Range-gated pulsed Doppler ultrasonographic evaluation of carotid arterial blood flow in small preterm infants with patent ductus arteriosus

Range-gated pulsed Doppler (RGPD) ultrasonography was utilized to study the effect of a patent ductus arteriosus (PDA) on carotid arterial blood flow in small preterm infants. Carotid arterial flow velocity studies were performed on 23 preterm infants, sampling right and left carotid arteries. Studies on seven infants after PDA ligation and on seven who developed no evidence of PDA were used as controls. A strong relationship was demonstrated between diastolic reversal in the carotid arteries and PDA. The results of this study indicate that the RGPD flow velocity curve from the carotid artery is more sensitive than M-mode echocardiography or clinical examination in detecting PDA, and that PDA in small preterm infants is associated with a distinct abnormality in the carotid arterial flow pattern.     

Cerebral blood flow fluctuation in low-risk preterm newborns.

Cerebral blood flow (CBF) fluctuation was studied by analyzing Doppler internal carotid blood velocity recordings of 13 healthy preterm newborns obtained in the course of their first 5 days of life. As measures of fluctuation we used the interquartile range (IQR) and the coefficient of variation (CV) of the ensemble of heart beats of a 20-s recording. In this way we determined fluctuation of the following velocity curve parameters (VCPs): end diastolic velocity; mean velocity; peak systolic velocity and pulsatility index (PI). The pooled data 5-95% intervals for fluctuation thus measured, were: 93-281% for CV; 0.6-3.7 cm/s for the IQR of the velocities; and 4-19% for the PI-IQR. Multiple regression analysis of IQR revealed significant relationships with: the VCP level; with restlessness; and with patency of the ductus arteriosus. Our findings imply that: (1) CBF has various qualities with different stability, mean velocity being the most stable; (2) for all the VCPs investigated, fluctuation is physiological in the early days after preterm birth; (3) most likely, there exists no age trend; (4) restlessness rather than wakefulness, enhances fluctuation; (5) patent ductus arteriosus destabilizes CBF; and (6) for a proper insight into fluctuation, the level of the VCP in question must be taken into account. We suggest that, the enhancing effect that patent ductus arteriosus has on fluctuation pays a contribution to the pathogenesis of brain damage. Finally, we conclude that the IQR represents fluctuation better than does the more commonly used CV.     

Cerebral and Abdominal Arterial Hemodynamics in Preterm Infants with Patent Ductus Arteriosus

Using Doppler echocardiography we evaluated the effect of ductal shunt flow on the cerebral and abdominal arterial blood flow in 25 preterm infants. Eligible for inclusion in this study were healthy preterm newborn infants. They were divided into two groups based on their gestational age: group A, 33-36 weeks (15 infants) and group B, 28–32 weeks (10 infants). Two-dimensional Doppler echocardiograms were obtained in each infant during the first 8 hours of life and repeated every 6–12 hours until no ductal shunt flow could be detected. Flow in the ductus arteriosus, the basilar artery and the coeliac artery were examined. Closure of the ductus arteriosus occurred significantly later(p< 0.05) in group B than in group A. Pulsatility indices of flow in the basilar and coeliac arteries were high when the ductus was patent, decreasing to a fixed level with closure. This study suggests that a shunt of the patent ductus arteriosus (PDA) adversely influences the cerebral and abdominal blood flow in preterm infants.     

Effects of indomethacin and ibuprofen on mesenteric and renal blood flow in preterm infants with patent ductus arteriosus

OBJECTIVE: To evaluate the effect of intravenous ibuprofen and indomethacin for treatment of patent ductus arteriosus (PDA) on mesenteric and renal blood flow velocity in preterm infants. STUDY DESIGN: Seventeen mechanically ventilated preterm infants (<33 weeks' gestation) with PDA received either 0.2 mg/kg indomethacin (n = 8) or 10 mg/kg ibuprofen (n = 9), infused over 15 minutes. Mesenteric and renal blood flow velocity were measured by using Doppler ultrasonography. RESULTS: Indomethacin caused a significant reduction in mesenteric and renal blood flow velocity 30 minutes after drug administration; mesenteric and renal blood flow velocity did not return to the pretreatment values by 120 minutes. Ibuprofen did not alter blood flow 30 minutes after treatment, and blood flow increased 120 minutes after treatment. Mesenteric and renal blood flow velocity changes were significantly different between the 2 treatment groups. CONCLUSIONS: Compared with indomethacin, ibuprofen did not significantly reduce mesenteric and renal blood flow velocity.     

Sensitivity,specificity and predictive value of clinical findings,m-mode echocardiography and continuous-wave Doppler sonography in the diagnosis of symptomatic patent ductus arteriosus in preterm infants

By means of probability analysis we have compared the diagnostic value of clinical symptoms, m-mode echocardiographic measurements and peripheral arterial flow, assessed by continuous-wave Doppler, in preterm infants with symptomatic patent ductus arteriosus (PDA). Data were obtained in 29 infants with PDA and in 29 controls. The most sensitive clinical finding was a hyperactive precordium. Bounding pulses and a heart murmur were absent in 15% and 20%, respectively of the patients with PDA. M-mode echocardiographic measurements were rather specific for the detection of a PDA but less sensitive. Diastolic backflow in the brachial and femoral arteries was present in the majority of patients with PDA and absent in about 67% of the controls. The values in probability analysis, however, were too low to base a therapy on these findings. The highest sensitivity and specificity (100% each) was found for a disturbed cerebral blood flow with absent or retrograde diastolic perfusion estimated by Doppler sonography.Abbreviations PDA patent ductus arteriosus - cw-Doppler continuous-wave Doppler - SF shortening fraction - LPEP/LVET, RPEP/RVET left and right ventricular systolic time intervals - R/F retrograde/forward flow Dedicated to Professor Dr. E. Kleihauer on the accasion of his 60th birthday     

Changes in cerebral,renal and mesenteric blood flow velocity during continuous and bolus infusion of indomethacin

Vasoconstriction induced by bolus injection of indomethacin reduces organ perfusion and has been related to the well-known side effects of indomethacin given for closure of the patent ductus arteriosus (PDA). The aim of the study was to compare the changes in cerebral, renal and mesenteric blood flow velocities after continuous infusion versus bolus injection of indomethacin for closure of the PDA. Thirty-two preterm infants (range 26-35 wk gestational age) with PDA were randomly assigned to receive the same amount of indomethacin either as three bolus injections (n = 14) or as a continuous infusion (n = 18) over 36 h. Blood flow velocities were measured in the internal carotid, right renal and superior mesenteric arteries at baseline and serially at 10, 30, 60 and 120 min and 12, 24, 36 and 48 h after the start of indomethacin treatment. There were no differences in blood flow velocities between both groups at baseline. During continuous infusion of indomethacin there was no significant change in the cerebral, renal and mesenteric blood flow velocities, whereas the flow velocities in the infants receiving bolus injections decreased significantly during the first 2 h after indomethacin administration in all arteries measured. There was a transient, but significant reduction in urine output after bolus injection of indomethacin. Conclusion: In contrast to bolus injections, decrease of organ blood flow and impairment of urine output do not accompany continuous infusion of indomethacin over 36 h.     

Severity of the ductal shunt: a comparison of different markers

BACKGROUND: When the ductus arteriosus (DA) is patent, the ductal shunt is proportional to the ratio of left ventricular output (LVO) to systemic blood flow. Systemic blood flow can be estimated by measuring flow in the superior vena cava (SVC). OBJECTIVE: To re-evaluate the accuracy of standard echocardiographic markers of patent ductus arteriosus (PDA) using LVO/SVC flow ratio. METHODS: Prospective study. Preterm infants of 24-30 weeks gestational age and postnatal age less than 48 hours. The following echocardiographic criteria were measured: left atrial to aortic root ratio (LA/Ao); DA diameter by B mode and colour Doppler; mean and end diastolic flow velocity of the left pulmonary artery (LPA); LVO; SVC flow. RESULTS: Twenty three preterm infants were enrolled (median gestational age 28 weeks (range 24-30), median birth weight 840 g (500-1440)). The DA was closed in eight (mean (SD) LVO/SVC 2.4 (0.3)) and open in 15 (mean (SD) LVO/SVC 4.5 (0.6)). An LA/Ao ratio > or =1.4, a DA diameter > or =1.4 mm/kg, and a mean and end diastolic flow velocity of LPA respectively > or =0.42 and > or =0.20 m/s identified an LVO/SVC > or =4 with a sensitivity and a specificity above 90%. CONCLUSION: This study indicates that LA/Ao ratio, DA diameter, and mean and end diastolic flow velocity of the LPA are accurate markers of PDA. These standard echocardiographic variables are easy to measure and need less skill and resources than direct measurements of ductal shunt.     

Cardiocirculatory effects of patent ductus arteriosus in extremely low-birth-weight infants with respiratory distress syndrome

BACKGROUND: Cardiocirculatory effects of hemodynamically significant patent ductus arteriosus (hsPDA) have not been systematically studied in extremely low-birth-weight (ELBW) infants with respiratory distress syndrome (RDS). The objective of the present study was to evaluate the effects of hsPDA on the left ventricular output (LVO) and organ blood flows in ELBW infants with RDS. METHODS: Extremely low-birth-weight infants (birth-weight <1000 g) treated with surfactant for RDS were studied by serial Doppler flow examinations. Doppler flow variables in 19 infants in whom hsPDA developed (hsPDA group) were compared with those in 19 infants without hsPDA matched for gestational age, birth-weight, and postnatal age (non-hsPDA group). All infants in the hsPDA group had pharmacologic closure of ductus arteriosus when hsPDA developed. RESULTS: Before pharmacological closure of PDA, the hsPDA group had significantly higher LVO, lower blood flow volume of the abdominal aorta, and lower mean blood flow velocities in the celiac artery, superior mesenteric artery, and renal artery than the non-hsPDA group. These alterations in the hsPDA group reverted to the levels in the non-hsPDA group after the closure of PDA and had no deleterious effects on the cardiorespiratory status. No significant differences between the groups were found in mean blood flow velocities of the anterior cerebral artery throughout the study period. CONCLUSION: These results indicate that although LVO is increased, the splanchnic and renal blood flows are decreased when hsPDA develops in ELBW infants with RDS. The effects of these alterations of LVO and organ blood flows on the cardiorespiratory course seem to be minor when early pharmacologic closure of PDA is done.     

A patent ductus arteriosus is associated with reduced middle cerebral artery blood flow velocity

The study objective was to determine the effect of a patent ductus arteriosus (PDA) on cerebral blood flow velocity in ventilated, very low birth weight neonates, in the first 5 days of life. Sonography of the right middle cerebral artery and ductus arteriosus was performed using a colour Doppler technique. Statistical analysis was by stepwise regression. Thirty-one neonates without and 43 with a PDA, mean (SD) birth weight 1004 g ± 192 and 1071 g ± 227 respectively, were studied. The end diastolic and mean velocities were reduced (P = 0.008 and P = 0.129) and the resistive index was increased (P = 0.047) by a PDA. pH was inversely related to end diastolic and mean velocities (P = 0.015 and P = 0.003), suggesting that low pH may increase cerebral artery blood flow velocity. Conclusion A patent ductus arteriosus reduces middle cerebral artery blood flow velocity in very low birth weight neonates. Received: 7 March 1997 / Accepted in revised form: 15 May 1998     

Investigations of renal artery blood flow velocity in preterm and term neonates by pulsed Doppler ultrasonography

So far, echo-Doppler studies of the renal arteries have only been performed in adult subjects. They dealt with qualitative parameters of blood flow, but absolute velocity values could not be determined. This paper presents a method for measurement of absolute values of renal artery blood flow velocity in infancy with a well-defined steep angle of insonation of less than 25° by using a range-gated Doppler system with Duplex-scan. The renal blood flow patterns were studied at specified sites by placement of the transducer below the costal arches on the right flank and left flank, respectively. Thus, a reference collective of 65 infants (26–40 weeks of gestational age, 650–3990 g body weight and 1–145 days of postnatal age at the time of examination) were studied. The time mean of maximum velocity significantly increased with the body weight from 17 cm/s below 1000 g to 29 cm/s above 3000 g of body weight. Whereas the pulsatility indices were independent of body weight. The reproducibility of the method, coefficient of variation (CV) 3%–9%, is comparable with the studies of cerebral vessels.Abbreviations RAs renal arteries - RRA right renal artery - LRA left renal artery - Vs peak systolic velocity - Vd end diastolic velocity - Vmax time mean of the maximum velocity - PI pulsatility index - 2-D two-dimensional - CV coefficient of variation - M motion     

Pulse wave patterns in patent ductus arteriosus.

Pulse wave patterns were analysed in 10 term and 10 preterm infants with patent ductus arteriosus (PDA) and in 2 matched control groups. A non-invasive technique was used to record the pulse waves from the axillary artery. The pulsatile ratio was calculated as the quotient between the amplitude of the incisural notch and the peak of the pulse wave above the end diastolic baseline. The pulsatile ratio was considerably lower in preterm and term infants with PDA compared with the ratio after closure of the ductus and the ratio in control infants. A pulsatile ratio less than 0.50 indicates the presence of a large PDA whereas a ratio over 0.55 is normal. The technique may be used to document and evaluate arterial pulse wave patterns and may be a useful diagnostic tool.     

Incidence and clinical features of patent ductus arteriosus in low-birthweight infants: a prospective analysis of 150 consecutively born infants.

The incidence of persistent patency of the ductus arteriosus beyond the third day of life was prospectively determined in 100 preterm infants with birthweights of 2,000 gm or less and 50 infants with birthweights of 2,001 to 2,500 gm. The overall incidence was 21% and was inversely related to increasing gestational age and birthweight. The data suggest that immaturity is the major determinant of the persistent patency of the ductus arteriosus. Spontaneous delayed closure of the ductus occurred in 79% of patients that survived the immediate neonatal period. There was a high degree of association between the presence of a patent ductus arteriosus (PDA) and respiratory distress syndrome (RDS). Eight infants with severe RDS and PDA developed heart failure and four required surgical ligation of the ductus. None of the infants with birthweights greater than 2,000 gm who had PDA developed heart failure or required surgical ligation of the ductus arteriosus.     

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.     

Indomethacin and cerebral blood flow in premature infants treated for patent ductus arteriosus

Central blood flow (CBF) was estimated by an intravenous 133-xenon technique in six preterm infants before and after administration of indomethacin for closure of patent ductus arteriosus. CBF fell in all infants (range 12%–40%), the mean fall was 24% (P<0.005). Though none of the infants showed signs of impaired cerebral function during or following the injections, the results do not indicate whether or not the use of indomethacin is a potential hazard.Abbreviations PDA patent ductus arteriosus - CBF cerebral blood flow - PaCO₂ arterial carbon dioxide tension - MAP mean arterial blood pressure     

Color-coded Doppler sonography of the kidney blood vessels in childhood. II. Pathological findings

Pathologic flow profiles in renal arteries can be found in cardiovascular and renovascular disease. Obstructions of the left hart (aortic stenosis, hypoplastic left heart syndrome, coarctation of the aorta) cause diminished flow with low peak systolic velocities. In renal arteries of infants with leakage of the aortic "Windkessel" (persistent ductus arteriosus, truncus arteriosus communis etc.) a low diastolic amplitude can be found. Significant left-to-right shunts can lead to a diminished or even retrograde diastolic flow. In renal artery stenosis a high velocity jet with spectral broadening can be found in the region of the stenosis. Distal to the stenosis low blood flow velocities can be shown. In renal vein thrombosis the obstruction of the peripheral vessels cause a missing or even negative diastolic flow in the renal arteries, whereas venous blood flow is diminished or even missing. Kidney diseases with swelling of the organ (acute rejection of a transplanted kidney) can cause diminished, missing or even retrograde diastolic flow in the renal arteries dependent on the severity of the edema. These alterations can be used for the early diagnosis of acute rejection which offers the opportunity for early and efficient therapeutic management.     

A meta-analysis of ibuprofen versus indomethacin for closure of patent ductus arteriosus

Ibuprofen (IBU) has previously been shown to be as effective as indomethacin (INDO) in closing the patent ductus arteriosus (PDA) of preterm infants, without severely affecting renal hemodynamics or basal cerebral blood flow. We conducted a meta-analysis of randomized trials to compare the efficacy and safety of IBU and INDO for treatment of PDA. Data from the nine relevant trials ( n =566), showed no significant difference in the efficacy of IBU and INDO in PDA closure ( P =0.70). However, five trials ( n =443) provided serum creatinine concentration data that revealed a significantly lower increase favoring IBU ( P < 0.001), and urine output data that showed a significantly lower decrease favoring IBU ( P < 0.001). In two trials ( n =188) the proportion of infants who required postnatal oxygen therapy at 28 days (defined as chronic lung disease) was significantly higher with IBU (52/94; 55.3%) than with INDO (38/94; 40.4%, P < 0.05). No statistically significant differences were found in mortality, intraventricular hemorrhage, necrotizing enterocolitis, surgical ligation, sepsis, retinopathy of prematurity, periventricular leukomalacia, length of hospital stay, gastrointestinal bleeding, re-opening of PDA, back-up treatment, surfactant therapy, or days on a ventilator. Conclusion:ibuprofen and indomethacin have similar efficacy in patent ductus arteriosus closure, but preterm infants treated with ibuprofen experience lower serum creatinine values, higher urine output, and less undesirable decreased organ blood flow and vasoconstrictive adverse effects.     

Serial Assessment of Left-Ventricular Function Using Tissue Doppler Imaging in Premature Infants Within 7 Days of Life

Although many echocardiographic parameters can assess cardiac function noninvasively in preterm infants, it has not been determined what indices are the best. We assessed left-ventricular performance in 101 very low-birth weight (VLBW) infants using tissue Doppler imaging (TDI) echocardiography. Echocardiographic examinations, including TDI, were performed serially within 7 days of life. Pulsed-Doppler TDI waveforms were recorded at the mitral valve annulus, and peak systolic velocities (Sa), early diastolic velocities (Ea), and late diastolic velocities (Aa) were measured. Sa and Aa velocities were both decreased significantly from 3 to 12 h and then gradually increased. Ea velocities showed no significant, longitudinal changes, but Ea values in premature groups appeared to be significantly lower than those in mature groups. The ratio of E to Ea (E/Ea) of VLBW infants seemed to be almost stable from birth to day 7, and this also showed no significant differences between different gestational age groups. E/Ea values in infants with patent ductus arteriosus (PDA) appeared to be greater than those in non-PDA infants. Our present findings suggest that TDI assessment in the early neonatal period might be useful in detecting latent systolic/diastolic failure of critically ill preterm infants.     

Internal carotid artery blood flow velocities before, during, and after extracorporeal membrane oxygenation.

Blood flow velocities in the internal carotid arteries were studied with pulsed Doppler in 25 neonatal patients (birth weight range, 2600 to 4100 g) who had extracorporeal membrane oxygenation (ECMO). Time averaged mean systolic, mean diastolic, and mean blood flow velocities were calculated. Five infants had right common carotid artery reconstruction. Blood flow velocities measured in 15 healthy full-term infants were used as controls. Findings during ECMO included the following: (1) forward flow in the right internal carotid artery in 50% of the infants; (2) significant increase in the mean diastolic and the mean flow velocities (48% and 128%, respectively) in the left internal carotid artery when compared with pre-ECMO and control infants' values; (3) the elevation in the mean and the mean diastolic velocities was associated with changes in the PaCO2 and with an increase in the diastolic blood pressure; and (4) forward blood velocities in the right internal carotid artery were comparable with blood velocities in the left internal carotid artery and with the blood velocities of control infants. After ECMO, the mean diastolic velocity in the left internal carotid artery decreased significantly, but it remained elevated when compared with pre-ECMO values. Infants with right common carotid reconstruction had blood velocities in the right internal carotid artery comparable with the simultaneous blood velocities in the left internal carotid artery and to the blood velocities of control infants. Twenty-eight percent of the infants had major neuroanatomic lesions. Right or left preponderance was not noted. No association between blood velocity values in the internal carotid arteries or flow direction and the presence or the absence of brain lesions was noted.     

Atrial natriuretic peptide in the diagnosis of patent ductus arteriosus

The aim of this study was to measure plasma atrial natriuretic peptide in preterm infants with a patent ductus arteriosus before and after closure with indomethacin. Atrial natriuretic peptide was measured in 28 preterm infants with clinical and echocardiographic evidence of a patent ductus arteriosus and in eight preterm infants who did not develop clinical evidence of a patent ductus arteriosus. Plasma concentration of atrial natriuretic peptide was measured by radioimmunoassay. In 18 infants the patent ductus arteriosus closed after one course of indomethacin; atrial natriuretic peptide levels decreased from median 1240 pg/ml (range 201-5483 pg/ml) to 266 pg/ml (range 62-1108 pg/ml). In four infants the patent ductus arteriosus closed after two courses of indomethacin and two infants had surgical ligation after indomethacin treatment failed. The patent ductus arteriosus closed spontaneously in four infants (atrial natriuretic peptide median level 152 pg/ml, range 61-495 pg/ml). In the eight infants without patent ductus arteriosus, atrial natriuretic peptide level was median 224 pg/ml (range 38-876 pg/ml). Measurement of plasma atrial natriuretic peptide concentration has a role in predicting when indomethacin treatment is indicated.     

Recovery of prostaglandin production associated with reopening of the ductus arteriosus after indomethacin treatment in preterm infants with respiratory distress syndrome

Increased PGE production has been demonstrated in 9 of 17 preterm infants with patent ductus arteriosus (PDA) associated with respiratory distress syndrome (RDS). Inhibition of PGE production in eight preterm infants with PDA and RDS was associated with marked improvement in the respiratory and circulatory function of all of them. However, in six of them this effect was only transient. In the posttreatment period of five and a half days reopening of the ductus arteriosus was frequently associated with increased PGE production and a drop of indomethacin serum levels. Three of these six infants were transferred for surgical ligation whereas the other three were successfully treated with a second course of indomethacin. However, the margin between closure of the ductus arteriosus and the deterioration of kidney function in preterm infants treated with a presently recommended indomethacin dosage was narrow. In conclusion, until an acceptable therapeutic serum level of indomethacin for ductal closure in preterm infants has been established and the duration of effective prostaglandin synthesis inhibition is known, it is too early for a general recommendation of a dosage regime of indomethacin for the pharmacological closure of PDA in infants with RDS.