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Impact of therapeutic hypothermia (TH) on echocardiography indices of pulmonary hemodynamics among neonates with hypoxic ischemic encephalopathy (HIE)

Journal of Perinatology (2024)Cite this article

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Therapeutic hypothermia (TH) is considered standard of care for neonates with perinatal asphyxia and subsequent moderate -severe HIE [1]. Impaired right ventricular (RV) function is independently associated with mortality, brain injury and adverse neurodevelopmental outcomes in patients with HIE undergoing TH [2]. Perinatal asphyxia and TH are both known to negatively impact the cardiopulmonary system in these critically ill neonates. Prior animal studies have demonstrated that TH has a modulatory effect on pulmonary vascular resistance (PVR) with a rodent model demonstrating a 1% increase per 1 °C temperature reduction [3, 4]. Of note, infants with hypoxemic respiratory failure and severe acute pulmonary hypertension (aPH) were excluded from randomized clinical trials of therapeutic hypothermia. Recent evidence demonstrates that severe aPH is 2.5 times more common in the setting of TH/HIE [5], which most likely relates to the extrapolation of practice to patients not originally included in the trials. In addition, there is recent evidence of the use of Extracorporeal Membrane Oxygenation (ECMO) in the setting of TH/HIE which most likely reflects the expanded use of TH to infants with aPH [6]. The modulator role of TH, however, on pulmonary hemodynamics and heart function among neonatal HIE patients undergoing TH is unknown. We hypothesized that initiation of TH was associated with an increase in echocardiography measures of pulmonary arterial pressure.

A single center longitudinal cohort echocardiography study of patients with HIE undergoing TH at the University of Iowa Neonatal Intensive Care Unit was performed between 11/2019 and 10/2020. Neonates >34 weeks gestational age (GA) with a diagnosis of moderate-severe HIE according to the Sarnat criteria [7], treated with TH, and where targeted neonatal echocardiography (TnECHO) was performed before and within 2 h of achieving target temperature (33.5° C) were eligible. Infants with major congenital heart disease were excluded (excluding patent foramen ovale, patent ductus arteriosus (PDA) and small ventricular septal defects)]. All assessments were performed using a Vivid E90 echocardiography machine with a 6mHz cardiac probe by expert sonographers (REG, ARB). Images were analyzed by a single evaluator (AV) and cardiovascular management was at the discretion of the medical team. Conventional echocardiography measures of RV [tricuspid annulus plane systolic excursion (TAPSE) and RV factional area change (FAC)] and LV systolic [ejection fraction] and diastolic performance, right (RVO) and left ventricular (LVO) outputs, pulmonary artery pressure [end-systolic eccentricity index (sEI) which is an objective measure of LV circularity and intraventricular septal wall flattening, % right-left flow across PDA], PVR (RVET: PAAT and presence of mid-systolic notching of PA Doppler), and ventricular-vascular coupling (TAPSE: PAAT) were performed. The primary outcome was sEI, which has been shown to positively correlate with pulmonary artery (PA) pressure [8]. We chose sEI as the primary outcome as tricuspid regurgitation (used to calculate right ventricular systolic pressure) is not consistently present; in addition, the ratio of right ventricular ejection time (RVET) to pulmonary artery acceleration time (PAAT) may not be a true measure of PVR in the presence of an open PDA due to the influence of systemic vascular resistance. The estimated RV systolic pressure derived from peak tricuspid jet velocity, the presence of a bidirectional or right to left shunt across the ductus arteriosus, and RV morphologic changes were also used to assess PA pressure. Based on normative data, where a normal sEI is less than 1.3 [9], and for a desired power of 0.9 and a Type I error of 0.01, a sample size of 9 patients was needed to detect a 20% increase in sEI. We hypothesized that initiation of TH was associated with an increase in sEI. Descriptive statistics were used to summarize patient clinical demographics and illness severity. Univariate analysis was performed, and paired T-test was used to compare clinical and TnECHO features before and after TH.

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Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, Columbia University Irving Medical Center, 3959 Broadway, New York, NY, 10032, USA

    Angelica M. Vasquez

  2. Division of Neonatology, Department of Pediatrics, University of Iowa, 200 Hawkins Drive, Iowa City, IA, 52242, USA

    Adrianne R. Bischoff, Regan E. Giesinger & Patrick J. McNamara

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  1. Angelica M. Vasquez
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  2. Adrianne R. Bischoff
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  3. Regan E. Giesinger
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  4. Patrick J. McNamara
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Contributions

REG - design, data collection, analysis, writing first draft. AMV, ARB, PJM - design, data collection, writing and approval of final draft.

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Correspondence to Patrick J. McNamara.

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Vasquez, A.M., Bischoff, A.R., Giesinger, R.E. et al. Impact of therapeutic hypothermia (TH) on echocardiography indices of pulmonary hemodynamics among neonates with hypoxic ischemic encephalopathy (HIE). J Perinatol (2024). https://doi.org/10.1038/s41372-024-01958-8

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