Shape of Pulmonary Artery Doppler Flow Profile and Right Ventricular Hemodynamics in Neonates.

OBJECTIVES: To characterize pulmonary artery Doppler flow profile (PAFP) patterns among infants receiving care in neonatal intensive care units and to examine the association of PAFP patterns with pulmonary and right ventricular (RV) hemodynamics. STUDY DESIGN: This is a retrospective study at 2 tertiary intensive care units over 4 years that included neonates who demonstrated a complete tricuspid regurgitation envelope on targeted neonatal echocardiography. Separate personnel reviewed TNEs to characterize PAFP patterns, divide cohort into PAFP groups, and measure quantitative indices of RV hemodynamics (RV systolic pressure, pulmonary artery acceleration time and its ratio with RV ejection time, tricuspid annular plane systolic excursion, and RV output), for intergroup comparisons. RESULTS: We evaluated TNEs from 186 neonates with median gestational age of 28.5 weeks (IQR, 25.9-35.9 weeks). Four distinct PAFP patterns were identified (A) near-isosceles triangle (22%), (B) right-angled triangle (29%), (C) notching (40%), and (D) low peak velocity (<0.4 m/s; 9%). Groups A-C demonstrated a stepwise worsening in all indices of PH, whereas pattern D was associated with lower tricuspid annular plane systolic excursion and RV output. Using common definitions of pulmonary hypertension (PH), pattern A performed best to rule out PH (sensitivity range, 81%-90%) and pattern C for diagnosing PH (specificity range, 63%-78%). CONCLUSIONS: Inspection of PAFP is a simple bedside echocardiography measure that provides clinically meaningful information on underlying RV hemodynamics and may aid in screening and monitoring of patients for PH in intensive care units.

Impact of Early Hemodynamic Screening on Extremely Preterm Outcomes in a High-Performance Center.

Rationale: Increasing survival of extremely preterm infants with a stable rate of severe intraventricular hemorrhage represents a growing health risk for neonates. Objectives: To evaluate the role of early hemodynamic screening (HS) on the risk of death or severe intraventricular hemorrhage. Methods: All eligible patients 22-26+6 weeks' gestation born and/or admitted <24 hours postnatal age were included. As compared with standard neonatal care for control subjects (January 2010-December 2017), patients admitted in the second epoch (October 2018-April 2022) were exposed to HS using targeted neonatal echocardiography at 12-18 hours. Measurements and Main Results: A primary composite outcome of death or severe intraventricular hemorrhage was decided a priori using a 10% reduction in baseline rate to calculate sample size. A total of 423 control subjects and 191 screening patients were recruited with a mean gestation and birth weight of 24.7 ± 1.5 weeks and 699 ± 191 g, respectively. Infants born at 22-23 weeks represented 41% (n = 78) of the HS epoch versus 32% (n = 137) of the control subjects (P = 0.004). An increase in perinatal optimization (e.g., antepartum steroids) but with a decline in maternal health (e.g., increased obesity) was seen in the HS versus control epoch. A reduction in the primary outcome and each of severe intraventricular hemorrhage, death, death in the first postnatal week, necrotizing enterocolitis, and severe bronchopulmonary dysplasia was seen in the screening era. After adjustment for perinatal confounders and time, screening was independently associated with survival free of severe intraventricular hemorrhage (OR 2.09, 95% CI [1.19, 3.66]). Conclusions: Early HS and physiology-guided care may be an avenue to further improve neonatal outcomes; further evaluation is warranted.

Safety and Feasibility of Riociguat Therapy for the Treatment of Chronic Pulmonary Arterial Hypertension in Infancy.

The effects of riociguat, an oral-soluble guanylate-cyclase stimulator, were studied in 10 infants with chronic pulmonary arterial hypertension. Respiratory status (n = 8/10), right heart dilation (n = 7/10), function (n = 9/10), and chronic pulmonary arterial hypertension (n = 8/10) improved. Median decrement in systolic (12 [4, 14]), diastolic (14 [7, 20]), and mean arterial (14 [10, 17]) pressures were noted; no critical hypotension or hypoxemia occurred.

Left ventricular function before and after percutaneous patent ductus arteriosus closure in preterm infants.

BACKGROUND: Definitive closure of the patent ductus arteriosus (PDA) is associated with significant changes in the loading conditions of the left ventricle (LV), which may lead to cardiovascular and respiratory instability. The objective of the study was to evaluate targeted neonatal echocardiography (TnECHO) characteristics and the clinical course of preterm infants ≤2 kg undergoing percutaneous PDA closure. METHODS: Retrospective cohort study of prospectively acquired pre- and post-closure TnECHOs to assess hemodynamic changes. Cardiorespiratory parameters in the first 24 h following PDA closure were also evaluated. RESULTS: Fifty patients were included with a mean age of 30.6 ± 9.6 days and weight of 1188 ± 280 g. LV global longitudinal strain decreased from -20.6 ± 2.6 to -14.9 ± 2.9% (p < 0.001) after 1 h. There was a decrease in LV volume loading, left ventricular output, LV systolic and diastolic parameters. Cardiorespiratory instability occurred in 24 (48%) [oxygenation failure in 44%] but systolic hypotension and/or need for cardiovascular medications was only seen in 6 (12%). Patients with instability had worse baseline respiratory severity score and lower post-closure early diastolic strain rates. CONCLUSIONS: Percutaneous PDA closure leads to a reduction in echocardiography markers of LV systolic/diastolic function. Post-closure cardiorespiratory instability is characterized primarily by oxygenation failure and may relate to impaired diastolic performance. IMPACT: Percutaneous patent ductus arteriosus closure leads to a reduction in echocardiography markers of left ventricular volume loading, cardiac output, and left ventricular systolic/diastolic function. Post-procedural cardiorespiratory instability is characterized primarily by oxygenation failure. Post-procedural cardiorespiratory instability may relate to impaired diastolic performance.

Rectal Acetaminophen Improves Shunt Volume and Reduces Patent Ductus Arteriosus Ligation in Extremely Preterm Infants.

OBJECTIVE: An alternative therapy for preterm infants with a hemodynamically significant patent ductus arteriosus (hsPDA) is needed when cyclooxygenase inhibitors fail or where treatment is contraindicated due to coexisting renal failure, necrotizing enterocolitis, and/or intestinal perforation. No studies have evaluated the efficacy of per rectum (PR) acetaminophen. The study aimed to evaluate the efficacy of PR acetaminophen in modulating the risk of PDA ligation. STUDY DESIGN: A retrospective matched case-control study was conducted to compare neonates born <29 weeks' gestation with evidence of hsDA, in an era when rescue rectal acetaminophen was used (January 2014-March 2018) as a treatment strategy, versus historical controls (July 2006-August 2012). All patients underwent comprehensive echocardiography assessment of ductal shunt volume according to a standardized protocol. Acetaminophen treated neonates were matched according to demographics, gestation, preintervention echocardiography features, and comorbidities. Control patients were selected when an echocardiography was performed at an equivalent postnatal age. Infants with a genetic syndrome, severe congenital malformation, or major forms of congenital heart disease excluding small atrial septal defect or ventricular septal defect, PDA, or patent formale ovale were excluded. The primary outcome was surgical ligation of the PDA. Secondary outcomes included echocardiography indices of hemodynamic significance, the composite of death, or severe BPD (defined by ventilator dependence at 36 weeks postmenstrual age). Descriptive statistics and univariate (t-tests, Fisher's exact test, and Mann-Whitney U test) analyses were used to evaluate clinical and echocardiography characteristics of the groups and compare outcomes. RESULTS: Forty infants (20 cases and 20 controls), with similar demographic and echocardiography features, were compared. Cases received 6.8 ± 0.7 days (60 mg/kg/day) of PR acetaminophen. Responders (n = 12, 60%) had echocardiography evidence of reduced ductal diameter (2.2 mm [1.9-2.6] to 1.1 mm [0-1.7], p = 0.002), left ventricular output (363 ± 108-249 ± 61 mL/min/kg; p = 0.002) and left atrium to aortic root ratio (1.7 ± 0.3-1.3 ± 0.2; p = 0.002) following treatment. The rate of PDA ligation was 50% lower (p = 0.02) and composite outcome of death or severe bronchopulmonary dysplasia was reduced (p = 0.04) in the acetaminophen group. CONCLUSION: Rectal acetaminophen was associated with improvement in echocardiography indices of PDA shunt volume, a 50% reduction in PDA ligation rates and a reduction in the composite outcome of death or severe BPD. Pharmacologic and further prospective clinical studies are needed. KEY POINTS: · Many preterm infants encounter the clinical consequences of a hemodynamically significant PDA.. · The merits and optimal timing of PDA ligation remains an area of controversy amongst neonatologists.. · Cyclooxygenase inhibitors are associated with adverse events or are often contraindicated..

Cardiovascular management following hypoxic-ischemic encephalopathy in North America: need for physiologic consideration.

BACKGROUND: Hypotension and hypoxemic respiratory failure are common among neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). Right ventricular (RV) dysfunction is associated with adverse neurodevelopment. Individualized management utilizing targeted neonatal echocardiography (TnECHO) may enhance care. METHODS: We evaluated the influence of TnECHO programs on cardiovascular practices in HIE/TH patients utilizing a 77-item REDCap survey. Nominated representatives of TnECHO (n = 19) or non-TnECHO (n = 96) sites were approached. RESULTS: Seventy-one (62%) sites responded. Baseline neonatal intensive care unit characteristics and HIE volume were comparable between groups. Most centers monitor invasive blood pressure; however, we identified 17 unique definitions of hypotension. TnECHO centers were likelier to trend systolic/diastolic blood pressure and request earlier echocardiography. TnECHO responders were less likely to use fluid boluses; TnECHO responders more commonly chose an inotrope first-line, while non-TnECHO centers used a vasopressor. For HRF, TnECHO centers chose vasopressors with a favorable pulmonary vascular profile. Non-TnECHO centers used more dopamine and more extracorporeal membrane oxygen for patients with HRF. CONCLUSIONS: Cardiovascular practices in neonates with HIE differ between centers with and without TnECHO. Consensus regarding the definition of hypotension is lacking and dopamine use is common. The merits of these practices among these patients, who frequently have comorbid pulmonary hypertension and RV dysfunction, need prospective evaluation. IMPACT: Cardiovascular care following HIE while undergoing therapeutic hypothermia varies between centers with access to trained hemodynamics specialists and those without. Because cardiovascular dysfunction is associated with brain injury, precision medicine-based care may be an avenue to improving outcomes. Therapeutic hypothermia has introduced new physiological considerations and enhanced survival. It is essential that hemodynamic strategies evolve to keep pace; however, little literature exists. Lack of consensus regarding fundamental definitions (e.g., hypotension) highlights the importance of collaboration among the scientific community to advance the field. The value of enhanced cardiovascular care guided by hemodynamic specialists requires prospective evaluation.

Cardiac Function and Ventricular Interactions in Persistent Pulmonary Hypertension of the Newborn.

OBJECTIVES: The aim of this study was to use a comprehensive imaging protocol to identify echocardiographic correlations of right and left ventricular size, function, and hemodynamics in neonates with persistent pulmonary hypertension of newborn and describe their relationship with key clinical variables. DESIGN: Retrospective case-control echocardiography-based study of persistent pulmonary hypertension of newborn. SETTING: A tertiary neonatal ICU in Canada. PATIENTS: Forty-nine neonates (gestational age ≥ 35 wk old) diagnosed with persistent pulmonary hypertension of newborn within first 3 days after birth and 50 age-matched controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The echocardiographic measurements comprised of right ventricular and left ventricular functional markers, including tricuspid annular plane systolic excursion, fractional area change, tissue Doppler imaging, and deformation imaging. Sample size was based on detecting an intergroup difference of 10% in tricuspid annular plane systolic excursion, which was considered the primary outcome. Linear correlations between the right and left ventricular indices, as well as their association with the outcome of death or extracorporeal membrane oxygenation were evaluated. Persistent pulmonary hypertension of newborn was associated with lower tricuspid annular plane systolic excursion (6.81 ± 1.92 vs 9.25 ± 1.30 mm), right-ventricular global longitudinal strain (16.9% ± 5.4% vs -21.6% ± 4.6%); left ventricular ejection fraction (49% ± 7% vs 55% ± 6%), left ventricular global longitudinal strain (-16.7% ± 3.3% vs -21.4% ± 2.0%) (all p < 0.01). Right and left ventricular diastolic and global function was also lower in persistent pulmonary hypertension of newborn, with more pronounced changes seen for the right ventricle. Moderate-to-strong linear correlations were observed between the right and left ventricular functional markers, with right ventricular global longitudinal strain and left ventricular global longitudinal strain being the strongest (r = 0.8). Within persistent pulmonary hypertension of newborn group, hypoxic ischemic encephalopathy was associated with lower right and left ventricular systolic and right ventricular diastolic performance. Tricuspid annular plane systolic excursion (p =0.08) and left ventricular systolic velocity (p = 0.09) tended to be lower in patients who subsequently died/needed extracorporeal membrane oxygenation. CONCLUSIONS: Persistent pulmonary hypertension of newborn is characterized by global cardiac dysfunction, involving both the right and left ventricles, with significant interventricular functional correlation. Cardiac dysfunction early in disease course may identify patients at highest risk of adverse outcome.

Assessment of superior vena cava flow and cardiac output in different patterns of patent ductus arteriosus shunt.

BACKGROUND: Despite the widespread use of superior vena cava (SVC) flow as a marker of systemic blood flow from the upper body, no previous studies have systematically evaluated the correlation between SVC flow and other echocardiography measures of systemic blood flow in the context of different patterns of patent ductus arteriosus (PDA) shunt direction METHODS: A retrospective cohort study of preterm infants (< 30 weeks, < 21 days of life) who underwent comprehensive targeted neonatal echocardiography (TnECHO) was performed. Patients were categorized as follows: (i) Hemodynamically significant left-to-right shunt; (ii): Bidirectional shunt; (iii) No PDA or insignificant shunt. SVC flow, as measured by two distinct methods, was compared to left and right ventricular outputs (LVO and RVO). Intra- and inter-observer reliability testing was performed RESULTS: In total, 45 patients were included (15 in each group) with a median [IQR] weight of 720 [539, 917] grams at the time of assessment. SVC dimensions and flow measurements were not different between the groups, although patients with left-to-right shunt had higher LVO/RVO ratio. SVC flow, as estimated using the modified method, had a strong correlation with LVO (r = .63, p = 0.012) and RVO (r = .635, p = 0.011) in patients with no PDA. Inter- and intra-observer reliability were both stronger for LVO and RVO when compared to SVC flow measurements CONCLUSION: SVC flow was comparable across all three groups irrespective of higher LVO and LVO/RVO ratio in patients with left-to-right shunts. This may reflect poor measurement reliability or compensation for left-to-right ductal shunt by increased LVO to maintain systemic perfusion.

Targeted neonatal echocardiography-guided therapy pre-embolisation for congenital hepatic vascular malformation: inhaled nitric oxide to prevent paradoxical embolisation to the systemic circulation.

Arteriovenous malformations may present with significant haemodynamic compromise in the neonatal period, typically with high output cardiac failure that may be accompanied by hypoxia and right ventricular dysfunction. Targeted neonatal echocardiography performed by trained neonatologists provides an enhanced physiology-based approach that can guide treatment and minimise complications. We present a case of a large hepatic vascular malformation whose therapy was guided by targeted neonatal echocardiography to prevent paradoxical embolisation of procedural glue to the systemic circulation.

Impaired Right Ventricular Performance Is Associated with Adverse Outcome after Hypoxic Ischemic Encephalopathy.

Rationale: Asphyxiated neonates with hypoxic ischemic encephalopathy (HIE) are at risk of myocardial dysfunction; however, echocardiography studies are limited and little is known about the relationship between hemodynamics and brain injury.Objectives: To analyze the association between severity of myocardial dysfunction and adverse outcome as defined by the composite of death and/or abnormal magnetic resonance imaging.Methods: Neonates with HIE undergoing therapeutic hypothermia were enrolled. Participants underwent echocardiography at 24 hours, 72 hours (before rewarming), and 96 hours (after rewarming). Cerebral hemodynamics were monitored by near-infrared spectroscopy and middle cerebral artery Doppler.Measurements and Main Results: Fifty-three patients with a mean gestation and birthweight of 38.8 ± 2.0 weeks and 3.33 ± 0.6 kg, respectively, were recruited. Thirteen patients (25%) had mild encephalopathy, 27 (50%) had moderate encephalopathy, and 13 (25%) had severe encephalopathy. Eighteen patients (34%) had an adverse outcome. Severity of cardiovascular illness (P < 0.001) and severity of neurologic insult (P = 0.02) were higher in neonates with adverse outcome. Right ventricle (RV) systolic performance at 24 hours was substantially lower than published normative data in all groups. At 24 hours, lower tricuspid annular plane systolic excursion (P = 0.004) and RV fractional area change (P < 0.001), but not pulmonary hypertension, were independently associated with adverse outcome on logistic regression. High brain regional oxygen saturation (P = 0.007) and low middle cerebral artery resistive index (P = 0.04) were associated with RV dysfunction on post hoc analysis.Conclusions: RV dysfunction is associated with the risk of adverse outcome in asphyxiated patients with HIE undergoing hypothermia. Echocardiography may be a valuable diagnostic and prognostic tool in this vulnerable population.

Abrupt Deflation after Sustained Inflation Causes Lung Injury.

RATIONALE: Ventilator management in acute respiratory distress syndrome usually focuses on setting parameters, but events occurring at ventilator disconnection are not well understood. OBJECTIVES: To determine if abrupt deflation after sustained inflation causes lung injury. METHODS: Male Sprague-Dawley rats were ventilated (low Vt, 6 ml/kg) and randomized to control (n = 6; positive end-expiratory pressure [PEEP], 3 cm H2O; 100 min) or intervention (n = 6; PEEP, 3-11 cm H2O over 70 min; abrupt deflation to zero PEEP; ventilation for 30 min). Lung function and injury was assessed, scanning electron microscopy performed, and microvascular leak timed by Evans blue dye (n = 4/group at 0, 2, 5, 10, and 20 min after deflation). Hemodynamic assessment included systemic arterial pressure (n = 6), echocardiography (n = 4), and right (n = 6) and left ventricular pressures (n = 6). MEASUREMENTS AND MAIN RESULTS: Abrupt deflation after sustained inflation (vs. control) caused acute lung dysfunction (compliance 0.48 ± 1.0 vs. 0.82 ± 0.2 m/cm H2O, oxygen saturation as measured by pulse oximetry 67 ± 23.5 vs. 91 ± 4.4%; P < 0.05) and injury (wet/dry ratio 6.1 ± 0.6 vs. 4.6 ± 0.4; P < 0.01). Vascular leak was absent before deflation and maximal 5-10 minutes thereafter; injury was predominantly endothelial. At deflation, left ventricular preload, systemic blood pressure, and left ventricular end-diastolic pressure increased precipitously in proportion to the degree of injury. Injury caused later right ventricular failure. Sodium nitroprusside prevented the increase in systemic blood pressure and left ventricular end-diastolic pressure associated with deflation, and prevented injury. Injury did not occur with gradual deflation. CONCLUSIONS: Abrupt deflation after sustained inflation can cause acute lung injury. It seems to be mediated by acute left ventricular decompensation (caused by increased left ventricular preload and afterload) that elevates pulmonary microvascular pressure; this directly injures the endothelium and causes edema, which is potentiated by the surge in pulmonary perfusion.

Accuracy and reliability of qualitative echocardiography assessment of right ventricular size and function in neonates.

BACKGROUND: Subjective assessment of right ventricular (RV) function by neonatal echocardiography lacks validation. Incorrect diagnostic assignment in patients with suspected pulmonary hypertension (PH) may lead to unnecessary treatment or missed treatment opportunities. METHODS: Six evaluators (experts [n = 3], novice [n = 3]) were asked to independently rate RV characteristics (global function, dilation, and septal flattening) based on standardized echocardiography images. We randomly selected 60 infants, ≥35 weeks gestation at birth, of whom 30 were clinically unwell with acute pulmonary hypertension (aPH) and 30 were healthy controls. aPH was defined by echocardiography presence of right-left shunting across transitional shunts or elevated right ventricular systolic pressure as estimated by the magnitude of the regurgitant jet across the tricuspid valve with impaired oxygenation. Inter-rater comparative evaluation within groups and between groups was performed using Kappa statistics. RESULTS: Global agreement between evaluators for subjective assessment of RV function (0.3 [0.03], P < 0.001), size (0.14 [0.02], P < 0.001), and septal flattening (0.2 [0.02], P < 0.001) was uniformly poor. Agreement in RV function assessment was marginally better for both expert (0.32 [0.08], P < 0.001 vs 0.13 [0.081], and P < 0.001) and novice (0.4 [0.08], P < 0.001 vs 0.06 [0.07], and P < 0.001) evaluators. Overall, the diagnosis of aPH vs control was misclassified in 18% of cases. CONCLUSION: This study demonstrated significant variability in qualitative assessment of RV size and function by trained evaluators, regardless of level of expertise attained. The reliability of objective measures of RV hemodynamics requires prospective evaluation.

Clinical and echocardiography predictors of response to inhaled nitric oxide in hypoxic preterm neonates.

AIM: To evaluate the clinical and echocardiography modulators of treatment response in hypoxemic preterm infants exposed to inhaled nitric oxide (iNO). METHODS: In this multicentre retrospective study, clinical parameters, including oxygenation, ventilation and haemodynamics, were collected for preterm infants <36 weeks gestation before and 2 h after initiation of iNO for acute hypoxemia. Comprehensive echocardiography, performed near the time iNO initiation, was analysed by experts blind to the clinical course. Multiple logistic regression analysis was used to identify factors associated with iNO response as defined by a reduction in the fraction of inspired oxygen by >0.20. RESULTS: A total of 213 infants met eligibility criteria, of which 73 had echocardiography data available and formed the study cohort. Response to iNO was demonstrated in 56% of patients. Younger post-natal age (odds ratio (OR) 0.94; 95% confidence interval (CI) 0.89, 0.99) and the presence of pulmonary hypertension (PH) (OR 4.47; 95% CI 1.23-11.9) were independently predictive of iNO response regardless of gestational age. Among neonates <72 h old with documented PH, iNO response was seen in 82%. The onset of a new diagnosis of severe (grade III/IV) intraventricular haemorrhage (IVH) after iNO treatment was seen in 6 of 40 patients <28 weeks' gestational age, with a greater frequency in responders (32 vs. 0%, P = 0.02). CONCLUSIONS: Positive response to iNO is greatest in the first 3 days of life and in patients with echo-confirmed PH, independent of gestational age. The association between critical illness, iNO administration and IVH in extremely premature infants may merit prospective delineation.

Adverse Heart-Lung Interactions in Ventilator-induced Lung Injury.

RATIONALE: In the original 1974 in vivo study of ventilator-induced lung injury, Webb and Tierney reported that high Vt with zero positive end-expiratory pressure caused overwhelming lung injury, subsequently shown by others to be due to lung shear stress. OBJECTIVES: To reproduce the lung injury and edema examined in the Webb and Tierney study and to investigate the underlying mechanism thereof. METHODS: Sprague-Dawley rats weighing approximately 400 g received mechanical ventilation for 60 minutes according to the protocol of Webb and Tierney (airway pressures of 14/0, 30/0, 45/10, 45/0 cm H2O). Additional series of experiments (20 min in duration to ensure all animals survived) were studied to assess permeability (n = 4 per group), echocardiography (n = 4 per group), and right and left ventricular pressure (n = 5 and n = 4 per group, respectively). MEASUREMENTS AND MAIN RESULTS: The original Webb and Tierney results were replicated in terms of lung/body weight ratio (45/0 > 45/10 ≈ 30/0 ≈ 14/0; P < 0.05) and histology. In 45/0, pulmonary edema was overt and rapid, with survival less than 30 minutes. In 45/0 (but not 45/10), there was an increase in microvascular permeability, cyclical abolition of preload, and progressive dilation of the right ventricle. Although left ventricular end-diastolic pressure decreased in 45/10, it increased in 45/0. CONCLUSIONS: In a classic model of ventilator-induced lung injury, high peak pressure (and zero positive end-expiratory pressure) causes respiratory swings (obliteration during inspiration) in right ventricular filling and pulmonary perfusion, ultimately resulting in right ventricular failure and dilation. Pulmonary edema was due to increased permeability, which was augmented by a modest (approximately 40%) increase in hydrostatic pressure. The lung injury and acute cor pulmonale is likely due to pulmonary microvascular injury, the mechanism of which is uncertain, but which may be due to cyclic interruption and exaggeration of pulmonary blood flow.

Cardiovascular Associations with Abnormal Brain Magnetic Resonance Imaging in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia and Rewarming.

OBJECTIVE: This article compares hemodynamic characteristics of neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) with normal versus abnormal brain magnetic resonance imaging (MRI). METHODS: Serial echocardiography (echo) was performed within 24 hours, after 48 to 72 hours of cooling, within 24 hours of normothermia, and after starting feeds. Pulmonary hemodynamics, cardiac output, and ventricular function were evaluated. All neonates underwent brain MRI (day 4-5), per clinical standard of care. Clinical cardiovascular and echocardiography characteristics were compared between patients with normal versus abnormal MRI. Cardiovascular changes during TH and after rewarming were identified. RESULTS: Twenty neonates at median gestation and birth weight of 40 weeks (interquartile range [IQR]: 39, 41) and 3,410 g (IQR: 2,885, 4,093), respectively, were enrolled. Increased median left ventricular output (LVO) (106-159 mL/kg/min, p < 0.001) and reduced isovolumic relaxation time (IVRT) (48-42 ms, p < 0.001) were seen after rewarming. Echocardiography evidence of pulmonary hypertension (PH) was identified in five neonates. Eight neonates (40%) had brain injury identified on MRI (watershed [n = 4], basal ganglia [n = 4]); this subgroup were more likely to have echo evidence of PH at 24 hours. CONCLUSION: Longitudinal changes in cardiac output were noted in neonates with HIE during TH and rewarming. Echocardiography evidence of PH, however, was associated with abnormal MRI brain. The prognostic relevance of these physiologic changes requires more comprehensive delineation.

Controversies in the identification and management of acute pulmonary hypertension in preterm neonates.

It is increasingly recognized that the abnormal physiologic consequences of pulmonary hypertension (PH) may contribute to poor cardiopulmonary health in premature babies. Conflicting literature has led to clinical uncertainty, pathological misinterpretation, and variability in treatment approaches among practitioners. There are several disorders with overlapping and interrelated presentations, and other disorders with a similar clinical phenotype but diverse pathophysiological contributors. In this review, we provide a diagnostic approach for acute hypoxemic respiratory failure in the preterm neonate, outline the pathophysiological conditions that may present as acute PH, and discuss the implications of high pulmonary vascular resistance (PVR) on the cardiovascular system. Although PVR and respiratory management are highly interrelated, there may be a population of preterm neonates in whom inhaled nitric oxide may improve illness severity and may relate to outcomes. A management approach based on physiology that considers common clinical conundrums is provided. A more comprehensive understanding of the physiology may help in informed decision-making in clinical situations where conclusive scientific evidence is lacking. Regardless, high-quality research is required, and appropriate definition of the target population is paramount. A thoughtful approach to cardiovascular therapy may also provide an avenue to improve neurodevelopmental outcomes while awaiting more clear answers.