Cerebral Autoregulation in Sick Infants:Current Insights

Cerebrovascular autoregulation is the ability to maintain stable cerebral blood flow within a range of cerebral perfusion pressures. When cerebral perfusion pressure is outside the limits of effective autoregulation, the brain is subjected to hypoperfusion or hyperperfusion, which may cause vascular injury, hemorrhage, and/or hypoxic white matter injury. Infants born preterm, after fetal growth restriction, with congenital heart disease, or with hypoxic-ischemic encephalopathy are susceptible to a failure of cerebral autoregulation. Bedside assessment of cerebrovascular autoregulation would offer the opportunity to prevent brain injury. Clinicians need to know which patient populations and circumstances are associated with impaired/absent cerebral autoregulation

Splanchnic oxygen saturation during reoxygenation with 21% or 100% O-2 in newborn piglets

Background Increasing evidence recognizes the harm of excess oxygen to lungs, eyes, and brain of preterm infants, but not yet to the intestine. We assessed changes in splanchnic oxygenation during reoxygenation with 21% compared to 100% O-2 in a newborn piglet model of perinatal asphyxia. Methods We randomized 25 piglets to control or intervention. Intervention groups underwent global hypoxia until acidosis and hypotension occurred. Piglets were reoxygenated for 30 min with 21% or 100% O-2 and observed for 9 h. We continuously measured regional splanchnic oxygen saturation (r(s)SO(2)) using near-infrared spectroscopy (NIRS). We calculated mean r(s)SO(2) and r(s)CoVar (as SD/mean). We measured PaO2 and SaO(2), sampled from the right carotid artery.  Results Reoxygenation after global hypoxia restored r(s)SO(2). Reoxygenation with 100% O-2 increased r(s)SO(2) to values significantly higher than baseline. In intervention groups, r(s)CoVar decreased during observation compared to baseline. We found a correlation between r(s)SO(2) and PaO2 (r = 0.420, P < 0.001) and between r(s)SO(2) and SaO(2) (r = 0.648, P < 0.001) in pooled data from the entire experiment. Conclusion Reoxygenation after global hypoxia improves splanchnic oxygenation, but is associated with reduced variability of r(s)SO(2). Reoxygenation with 100% O-2 exposes the intestine to hyperoxia. Splanchnic NIRS is able to detect intestinal hypoxia and hyperoxia. Impact Splanchnic oxygenation improves during reoxygenation after global hypoxia, though reoxygenation with 100% O2 exposes the intestine to hyperoxia. Decreased variability of splanchnic oxygenation several hours after hypoxia and reoxygenation seems to be independent of the resuscitation strategy, and may indicate intestinal injury. Splanchnic NIRS monitoring was able to detect intestinal hypoxia and exposure to hyperoxia, as evidenced by a strong correlation between splanchnic oxygenation and arterial oxygen content

Inotropes for preterm infants: fifty years on are we any wiser?

For almost half a century, inotropes have been administered to preterm infants with the ultimate goal of increasing their blood pressure. A number of trials, the majority of which focused on dopamine administration, have demonstrated increased blood pressure following inotrope administration in preterm infants and have led to continued use of inotropes in our neonatal units. We have also seen an increase in the number of potential agents available to the clinician. However, we now know that hypotension is a much broader concept than blood pressure alone, and our aim should instead be focused on improving end organ perfusion, specifically cerebral perfusion. Only a limited number of studies have incorporated the organ-relevant hemodynamic changes and long-term outcomes when assessing inotropic effects in neonates, the majority of which are observational studies or have a small sample size. In addition, important considerations, including the developing/maturing adrenergic receptors, polymorphisms of these receptors, and other differences in the pharmacokinetics and pharmacodynamics of preterm infants, are only recently being recognized. Certainly, there remains huge variation in practice. The lack of well-conducted randomized controlled trials addressing these relevant outcomes, along with the difficulty executing such RCTs, leaves us with more questions than answers. This review provides an overview of the various inotropic agents currently being used in the care of preterm infants, with a particular focus on their organ/cerebral hemodynamic effects both during and after transition

Antenatal Magnesium Sulfate and Preeclampsia Differentially Affect Neonatal Cerebral Oxygenation

Introduction: Magnesium sulfate (MgSO4) is frequently administered for maternal and fetal neuroprotection in preeclampsia (PE) and imminent preterm birth, respectively. Objective: To assess whether MgSO4 affects neonatal cerebral oxygenation, blood flow, and cerebral autoregulation (CAR) during the first postnatal days independently from PE. Methods: 148 neonates 0.5) was determined. Linear mixed models were applied. Results: MgSO4 exposure was recorded in 77 neonates. Twenty-nine neonates were born following PE. MgSO4 independently lowered cFTOE (B: -0.026, 95% CI: -0.050 to 0.002, p < 0.05) but did not affect PSV and RI. PE was associated with a lower cFTOE (B: -0.041, 95% CI: -0.067 to -0.015, p < 0.05) and a tendency towards both lower PSV (B: -4.285, 95% CI: -9.067 to 0.497, p < 0.1) and more impaired CAR (B: 4.042, 95% CI: -0.028 to 8.112, p < 0.1), which seemed to be strongly mediated by fetal brain sparing. MgSO4 did not alter CAR. Conclusions: In contrast to fetal brain sparing in PE, MgSO4 seems to lower cFTOE by lowering cerebral oxygen demands in preterm neonates without affecting the cerebrovasculature

Near-infrared spectroscopy as a diagnostic tool for necrotizing enterocolitis in preterm infants

BACKGROUND: We aimed to investigate whether splanchnic tissue oxygen saturation (rsSO2) measured by near-infrared spectroscopy (NIRS) could contribute to the early diagnosis of necrotizing enterocolitis (NEC). METHODS: We retrospectively included infants with suspected NEC, gestational age <32 weeks and/or birth weight <1200 g in the first 3 weeks after birth. We calculated mean rsSO2, cerebral tissue oxygen saturation (rcSO2), variability of rsSO2 (coefficients of variation [rsCoVAR] = SD/mean), and splanchnic-cerebral oxygenation ratio ([SCOR] = rsSO2/rcSO2) in the period around the abdominal radiograph to confirm or reject NEC. RESULTS: Of the 75 infants, 21 (28%) had NEC (Bell's stage ≥2). Characteristics of infants with and without NEC differed only on mechanical ventilation and nil-per-os status. RsSO2 tended to be higher and rcSO2 lower in infants with NEC. RsCoVAR (median [range]) was lower (0.11 [0.03-0.34]) vs. 0.20 [0.01-0.52], P = 0.002) and SCOR higher (0.64 [0.37-1.36]) vs. 0.47 [0.16-1.09], P = 0.004) in NEC infants. Adjusted for postnatal age, mechanical ventilation, and nil-per-os status, a 0.1 higher rsCoVAR decreased the likelihood of NEC diagnosis with likelihood ratio (LR) 0.38 (95% CI 0.18-0.78) and a 0.1 higher SCOR increased it with LR 1.28 (1.02-1.61). CONCLUSIONS: Using NIRS, high SCOR may confirm NEC and high variability of rsSO2 may rule out NEC, when suspicion arises. IMPACT: Near-infrared spectroscopy may contribute to the diagnosis of necrotizing enterocolitis.When clinical signs are present a high splanchnic-cerebral oxygenation may indicate necrotizing enterocolitis.A low splanchnic-cerebral oxygenation ratio and high variability of splanchnic tissue oxygen saturation may rule out necrotizing enterocolitis.Whether a bedside real-time availability of the splanchnic-cerebral oxygenation ratio and variability of splanchnic tissue oxygen saturation improves NEC diagnosis needs to be further investigated

Anemia and Red Blood Cell Transfusions, Cerebral Oxygenation, Brain Injury and Development, and Neurodevelopmental Outcome in Preterm Infants:A Systematic Review

Background: Anemia remains a common comorbidity of preterm infants in the neonatal intensive care unit (NICU). Left untreated, severe anemia may adversely affect organ function due to inadequate oxygen supply to meet oxygen requirements, resulting in hypoxic tissue injury, including cerebral tissue. To prevent hypoxic tissue injury, anemia is generally treated with packed red blood cell (RBC) transfusions. Previously published data raise concerns about the impact of anemia on cerebral oxygen delivery and, therefore, on neurodevelopmental outcome (NDO). Objective: To provide a systematic overview of the impact of anemia and RBC transfusions during NICU admission on cerebral oxygenation, measured using near-infrared spectroscopy (NIRS), brain injury and development, and NDO in preterm infants. Data Sources: PubMed, Embase, reference lists. Study Selection: We conducted 3 different searches for English literature between 2000 and 2020; 1 for anemia, RBC transfusions, and cerebral oxygenation, 1 for anemia, RBC transfusions, and brain injury and development, and 1 for anemia, RBC transfusions, and NDO. Data Extraction: Two authors independently screened sources and extracted data. Quality of case-control studies or cohort studies, and RCTs was assessed using either the Newcastle-Ottawa Quality Assessment Scale or the Van Tulder Scale, respectively. Results: Anemia results in decreased oxygen-carrying capacity, worsening the burden of cerebral hypoxia in preterm infants. RBC transfusions increase cerebral oxygenation. Improved brain development may be supported by avoidance of cerebral hypoxia, although restrictive RBC transfusion strategies were associated with better long-term neurodevelopmental outcomes. Conclusions: This review demonstrated that anemia and RBC transfusions were associated with cerebral oxygenation, brain injury and development and NDO in preterm infants. Individualized care regarding RBC transfusions during NICU admission, with attention to cerebral tissue oxygen saturation, seems reasonable and needs further investigation to improve both short-term effects and long-term neurodevelopment of preterm infants

Neonatal anemia relates to intestinal injury in preterm infants

BACKGROUND: Anemia is associated with decreased tissue oxygenation in preterm infants and may contribute to developing necrotizing enterocolitis (NEC). We aimed to investigate whether hemoglobin level is associated with intestinal injury, by comparing anemic infants 10 days prior to red blood cell (RBC) transfusion with non-anemic controls. METHODS: A nested case-control study in which we matched anemic preterms (gestational age (GA) < 32 weeks) with non-anemic controls (1:1), based on GA, birth weight (BW), and postnatal age. We measured urinary intestinal fatty acid-binding protein, I-FABP, marker for intestinal injury, twice weekly. Simultaneously, we assessed splanchnic oxygen saturation (rsSO2) and rsSO2 variability. RESULTS: Thirty-six cases and 36 controls were included (median GA 27.6 weeks, BW 1020 grams). Median I-FABP level was higher in cases from 6 days to 24-h before transfusion (median ranging: 4749-8064 pg/ml versus 2194-3751 pg/ml). RsSO2 and rsSO2 variability were lower in cases than controls shortly before transfusion. Hemoglobin levels correlated negatively with rsSO2 and rsSO2 variability in cases, and negatively with I-FABP in cases and controls together. CONCLUSIONS: Urinary I-FABP levels were higher in anemic infants before RBC transfusion than in non-anemic matched controls, suggesting intestinal injury associated with anemia. This may predispose to NEC in some anemic preterm infants. IMPACT: Anemia is a common comorbidity in preterm infants and may lead to impaired splanchnic oxygen saturation and intestinal tissue hypoxia, a proposed mechanism for NEC. Lower hemoglobin level is associated with higher urinary I-FABP levels, a marker for intestinal injury, both in anemic preterm infants and in cases and controls together. Lower splanchnic oxygen saturation and reduction of its variability are associated with higher urinary I-FABP levels in anemic preterm infants before their first RBC transfusion. These results support the hypothesis that anemia in very preterm infants results in intestinal cell injury, which may precede NEC development in some

Interpretation of cerebral oxygenation changes in the preterm infant

Near-infrared spectroscopy (NIRS) allows for continuous, non-invasive monitoring of end-organ tissue oxygenation. The use of NIRS, cerebral NIRS (cNIRS) in particular, in neonatal care has increased significantly over the last few years. This dynamic monitoring technique provides real-time information on the cerebral and haemodynamic status of the neonate and has the potential to serve as an important adjunct to patient care with some centres routinely utilising cNIRS to aid decision-making at the bedside. cNIRS values may be influenced by many variables, including cardiac, respiratory and metabolic parameters, and therefore it is essential to understand the pathophysiology behind alterations in cNIRS values. Correct interpretation is required to direct appropriate patient-specific interventions. This article aims to assist clinicians in deciphering cNIRS values by providing an overview of potential causes of fluctuations in cNIRS values, illustrated by common clinical scenarios, with particular emphasis on the preterm infant

Pulmonary hypertension in extremely preterm infants:a call to standardize echocardiographic screening and follow-up policy

Pulmonary hypertension (PH) is a frequent complication in extremely preterm born infants that seriously affects outcome. We aimed to describe the prevalence of PH in extremely preterm infants and the policy on screening and follow-up in the ten Dutch intensive care units (NICUs). We performed a retrospective cohort study at the University Medical Centre Groningen on infants with gestational age <30 weeks and/or birthweight <1000 g, born between 2012 and 2013. Additionally, we carried out a survey among the Dutch NICUs covering questions on the awareness of PH, the perceived prevalence, and policy regarding screening and following PH in extremely preterm infants. Prevalence of early-onset PH in our study was 26% and 5% for late-onset PH. PH was associated with poor survival and early-onset PH was associated with subsequent development of bronchopulmonary dysplasia (BPD). All the NICUs completed the questionnaire and we found that no standardized policy existed regarding screening and following PH in extremely preterm infants. Conclusion: Despite the frequent occurrence of PH and its clinically important consequences, (inter-)national standardized guidelines regarding screening and following of PH in extremely preterm infants are lacking. Standardizing screening and follow-up will enable early identification of infants with late-onset PH and allow for earlier treatment. Additionally, greater clarity is required regarding the prevalence of early PH as are new preventive treatment strategies to combat BPD. What is known? center dot Pulmonary hypertension (PH) substantially impairs the survival of extremely preterm infants. center dot PH is associated with bronchopulmonary dysplasia (BPD): Early-onset PH predicts the development of BPD. Late-onset PH is prevalent in infants with severe BPD. What is new? center dot Pulmonary hypertension (PH) is prevalent in preterm infants. Its consequences for morbidity and mortality justify a standardized policy aimed at early detection to improve prevention and treatment. center dot No structured policy exists in the Netherlands regarding screening/follow-up for PH in extremely preterm infants