform data, sampled at 100Hz, were extracted from our multimodality neuromonitoring database, then de-noised and filtered to remove artifacts.(15)
Calculation of Hypotension Burden, Duration, and Magnitude
For EHR-documented BPs, MAP was calculated using the formula MAP = ⅓*systolic BP + ⅔*diastolic BP. Missingness was defined as proportion of measurements >90 mins apart. For continuous high-resolution BPs, MAP was calculated using a 5-second rolling average. We defined hypotension as <10th percentile-for-age in accordance with consensus recommendations.(16–18) Normative values for 10th percentile for age were determined using published norms for an inpatient pediatric population.(Table S1, 19)
For each patient and sampling method, we calculated: (Figure 1)
Hypotension duration: percent of total recording time with hypotensive MAP.
Hypotension magnitude: median difference between patient MAP and hypotension threshold during epochs when MAP was hypotensive.
Hypotension burden: area between patient MAP and hypotension threshold, during epochs when MAP was less than threshold, divided by total duration of recording.(15)
Figure 1: Hypotension burden below 10th percentile-for-age determined from EHR-documented BPs vs. continuous high-resolution BPs.
MAP = mean arterial pressure. Black horizontal line presents the 10th percentile-for-age threshold. Hypotension duration and magnitude are represented schematically as x- and y-deviations from the 10th percentile-for-age MAP threshold. Hypotension burden is represented by shaded area. For EHR-documented BPs, red dots represent invasively measured BPs and blue dots represented non-invasively measured BPs. When simultaneous invasive and non-invasive measurements are available (red and blue dots both present at the same x-value), the invasive measurement is used for hypotension burden calculation.
Patient Outcomes
Outcome was defined by Pediatric Cerebral Performance Category (PCPC) score, a validated 6-point scoring system for assessment of global brain function.(20–23) PCPC scores were determined by blinded research coordinators using retrospective chart review at hospital discharge or 30 days post-arrest, whichever came first. Unfavorable outcome was defined as a PCPC score of ≥3 with change from pre-arrest PCPC.
Statistical Analysis
Patient demographics were compared with chi-squared tests or Mann-Whitney tests. Analyses of hypotension duration, magnitude, and burden were restricted to periods when simultaneous EHR-documented and continuous high-resolution BPs were available. Metrics were summarized using medians with interquartile ranges and compared using Mann-Whitney tests. Multivariable logistic regression evaluated the association between hypotension duration, magnitude, and burden with outcome, controlling for age, sex, arrest location, initial rhythm, and lactate after ROSC.(15)
We compared hypotension burden calculated using EHR-documented vs. continuous high-resolution BPs with Mann-Whitney tests. Differences and biases in measurement were compared between EHR-documented vs. continuous high-resolution BPs using Bland-Altman analysis.(24)
Data were analyzed in Python 3 (Python Software Foundation, Wilmington, DE).
The study was approved by an Institutional Review Board with a waiver of consent (IRB #19–016118, approved 4/17/19, Acute Brain Injury Neuromonitoring). Procedures followed policies outlined by the Children’s Hospital of Philadelphia Research Institute and the Helsinki Declaration of 1975.
Results
145 patients met inclusion criteria. Six patients were excluded due to excessive artifact. Among 139 patients (61% male, median age 54 [11,147] months), 87 (63%) had an unfavorable outcome (Table 1).
Table 1:
Demographic and cardiac arrest characteristics for patients with favorable versus unfavorable outcome
| Patient and cardiac arrest characteristics | All Patients (n = 139) | Favorable (n = 52) | Unfavorable (n = 87) | p-value |
|---|---|---|---|---|
| Age (months) [median (IQR)] | 54 [11,147] | 98 [21,157] | 34 [10,140] | 0.084 |
| Sex (%) | ||||
| Male | 84 (60.7) | 33 (63.5) | 51 (58.6) | 0.572 |
| Female | 55 (39.6) | 19 (36.5) | 36 (41.4) | |
| Race (%) | 0.216 | |||
| White | 52 (37) | 22 (42) | 30 (34) | |
| Black/African American | 38 (27) | 23 (23) | 26 (30) | |
| Asian | 3 (2) | 2 (4) | 1 (1) | |
| Other | 36 (26) | 10 (19)) | 26 (30) | |
| Unknown | 10 (7) | 6 (12) | 4 (5) | |
| Ethnicity (%) | ||||
| Hispanic/Latino | 28 (20) | 10 (19) | 18 (21) | 0.976 |
| Not Hispanic/Latino | 100 (71) | 38 (73) | 62 (70) | |
| Other/Unknown | 11 (8) | 4 (7) | 7 (8) | |
| Prior medical history | 0.146 | |||
| None | 47 | 17 | 30 | |
| Premature birth | 20 | 8 | 12 | |
| Congenital heart disease | 14 | 5 | 9 | |
| Non-cardiac malformation | 14 | 4 | 10 | |
| Chronic lung disease | 22 | 9 | 13 | |
| Neurologic disorder | 31 | 12 | 19 | |
| Metabolic/renal/hepatic disease | 17 | 4 | 13 | |
| Arrest location (%) | 0.346 | |||
| In-Hospital | 55 (39) | 27 (52) | 38 (43) | |
| Out-of-Hospital | 74 (53) | 25 (48) | 49 (56) | |
| Arrest etiology (%) | 0.105 | |||
| Respiratory failure | 62 (44) | 23 (44) | 39 (44) | |
| Shock | 25 (18) | 10 (19) | 15 (17) | |
| Arrhythmia | 12 (9) | 8 (15) | 4 (5) | |
| Other/unknown | 40 (29) | 11 (21) | 29 (33) | |
| Initial rhythm | 0.021 | |||
| PEA/asystole | 63 (45) | 18 (35) | 45 (51) | |
| Bradycardia | 33 (24) | 18 (35) | 15 (17) | |
| V-fib/V-tach | 14 (10) | 8 (15) | 6 (7) | |
| Unknown | 29 (21) | 8 (15) | 21 (24) | |
| CPR duration (minutes) | 10 [5,22] | 6 [4,12] | 12 [8,30] | <0.001 |
| Initial post-ROSC pH | 7.20 [6.95,7.30] | 7.27 [7.19,7.38] | 7.11 [6.84,7.26] | <0.001 |
| Initial post-ROSC lactate (mmol/L) | 6.5 [3.0,9.0] | 4.1 [2.1,7.6] | 7.0 [4.0,11.5] | 0.001 |
PEA = pulseless electrical activity, V-fib = ventricular fibrillation, V-tach = ventricular tachycardia. One patient had single-ventricle cardiac physiology and was unrepaired at the time of arrest. Data re-presented with modified cohort from previous publication.(15)
EHR-documented BPs were available for a median of 23 [22.5,23.3] hours; continuous high-resolution BPs were available for 19 [7,24] hours (p=0.006). Time from ROSC to first EHR-documented and continuous high-resolution measurement was 26 [8,41] and 65 [0,103] minutes, respectively (p=0.613). For EHR-documented BPs, median sampling interval was 30 [10,60] mins, with 0% missingness; 8 [3,22]% were noninvasive.
Hypotension duration, magnitude, and burden calculated via EHR-documented BPs
Hypotension duration, magnitude, and burden were greater in patients with unfavorable compared to favorable outcome (Table 2a). On multivariable logistic regression, hypotension magnitude and burden, but not duration, were associated with unfavorable outcome (Tables 2b, S2).
Table 2a:
Univariable association of hypotension duration, magnitude, and burden <10th percentile-for-age with unfavorable outcome using EHR-documented BPs
| All Patients (n = 139) | Favorable (n = 52) | Unfavorable (n = 87) | p-value | |
|---|---|---|---|---|
| Duration (%) | 0.24 [0,6.62] | 0 [0,1.31] | 1.54 [0,10.3] | 0.009 |
| Magnitude (mmHg) | 0.33 [0,5] | 0 [0,2.08] | 2.33 [0,5.83] | 0.001 |
| Burden (mmHg-hrs) | 0.03 [0,0.26] | 0 [0,0.04] | 0.05 [0,0.37] | 0.002 |
Values reported as median [IQR]. Bold p-values indicate p<0.05.
Table 2b:
Multivariable association of hypotension duration, magnitude, and burden <10th percentile-for-age with unfavorable outcome using EHR-documented BPs, adjusted for age, sex, arrest location, initial rhythm, and lactate
| Adjusted OR [95% CI] | p-value | |
|---|---|---|
| Duration | 1.02 [0.99,1.05] | 0.226 |
| Magnitude | 1.22 [1.06,1.39] | 0.004 |
| Burden | 4.64 [1.21,17.6] | 0.025 |
Values reported as [95% CI]. Bold p-values indicate p<0.05.
Hypotension burden using EHR-documented BPs vs. continuous high-resolution BPs
Hypotension burden was similar using EHR-documented vs. continuous high-resolution BPs (0.03 [0,0.26] vs 0.04 [0,0.38] mmHg-hrs, p=0.165). On Bland-Altman analysis, there was no bias in paired difference between EHR-documented vs. continuous high-resolution hypotension burden (0.22±0.95, p= 0.096, Figure 2). On linear regression, there was no correlation between mean burden and difference of burdens between EHR-documented vs. continuous high-resolution BPs (r2=0.143).
Figure 2: Bland-Altman analysis of systematic error between hypotension burden calculated via EHR-documented BPs vs. continuous high-resolution BPs.
Δ = difference of burdens (EHR-documented minus continuous high-resolution). Solid line represents mean difference of burdens, while dotted lines represent 2 standard deviations above/below the mean.
Discussion
In a retrospective cohort of pediatric post-arrest patients, increased hypotension burden <10th percentile-for-age using EHR-documented BPs values over the first 24 hours post-ROSC was associated with increased odds of unfavorable outcome, and approximated burden computed from continuous high-resolution BPs. This is the first study to our knowledge which compares EHR-documented with continuous high-resolution BPs in a pediatric post-arrest population. These findings suggest that EHR-derived hypotension burden is a potentially valuable parameter for post-arrest research and clinical care, particularly when high-resolution BPs are not available.
The goal of post–cardiac arrest care is to maintain organ perfusion and prevent secondary injury.(25–28) Hypotension burden may provide a more quantitative, sensitive, and biologically relevant assessment of malperfusion than the more commonly studied lowest blood pressure. Our findings demonstrate that high-resolution continuous physiologic signals are not required to calculate this metric, only routinely documented BPs. As post-arrest care becomes increasingly personalized, targeting physiologically grounded and operationally feasible metrics like hypotension burden may improve outcomes. Health systems could operationalize hypotension burden as a real-time measure to support clinician decision-making, analogous to other noninvasive hemodynamic monitoring tools.(29, 30).
Measuring hypotension burden may also allow clinical investigators to generate more personalized, quantitative hypotheses, as the increasing personalization of post-cardiac arrest care leads to more heterogeneous treatment effects.(31). For example, investigators could stratify patients or randomize treatment groups using burden-based metrics to evaluate differences in exposures or patient characteristics that modify the relationship between hypotension and outcome.(32) Retrospective analyses could also leverage EHR-documented BPs already collected from prior post-cardiac arrest studies.(16, 33, 34)
Interestingly, on multivariable analysis, we found that hypotension magnitude, but not duration, was associated with outcome, similar to the association we reported using continuous high-resolution BPs.(15) These findings suggest that more profound hypotension may be related to more severe cerebral ischemic injury, whereas longer periods of mild hypotension may allow for changes in cerebral autoregulation to re-establish adequate cerebral blood flow.(35)
Limitations
Our definitions for 10th percentile-for-age blood pressure are based on inpatient reference data which differ from norms generated from ambulatory patients, and which may be confounded by the underlying illness requiring hospitalization, hospital-acquired morbidities (e.g., pain, anxiety, or delirium), and clinicians’ therapeutic blood pressure goals. This may limit whether our analyses and conclusions are applicable in different populations and contexts. We included EHR-documented BPs derived primarily from invasive measurements, so our results are not generalizable to settings with primarily non-invasive blood pressure. We excluded EHR-documented BPs when corresponding continuous high-resolution BPs were not available, which enabled more direct comparison between measurements. However, EHR-documented BPs may have pragmatic advantages by being easier to measure, especially during the early post-arrest course when continuous high-resolution BPs may be unavailable. We analyzed only the first 24 hours of data after ROSC, which does not address any potential association of later-onset hypotension with outcome. This study did not determine whether hypotension burden using EHR-documented BPs at alternative thresholds (e.g., 5th percentile-for-age) is associated with outcome. Determining the optimal BP threshold during post-cardiac arrest care is an important avenue for future research. PCPC scores were assigned retrospectively, and the PCPC scale provides a global assessment rather than a granular evaluation of neurologic function. Given the exploratory nature of this study, findings meeting conventional thresholds for statistical significance (95% CI not crossing 1.0 and p<0.05) should be considered statistically suggestive rather than confirmatory, because p-values do not account for the prior probability that an association is present. The frequency of BP documentation was not protocolized and may have been subject to selection bias and variability in clinical judgment, which may have biased results toward similarity between intermittent and continuous data. Our study’s single-center retrospective nature limits generalizability.
Conclusions
Hypotension burden <10th percentile-for-age using EHR-documented BPs during the first 24 hours after pediatric cardiac arrest was associated with unfavorable outcome. Hypotension burden using EHR-documented BP values closely approximated burden using continuous high-resolution BPs.
Supplementary Material
Supplementary Table 1: Normative values for 10th percentile-for-age mean arterial pressure
Mean arterial pressure (MAP) values used to define 10th percentile-for-age are shown above. Data and table adapted from Roberts et al., Pediatric Critical Care Medicine 2020 (19).
Supplementary Table 2: Multivariable association of hypotension duration, magnitude, and burden <10th percentile-for-age with unfavorable outcome using EHR-documented BPs, including all modeled covariates
Models for a) hypotension duration b) hypotension magnitude, and c) hypotension burden are displayed, with individual adjusted odds ratios and confidence intervals for all covariates: age, sex, arrest location, and initial lactate after ROSC. Bold p-values indicate <0.05.
Highlights.
EHR-documented blood pressure can be used to calculate hypotension burden
EHR-documented hypotension burden is associated with pediatric post-arrest neurologic outcome
Hypotension burden is similar when using EHR-documented BPs or continuous high-resolution BPs
EHR-documented hypotension burden is a widely available, valuable monitoring tool
Study Funding:
NINDS K23NS116120, CHOP Resuscitation Science Center
Author Disclosures
R. Liu reports no disclosures relevant to the manuscript.
V. Nadkarni was the president of the Society of Critical Care Medicine (SCCM) 2023. This work is not intended to reflect the views of SCCM.
R. Berg reports no disclosures relevant to the manuscript.
R. Morgan receives research support from the NIH to his institution from the National Heart, Lung, and Blood Institute (K23HL148541).
A. Topjian serves as an editor for Resuscitation.
M. P. Kirschen receives research support from the NIH to his institution (NINDS K23NS116120)
Footnotes
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Declaration of transparency/disclosure
Given their role as an Associate Editor, Alexis Topjian, had no involvement in the peer review of this article and had no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to another journal editor.
Author Conflicts of Interest
R. Liu reports no conflicts of interest.
V. Nadkarni was the president of the Society of Critical Care Medicine (SCCM) 2023. This work is not intended to reflect the views of SCCM.
R. Berg reports no conflicts of interest.
R. Morgan reports no conflicts of interest.
A. Topjian serves as an editor of Resuscitation.
M. Kirschen reports no conflicts of interest.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplementary Table 1: Normative values for 10th percentile-for-age mean arterial pressure
Mean arterial pressure (MAP) values used to define 10th percentile-for-age are shown above. Data and table adapted from Roberts et al., Pediatric Critical Care Medicine 2020 (19).
Supplementary Table 2: Multivariable association of hypotension duration, magnitude, and burden <10th percentile-for-age with unfavorable outcome using EHR-documented BPs, including all modeled covariates
Models for a) hypotension duration b) hypotension magnitude, and c) hypotension burden are displayed, with individual adjusted odds ratios and confidence intervals for all covariates: age, sex, arrest location, and initial lactate after ROSC. Bold p-values indicate <0.05.