Cardiac output calculation using the Liljestrand and Zander formula: is this method applicable during immediate transition after birth? - A post hoc analysis.

The transition from intrauterine to extrauterine life is a critical period for neonates. Assessing the cardiovascular transition during this period immediately after birth is crucial but challenging. The present study compares adjusted estimated cardiac output values calculated by the Liljestrand and Zander formula (COest/adj LaZ) with non-invasively measured cardiac output values (CO-bioimpedance) during immediate transition after birth. We performed a secondary outcome analysis of a prospective observational study in preterm and term neonates. Ten and 15 min after birth, arterial blood pressure and heart rate were assessed, and CO-bioimpedance was measured using electrical bioimpedance method (Aesculon monitor, Osypka, Germany). We calculated COest/adj LaZ and compared it to CO-bioimpedance. Further, we performed a correlation analysis. Thirty-two neonates with a median (IQR) gestational age of 37.0 (32.0-39.4) weeks were included. Mean ± SD CO-bioimpedance was 0.62 ± 0.15 l/min, and COest/adj LaZ was calculated to be 0.64 ± 0.10 l/min, whereby both correlated significantly (p = 0.025, r = 0.359) with each other.  Conclusion: The present study demonstrates high comparability of COest/adj LaZ and CO-bioimpedance in neonates during immediate transition after birth, suggesting that cardiac output can be derived in a cost-effective and feasible manner if other methods are not available. What is Known: • Echocardiography is considered the gold standard for non-invasive CO evaluation, but its feasibility during the immediate transition period is limited. What is New: • Non-invasive methods such as CO-bioimpedance for cardiac output (CO) measurement and the Liljestrand and Zander (LaZ) formula for estimating CO offer promising alternatives during the immediate transition period.

Peripheral muscle fractional tissue oxygen extraction in stable term and preterm neonates during the first 24†h after birth.

Background: Peripheral muscle fractional tissue oxygen extraction (pFTOE) represents the relative extraction of oxygen from the arterial to venous compartment, providing information about dynamic changes of oxygen delivery and oxygen consumption. The aim of the present study was to establish reference values of pFTOE during the first 24 h after birth in stable term and late preterm neonates. Methods: The present study is a post-hoc analysis of secondary outcome parameters of prospective observational studies. Only stable neonates without infection, asphyxia and any medical support were eligible for our analysis to obtain normal values. For measurements of peripheral muscle tissue oxygenation index (pTOI) during the first 24 h after birth in term and preterm neonates, the NIRO200/NIRO200NX was used. Arterial oxygen saturation (SpO2) was obtained by pulse oximetry. pFTOE was calculated out of pTOI and SpO2: pFTOE = (SpO2-pTOI)/SpO2. Measurements of neonates were stratified into four groups according to their respective measurement time point (6 h periods) after birth. Term and preterm neonates were analyzed separately. Mean values of measurements during the first time period (0-6 h after birth) were compared to measurements of the following time periods (second = 7-12 h, third = 13-18 h, fourth = 19-24 h after birth). Results: Two-hundred-fourty neonates (55 term and 185 late preterm neonates) had at least one peripheral muscle NIRS measurements within the first 24 h after birth. Mean gestational age and birth weight were 39.4 ± 1.1 weeks and 3360 (2860-3680)g in term neonates and 34.0 ± 1.4 weeks and 2060 (1750-2350)g in preterm neonates, respectively. In term neonates pFTOE was 0.264 (0.229-0.300), 0.228 (0.192-0.264), 0.237 (0.200-0.274) and 0.220 (0.186-0.254) in the first, second, third and fourth time period. In preterm neonates pFTOE was 0.229 (0.213-0.246), 0.225 (0.209-0.240), 0.226 (0.210-0.242) and 0.238 (0.222-0.255) in the first, second, third and fourth time period. pFTOE did not show any significant changes between the time periods, neither in term nor in preterm neonates. Conclusion: We provide reference values of pFTOE for stable term and late preterm neonates within the first 24 h after birth, which were stable when comparing four 6-h periods. These normal values are of great need for interpreting pFTOE in scientific context as well as for potential future clinical applications.

Cerebral oxygenation immediately after birth and long-term outcome in preterm neonates-a retrospective analysis.

BACKGROUND: Prematurity is associated with increased risk for morbidity and mortality. Aim of this study was to evaluate whether cerebral oxygenation during fetal-to-neonatal transition period was associated with long-term outcome in very preterm neonates. METHODS: Preterm neonates ≤ 32 weeks of gestation and/or ≤ 1500 g with measurements of cerebral regional oxygen saturation (crSO2) and cerebral fractional tissue oxygen extraction (cFTOE) within the first 15 min after birth were analysed retrospectively. Arterial oxygen saturation (SpO2) and heart rate (HR) were measured with pulse oximetry. Long-term outcome was assessed at two years using "Bayley Scales of Infant Development" (BSID-II/III). Included preterm neonates were stratified into two groups: adverse outcome group (BSID-III ≤ 70 or testing not possible due to severe cognitive impairment or mortality) or favorable outcome group (BSID-III > 70). As the association between gestational age and long-term outcome is well known, correction for gestational age might disguise the potential association between crSO2 and neurodevelopmental impairment. Therefore, due to an explorative approach the two groups were compared without correction for gestational age. RESULTS: Forty-two preterm neonates were included: adverse outcome group n = 13; favorable outcome group n = 29. Median(IQR) gestational age and birth weight were 24.8 weeks (24.2-29.8) and 760 g (670-1054) in adverse outcome group and 30.6 weeks (28.1-32.0) (p = 0.009*) and 1250 g (972-1390) (p = 0.001*) in the favorable outcome group, respectively. crSO2 was lower (significant in 10 out of 14 min) and cFTOE higher in adverse outcome group. There were no difference in SpO2, HR and fraction of inspired oxygen (FiO2), except for FiO2 in minute 11, with higher FiO2 in the adverse outcome group. CONCLUSION: Preterm neonates with adverse outcome had beside lower gestational age also a lower crSO2 during immediate fetal-to-neonatal transition when compared to preterm neonates with age appropriate outcome. Lower gestational age in the adverse outcome group would suggest beside lower crSO2 also lower SpO2 and HR in this group, which were however similar in both groups.

Cardiac output and regional-cerebral-oxygen-saturation in preterm neonates during immediate postnatal transition: An observational study.

AIM: To examine potential correlations between cardiac output (CO) with cerebral-regional-oxygen-saturation (crSO2 ) and cerebral-fractional-tissue-oxygen-extraction (cFTOE) during immediate foetal-to-neonatal transition in term and preterm neonates with and without respiratory support. METHODS: Post hoc analyses of secondary outcome parameters of prospective observational studies were performed. We included neonates with cerebral near-infrared-spectroscopy (NIRS) monitoring and an oscillometric blood pressure measurement at minute 15 after birth. Heart rate (HR) and arterial oxygen saturation (SpO2 ) were monitored. CO was calculated with Liljestrand and Zander formula and correlated with crSO2 and cFTOE. RESULTS: Seventy-nine preterm neonates and 207 term neonates with NIRS measurements and calculated CO were included. In 59 preterm neonates (mean gestational age (GA): 29.4 ± 3.7 weeks) with respiratory support, CO correlated significantly positively with crSO2 and significantly negatively with cFTOE. In 20 preterm neonates (GA 34.9 ± 1.3 weeks) without respiratory support and in 207 term neonates with and without respiratory support, CO correlated neither with crSO2 nor with cFTOE. CONCLUSION: In compromised preterm neonates with lower gestational age and in need of respiratory support, CO was associated with crSO2 and cFTOE, whereas in stable preterm neonates with higher gestational age as well as in term neonates with and without respiratory support, no associations were observed.

Correlation between arterial blood pressures and regional cerebral oxygen saturation in preterm neonates during postnatal transition-an observational study.

Objective: To assess whether blood pressure (systolic (SABP), diastolic (DABP), and mean arterial blood pressure (MABP) and cerebral-regional-oxygen-saturation (crSO2) and cerebral-fractional-tissue-oxygen-extraction (cFTOE) are associated after immediate fetal-to-neonatal transition in preterm neonates with and without respiratory support. Study design: Post-hoc analyses of secondary outcome parameters of prospective observational studies were performed. We included moderate and late preterm neonates with and without respiratory support with cerebral NIRS monitoring (INVOS 5100c) and an oscillometric blood pressure measurement at minute 15 after birth. Heart rate (HR) and arterial oxygen saturation (SpO2) were monitored routinely. Blood pressure values were correlated with crSO2 and cFTOE. Results: 47 preterm neonates with NIRS measurements and blood pressure measurement during immediate transition after birth were included. Twenty-five preterm neonates (gestational age: 34.4±1.6 weeks) received respiratory support. In these neonates crSO2 correlated significantly positively with systolic blood pressure (SABP; r = 0.46, p = 0.021), diastolic blood pressure (DABP; r = 0.51, p = 0.009) and, mean arterial pressure (MABP; r = 0.48, p = 0.015). cFTOE correlated significantly negatively with SABP (r = -0.44, p = 0.027), DABP (r = -0.49, p = 0.013) and mean MABP (r = -0.44, p = 0.029). Twenty-two preterm neonates (gestational age: 34.5 ± 1.5 weeks) did not receive respiratory support. In those neonates, neither crSO2 nor cFTOE correlated with blood pressure. Conclusion: In compromised moderate and late preterm neonates with respiratory support, both, crSO2 and cFTOE correlated with blood pressure. These findings suggest that passive pressure-dependent cerebral perfusion was present in preterm neonates with respiratory support, indicating an impaired cerebral autoregulation in those compromised preterm neonates.

Fetal Hemoglobin and Cerebral Tissue Oxygenation during Immediate Postnatal Transition.

INTRODUCTION: Concentration of fetal hemoglobin (HbFc) in human neonates determines oxygen-carrying capacity of blood and the position of oxyhemoglobin dissociation curve. Near-infrared spectroscopy enables the measurement of regional cerebral tissue oxygen saturation (rScO2) and in combination with measurements of pulsatile arterial oxygen saturation (SpO2), the calculation of cerebral fractional tissue oxygen extraction (cFTOE). METHODS: We aimed to investigate the impact of HbFc on rScO2, cFTOE, and SpO2 in preterm and term neonates during the first 15 min after birth. Blood analyses provided total blood hemoglobin (Hb) and HbFc measurements. Correlations between HbFc, Hb and rScO2, cFTOE, and SpO2 in each minute were analyzed. RESULTS: Ninety term and 19 preterm neonates without medical support were included. HbFc was significantly higher in preterm neonates, whereas there were no significant differences in Hb between the groups. In preterm neonates, we found positive correlations of both HbFc and Hb with rScO2 and negative correlations of HbFc and Hb with cFTOE in the first minutes after birth. In contrast, there were no significant correlations between the same parameters in term neonates. Correlations between HbFc or Hb and SpO2 were either insignificant, negligible, or very low in both groups. DISCUSSION/CONCLUSION: In preterm neonates, higher HbFc was associated with higher rScO2 and lower cFTOE in the first minutes after birth. This phenomenon could not be confirmed in term neonates and might reflect immature autoregulation of oxygen delivery to the brain or lower oxygen consumption in preterm neonates in the first minutes of immediate postnatal transition.

Non-invasively Measured Venous Oxygen Saturation as Early Marker of Impaired Oxygen Delivery in Preterm Neonates.

INTRODUCTION: Adequate oxygen supply for preterm neonates may be defined through non-invasive measurement of venous oxygen saturation (SvO2) and fractional oxygen extraction using near-infrared spectroscopy (NIRS). We investigated whether there was a difference in peripheral muscle SvO2 (pSvO2) and peripheral fractional oxygen extraction (pFOE) in preterm neonates with early inflammation/infection compared to healthy subjects during the first 72 h after birth. MATERIALS AND METHODS: We retrospectively analyzed secondary outcome parameters of prospective observational studies, including preterm neonates at risk of infection in whom peripheral NIRS measurements were performed in combination with venous occlusions. Early neonatal inflammation/infection was diagnosed by clinical signs and laboratory parameters. Peripheral muscle tissue oxygenation index (pTOI) was measured using either NIRO 300 or NIRO 200-NX (both Hamamatsu Photonics, Japan) on the patients' lower legs. Using 20-s venous occlusions, pSvO2 and pFOE were calculated incorporating simultaneous measurements of arterial oxygen saturation (SpO2). RESULTS: We analyzed measurements from 226 preterm neonates (median gestational age 33.9 weeks), 64 (28.3%) of whom were diagnosed with early neonatal inflammation/infection. During the first 24 h after birth, pSvO2 (66.9% [62.6-69.2] vs. 69.4% [64.6-72.0]; p = 0.04) and pTOI (68.6% [65.3-71.9] vs. 71.7% [67.3-75.1]; p = 0.02) were lower in those neonates with inflammation/infection, while there was no such difference for measurements between 24-48 and 48-72 h. DISCUSSION: NIRS measurement of pSvO2 and pFOE is feasible and may be utilized for early detection of impaired peripheral oxygen delivery. As pTOI was also significantly lower, this parameter may serve as substitute for diminished regional oxygen supply.

Cardiac Output and Cerebral Oxygenation in Term Neonates during Neonatal Transition.

The immediate transition from foetus to neonate includes substantial changes, especially concerning the cardiovascular system. Furthermore, the brain is one of the most vulnerable organs to hypoxia during this period. According to current guidelines for postnatal stabilization, the recommended parameters for monitoring are heart rate (HR) and arterial oxygen saturation (SpO2). Recently, there is a growing interest in advanced monitoring of the cardio-circulatory system and the brain to get further objective information about the neonate's condition during the immediate postnatal transition after birth. The aim of the present study was to combine cardiac output (CO) and brain oxygenation monitoring in term neonates after caesarean section in order to analyse the potential influence of CO on cerebral oxygenation during neonatal transition. This was a monocentric, prospective, observational study. For non-invasive cardiac output measurements, the electrical velocimetry (EV) method (Aesculon Monitor, Osypka Medical, CA, USA) was used. The pulse oximeter probe for SpO2 and HR measurements was placed on the right hand or wrist. The cerebral tissue oxygen index (cTOI) was measured using a NIRO-200NX monitor with the near-infrared spectroscopy (NIRS) transducer on the right frontoparietal head. Monitoring started at minute 1 and was continued until minute 15 after birth. At minutes 5, 10, and 15 after birth, mean CO was calculated from six 10 s periods (with beat-to-beat analysis). During the study period, 99 term neonates were enrolled. Data from neonates with uncomplicated transitions were analysed. CO showed a tendency to decrease until minute 10. During the complete observational period, there was no significant correlation between CO and cTOI. The present study was the first to investigate a possible correlation between CO and cerebral oxygenation in term infants during the immediate neonatal transition. In term infants with uncomplicated neonatal transition after caesarean section, CO did not correlate with cerebral oxygenation.

Sex related difference in cardiac output during neonatal transition in term neonates.

BACKGROUND: The immediate transition from foetus to neonate includes substantial changes especially concerning the cardiovascular system. As sex related differences have been shown in cardiovascular medicine, this topic warrants further investigation in neonatology. Aim: The aim of this present study was to measure cardiac output (CO) and cerebral oxygenation (cTOI) non-invasively in term neonates and to investigate potential sex related differences between female and male neonates after birth. METHODS: This is a mono-centric prospective observational study. For CO-measurements, the electrical velocimetry method was used. The pulse oximetry for arterial oxygen saturation and heart-rate measurements was placed on the right hand or wrist. cTOI was measured using a NIRO 200NX monitor. The near-infrared spectroscopy probe was positioned on the right side of forehead in each infant. Monitoring started at minute 1 and was continued until minute 15 after birth. At minutes 5, 10, and 15 after birth, CO was calculated as an average out of six 10-second periods. RESULTS: 99 term neonates were enrolled. In our study population, we could identify 54 female and 45 male neonates. Males had higher cardiac output compared to females throughout the observational period, with a significant difference in minute 15 after birth (217, 95% CI: 203-231 mL/kg/min versus 178, 95% CI: 163-192 mL/kg/min; P<0.001). cTOI, SpO2, and HR did not differ between male and female neonates. CONCLUSIONS: The present work is the first to investigate sex related differences concerning cardiac output in term neonates during postnatal transition, showing a significantly higher cardiac output in male neonates 15 minutes after birth.

Avoiding Arterial Hypotension in Preterm Neonates (AHIP)-A Single Center Randomised Controlled Study Investigating Simultaneous Near Infrared Spectroscopy Measurements of Cerebral and Peripheral Regional Tissue Oxygenation and Dedicated Interventions.

INTRODUCTION: Up to 50% of preterm infants admitted to intensive care units require cardiocirculatory support. The aim of the present study was to assess whether simultaneous monitoring of cerebral tissue oxygenation index (cTOI) and peripheral tissue oxygenation index (pTOI) using near-infrared spectroscopy (NIRS) in combination with dedicated intervention guidelines may help avoiding arterial hypotension and catecholamine administration in preterm neonates. STUDY DESIGN: Preterm neonates <37 weeks of gestation were included in a single center randomized controlled study. Blood pressure was measured non-invasively or invasively. In the NIRS group, simultaneous cTOI and pTOI monitoring was used starting within 6 h after birth for 24 h to calculate changes in cTOI/pTOI ratio over time. Depending on these changes, interventions including echocardiography, administration of volume or patent ductus arteriosus treatment were performed. In the control group, only routine monitoring and treatment were performed and NIRS signals were not visible. The primary outcome was burden of hypotension within 48 h after initiation of NIRS monitoring. RESULTS: 49 preterm neonates were included in each group: NIRS group 33.1 (32.0-34.0) (median: 25-75 centile) weeks of gestation and control group 33.4 (32.3-34.3) weeks of gestation. In the NIRS group, echocardiography was performed in 17 preterm neonates due to NIRS measurements, whereby six neonates received further treatment. Percentage of neonates with any hypotensive episode during the 48-h observational period was 32.6% in the NIRS group and 44.9% in the control group (p = 0.214). Burden of hypotension (i.e., %mmHg of mean arterial pressure < gestational age) was 0.0 (0.0-2.1) mmHg h in the NIRS group and 0.4 (0.0-3.3) mmHg h in the control group (p = 0.313), with observed burden of hypotension being low in both groups. No severe adverse reactions were observed. CONCLUSION: In preterm neonates using simultaneous peripheral and cerebral NIRS measurements for early detection of centralization followed by predefined interventions led to a non-significant reduction in burden of arterial hypotension. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier: NCT01910467.

Peripheral Muscle Near-Infrared Spectroscopy in Neonates: Ready for Clinical Use? A Systematic Qualitative Review of the Literature.

BACKGROUND: Peripheral muscle near-infrared spectroscopy (NIRS) measurements are of increasing interest especially in the care of critically ill patients. OBJECTIVE: The aim was to perform a systematic qualitative review on peripheral muscle NIRS measurements in the clinical care of term and preterm neonates. METHODS: A systematic search of PubMed and Ovid Embase was performed using the following terms: neonate, neonates, newborn, newborns, infant, infants, near-infrared spectroscopy, NIRS, oxygenation, perfusion, oxygen extraction, peripheral, tissue, muscle, calf, forearm and thigh. Additional articles were identified by a manual search of the cited references. Only human studies were included. RESULTS: Twenty-one studies were identified to use peripheral muscle NIRS measurements as a single method, 17 studies combined cerebral and peripheral muscle NIRS measurements and 1 study used multi-site NIRS measurements in human neonates. Two randomized studies were identified. Two additional publications were included because they provided important general information about peripheral muscle NIRS measurements. CONCLUSION: In the care of critically ill neonates peripheral muscle NIRS measurements alone or in combination with cerebral or multi-site NIRS measurements provide useful additional information about peripheral circulation and oxygenation. This method is a promising tool in the recognition of early states of centralization (compensated shock) in this vulnerable group of patients. However, before this method can be used in the clinical routine it has to be tested as monitoring to guide interventions in further studies.