Cerebral Oximetry Monitoring in Extremely Preterm Infants.

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).

Cerebral autoregulation in the preterm newborn using near-infrared spectroscopy: a comparison of time-domain and frequency-domain analyses.

The aim was to compare two conventional methods used to describe cerebral autoregulation (CA): frequency-domain analysis and time-domain analysis. We measured cerebral oxygenation (as a surrogate for cerebral blood flow) and mean arterial blood pressure (MAP) in 60 preterm infants. In the frequency domain, outcome variables were coherence and gain, whereas the cerebral oximetry index (COx) and the regression coefficient were the outcome variables in the time domain. Correlation between coherence and COx was poor. The disagreement between the two methods was due to the MAP and cerebral oxygenation signals being in counterphase in three cases. High gain and high coherence may arise spuriously when cerebral oxygenation decreases as MAP increases; hence, time-domain analysis appears to be a more robust­and simpler­method to describe CA.

Dopamine therapy is associated with impaired cerebral autoregulation in preterm infants.

AIM: Hypotension is a common problem in newborn infants and is associated with increased mortality and morbidity. Dopamine is the most commonly used antihypotensive drug therapy, but has never been shown to improve neurological outcomes. This study tested our hypothesis that dopamine affects cerebral autoregulation (CA). METHODS: Near-infrared spectroscopy was used to measure the cerebral oxygenation index in 60 very preterm infants, and mean arterial blood pressure was monitored towards the end of their first day of life. Measurements were performed continuously for two to three hour periods. CA was quantified as the cerebral oximetry index (COx). RESULTS: We treated 13 of the 60 infants (22%) with dopamine during the measurements. COx was higher in the dopamine group than the untreated group (0.41 ± 0.25 vs. 0.08 ± 0.25, p < 0.001). Blood pressure tended to be lower in the dopamine group, but the anticipated difference in cerebral oxygenation was not detected. The need for mechanical ventilation in the first day of life and incidences of mortality was higher in the dopamine group. CONCLUSION: Dopamine therapy was associated with decreased CA in preterm infants. We were unable to determine whether dopamine directly impaired CA or was merely an indicator of illness.

Sidestream dark field images of the microcirculation: intra-observer reliability and correlation between two semi-quantitative methods for determining flow.

BACKGROUND: Since analysis of Sidestream Dark Field images still requires subjective interpretation, we wanted to determine intra-observer repeatability and to estimate the correlation between different evaluation methods. METHODS: Fifty-four Sidestream Dark Field videos were analyzed twice by the same blinded observer using validated software. Vessels were detected, generating the parameter Total Vessel Density (TVD), and flow was determined by (i) classifying each vessel separately, generating the parameters Perfused Vessel Density (PVD) and Proportion of Perfused Vessels (PPV), and by (ii) the "Boerma" method, generating a Microvascular Flow Index (MFI) by quadrants. RESULTS: Intraclass Correlation Coefficients (ICCs) were above 0.9 for TVD and above 0.8 for PDV and PPV. MFIby quadrants had the lowest reliability (ICC = 0.52 for capillaries and ICC = 0.59 for all vessels), significantly lower than for PVD (ICC = 0.89, p < 0.001 for capillaries and ICC = 0.90, p < 0.001 for all vessels) and PPV (ICC = 0.82, p = 0.003 for capillaries and ICC = 0.83, p = 0.01 for all vessels). Correlation coefficient (r) between PPV and MFIby quadrants corrected for measurement error was 0.39 (0.10 - 0.64) for capillaries and 1.01 (0.85 - 1.16) for all vessels. CONCLUSIONS: Intra-observer reliability for full evaluation of Sidestream Dark Field images was good for vessel detection and for flow classification but significantly poorer for the faster "Boerma" method. Furthermore, the Boerma method is likely to estimate different aspects of capillary flow than do the standard methods.

Cerebral effects of commonly used vasopressor-inotropes: a study in newborn piglets.

BACKGROUND: Despite widespread use in sick infants, it is still debated whether vasopressor-inotropes have direct cerebral effects that might affect neurological outcome. We aimed to test direct cerebrovascular effects of three commonly used vasopressor-inotropes (adrenaline, dopamine and noradrenaline) by comparing the responses to those of nonpharmacologically induced increases in blood pressure. We also searched for reasons for a mismatch between the response in perfusion and oxygenation. METHODS: Twenty-four piglets had long and short infusions of the three vasopressor-inotropes titrated to raise mean arterial blood pressure (MAP) 10 mmHg in random order. Nonpharmacological increases in MAP were induced by inflation of a balloon in the descending aorta. We measured cerebral oxygenation (near-infrared spectroscopy), perfusion (laser-Doppler), oxygen consumption (co-oximetry of arterial and superior sagittal sinus blood), and microvascular heterogeneity (side stream dark field video microscopy). RESULTS: Vasopressor-inotropes increased cerebral oxygenation significantly less (p≤0.01) compared to non-pharmacological MAP increases, whereas perfusion was similar. Furthermore, cerebral total hemoglobin concentration increased significantly less during vasopressor-inotrope infusions (p = 0.001). These physiologic responses were identical between the three vasopressor-inotropes (p>0.05). Furthermore, they induced a mild, although insignificant increase in cerebral metabolism and microvascular heterogeneity (p>0.05). Removal of the scalp tissue did not influence the mismatch (p>0.05). CONCLUSION: We demonstrated a moderate vasopressor-inotrope induced mismatch between cerebral perfusion and oxygenation. Scalp removal did not affect this mismatch, why vasopressor-inotropes appear to have direct cerebral actions. The statistically nonsignificant increases in cerebral metabolism and/or microvascular heterogeneity may explain the mismatch. Alternatively, it may simply reflect a vasopressor-inotrope-induced decrease in the arterial-to-venous volume ratio as detected by near-infrared spectroscopy.

Cerebral vascular effects of hypovolemia and dopamine infusions: a study in newborn piglets.

AIM: Despite widespread use, effects of volume boluses and dopamine in hypotensive newborn infants remain controversial. We aimed to elucidate if hypovolemia alone impairs cerebral autoregulation (CA) and if dopamine affects cerebral vasculature. METHODS: In 12 piglets, cerebral perfusion (laser-Doppler flux) and oxygenation [near-infrared spectroscopy (NIRS)] were examined during dopamine (20-50 µg/kg per minute) and nonpharmacologically induced blood pressure (ABP) changes. Effect on cerebral perfusion and oxygenation was quantified as frequency gain between ABP and laser-Doppler flux (gain-LDF) and NIRS [gain-oxygenation index (OI)], respectively. Gain quantifies change in perfusion or oxygenation per ABP-change. CA was estimated as gain-LDF during nonpharmacologically induced ABP changes, that is, as degree of impairment. Dopamine's cerebrovascular effect was estimated by contrasting gain during dopamine- and nonpharmacologically induced ABP changes. Measurements were conducted during both normovolemia- and haemorrhage-induced hypovolemia. RESULTS: Hypovolemia elicited hypotension (p = 0.02) as well as increasing impairment of CA (p = 0.01). However, hypovolemia without hypotension did not affect CA significantly. Dopamine increased perfusion significantly compared to nonpharmacological challenges (mean difference: 1.5%/mmHg, 95% CI: 0.5-2.6, p = 0.007). Oxygenation was, however, similar (mean difference: 0.01 µmol/L per mmHg, 95% CI: -0.03 to 0.05, p = 0.7). CONCLUSION: Our findings do not support that hypovolemia alone impairs CA. Furthermore, dopamine seems to increase cerebral perfusion but not oxygenation.

Applicability of near-infrared spectroscopy to measure cerebral autoregulation noninvasively in neonates: a validation study in piglets.

Impaired cerebral autoregulation (CA) is common and is associated with brain damage in sick neonates. Frequency analysis using spontaneous changes in arterial blood pressure (ABP) and cerebral near-infrared spectroscopy (NIRS) has been used to measure CA in several clinical studies. Coherence of the NIRS and ABP signals (i.e. correlation in the frequency domain) detects impairment of CA, whereas gain (i.e. magnitude of ABP variability passing from systemic to cerebral circulation) estimates the degree of this impairment. So far, however, this method has not been validated. In 12 newborn piglets, we compared NIRS-derived measures of CA with a conventional measure of CA: cerebral blood flow was measured by laser Doppler flowmetry, and changes in ABP were induced by inflating a thoracic aorta balloon. CA capacity was calculated as %ΔCVR/%ΔABP (i.e. percentage of full autoregulatory capacity), where CVR (i.e. cerebral vascular resistance) was estimated as ABP/Doppler flux. Correlation between coherence and CA capacity (r = -0.34, n = 24, p > 0.05) and between gain and CA capacity (r = -0.11, n = 24, p > 0.05) was limited. As expected, however, gain was significantly associated with CA capacity in measurements with significant coherence (r = -0.55, n = 15, p = 0.03). In conclusion, our data validate frequency analysis for estimation of CA in clinical research. Low precision, however, hampers its clinical application.