Cerebral blood flow velocity and cardiac output in infants of insulin-dependent diabetic mothers.

Cardiac output and cerebral blood flow velocity in the anterior cerebral and internal carotid arteries were investigated in eight large-for-date infants of insulin-dependent diabetic mothers and 12 healthy term infants during the first four days of life using two-dimensional/pulsed Doppler ultrasound. Temporal mean flow velocity was used as an indicator of changes in cerebral blood flow. Six of the eight infants of diabetic mothers had ventricular septal hypertrophy with reduced cardiac outputs and stroke volumes. Mean flow velocity in both cerebral vessels showed a comparable pattern in both groups throughout the study period and was independent of mean arterial pressure, suggesting unaltered cerebral hemodynamics in the infants of diabetic mothers.     

Effects of partial plasma exchange transfusion on blood flow velocity in large arteries of arm and leg, and in cerebral arteries in polycythaemic newborn infants

Continuous wave Doppler velocimetry was performed in brachial, femoral and cerebral arteries in four preterm, four small-for-gestational-age (SGA) and eight appropriate-for-gestational age (AGA) polycythaemic newborns before and at 3 and 24 h after partial plasma exchange transfusion and in 18 matched controls at 3 and 24 h after birth. In peripheral arteries, end-diastolic flow velocity was zero in all eight AGA controls, but only in two of the other infants. Consequently, mean flow velocity and red cell transport in AGA controls were significantly lower than in the other five groups, which did not differ. Partial plasma exchange transfusion did not influence flow velocities and red cell transport in peripheral arteries, but normalized the flow velocities in cerebral arteries in all three subgroups of polycythaemic infants, which were lower than in control infants. Cerebral red cell transport in controls increased significantly between 3 and 24 h, and in polycythaemic infants between 0 and 3 h after partial plasma exchange transfusion. In conclusion, reduction in haematocrit had different effects on blood flow velocity and red cell transport of peripheral and cerebral vessels, suggestirng that the increased cerebral blood flow velocity after partial plasma exchange transfusign is not simply due to a reduction in viscosity or oxygen content of the blood. The lower peripheral blood flow velocities in normocythaemic AGA infants as compared to all other groups, suggest that the level of maturity is an important determinant for the capacity to regulate blood flow.     

Cerebral blood flow velocity regulation in preterm infants

Cerebrovascular autoregulation is the mechanism by which changes in cerebral blood flow are prevented during fluctuations in mean arterial blood pressure. Doppler ultrasound measurement of cerebral blood flow velocity provides a reliable indirect technique to estimate cerebral blood flow. In 48 stable preterm infants less than or equal to 32 weeks gestation, we studied the mean flow velocity in the pericallosal artery at 12, or at 12 and 72 h of age with two-dimensional/pulsed Doppler ultrasound and correlated the mean flow velocity with the simultaneously obtained mean arterial blood pressure values. Mean flow velocity was stable at a mean arterial blood pressure ranging from 31 to 40 mm Hg, but changed proportionally with mean arterial blood pressure values outside this narrow range. Multiple regression analysis showed that mean flow velocity was primarily determined by mean arterial blood pressure. These data suggest that in preterm infants regulation of cerebral blood flow velocity occurs only over a narrow range of mean arterial blood pressure values.     

Cerebral blood flow velocity changes in preterm infants after a single dose of indomethacin: duration of its effect

Indomethacin decreases cerebral blood flow velocity and blood flow in the preterm infant. The duration of this negative effect has not been established. Cerebral blood flow velocity was evaluated in 24 preterm infants with symptomatic patent ductus arteriosus before and during the first 12 hours after a single intravenous dose of indomethacin, 0.1 mg/kg. Cerebral blood flow velocity was estimated by serial Doppler investigations of the anterior cerebral arteries. Indomethacin administration led to an instantaneous decrease of peak systolic flow velocity, temporal mean flow velocity, and end-diastolic flow velocity of the anterior cerebral arteries in all infants, which was maximal between 2 and 40 minutes after indomethacin administration and was followed by a more sustained recovery of all velocities to baseline values. Temporal mean flow velocity was not different from pre-indomethacin values at 3 hours after the administration. It is concluded that indomethacin can impact the cerebral circulation of the preterm infant for at least 2 hours. This may have consequences in preterm infants with unstable hemodynamics and pulmonary function.     

Poor Reversibility of EEG Abnormality in Hypotensive, Preterm Neonates

ABSTRACT. Twenty-four infants, 32 weeks of gestation or less, were studied with continuous recording of amplitude integrated electroencephalogram (aEEG) and repeated Doppler ultrasound determination of the mean blood flow velocity in the internal carotid artery (cMFV). The recording was started after the initiation of mechanical ventilation for respiratory distress. Of twelve infants receiving blood or albumin transfusion to expand the intravascular volume and in whom adequate data were available, both mean arterial blood pressure and cMFV increased in eight, and cMFV but not blood pressure in further two. In the present circumstances we consider the cMFV increases to represent true increases in cerebral blood flow. aEEG burst rate increased distinctly in five of the twelve infants during or immediately following transfusion, but did only approach the level of the four non-transfused infants after several hours, indicating a dysfunction of neural tissue not readily reversible by improved blood flow.     

Poor reversibility of EEG abnormality in hypotensive, preterm neonates

Twenty-four infants, 32 weeks of gestation or less, were studied with continuous recording of amplitude integrated electroencephalogram (aEEG) and repeated Doppler ultrasound determination of the mean blood flow velocity in the internal carotid artery (cMFV). The recording was started after the initiation of mechanical ventilation for respiratory distress. Of twelve infants receiving blood or albumin transfusion to expand the intravascular volume and in whom adequate data were available, both mean arterial blood pressure and cMFV increased in eight, and cMFV but not blood pressure in further two. In the present circumstances we consider the cMFV increases to represent true increases in cerebral blood flow. aEEG burst rate increased distinctly in five of the twelve infants during or immediately following transfusion, but did only approach the level of the four non-transfused infants after several hours, indicating a dysfunction of neural tissue not readily reversible by improved blood flow.     

The effect of phototherapy on cerebral blood flow velocity in preterm infants

Cerebral blood flow velocity was studied with two-dimensional/pulsed Doppler ultrasound before, during and after discontinuation of phototherapy in 22 preterm infants (gestational age ≤32 weeks), who were treated for a minimum of 12h with blue-light phototherapy for non-haemolytic hyperbilirubinaemia. Before the cerebral blood flow velocity measurements, patency of the ductus arteriosus was diagnosed by Doppler echocardiography. All infants had normal brain ultrasound scans. Mean cerebral blood flow velocity increased significantly after initiation of phototherapy in all infants. Only in “healthy” (non-ventilated) infants did cerebral blood flow velocity return to pre-phototherapy values (baseline) after discontinuation of phototherapy, whereas in “unhealthy” (ventilated) infants cerebral blood flow velocity did not return to baseline. In 10 infants the ductus arteriosus reopened during phototherapy. In those infants, mean cerebral blood flow velocity returned to pre-phototherapy values after 2h of phototherapy prior to its discontinuation.     

Myocardial dysfunction and cerebral blood flow velocity following birth asphyxia

Birth asphyxia often leads to left ventricular myocardial dysfunction. To assess the effect of myocardial dysfunction on cerebral perfusion, we evaluated cardiac output and cerebral blood flow velocity in the anterior cerebral and internal carotid arteries in 20 asphyxiated term newborn infants during the first 4 days of life using 2-dimensional/pulsed Doppler ultrasound. In 8 infants with myocardial dysfunction cardiac output was reduced on days 1 and 2 and within normal limits thereafter. In these infants changes in mean cerebral blood flow velocity and pulsatility index were passively related to changes in mean arterial pressure and cardiac output. In 12 infants without myocardial dysfunction a stable cerebral blood flow velocity pattern was found, which was unaffected by changes in mean arterial pressure. We conclude that infants presenting with a reduced cardiac output after deliveries associated with severe asphyxia may be at risk for additional ischemic or hemorrhagic cerebral damage because of lack of autoregulation.     

Effect of indomethacin on superior mesenteric artery blood flow velocity in preterm infants

In 15 preterm infants with symptomatic patent ductus arteriosus, blood flow velocity changes in the superior mesenteric artery were investigated with Doppler ultrasound just before and during the first 12 hours after a single dose of indomethacin. Indomethacin administration led to an instantaneous decrease in all infants of temporal mean flow velocity in the superior mesenteric artery, which was maximal 10 minutes after administration of indomethacin, followed by a more sustained recovery, slightly greater than baseline values, 12 hours after indomethacin treatment. Simultaneously determined temporal mean flow velocity of the anterior cerebral artery, used as an indicator of changes in cerebral blood flow, had a similar pattern as in the mean flow velocity in the superior mesenteric artery (r = 0.49; p less than 0.001). Our data suggest that indomethacin lowered blood supply to the bowel, similar to its action on cerebral blood flow.     

Effects of partial plasma exchange transfusion on cerebral blood flow velocity in polycythaemic preterm,term and small for date newborn infants

Isovolemic haemodilution with plasma was performed in 36 newborn infants with polycythaemia 3 h after birth. Continuous wave Doppler ultrasonography was used to study the short and longer term influence of partial plasma exchange transfusion on cerebral blood flow velocity in both the anterior cerebral and mid cerebral arterial system up to 24 h after haemodilution. The study group consisted of 11 preterm infants, 12 term infants, and 13 small for date infants. After exchange transfusion peripheral venous haemotocrit decreased from 72.5% to 59.4%. In all experimental groups cerebral blood flow velocity (CBFV) before exchange transfution was significantly lower (18%–44%) than matched controls, and increased to control levels after exchange transfusion. CBFV improved most in preterm infants. After the transfusion the values were no different from the age-, weight-, sex-and parity-matched control groups, and they remained at this level during the next 24 h. No differences could be found between the anterior and mid-cerebral arterial system. When clinical symptoms were present, they subsided in all infants. In conclusion, partial plasma exchange transfusion has a favourable effect for at least 24 h on cerebral blood flow velocity in newborn infants with polycythaemia.Abbreviations AUC area under the curve (mean flow velocity) - CBFV cerebral blood flow velocity - EDFV end diastolic flow velocity - Hct haematocrit - PI pulsatility index according to Pourcelot - PRET partial plasma exchange transfusion - PSFV peak systolic flow velocity     

Changes in Doppler ultrasonography in asphyxiated term infants with hypoxic-ischaemic encephalopathy

Cerebral blood flow velocity was assessed by pulsed-Doppler ultrasonography in 39 asphyxiated and 35 healthy term newborn infants during the first days of life. Asphyxiated infants, investigated at the age of 12±2h, with moderate stage hypoxic-ischaemic encephalopathy (HIE) (n = 7) had decreased (15.6±3.9cm/s) and infants with severe stage of HIE (n = 8) increased (26.5±9.6cm/s) mean cerebral blood flow velocity in medial cerebral artery compared to the control group (20.9±3.7cm/s). Four out of six infants with severe stage of HIE and mean cerebral blood flow velocity of 3SD above the mean for normal infants at the age of 12h died and two developed multicystic encephalopathy during the neonatal period. We conclude that severe post-hypoxic increase of mean cerebral blood flow velocity at the age of 12±2h is connected with development of severe stage HIE and poor prognosis.     

Myocardial Dysfunction and Cerebral Blood Flow Velocity Following Birth Asphyxia

ABSTRACT. Birth asphyxia often leads to left ventricular myocardial dysfunction. To assess the effect of myocardial dysfunction on cerebral perfusion, we evaluated cardiac output and cerebral blood flow velocity in the anterior cerebral and internal carotid arteries in 20 asphyxiated term newborn infants during the first 4 days of life using 2-dimensional/pulsed Doppler ultrasound. In 8 infants with myocardial dysfunction cardiac output was reduced on days 1 and 2 and within normal limits thereafter. In these infants changes in mean cerebral blood flow velocity and pulsatility index were passively related to changes in mean arterial pressure and cardiac output. In 12 infants without myocardial dysfunction a stable cerebral blood flow velocity pattern was found, which was unaffected by changes in mean arterial pressure. We conclude that infants presenting with a reduced cardiac output after deliveries associated with severe asphyxia may be at risk for additional ischemic or hemorrhagic cerebral damage because of lack of autoregulation.     

Quantification of cardiovascular instability in premature infants using spectral analysis of waveforms

Spectral analysis was applied to blood pressure and cerebral blood flow velocity recordings in premature infants with respiratory distress in order to quantify respiration-induced cardiovascular variability. Aortic blood pressure was transduced via an umbilical arterial catheter and cerebral blood flow velocity measured in the anterior cerebral artery using a 10 MHz continuous wave Doppler velocimeter in 16 infants less than or equal to 32 wk gestational age. Spectral analysis of the resulting waveforms revealed heart rate and respiratory rate components whose relative amplitudes (heart rate/respiratory rate amplitude ratio) represent an index of that component of variability induced by respiratory events. The mean (heart rate/respiratory rate amplitude) ratio was 47.2 in spontaneously breathing infants and rose to 165.9 in infants who were ventilated during muscle paralysis (p = 0.0003). Cerebral blood flow velocity recordings showed R components in only 22 of 38 simultaneous recordings. This method can be used to quantify respiration-induced cardiovascular variability and its response to therapy, and may provide a means of identifying infants at risk from brain injury due to an inability to regulate cerebral blood flow.     

Increased cerebral blood flow velocity in infants of mothers who abuse cocaine

The pharmacologic effects of cocaine are considered to be secondary to an enhancement of the effects of circulating catecholamines. The effect of intrauterine cocaine exposure on the cerebral blood flow velocity was studied in 20 full-term newborn infants whose urine screens were positive for cocaine and in 18 nonexposed healthy full-term newborn infants whose urine screens were negative for cocaine metabolites. On the first day of life, peak systolic, end diastolic, and mean flow velocities in the pericallosal, internal carotid, and basilar arteries and mean arterial blood pressures were significantly greater in infants who had been exposed to cocaine. On day 2, cerebral blood flow velocities and mean arterial blood pressures were similar in exposed and nonexposed infants. The increase in mean arterial blood pressure and in cerebral blood flow velocity on the first day of life indicates a hemodynamic effect of cocaine that may put the infant exposed to cocaine at a greater risk of intracranial hemorrhage.     

Cerebral blood flow velocity during neonatal seizures.

AIM: To determine if cerebral blood flow velocity increases during all types of neonatal seizure, and whether the effect is due solely to an increase in blood pressure, transmitted to the cerebral circulation when autoregulation is impaired. METHODS: Seizures were diagnosed in 11 high risk neonates using cotside 16 channel video-EEG polygraphy. EEG, cerebral blood flow velocity (CBFV) using transcranial Doppler ultrasound, and arterial blood pressure (ABP) measurements were made. At least two 5-10 minute epochs of simultaneous measurements were performed on each infant. These epochs were then reviewed to eliminate artefacts, and one minute data periods containing a clear seizure onset were created. Each period contained 20 seconds before the seizure. Data periods without seizures from the same infants were also analysed and compared with seizure periods. RESULTS: Four infants had purely electrographic seizures-without clinical manifestations. Six infants had electroclinical seizures. One infant displayed both seizure types. A random effects linear regression analysis was used to determine the effect of seizures on CBFV and ABP. A significant increase was found in mean CBFV in those periods containing seizures. The mean percentage change in velocity for all infants was 15.6%. Three infants showed a significant increase in mean ABP after seizures but the overall increase in ABP for all infants was not significant. CONCLUSION: Electroclinical and electrographic neonatal seizures produce an increase in CBFV. In some infants the increase is not associated with an increase in blood pressure. These preliminary results suggest that electrographic seizures are associated with disturbed cerebral metabolism. Treatment of neonatal seizures until electrographic seizure activity is abolished may improve outcome for these infants.     

Vasoactivity of the major intracranial arteries in newborn infants.

Blood flow to the head and arms was measured by a new volumetric Doppler technique in 30 preterm infants and 10 full term infants. At least 80% of this blood flow is considered to perfuse the brain. At the same time mean blood velocity in the middle and anterior cerebral arteries was measured by Duplex Doppler scanning. While blood flow to the head and arms remained substantially constant in both groups over the first 48 hours of life (60 ml/100 g brain weight/min), blood velocity doubled in both cerebral arteries in the preterm group. The term infants had higher blood velocities in both arteries at all times, but the velocities also increased over 48 hours, although to a lesser extent than in the preterm group. These findings imply that the major intracranial arteries are themselves vasoactive, being dilated at birth and subsequently constricting, possibly as an autoregulatory response to rising arterial blood pressure. While vasodilated, the cerebral arteries will be less efficient at damping pressure transients, placing preterm infants at particular risk of periventricular haemorrhage during the early hours of life. The implications for possible approaches to the prevention of cerebral haemorrhage are discussed.     

Postnatal Changes in Intracranial Blood Flow Velocity in Preterm Infants

ABSTRACT. Postnatal changes in intracranial arterial blood flow velocity, were studied in preterm infants of less than 34 weeks of gestation. The blood flow velocity was measured in an artery on the base of the skull, using a range-gated Doppler ultrasound velocimeter. Ten healthy infants (mean gestational age 32.5 weeks), and ten infants with transitional respiratory disease (mean gestational age 31.3 weeks) were studied at 1, 2, 5, 24 h, and 2, 3, 5 and 10 days after birth. The healthy infants showed a consistent pattern of changes on the first day, with an average reduction in mean flow velocity of 29% between 1 and 5 h. At 24 h after birth, mean flow velocity had almost returned to the level of the 1 h recording. After 24 h there was a gradual increase in systolic and mean flow velocity until 10 days, while diastolic flow velocity remained unchanged. In the infants with respiratory disease there were no systematic changes in mean flow velocity on the first day, although large individual changes were seen. After 24 h no differences were seen between the healthy infants and the infants with respiratory disease. These findings indicate a transient decrease in cerebral perfusion during early circulatory transition in healthy preterm infants, and that mild to moderate respiratory disease causes larger individual variations in intracranial blood flow velocity.     

Postnatal changes in intracranial blood flow velocity in preterm infants

Postnatal changes in intracranial arterial blood flow velocity, were studied in preterm infants of less than 34 weeks of gestation. The blood flow velocity was measured in an artery on the base of the skull, using a range-gated Doppler ultrasound velocimeter. Ten healthy infants (mean gestational age 32.5 weeks), and ten infants with transitional respiratory disease (mean gestational age 31.3 weeks) were studied at 1, 2, 5, 24 h, and 2, 3, 5 and 10 days after birth. The healthy infants showed a consistent pattern of changes on the first day, with an average reduction in mean flow velocity of 29% between 1 and 5 h. At 24 h after birth, mean flow velocity had almost returned to the level of the 1 h recording. After 24 h there was a gradual increase in systolic and mean flow velocity until 10 days, while diastolic flow velocity remained unchanged. In the infants with respiratory disease there were no systematic changes in mean flow velocity on the first day, although large individual changes were seen. After 24 h no differences were seen between the healthy infants and the infants with respiratory disease. These findings indicate a transient decrease in cerebral perfusion during early circulatory transition in healthy preterm infants, and that mild to moderate respiratory disease causes larger individual variations in intracranial blood flow velocity.     

Alterations in regional cerebral blood flow in neonatal stroke: preliminary findings with color Doppler sonography

Little information is available regarding alterations in regional cerebral blood flow and vascularity on cranial sonography in infants with focal ischemic brain injury. This study describes the use of color Doppler sonography in the characterization of these changes following acute neonatal stroke. Color Doppler examinations were performed as part of the series of clinically indicated cranial sonograms in eight infants with clinical, sonographic, and CT evidence of acute cerebral infarction. The cerebral vascularity of each hemisphere was assessed for symmetry and for presence of abnormal blood vessels. Initial Doppler study in four infants with hypoxic-ischemic infarcts showed increased size and number of visible vessels in the periphery of the infarct and increased mean blood flow velocity in vessels supplying or draining the infarcted areas. Diminished vessel number and size and frequency shifts suggestive of decreased hemispheric perfusion was identified in one infant with middle cerebral artery insufficiency. Repeat Doppler studies were performed on two infants. These showed the development of multiple small, irregular blood vessels in the periphery of the infarct. Focal abnormalities in regional cerebral blood flow may be present as part of the normal healing process following neonatal stroke, and can be demonstrated with color Doppler sonography.     

Cerebral blood flow velocity in term newborn infants: changes associated with ductal flow

The effects of ductal closure on range-gated pulsed Doppler cerebral blood flow velocity (CBFV) patterns in the internal carotid, anterior cerebral, and middle cerebral arteries were studied in 10 normal term infants (mean birth weight 3302 +/- 294 g (SD) and mean gestational age 39.6 +/- 1.3 weeks). Pulsatility was calculated from flow velocities and used as an estimate of cerebral blood flow (CBF). Ductal closure was associated with a rise in mean blood pressure from 45.0 +/- 4.2 to 51.3 +/- 6.5 mm Hg (P less than 0.05) and a significant decrease in pulsatility in all three vessels (mean = 0.77 +/- 0.07 vs 0.70 +/- 0.05 (P less than 0.02]. Changes in pulsatility were correlated with changes in mean blood pressure (P less than 0.02), providing evidence that systemic blood pressure may influence postnatal cerebral arterial pulsatility indices. We also noted significant differences in the velocity and pulsatility of individual vessels that were independent of blood pressure, suggesting that Doppler flow studies may be useful in describing regional CBF patterns. The temporal association between ductal closure and decreased pulsatility suggests that CBFV patterns reflect ductal shunting in normal term newborn infants. Diastolic runoff and reduced systemic blood pressure in the presence of ductal shunting appear to reduce diastolic flow velocity and increase CBFV pulsatility in normal term infants during the first days of life. Normal mechanisms of cerebral autoregulation compensate for decreased flow with vasodilation; therefore the increased pulsatility associated with ductal shunting may be due to diastolic runoff rather than increased cerebrovascular resistance.