Fluctuating pressure-passivity is common in the cerebral circulation of sick premature infants

Cerebral blood flow pressure-passivity results when pressure autoregulation is impaired, or overwhelmed, and is thought to underlie cerebrovascular injury in the premature infant. Earlier bedside observations suggested that transient periods of cerebral pressure-passivity occurred in premature infants. However, these transient events cannot be detected reliably by intermittent static measurements of pressure autoregulation. We therefore used continuous bedside recordings of mean arterial pressure (MAP; from an indwelling arterial catheter) and cerebral perfusion [using the near-infrared spectroscopy (NIRS) Hb difference (HbD) signal) to detect cerebral pressure-passivity in the first 5 d after birth in infants with birth weight <1500 g. Because the Hb difference (HbD) signal [HbD = oxyhemoglobin (HbO2) - Hb] correlates with cerebral blood flow (CBF), we used coherence between MAP and HbD to define pressure-passivity. We measured the prevalence of pressure-passivity using a pressure-passive index (PPI), defined as the percentage of 10-min epochs with significant low-frequency coherence between the MAP and HbD signals. Pressure-passivity occurred in 87 of 90 premature infants, with a mean PPI of 20.3%. Cerebral pressure-passivity was significantly associated with low gestational age and birth weight, systemic hypotension, and maternal hemodynamic factors, but not with markers of maternal infection. Future studies using consistent serial brain imaging are needed to define the relationship between PPI and cerebrovascular injury in the sick premature infant.     

Reproducibility of cerebral near infrared spectroscopy in neonates

Near infrared spectroscopy (NIRS) allows to study cerebral hemodynamics and oxygenation in neonates, which may be useful for early detection of cerebral hypoxemia. So far this method is not reliable enough to be used clinically. Reproducibility is one of the prerequisites for reliable quantitative monitoring. The aim of this study was to assess the reproducibility of the NIRS parameters HbO(2) and HbD (oxygenated and deoxygenated hemoglobin concentration) and the derived NIRS parameters HbT (tissue hemoglobin concentration, HbT = HbO(2) + HbD) and rSO(2) (regional cerebral oxygen saturation, rSO(2) = HbO(2)/HbT). Two observers repeated a total number of 500 measurements in 25 neonates. Additionally, a baseline measurement was done to assess the physiological variation in every neonate. For all NIRS parameters, the inter-patient variance contributed most to the total variance, while the interobserver variance was the smallest variance component. The cerebral oxygen saturation parameter rSO(2) showed a good reproducibility, with an inter-measurement variance slightly but not significantly higher than the physiological baseline variation. The NIRS concentration parameters HbO(2), HbD, and HbT were less reproducible, with significant variation due to repeated sensor replacement. However, for cerebral oximetry rSO(2) is likely to be more important than the other NIRS parameters, so that NIRS has the potential to become a quantitative cerebral monitoring method.     

CSF removal in infantile posthemorrhagic hydrocephalus results in significant improvement in cerebral hemodynamics

Rational intervention in infants with posthemorrhagic hydrocephalus (PHH) would be facilitated greatly by bedside measure of impaired cerebral perfusion, as there is substantial evidence that impaired perfusion and oxidative metabolism contribute to irreversible brain injury in hydrocephalus. Near-infrared spectroscopy (NIRS) measures changes in the cerebral concentration of oxygenated and deoxygenated hemoglobin and oxidized cytochrome oxidase at the bedside of infants continuously and noninvasively. The total hemoglobin and the hemoglobin difference signal are derived from the sum and difference, respectively, of oxygenated and deoxygenated hemoglobin. Changes in total hemoglobin reflect changes in cerebral blood volume; our previous work has shown that changes in hemoglobin difference signal reflect changes in cerebral blood flow. We hypothesized that cerebrospinal fluid (CSF) removal in infants with PHH would result in significant increases in cerebral perfusion, cerebral blood volume, and oxidative metabolism, as measured by NIRS. Continuous NIRS recordings were performed during CSF removal on 16 infants with PHH. There was a statistically significant increase in oxygenated hemoglobin (p < 0.001), total hemoglobin (p = 0.001), and hemoglobin difference signal (p = 0.006), but not oxidized cytochrome oxidase, accompanying CSF removal. There was no significant correlation between either the volume of CSF removed (in milliliters per kilogram body weight) or the opening pressure and the change in any of the measured or calculated NIRS signals. These findings demonstrate the pronounced effect of CSF removal on cerebral perfusion in infants with PHH. NIRS may be a useful technique to detect impending cerebral ischemia in such infants and thereby provide a means to guide the rational management of PHH.     

Transient hyperoxia and residual cerebrovascular effects in the newborn rat

Unrestricted use of oxygen in the delivery room after preterm birth has been associated with reduced cerebral blood flow (CBF) 2 h later. To further investigate residual cerebrovascular effects of transient hyperoxia, we developed a newborn rat model in which laser-Doppler flowmetry (LDF) and near-infrared spectroscopy (NIRS) were used to monitor changes in cerebral perfusion. The hypothesis to be tested was that hyperoxic exposure limits cerebral vasodilation in response to increase in carbon dioxide tension (Pco(2)). Twenty-four 3- to 5-d-old rats were kept on spontaneous breathing with doxapram under light isoflurane anesthesia, randomized into two groups, and exposed to either room air or 100% oxygen for 30 min. Then, after 15 min of stabilization in normoxia, 8% CO(2) was given for 5 min. No significant differences in CO(2) responses were observed between the two groups: mean CBF-CO(2) reactivity as measured by NIRS was 13.3 +/- 3.9 %/kPa in the normoxia-group versus 8.8 +/- 4.1 %/kPa in the hyperoxia group (NS). The oxygenation index [(HbO(2) - Hb)/2] increased by 0.67 +/- 0.17 micromol/L/kPa in the normoxia group compared with 1.18 +/- 0.19 micromol/L/kPa in the hyperoxia group (NS). Cortical perfusion, monitored by LDF, increased by 7.3 +/- 1.5 %/kPa versus 6.8 +/- 1.8 %/kPa in the normoxia and hyperoxia groups, respectively (NS). We conclude that in newborn rats the CBF-CO(2) reactivity remains intact after 30 min of oxygen exposure.     

Fetal and neonatal cerebral oxygen monitoring with NIRS: theory and practice.

Near infra-red spectroscopy (NIRS) is a comparatively new method for monitoring the oxygenation in blood and tissue in the brain of the fetus and the neonate. Absorption of light in the wavelength range 700-1000 nm through such tissue is measured, which is then used to calculate changes in the concentration of cerebral oxygenated and de-oxygenated haemoglobin (HbO2 and Hb) and hence cerebral blood volume (CBV). Studies carried out on several groups of newborn babies have shown clear changes in HbO, Hb and CBV with hypoxia and bradycardia. These changes may well have implications in the occurrence of hypoxic/ischaemic brain injury. Intra partum NIR measurements on the fetal brain have demonstrated clear changes in HbO2, Hb and CBVm, coinciding with the onset of contractions.     

近红外光谱仪监测脑血流及血管自主调节功能的实验研究

目的评价近红外光谱仪（NIRS）脑氧合指标与新生猪脑血流的相关性,以寻找能最好反映脑血流变化及脑血管自主调节功能的NIRS指标。方法10头出生前1～3d新生猪随机分为两组：正常对照组（6头）、低血压组（4头）。人为动脉放血造成血压及脑血流的改变。应用NIRS连续监测脑组织氧合血红蛋白（△HbO2）与还原血红蛋白（△HHb）的动态变化,计算二者之和tHb（△tHb=△HbO2＋△HHb）．及二者之差△HbD（△HbD=△HbO2-△HHb）。同时应用彩色微球技术定量测定脑血流的变化,并对测定结果进行线性回归分析。结果对NIRS测定的△tHb、△HbD和彩色微球定量测得的全脑（GCBF）以及大脑皮层脑血流（CBFc）之间的关系进行线性回归分析。正常生理条件下,△HbD和△tHb与GCBF存在显著相关,相关系数分别为r1a=0．409和r1b=0．440,P均〈0．05;△HbD和△tHb与CBFc也存在显著相关,相关系数分别为r2a=0．394和r2b=0．400,P均〈0．05。低血压条件下,新生猪仅在M△BP降至35mmHg（1mmHg=0．133kPa）时脑血流才显著降低（P〈0．05）,而随着血压的逐渐降低,△HHb逐渐增高（P〈0．01）,△HbO,和△tHb先有升高趋势（P〈0．05）,然后在M△BP降至35mmHg时才显著降低（P〈0．01）,△HbD与GCBF、CBFc采用线性回归分析所得的相关系数r3a=0．890、r3b=0．887差异有统计学意义,P均〈0．01;而△tHb与GCBF、CBFc采用线性回归分析所得的相关系数r4a=0．395、r4b=0．375差异均无统计学意义,P均〉0．05,△HbD与脑血流的变化趋势相同,二者密切相关;而△tHb与脑血流的变化未存在相关。新生猪M△BP〉35mmHg时脑血流与血压不相关,提示自主调节功能完整,将调节功能完整的新生猪脑血流、△HbD与相应的M△BP值行线性回归分析显示相关系数〈0．5;M△BP〈35mmHg时脑血流与血压相关,提示自主调节功能受损,将调节功能受损的新生猪脑血流、△HbD与相应的M△BP值行线性回归分析显示相关系数〉0．5。结论正常生理及低血压条件下,△HbD均能很好反映出脑血流的动态变化;△tHb仅在正常生理条件下能用来反映脑血流的动态变化。1～3d新生猪脑血管自主调节的下限为35mmHg,NIRS氧合指标△HbD与M△BP的相关性可以反映新生猪的脑血管自主调节状态。     

Cerebral pressure autoregulation and vasoreactivity in the newborn rat

Perinatal brain injury has been associated with impaired cerebral blood flow (CBF) pressure autoregulation. The brain of 3- to 5-d-old rat pups is immature and similar to that of a preterm infant, and therefore we tested cerebral vasoreactivity in that animal. CBF pressure autoregulation was tested in 20 Wistar pups during normocapnia and hypercapnia, respectively. Hypotension was induced by hemorrhage and cerebral perfusion was monitored with laser Doppler flowmetry and near-infrared spectroscopy. Systolic blood pressure was measured noninvasively from the tail. During normocapnia, the autoregulatory plateau was narrow. Resting systolic blood pressure (SBP) was 39.2 mm Hg and CBF remained constant until SBP decreased below 36.0 mm Hg (SE 0.8). Below the lower limit, CBF declined by a mean of 2.7% per mm Hg [95% confidence interval (CI), 2.4-3.0%], and hemoglobin difference (HbD) and total hemoglobin (HbT) changed proportionally to CBF. After inhalation of carbon dioxide, CBF increased significantly by a mean of 17.7% (95% CI, 13.7-22.8%). The CBF-CO2 reactivity was estimated to 13.4% per kPa (95% CI, 2-24.8%), p=0.026. Over the range of SBP (6-54 mm Hg), a linear relationship between CBF and SBP was found during hypercapnia, indicating abolished pressure autoregulation. A linear correlation between CBF and HbD was found (r=0.80). CBF pressure autoregulation and reactivity to CO2 operate in the newborn rat. This model may be useful for future investigations concerning perinatal pathophysiology in the immature brain.     

Arterial oxygenation determines autoregulation of cerebral blood flow in the fetal lamb

We examined autoregulation of cerebral blood flow (CBF) over the range of oxygen tension commonly observed in the chronic fetal lamb preparation. Seventeen animals were surgically prepared under general anesthesia for chronic in utero studies. Based on measured resting arterial PO2 and calculated % saturation 24-48 h after surgery, two groups were defined: a normoxic group of eight with saturation of 57% or higher (our laboratory normal for physiologically stable preparations) and an hypoxic group of nine with saturation less than 57%. Regional CBF was measured with radiolabeled 15-microns microspheres. Autoregulation of CBF was assessed by measuring the change in CBF when fetal mean arterial blood pressure (MABP) was acutely decreased and increased by withdrawal and reinfusion of fetal blood. In normoxic animals CBF was constant over an MABP range of 42-61 torr in all four areas of the brain examined: cerebral hemispheres, basal ganglia, cerebellum, and brain stem. In hypoxic animals CBF was pressure dependent in all areas over an MABP range of 46-73 torr, i.e., autoregulation was abolished. These studies demonstrate that the mechanism of autoregulation is functionally developed in the mature fetal lamb, but operationally dependent upon arterial oxygen concentration. Below a saturation of approximately 50-60% CBF varies directly with perfusion pressure.     

Influence of intravenous sildenafil on cerebral oxygenation measured by near-infrared spectroscopy in infants after cardiac surgery

Sildenafil (Viagra) has been shown to be an effective pulmonary vasodilator and is increasingly used in patients with pulmonary hypertension. Its effects on the cerebral circulation are unclear and have not yet been described. We investigated the effect of i.v. sildenafil treatment on cerebral oxygenation in 13 children with elevated pulmonary vascular resistance due to congenital heart defects after cardiac surgery using near-infrared spectroscopy (NIRS). Median age was 4.5 mo, and median weight was 5.5 +/- 1.8 kg. Sildenafil was administered in three steps of 15 min each with cumulative doses of 0.025, 0.1, and 0.25 mg/kg. We examined the changes of oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (HHb), total hemoglobin (tHb) concentration, cytochrome oxidase (CytOx) oxygenation, and cerebral tissue oxygenation index (TOI) in 13 children. A significant increase in cerebral HbO2 and tHb at the beginning of i.v. sildenafil administration with a decrease in HHb was observed. These changes led to a significant elevation in cerebral TOI from 63.4 +/- 2.5% to 65.7 +/- 2.8%, whereas mean systemic arterial pressure and arterial oxygen partial pressure tended to decrease. In conclusion, we observed a reversible increase of HbO2, tHb, and hemoglobin oxygen saturation in the scanned tissue section after i.v. sildenafil administration. These findings may be clinically relevant because they indicate that after cardiac surgery, sildenafil may increase cerebral blood flow (CBF), probably due to general endothelial dysfunction after cardiopulmonary bypass (CPB).     

Near-infrared spectroscopy measurement of oxygen extraction fraction and cerebral metabolic rate of oxygen in newborn piglets

Cerebral metabolic rate of oxygen (CMRO2), the rate at which O2 is consumed in the brain by metabolic processes, is one of the most useful measures of normal brain function. The present study investigated the use of near-infrared spectroscopy (NIRS) in the noninvasive measurement of O2 extraction fraction (OEF) and CMRO2 in the newborn piglet. Indomethacin, although used successfully to effect closure of patent ductus arteriosus in the preterm infant, is known to cause transient reductions in cerebral blood flow (CBF) in both infant and adult humans and pigs. As a test of the NIRS method, the present study also examined the effect of indomethacin-induced reductions in CBF on both OEF and CMRO2. CBF, OEF, and CMRO2 were assessed in 20 newborn piglets, 0.2-3.0 d old. Ten piglets received 0.2 mg/kg of indomethacin infused over 30 min; remaining piglets received saline infusion as control. CBF, OEF, and CMRO2 measurements were performed before infusion and at 30-min intervals for a period of 90 min post-infusion. Saline infusion elicited no response in CBF, OEF, or CMRO2. Immediately after indomethacin infusion, CBF decreased 18.1% below (p < 0.05) and OEF increased 26.2% above (p < 0.05) pre-infusion values, whereas CMRO2 showed no significant changes throughout the study. Both CBF and OEF returned to baseline within 60 min after infusion of indomethacin. The proficiency of NIRS in the measurement of OEF and CMRO2 was demonstrated through the observation of transient increases in OEF, which served to maintain CMRO2 during indomethacin-induced reductions in CBF.     

Brain haemodynamic effects of nasal continuous airway pressure in preterm infants of less than 30 weeks' gestation

AIM: To evaluate the hypothesis that increasing levels of nasal continuous positive airway pressure (NCPAP) may decrease cerebral blood volume (CBV) and cerebral oxygenation in infants with gestational age (GA) less than 30 weeks. METHODS: We prospectively studied a cohort of preterm infants treated with NCPAP using near-infrared spectroscopy (NIRS). The pressure limit of NCPAP was set at 2, 4, 6 and again 2 cm H(2)O for 30 min. RESULTS: Changes of pressure levels were not followed by significant changes of oxygenated haemoglobin (O(2)Hb), deoxygenated haemoglobin (HHb), cerebral intravascular oxygenation (HbD), oxidized-reduced cytochrome aa3 (CtOx), tissue oxygenation index (TOI), tissue haemoglobin index (THI) and cerebral blood volume (DeltaCBV). CONCLUSION: NCPAP at 2-6 cm H(2)O pressure levels did not affect cerebral oxygenation and CBV. These findings are reassuring and confirm the safety of NCPAP in preterm infants with GA less than 30 weeks.     

Identification of pressure passive cerebral perfusion and its mediators after infant cardiac surgery

Cerebrovascular pressure autoregulation (CPA) regulates cerebral blood flow (CBF) in relation to changes in mean arterial blood pressure (MAP). Identification of a pressure-passive cerebral perfusion and the potentially modifiable physiologic factors underlying it has been difficult to achieve in sick infants. We previously validated the near-infrared spectroscopy-derived hemoglobin difference (HbD) signal (cerebral oxyhemoglobin - deoxyhemoglobin) as a reliable measure of changes in CBF in animal models. We now sought to determine whether continuous measurements of DeltaHbD would correlate to middle cerebral artery flow velocity (CBFV), allow identification and quantification of pressure-passive state, and help to delineate potentially modifiable factors. We enrolled 43 infants (2 d to 7 mo old) who were undergoing open cardiac surgery and cardiopulmonary bypass. At 6 and 20 h after surgery, we measured changes in HbD, CBFV (by transcranial Doppler), and MAP at different end-tidal CO(2) levels. We assigned a pressure-passive index (PPI) to each study on the basis of the relative duration of significant coherence between DeltaMAP and DeltaHbD. We found a significant relationship between DeltaHbD and DeltaCBFV at both time points. At 6 h after surgery, we showed high concordance (coherence > 0.5; PPI > or = 41%) between DeltaMAP and DeltaHbD, consistent with disturbed CPA in 13% of infants. End-tidal CO(2) values > or = 40 mm Hg and higher MAP variability both were associated with increased odds (p < 0.001) of autoregulatory failure. This approach provides a means to identify and quantify disturbances of CPA. High CO(2) levels and fluctuating MAP are two important preventable factors associated with disturbed CPA.     

Cerebral perfusion in newborn infants treated with high-frequency oscillation ventilation

The effects of high-frequency oscillatory ventilation (HFOV) on hemodynamic parameters have been shown in animal as well as in clinical studies. In a further study we could demonstrate, that after change of a conventional positive pressure ventilation (CMV) to HFOV flow velocities in cerebral arteries decreased. In the following we added to the dopplerflow method the continuous examination of cerebral oxygenation with near infrared spectroscopy (NIRS). PATIENTS: 19 measurements were prospectively conducted in 18 neonates. The infants were mechanically ventilated with HFOV and were in a stable condition. METHODS: Before change from HFOV to CMV doppler signals of the anterior cerebral artery were measured. We repeated this at the end of the study in each patient. NIRS-optodes were placed on the front and the os parietale of each infant. After stabilization of the system we changed from HFOV to CMV without disconnection of the patient from the machine. PCO2 was registered continuously via a transcutaneous probe, as well as oxygen saturation via pulse oxymetry. Statistical analysis was performed with Wilcoxon test. RESULTS: There were no significant changes of doppler-signals during the study (median vs. 25 cm/s (+/- 6) during HFOV, 28 cm/s (+/-/) during CMV). The parameter of NIRS, oxygenated hemoglobin HbO [-1.5 U (+/- 22.78)] at 15 minutes after change), reduced hemoglobin HbR [-1.17 U (+/- 5.26)] and total hemoglobin HbT [-2.68 U (+/- 18.7)] remained stable during the change from HFOV to CMV, too. In five infants there was a decrease and in two an increase of HbO 15 minutes after change, which correlated with decrease or increase of pCO2. CONCLUSION: In a combined measurement of dopplerflow and NIRS we found no special effect of HFOV on cerebral hemodynamics comparing with CMV. Changes of cerebral oxygenation in NIRS correlated with pCO2.     

Effects of rapid versus slow infusion of sodium bicarbonate on cerebral hemodynamics and oxygenation in preterm infants

BACKGROUND: Sodium bicarbonate (NaHCO3) is often used for correction of metabolic acidosis in preterm infants. The effects of NaHCO3 administration on cerebral hemodynamics and oxygenation are not well known. Furthermore, there is no consensus on infusion rate of NaHCO3. OBJECTIVES: To evaluate the effects of rapid versus slow infusion of NaHCO3 on cerebral hemodynamics and oxygenation in preterm infants. METHODS: Twenty-nine preterm infants with metabolic acidosis were randomized into two groups (values are mean +/-SD): In group A (GA 30.5 +/- 1.7 weeks, b.w. 1,254 +/- 425 g) NaHCO3 4.2% was injected as a bolus. In group B (GA 30.3 +/- 1.8 weeks, b.w. 1,179 +/- 318 g) NaHCO3 4.2% was administered over a 30-min period. Concentration changes of oxyhemoglobin (cO2Hb) and deoxyhemoglobin (cHHb) were assessed using near infrared spectrophotometry. Changes in HbD (= cO2Hb - cHHb) represent changes in cerebral blood oxygenation and changes in ctHb (= cO2Hb + cHHb) reflect changes in cerebral blood volume. Cerebral blood flow velocity was intermittently measured using Doppler ultrasound. Longitudinal data analysis was performed using linear mixed models (SAS procedure MIXED), to account for the fact that the repeated observations in each individual were correlated. RESULTS: Administration of NaHCO3 resulted in an increase of cerebral blood volume which was more evident if NaHCO3 was injected rapidly than when infused slowly. HbD and cerebral blood flow velocity did not show significant changes in either group. CONCLUSION: To minimize fluctuations in cerebral hemodynamics, slow infusion of sodium bicarbonate is preferable to rapid injection.     

Effect of sympathetic nervous system on cerebral blood flow in the newborn piglet

The role of the sympathetic nervous system on cerebral blood flow (CBF) autoregulation was evaluated in newborn piglets. Six animals were studied after ablation of the right superior sympathetic ganglion and compared to 6 control animals. Mean arterial blood pressure (MABP) was decreased by successive blood withdrawal and CBF was measured by radioactive microspheres. In denervated animals, MABP and CBF correlated positively according to a parabolic curve showing an absence of autoregulation when MABP is above 50 mm Hg (y = 0.079x2 - 5.9x + 154, p less than 0.01). In control animals, CBF remains stable throughout the experiment (y = 0.28x + 5). These data suggest a shift to the left of the upper limit of the autoregulation range in denervated animals and consequently a poor adaptation to increased MABP.     

Cerebral oxygenation is affected by filling mode and perfluorochemical volume in partial liquid ventilation of healthy piglets

Intrapulmonary administration of perfluorochemicals (PFC) has been suggested for reasons other than respiratory insufficiency. PFC application has been described to affect cerebral Hb concentration, however, data for healthy lungs are missing. Newborn piglets were randomized into 3 groups (30-ml slow-filling, 10-ml slow-filling and 30-ml rapid-filling), orally intubated and mechanically ventilated. Partial liquid ventilation (PLV) was initiated by filling the lung with PF5080 (10 or 30 ml/kg) at a rate of 1.5 ml/min (slow filling) or within 45 s (rapid filling). Vital signs, blood gases, tidal volume (VT) and changes in the cerebral concentration of oxygenated hemoglobin (HbO(2)) and total Hb were determined for up to 20 min. Rapid administration of PFC caused an immediate drop in HbO(2), PaO(2) and VT. The concentration of oxygenated and total Hb increased thereafter and remained high. We found a slow increase in PaCO(2), HbO(2) and total Hb in the 30-ml slow-filling group, but almost no changes in the 10-ml slow filling group (except for a decrease in PaO(2)). According to our data, PLV with 10 ml/kg should be preferred since cerebral alterations are minimal. If complete filling of the lung is needed PFC should be administered slowly to minimize side effects.     

Comparison of anterior cerebral artery blood flow velocity and cerebral blood flow during hypoxia

Measurement of anterior cerebral artery blood flow velocity with a continuous wave bidirectional Doppler was compared with cerebral blood flow (CBF) measured with radioactive microspheres in 11 paralyzed newborn lambs during hypoxic hypoxia. The Doppler probe was maintained in a fixed position during each experiment. The objectives of the study were to validate this noninvasive technique that is being used widely in the clinical setting to qualitatively assess changes in CBF, and to evaluate which of the velocity parameters measured provide the most information. Diastolic velocity (DV), peak systolic velocity (PSV), area under the velocity curve (AUC), and pulsatility index (PI) were examined under conditions of varied arterial oxygen content and compared to microsphere CBF. DV (r = 0.72, p less than 0.001), AUC (r = 0.72, p less than 0.001), and PSV (r = 0.63, p less than 0.001) demonstrated stronger correlations with changes in CBF than did the PI (r = -0.41, p less than 0.05). DV (r = 0.81, p less than 0.001), AUC (r = 0.80, p less than 0.001), and PSV (r = 0.75, p less than 0.001) also exhibited stronger relationships with changes in arterial oxygen content than did the PI (r = -0.36, p less than 0.05). These data demonstrate that changes in cerebral blood flow velocity are useful qualitative measures of changes in cerebral blood flow. However, the utility of this technique is dependent upon a stable probe position, and assessment of the actual velocity measurements (DV, PSV, AUC) rather than simply the pulsatility index.     

A piglet model for evaluation of cerebral blood flow and brain oxidative metabolism during gradual cerebral perfusion pressure decrease.

A piglet model was developed to study the effect of epidural volume expansion on cerebral perfusion pressure (CPP) by stepwise elevating intracranial pressure (ICP). Mean arterial blood pressure (ABP) was strictly maintained using an extracorporeal ABP controller. Two-week-old piglets (n = 10) were studied by surgically placing an epidural balloon over the right parietal region and gradually increasing the inflation to increase ICP to 25, 35 and 45 mm Hg, maintaining each pressure level for 30 min. Regional cerebral blood flow was measured using the colored microsphere technique, and cerebral oxygen delivery and cerebral metabolic rate of oxygen were calculated at baseline conditions and after reaching ICP levels of 25, 35 and 45 mm Hg. The results showed that this model of epidural volume expansion reproducibly reduces CPP to 70, 50 and 33% of baseline CPP values with elevation of ICP, and that the physiological variables remained stable throughout each increase in ICP. We conclude that the model simulates the effects of an acute intracranial focal mass expansion and is well suited for the evaluation of different therapeutical strategies for increased ICP in newborns and infants.     

Brain auditory activation measured by near-infrared spectroscopy (NIRS) in neonates

This study presents a new measure of the hemodynamic changes to an auditory stimulus in newborns. Nineteen newborns born at 28-41 wk and aged 1 to 49 d were studied in waking and/or sleeping state, for a median time of 4 min 40 s before, 2 min 40 s during, and 3 min 5 s after an acustic stimulus (tonal sweep of frequency increasing from 2 to 4 kHz, intensity 90 dB SPL) originating 5 cm from the external auditory meatus. The emitter and detector optodes were placed over the left or right temporal region, corresponding to T3 or T4 EEG electrodes. The concentration changes in cerebral chromophores Delta[HbO2], Delta[Hb] and Deltaoxidized-reduced cytochrome aa(3) were recorded every 5 s. Changes in cerebral blood volume were calculated from the changes in total Hb x 0.89/large vessel Hb concentration. Increased oxyhemoglobin, Delta[HbO2], total Hb, Delta[Hb (sum)], and cerebral blood volume, DeltaCBV, were found in 13/19 neonates, with the exception of a neonate who only had increased in Delta[Hb], Delta[Hb (sum)] and DeltaCBV. During the stimulation phase there was a significant increase in DeltaCBV (t test, p = 0.00006) in the responsive newborns from a mean value of 0.006 (+/-0.02) mL/100 g in the pretest phase to 0.09 (+/-0.06) mL/100 g during the auditory stimulus. After the test DeltaCBV decreased to 0.04 (+/-0.07) mL/100 g (t test, p = 0.01), so did Delta[Hb (sum)] (p = 0.02). Hemodynamic responses of the subjects who showed increases in Delta[Hb (sum)] and Delta[HbO(2)] were analyzed to study the Delta[Hb]. The responder subjects could be classified into two groups according to Delta[Hb] changes: 8/13 (61.5%) showed an increase of Delta[Hb] (pattern A), while 5/13 (38.4%) showed a decrease (pattern B) (t test, p = 0.03). These two patterns did not show differences related to Delta[HbO(2)] and Delta[Hb (sum)]. The DeltaCBV changes in nonresponders presented a decrease during the test phase (t test, p = 0.04). CBV did not return to pretest values, suggesting a fronto-temporal brain pathway for storing unusual sounds. The increase in CBV followed the local increase in oxyhemoglobin and total Hb concentrations due to a greater use of oxygen in the homolateral temporal cortex of the newborns.     

Blood withdrawal and infusion via umbilical catheters: effect on cerebral perfusion and influence of ibuprofen

Withdrawal and infusion of blood via umbilical catheters can affect cerebral blood flow in preterm infants. We compared the effects on cerebral perfusion of 3 ml/kg blood withdrawal and infusion via umbilical arterial (UAC) and venous (UVC) catheters in 16 infants < or =32 weeks gestation, age <24 h, on mechanical ventilation. Near infrared spectroscopy was used to monitor changes in cerebral oxy- and deoxyhemoglobin, total cerebral hemoglobin (an index of cerebral blood volume; CBV) and HbD (an index of cerebral intravascular oxygenation). In 10 infants the study was repeated 1 h after intravenous administration of 10 mg/kg ibuprofen as prophylaxis against PDA. Withdrawal and infusion via the UVC caused significant MABP and concordant HbD and CBV changes. Smaller modifications were seen following blood withdrawal and infusion via the UAC. Ibuprofen attenuated cerebral hemodynamic changes associated with withdrawal, but not infusion, from UAC and UVC.