Titration of inspired oxygen in preterm infants with hypoxemic respiratory failure using near-infrared spectroscopy and pulse oximetry: A new approach.

BACKGROUND: Titration of inspired oxygen is a challenge in preterm infants with hypoxemic respiratory failure (HRF). Monitoring of brain oxygen by near-infrared spectroscopy (NIRS) has been proven to minimize the burden of hyperoxia and hypoxemia; with a better understanding of cerebral autoregulation, integrating NIRS and pulse oximetry for titrating inspired oxygen in preterm infants is a novel approach. METHODS: We studied the impact of integrated monitoring of oxygen saturation by pulse oximetry (SpO2 ) and cerebral regional tissue oxygen (crRTO) by NIRS during a stepwise oxygen reduction test (ORT) on reducing oxygen requirement in preterm infants with HRF. The correlation between SpO2 with crRTO, and fractional oxygen extraction (FOE) was assessed, concordance levels (r > 0.5) were determined during the assessment period and were considered as a sign of impaired autoregulation. The primary outcome was the achievement of significantly lower FiO2 at 72 h after the start of the integrated monitoring. RESULTS: A total of 38 preterm infants were included, 27 had normal cerebral autoregulation (CAR) (Group 1) in whom SpO2 was poorly correlating with crRTO with (r < 0.5) and had a significantly greater percentage of reduction below baseline in FiO2 (mean: 34%). Eleven infants had impaired CAR (Group 2) with SpO2 significantly correlating with crRTO (r > 0.5) and had a linear trend of FOE inverse to SpO2 and crRTO; this was considered as an arterial saturation dependent oxygen delivery (SadDO2 ). CONCLUSION: Integrated monitoring of preterm infants by SpO2 and crRTO was associated with easier weaning of oxygen with less burden of both hyperoxia and hypoxemia.

Lung ultrasound predicts histological lung injury in a neonatal model of acute respiratory distress syndrome.

RATIONALE: Point-of-care ultrasound (POCUS) is used to evaluate pulmonary edema in adults with acute respiratory distress syndrome (ARDS). Its use has not been validated in neonatal models. OBJECTIVES: We compared an in vivo lung ultrasound score against clinical and histological markers of acute lung injury, in a neonatal animal model, hypothesizing that POCUS would sensitively diagnose early acute lung injury in neonates and discern its severity. METHODS: Fifteen anesthetized, ventilated 3-day-old neonatal piglets were divided into controls, moderate lung injury, or severe lung injury by graded treatment with oleic acid. Degree of lung injury was quantified at baseline, immediately after oleic acid administration, and 1 hour after the evolution of acute lung injury, by blood gases, ventilation parameters and calculated oxygenation deficit; hemodynamic indices by echocardiography, and lung ultrasound obtained in an 8-region grid of anterior and posterior zones, semi-quantitatively analyzed by a blinded observer. Lungs were inflation-fixed postmortem at last mean airway pressure, for histological assessment. RESULTS: Acute lung injury manifested in oleic acid-treated groups as dose-dependent capillary leak causing intravascular depletion and cardiac failure, hypoxemia with increasing intrapulmonary shunt fraction, decreased lung compliance, and resistance. Ultrasound scores of anterior regions distinguished moderate from severe injury; scores in posterior regions reached maximum values immediately after lung injury. POCUS score correlated with calculated intrapulmonary shunt fraction (R2 = .65) and with histological injury score (R2 = .61), P < .01. CONCLUSION: We conclude that POCUS may be valuable in neonates for early quantification of acute lung injury or ARDS; and that nondependent ultrasound regions clearly distinguish severity of pulmonary edema.

Effect of vasopressin on a porcine model of persistent pulmonary hypertension of the newborn.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is due to a failure of pulmonary vascular relaxation. Vasopressin, a systemic vasoconstrictor acting on smooth muscle AVPR1a receptors, is used in treatment of PPHN. We sought to determine acute effects of vasopressin infusion on pulmonary hemodynamics in a large animal model of hypoxic PPHN. METHODS: PPHN was induced in 6 newborn piglets by 72 h normobaric hypoxia (FiO2 = 0.10); controls were 7 age-matched 3-day-old piglets. Animals were anesthetized and ventilated with central venous and arterial lines, and after stabilization, randomized using a crossover design to normoxic or hypoxic ventilation, then 30 min infusion of 0.0012 U/kg/min vasopressin, followed by 45 min vasopressin washout period. Echocardiographic parameters and oxygen consumption were measured before and after vasopressin. Relaxation to vasopressin was tested in isolated PPHN and control pulmonary arteries by isometric myography. Expression of AVPR1a receptor mRNA was quantified in arterial and myocardial tissues. RESULTS: Vasopressin did not alleviate hypoxia-responsiveness of PPHN pulmonary circuit. There were no significant differences in pulmonary hypertension, cardiac function indices, or oxygenation indices after vasopressin infusion. Vasopressin did not dilate control or PPHN pulmonary arteries, and AVPR1 was minimally expressed. CONCLUSIONS: Vasopressin does not have a direct pulmonary vasodilator effect in PPHN, within the timeframe studied.

Lung Ultrasound as a New Technique for Diagnosis of Neonatal Respiratory Diseases.

Point-of-care ultrasound in the NICU is becoming more commonplace and is now used for a number of indications. Over the past ten years, the use of ultrasound as an alternative to a chest x-ray for the diagnosis of neonatal lung disease has been explored, and protocols were developed to refine the interpretation of ultrasound images in neonatal lung disease. The purpose of this column is to briefly explain the physics of ultrasound and describe the application of ultrasound to neonatal lung assessment.

Integrated evaluation of hemodynamics: a novel approach for the assessment and management of preterm infants with compromised systemic circulation.

OBJECTIVE: To establish normal reference values for tissue oxygen delivery and consumption in preterm infants and demonstrate the usefulness of the integrated evaluation of hemodynamics (IEH) in preterm infants with compromised systemic circulation (CSC). METHODS: This study included 32 stable preterm infants and 6 infants (selected cases) who underwent IEH. IEH is a multimodal approach which integrates clinical parameters: data obtained from near-infrared spectroscopy (NIRS) and targeted neonatal echocardiography (TNE). RESULTS: Thirty-two hemodynamically stable preterm infants underwent 57 IEH studies. The mean (10th and 90th percentiles) were 0.23 (0.14 and 0.29) for cerebral fractional oxygen extraction (crFOE), 0.2 (0.13 and 0.24) for renal fractional oxygen extraction (rnFOE), and 0.22 (0.19 and 0.27) for mesenteric fractional oxygen extraction (msFOE). The time to full clinical recovery in all sick infants after the change of management was between 4 and 48 h. CONCLUSION: IEH was useful in targeting the management of preterm infants with CSC.

The Impact of Hypoxemia on the Development of Retinopathy of Prematurity in Infants Less Than 29 Weeks of Gestation.

OBJECTIVE: To study the impact of cumulative exposure to hypoxemia on the development of retinopathy of prematurity (ROP) in preterm infants less than 29 weeks' gestation. STUDY DESIGN: This is a retrospective analysis of the effect of cumulative exposure to hypoxemia during the first 10 weeks of life in preterm infants <29 weeks' gestation. Cumulative time spent at various levels of oxygen saturation was calculated by converting the daily percentage of time to minutes per day. Cumulative exposure to hypoxemia (cT<80 or oxygen saturation <80%) was calculated weekly and compared between outcomes. The primary outcome was the development of ROP requiring treatment. RESULTS: Cumulative hypoxemia exposure was significantly associated with ROP requiring treatment. When adjusted for other neonatal morbidities, only gestation was consistently associated with ROP requiring treatment. CONCLUSION: Cumulative exposure to hypoxemia in the first few weeks was not associated with ROP or treatment of ROP after adjustment for confounders.

Cardiac Air Embolism in Neonates: A Hemodynamic Perspective.

Cardiac air embolism should be suspected in any neonate with acute unexplained cardiovascular collapse or worsening oxygenation. We present here five cases that presented with the above symptoms. A comprehensive evaluation including targeted neonatal echocardiography and near-infrared spectroscopy helped confirm the diagnosis and assess the hemodynamic state. Management was supportive including left lateral positioning, chest compressions, and cardiovascular medications to treat pulmonary hypertension and systemic hypotension.

Predictors of PDA Treatment in Preterm Neonates Who Had Received Prophylactic Indomethacin.

OBJECTIVE: To identify clinical factors those predict the need for patent ductus arteriosus (PDA) treatment in preterm neonates who had received prophylactic indomethacin. PATIENTS AND METHODS: Preterm neonates with <28 weeks' gestational age admitted to level III neonatal intensive care units (NICUs) in Canada between 2010 and 2015 and who had received prophylactic indomethacin were included. Primary outcome was surgical ligation of PDA, while secondary outcomes were any PDA treatment and common neonatal morbidities. RESULTS: Of the 7,024 eligible neonates, 843 (12%) neonates had received prophylactic indomethacin. Of them, 84 neonates (10%) required surgical ligation while 367 neonates (44%) received medical or surgical treatment for PDA. Logistic regression analyses identified gestational age (odds ratio [OR]: 0.71, 95% confidence interval [CI]: 0.58-0.87) and outborn status (OR: 2.07, 95% CI: 1.09-3.93) as predictors for surgical ligation. Maternal hypertension (OR: 0.57, 95% CI: 0.37-0.89), rupture of membranes (ROM) ≥24 hours (OR: 0.68, 95% CI: 0.48-0.96), and surfactant treatment (OR: 1.70, 95% CI: 1.09-2.66) were predictors for medical or surgical treatment of PDA. CONCLUSION: In extremely preterm neonates who had received prophylactic indomethacin, gestational age and outborn status were predictors for surgical ligation of PDA, while maternal hypertension, ROM ≥24 hours, and surfactant treatment were associated with the medical or surgical treatment of PDA.

Patent Ductus Arteriosus in Preterm Infants, Part 1: Understanding the Pathophysiologic Link Between the Patent Ductus Arteriosus and Clinical Complications.

The clinical guidelines for treating patent ductus arteriosus (PDA) have significantly evolved over the last decades from treating any ductal shunt to more conservative management where only the hemodynamically significant patent ductus arteriosus (HSPDA) is treated. This shift has resulted largely from a lack of evidence from randomized controlled trials supporting a relationship between treating a PDA and improving long-term neonatal outcomes. However, there are many unresolved issues. There is no consensus on the precise definition of HSPDA requiring treatment or a clear understanding of when to treat HSPDA. Moreover, the current evidence shows worsening of the long-term neurodevelopmental outcome for infants undergoing surgical PDA ligation.
The presence of physiologic variability among preterm infants, and the presence of different compensatory mechanisms may make it difficult to establish a link between pathophysiology and long-term outcomes. That is, the physiologic variability cannot be simply assessed by randomly assigning infants into two arms of a study. Relying on research from animal and human studies, this article explains the link between the pathophysiology of a PDA and neonatal outcomes.

The Impact of Integrated Evaluation of Hemodynamics on Management of Preterm Infants with Late-Onset Compromised Systemic Circulation.

Objectives To study the impact of integrated evaluation of hemodynamics (IEH), using targeted neonatal echocardiography (TNE), cerebral regional tissue oxygenation (crRTO), and fractional oxygen extraction (FOE), using near-infrared spectroscopy (NIRS) on the management of infants with late-onset compromised systemic circulation (LCSC), and evaluation of the hemodynamic characteristics. Study Design Retrospective cohort study comparing infants with LCSC who underwent IEH (April 2014 to May 2016) with an earlier EPOCH who did not undergo IEH (January 2012 to March 2014). The primary outcome was the time to recovery. Results Total 43 infants were included; 18 infants underwent IEH with a median (IQR) 2 (1-3) assessments per infant. The time to recovery was shorter in IEH group with a median (IQR) 28 hours (15-62) compared with non-IEH group 96 hours (30-160). Autoregulation was compromised in 50%, and systemic vascular resistance (SVR) was low in 67%. Conclusion IEH was associated with shorter time to recovery in infants with LCSC.

Integrated Evaluation of Neonatal Hemodynamics, Part 2: Systematic Bedside Assessment.

Intact hemodynamics results when there is adequate oxygen uptake by the respiratory system, normal cardiac output, sufficient oxygen-carrying capacity of blood, and intact autoregulatory mechanisms to maintain enough oxygenation for normal end-organ function. The current routine monitoring of cardiovascular dynamics in sick preterm and term infants has been based on incomplete evaluation and relies on nonspecific and sometimes misleading clinical markers such as blood pressure. A thorough understanding of perinatal and neonatal cardiovascular, respiratory, oxygen, and other specific end-organ physiology is also mandatory for proper targeted interpretation.

Integrated Evaluation of Neonatal Hemodynamics Program Optimizing Organ Perfusion and Performance in Critically Ill Neonates, Part 1: Understanding Physiology of Neonatal Hemodynamics.

Integrated evaluation of neonatal hemodynamics is the integration of information obtained by echocardiography, clinical evaluation, and biochemical markers, in addition to the clinical information obtained from noninvasive and invasive monitoring of blood pressure and arterial and tissue oxygenation, leading to the formulation of a medical recommendation. This review will focus on the physiology of cardiovascular dynamics and oxygen delivery.

A Patent Ductus Arteriosus Severity Score Predicts Chronic Lung Disease or Death before Discharge.

OBJECTIVES: To test the hypothesis that a patent ductus arteriosus (PDA) severity score (PDAsc) incorporating markers of pulmonary overcirculation and left ventricular (LV) diastolic function can predict chronic lung disease or death before discharge (CLD/death). STUDY DESIGN: A multicenter prospective observational study was conducted for infants <29 weeks gestation. An echocardiogram was carried out on day 2 to measure PDA diameter and maximum flow velocity, LV output, diastolic flow in the descending aorta and celiac trunk, and variables of LV function using tissue Doppler imaging. Predictors of CLD/death were identified using logistic regression methods. A PDAsc was created and a receiver operating characteristic curve was constructed to assess its ability to predict CLD/death. RESULTS: We studied 141 infants at a mean (SD) gestation and birthweight of 26 (1.4) weeks and 952 (235) g, respectively. Five variables were identified that were independently associated with CLD/death (gestation at birth, PDA diameter, maximum flow velocity, LV output, and LV a' wave). The PDAsc had a range from 0 (low risk) to 13 (high risk). Infants who developed CLD/death had a higher score than those who did not (7.3 [1.8] vs 3.8 [2.0], P < .001). PDAsc had an area under the curve of 0.92 (95% CI 0.86-0.97, P < .001) for the ability to predict CLD/death. A PDAsc cut-off of 5 has sensitivity and specificity of 92% and 87%, and positive and negative predictive values of 92% and 82%, respectively. CONCLUSIONS: A PDAsc on day 2 can predict the later occurrence of CLD/death further highlighting the association between PDA significance and morbidity.