Regional oxygenation, perfusion and body and/or head position: Are preterm infants adversely impacted? A systematic review.

This review addresses regional oxygenation and perfusion changes for preterm infants and changes with body position, with or without head rotation. Future directions for improving neurodevelopmental and clinical outcomes are suggested. The MEDLINE, Embase and Scopus databases were searched up to July 2021. Fifteen out of 470 studies met the inclusion criteria. All were prospective, observational studies with a moderate risk of bias. Significant variation was found for the baseline characteristics of the cohort, postnatal ages, and respiratory support status at the time of monitoring. When placed in a non-supine position, preterm infants showed a transient reduction in cardiac output and stroke volume without changes to heart rate or blood pressure. No studies reported on long-term neurodevelopmental outcomes. Overall, side lying or prone position does not appear to adversely affect regional, and specifically cerebral, oxygenation or cerebral perfusion. The effect of head rotation on regional oxygenation and perfusion remains unclear.

Modeling, Simulation and Validation of Alteration in Blood Flow and Regional Oxygenation Under Arterial Occlusion.

The paper presents the mathematical modeling along with an experimental approach for the identification of arterial occlusion condition. Arterial occlusion occurs due to development of constriction and/or thrombus in the lumen of the artery. A geometry of the thrombus has been modeled for the analysis of the arterial occlusion condition in modeling part. The proposed model of the thrombus has been simulated using Comsol® multiphysics considering different hemodynamic parameters. Variation in regional oxygen saturation (rSO2) of the arterial occlusion condition has been validated with experimental process, where occlusion of the artery has been done by applying external pressure. The experimental study has been conducted to monitor alteration in rSO2 level profile for occlusion using near infrared spectroscopy (NIRS) methodology. NIRS signal data has been collected from twenty-three subjects with no reported musculoskeletal, psychiatric, or any other neurological deficits using Mespere NeurOs® oxymeter. Experimental data reveal that the oxygenation level decreases considerably due to arterial occlusion as compared to the healthy condition at 95% of confidence interval (p < .05). Dynamic time warping algorithm reveals that variation in rSO2 due to proposed thrombus geometry has more similarity with experimental study.

Cerebral Oxygenation and Perfusion when Positioning Preterm Infants: Clinical Implications.

OBJECTIVES: To evaluate cerebral tissue oxygenation (cTOI) and cerebral perfusion in preterm infants in supine vs prone positions. STUDY DESIGN: Sixty preterm infants, born before 32 weeks of gestation, were enrolled; 30 had bronchopulmonary dysplasia (BPD, defined as the need for respiratory support and/or supplemental oxygen at 36 weeks of postmenstrual age). Cerebral perfusion, cTOI, and polysomnography were measured in both the supine and prone position with the initial position being randomized. Infants with a major intraventricular hemorrhage or major congenital abnormality were excluded. RESULTS: Cerebral perfusion was unaffected by position or BPD status. In the BPD group, the mean cTOI was higher in the prone position compared with the supine position by a difference of 3.27% (P = .03; 95% CI 6.28-0.25) with no difference seen in the no-BPD group. For the BPD group, the burden of cerebral hypoxemia (cumulative time spent with cTOI <55%) was significantly lower in the prone position (23%) compared with the supine position (29%) (P < .001). In those without BPD, position had no effect on cTOI. CONCLUSIONS: In preterm infants with BPD, the prone position improved cerebral oxygenation and reduced cerebral hypoxemia. These findings may have implications for positioning practices. Further research will establish the impact of position on short- and long-term developmental outcomes.

Cerebral oxygenation monitoring of ex-preterm infants during the infant car seat challenge test.

The American Academy of Pediatrics and until recently the Canadian Paediatric Society recommend preterm infants undergo an Infant Car Seat Challenge test prior to discharge to rule out systemic oxygen desaturation when placed at a 45-degree angle in a car seat. Near-infrared spectroscopy (NIRS) provides objective measurements of the impact of systemic oxygen (SO2) desaturation, bradycardia, or both on cerebral regional oxygen saturation (rSO2). OBJECTIVE: To characterize baseline cerebral rSO2 during a car seat trial in preterm infants ready for discharge. DESIGN/METHODS: A prospective observational study was performed in 20 infants (32 ± 5 weeks [mean] at a postmenstrual age 37 ± 6 weeks [mean]). Cerebral rSO2 was continuously monitored by placing a NIRS transducer on head during Infant Car Seat Challenge (ICSC). Failure of an ICSC was defined as two SO2 desaturation events below 85% for more than 20 seconds or one event below 80% for 10 seconds. RESULTS: The lowest SO2 was 70% with a lowest NIRS recording of 68%. Three infants failed their ICSC, with the lowest rSO2 in these three infants being 68%, above the lowest acceptable limit of 55%. Heart rate but not SO2 appears to influence rSO2 over the range of cerebral oxygenation seen. CONCLUSIONS: Baseline cerebral rSO2 during ICSC oscillates between 68 and 90%. There were no episodes of significant cerebral oxygen desaturation in studied infants regardless of whether they passed or failed the ICSC. We postulate that former preterm infants are capable through cerebral autoregulation, of maintaining adequate cerebral blood flow in the presence of either systemic oxygen desaturation or bradycardia when they are otherwise ready for discharge.

Noninvasive Monitoring to Demonstrate Postoperative Differences in Regional Hemodynamics in Newborn Infants With d-Transposition of the Great Arteries and Hypoplastic Left Heart Syndrome.

BACKGROUND: The adequacy of tissue O2 delivery in infants receiving intensive care is difficult to measure directly. Regional O2 (rSO2) and fractional tissue O2 extraction (FTOE), the ratio of O2 consumption to O2 delivery, obtained from newer noninvasive tools, such as near-infrared spectroscopy (INVOS) and microvascular tissue oximetry (T-Stat) can provide important information on the adequacy of tissue oxygenation and aid in managing critically ill infants. METHODS: We prospectively evaluated differences in rSO2 and FTOE in 26 infants with hypoplastic left heart syndrome (HLHS) (n = 12) or d-transposition of the great arteries (d-TGA) (n = 14). Continuous noninvasive monitoring of SpO2, heart rate, and perfusion index with pulse oximetry, cerebral-rSO2 and renal-rSO2 with INVOS, and buccal tissue oxygenation using T-Stat were performed during immediate postoperative period for 24 hours. RESULTS: The SpO2 and rSO2 in infants with d-TGA were higher compared with the infants with HLHS at all measured sites (buccal mucosa, cerebral, and renal). Significant regional differences were also observed in FTOE across all infants with the highest at the buccal mucosa tissue level, followed by cerebral and renal measurement sites. As compared with infants with d-TGA, infants with HLHS had higher regional FTOE and heart rate, with a lower arterial O2 content and perfusion index. CONCLUSIONS: Our study demonstrates the utility of noninvasive hemodynamic monitoring to assess regional oxygenation and perfusion, as evidenced by significant differences in infants with HLHS and d-TGA, conditions with different circulation physiologies. Such comprehensive monitoring can potentially aid in evaluating treatment strategies aimed at preventing organ damage from O2 insufficiency.

Regional Splanchnic Oxygenation during Continuous versus Bolus Feeding among Stable Preterm Infants.

INTRODUCTION: There is no agreement regarding the best method for tube-feeding preterm infants. Few studies, to date, have evaluated the influence of different methods of enteral feeding on intestinal oxygenation. The use of near-infrared spectroscopy (NIRS) has permitted the noninvasive measurement of splanchnic regional oxygenation (rSO2S) in different clinical conditions. The aim of this prospective, single-center study was to compare rSO2S during continuous versus bolus feeding among stable preterm infants. METHODS: Twenty-one preterm infants, less than 32 weeks gestation and appropriate for gestational age, were enrolled. All infants were clinically stable and on full tube feedings. Each infant received a bolus feeding initially (20 min duration), and after 3 h, a continuous feeding (5 h duration). Infants were evaluated 30 min before and 30 min after the bolus and continuous feedings. The regional splanchnic saturation (rSO2S) was measured using near-infrared spectroscopy (NIRS) technology and systemic saturation was measured with pulse oximetry. From these measurements, we calculated the splanchnic fractional oxygen extraction ratio (FOES) for each of the four intervals. RESULTS: rSO2S decreased after continuous vs. bolus feeding (p = 0.025), while there was a trend toward decreased SaO2 after bolus feeding (p = 0.055). The FOES, which reflects intestinal oxygen extraction, was not affected by the feeding mode (p = 0.129). DISCUSSION/CONCLUSION: Continuous vs. bolus feeding decreases rSO2S but does not affect oxygen extraction by intestinal tissue; after bolus feeding there was a trend towards decreased systemic saturation.

Could Near Infrared Spectroscopy (NIRS) be the new weapon in our fight against Necrotising Enterocolitis?

There is no ideal single gut tissue or inflammatory biomarker available to help to try and identify Necrotising Enterocolitis (NEC) before its clinical onset. Neonatologists are all too familiar with the devastating consequences of NEC, and despite many advances in neonatal care the mortality and morbidity associated with NEC remains significant. In this article we review Near Infrared Spectroscopy (NIRS) as a method of measuring regional gut tissue oxygenation. We discuss its current and potential future applications, including considering its effectiveness as a possible new weapon in the early identification of NEC.

Remote ischemic preconditioning enhances aerobic performance by accelerating regional oxygenation and improving cardiac function during acute hypobaric hypoxia exposure.

Remote ischemic preconditioning (RIPC) may improve exercise performance. However, the influence of RIPC on aerobic performance and underlying physiological mechanisms during hypobaric hypoxia (HH) exposure remains relatively uncertain. Here, we systematically evaluated the potential performance benefits and underlying mechanisms of RIPC during HH exposure. Seventy-nine healthy participants were randomly assigned to receive sham intervention or RIPC (4 × 5 min occlusion 180 mm Hg/reperfusion 0 mm Hg, bilaterally on the upper arms) for 8 consecutive days in phases 1 (24 participants) and phase 2 (55 participants). In the phases 1, we measured the change in maximal oxygen uptake capacity (VO2max) and muscle oxygenation (SmO2) on the leg during a graded exercise test. We also measured regional cerebral oxygenation (rSO2) on the forehead. These measures and physiological variables, such as cardiovascular hemodynamic parameters and heart rate variability index, were used to evaluate the intervention effect of RIPC on the changes in bodily functions caused by HH exposure. In the phase 2, plasma protein mass spectrometry was then performed after RIPC intervention, and the results were further evaluated using ELISA tests to assess possible mechanisms. The results suggested that RIPC intervention improved VO2max (11.29%) and accelerated both the maximum (18.13%) and minimum (53%) values of SmO2 and rSO2 (6.88%) compared to sham intervention in hypobaric hypoxia exposure. Cardiovascular hemodynamic parameters (SV, SVRI, PPV% and SpMet%) and the heart rate variability index (Mean RR, Mean HR, RMSSD, pNN50, Lfnu, Hfnu, SD1, SD2/SD1, ApEn, SampEn, DFA1and DFA2) were evaluated. Protein sequence analysis showed 42 unregulated and six downregulated proteins in the plasma of the RIPC group compared to the sham group after HH exposure. Three proteins, thymosin ß4 (Tß4), heat shock protein-70 (HSP70), and heat shock protein-90 (HSP90), were significantly altered in the plasma of the RIPC group before and after HH exposure. Our data demonstrated that in acute HH exposure, RIPC mitigates the decline in VO2max and regional oxygenation, as well as physiological variables, such as cardiovascular hemodynamic parameters and the heart rate variability index, by influencing plasma Tß4, HSP70, and HSP90. These data suggest that RIPC may be beneficial for acute HH exposure.

Prenatal Use of Sildenafil in Fetal Growth Restriction and Its Effect on Neonatal Tissue Oxygenation-A Retrospective Analysis of Hemodynamic Data From Participants of the Dutch STRIDER Trial.

Objective: Sildenafil is under investigation as a potential agent to improve uteroplacental perfusion in fetal growth restriction (FGR). However, the STRIDER RCT was halted after interim analysis due to futility and higher rates of persistent pulmonary hypertension and mortality in sildenafil-exposed neonates. This hypothesis-generating study within the Dutch STRIDER trial sought to understand what happened to these neonates by studying their regional tissue oxygen saturation (rSO2) within the first 72 h after birth. Methods: Pregnant women with FGR received 25 mg placebo or sildenafil thrice daily within the Dutch STRIDER trial. We retrospectively analyzed the cerebral and renal rSO2 monitored with near-infrared spectroscopy (NIRS) in a subset of neonates admitted to two participating neonatal intensive care units, in which NIRS is part of standard care. Secondarily, blood pressure and heart rate were analyzed to aid interpretation. Differences in oxygenation levels and interaction with time (slope) between placebo- and sildenafil-exposed groups were tested using mixed effects analyses with multiple comparisons tests. Results: Cerebral rSO2 levels were not different between treatment groups (79 vs. 77%; both n = 14) with comparable slopes. Sildenafil-exposed infants (n = 5) showed lower renal rSO2 than placebo-exposed infants (n = 6) during several time intervals on day one and two. At 69-72 h, however, the sildenafil group showed higher renal rSO2 than the placebo group. Initially, diastolic blood pressure was higher and heart rate lower in the sildenafil than the placebo group, which changed during day two. Conclusions: Although limited by sample size, our data suggest that prenatal sildenafil alters renal but not cerebral oxygenation in FGR neonates during the first 72 post-natal hours. The observed changes in renal oxygenation could reflect a vasoconstrictive rebound from sildenafil. Similar changes observed in accompanying vital parameters support this hypothesis.

Comparing liver and lower abdomen near-infrared spectroscopy in preterm infants.

BACKGROUND: Near-infrared spectroscopy (NIRS) is being increasingly used to investigate regional oxygenation (rSO2) and perfusion in areas such as the abdomen in preterm infants prone to feeding intolerance. Lower abdominal rSO2 values are extremely variable, high sensitivity and currently low specificity tools. The liver, a solid organ, could provide a more reliable site for splanchnic oxygenation and perfusion monitoring. AIMS: Compare liver and lower abdomen rSO2 values in stable preterm infants in response to feeding. STUDY DESIGN: We prospectively evaluated the correlation between rSO2 over the liver and lower abdomen in 16 preterm infants born between 28 and 32 weeks' gestational age using 48 h of continuous NIRS data. OUTCOME MEASURES: Mean liver and lower abdomen rSO2 values. RESULTS: The overall mean liver rSO2 were higher than the overall mean lower abdomen values, 78.4 ± 7.1 vs. 65.1 ± 24.9 respectively. Time series analysis showed a mean maximum cross correlation between the liver and lower abdomen of 0.28 (SD ± 0.03; p < 0.001); the liver signal lagged the lower abdomen by an average of 5.4 s (SD ± 1.2 s, Range 0-16 s). Mixed models analysis showed that during bolus feeding, liver values increased 10 to 30 min after the start of feeding (p < 0.01) while lower abdomen increased from 20 to 60 min after the start of feeding (p < 0.05) and liver values were less variable than lower abdomen values. CONCLUSION: Liver rSO2 appears to be a more stable surrogate for splanchnic oxygenation and perfusion than lower abdomen rSO2.

Sleep-wake cycling and cerebral oxygen metabolism among critically ill neonates.

Among adults, wakefulness and rapid eye movement (REM) sleep, compared to non-REM sleep, require higher overall brain metabolism, but in neonates analogous data are not available. Behavioral states with higher metabolic demand could increase vulnerability to hypoperfusion or hypoxia in the compromised neonatal brain. Using cerebral oximetry (near-infrared spectroscopy), and simultaneous polysomnography, we evaluated whether brain oxygen metabolism varies by sleep-wake state among critically ill newborns. For each of 10 infants, sleep-wake cycling was detectable and cerebral oximetry varied (P < .0001) across behavioral states, but the patterns differed among subjects. We conclude that cerebral oxygen metabolism varies with sleep-wake states in high-risk newborns. The direction and degree of these changes are variable and subject-specific in this initial sample, but could reflect or affect brain injury and vulnerability.

Tissue hypoxia: implications for the respiratory clinician.

Oxygen is essential for normal aerobic metabolism in mammals. Hypoxia is the presence of lower than normal oxygen content and pressure in the cell. Causes of hypoxia include hypoxemia (low blood oxygen content and pressure), impaired oxygen delivery, and impaired cellular oxygen uptake/utilization. Many compensatory mechanisms exist at the global, regional, and cellular levels to allow cells to function in a hypoxic environment. Clinical management of tissue hypoxia usually focuses on global hypoxemia and oxygen delivery. As we move into the future, the clinical focus needs to change to assessing and managing mission-critical regional hypoxia to avoid unnecessary and potential toxic global strategies. We also need to focus on understanding and better harnessing the body's own adaptive mechanisms to hypoxia.