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Contains fulltext : 168747.pdf (Publisher’s version ) (Open Access) Increased extravascular lung water (EVLW) may contribute to respiratory failure in neonates. Accurate measurement of EVLW in these patients is limited due to the lack of bedside methods. The aim of this pilot study was to investigate the reliability of the transpulmonary ultrasound dilution (TPUD) technique as a possible method for estimating EVLW in a neonatal animal model. Pulmonary edema was induced in 11 lambs by repeated surfactant lavages. In between the lavages, EVLW indexed by bodyweight was estimated by TPUD (EVLWItpud) and transpulmonary dye dilution (EVLWItpdd) (n = 22). Final EVLWItpud measurements were also compared with EVLWI estimations by gold standard post mortem gravimetry (EVLWIgrav) (n = 6). EVLWI was also measured in two additional lambs without pulmonary edema. Bland-Altman plots showed a mean bias between EVLWItpud and EVLWItpdd of -3.4 mL/kg (LOA +/- 25.8 mL/kg) and between EVLWItpud and EVLWIgrav of 1.7 mL/kg (LOA +/- 8.3 mL/kg). The percentage errors were 109 and 43 % respectively. The correlation between changes in EVLW measured by TPUD and TPDD was r2 = 0.22. Agreement between EVLWI measurements by TPUD and TPDD was low. Trending ability to detect changes between these two methods in EVLWI was questionable. The accuracy of EVLWItpud was good compared to the gold standard gravimetric method but the TPUD lacked precision in its current prototype. Based on these limited data, we believe that TPUD has potential for future use to estimate EVLW after adaptation of the algorithm. Larger studies are needed to support our findings.

Contains fulltext : 171928.pdf (Publisher’s version ) (Open Access) During positive pressure ventilation, arterial pressure variations, like the pulse pressure variation (PPV), are observed in neonates. However, the frequency of the PPV does not always correspond with the respiratory rate. It is hypothesized that PPV is caused by cardiopulmonary interaction, but that this mismatch is related to the low respiratory rate/heart rate ratio. Therefore, the goal of this study is to investigate the relation between PPV and ventilation in neonates. A prospective observational cross-sectional study was carried out in a third-level neonatal intensive care unit in a university hospital. Neonates on synchronized intermittent mandatory ventilation (SIMV) or high-frequency ventilation (HFV) participated in the study. The arterial blood pressure was continuously monitored in 20 neonates on SIMV and 10 neonates on HFV. In neonates on SIMV the CO2 waveform and neonates on HFV the thorax impedance waveform were continuously monitored and defined as the respiratory signal. Correlation and coherence between the respiratory signal and pulse pressure were determined. The correlation between the respiratory signal and pulse pressure was -0.64 +/- 0.18 and 0.55 +/- 0.16 and coherence at the respiratory frequency was 0.95 +/- 0.11 and 0.76 +/- 0.4 for SIMV and HFV, respectively. The arterial pressure variations observed in neonates on SIMV or HFV are related to cardiopulmonary interaction. Despite this relation, it is not likely that PPV will reliably predict fluid responsiveness in neonates due to physiological aliasing.

Contains fulltext : 108353.pdf (Publisher’s version ) (Closed access) BACKGROUND: /st> Transpulmonary ultrasound dilution (TPUD) is a promising method for cardiac output (CO) measurement in severely ill neonates. The incidence of lung injury in this population is high, which might influence CO measurement using TPUD because of altered lung perfusion. We evaluated the influence of lung injury on the accuracy and precision of CO measurement using TPUD in an animal model. METHODS: /st> In nine neonatal lambs, central venous and arterial catheters were inserted and connected to the TPUD monitor. Repeated lavages with warmed isotonic saline were performed to gradually induce lung injury. CO measurements with TPUD (COtpud) were compared with those obtained by an ultrasonic transit-time flow probe around the main pulmonary artery (COufp). An increase in oxygenation index was used as an indicator of induced lung injury during the experiment. Post-mortem lung injury was confirmed by histopathological examination. RESULTS: /st> Fifty-five sessions of three paired CO measurements were analysed. The mean COufp was 1.53 litre min(-1) (range 0.66-2.35 litre min(-1)), and the mean COtpud was 1.65 litre min(-1) (range 0.78-2.91 litre min(-1)). The mean bias (standard deviation) between the two methods was 0.13 (0.15) litre min(-1) with limits of agreement of +/-0.29 litre min(-1). The overall percentage error was 19.1%. The accuracy and precision did not change significantly during progressive lung injury. Histopathological severity scores were consistent with heterogeneous lung injury. The capability to track changes in CO using TPUD was moderate to good. CONCLUSIONS: /st> The accuracy and precision of CO measurement using TPUD is not influenced in the presence of heterogeneous lung injury in an animal model.

Background: It remains a great challenge to measure systemic blood flow in critically ill newborns. In a former study we validated the modified carbon dioxide Fick (mCO2F) method for measurement of cardiac output in a newborn lamb model. In this new study we studied the influence of a left-to-right shunt on the accuracy of the mCO2F method. Objective: To analyze the influence of a left-to-right shunt on the agreement between cardiac output measurement with the mCO2F method and ultrasonic transit time pulmonary blood flow in a lamb model. Methods: The study was approved by the Ethical Committee on Animal Research of the Radboud University Nijmegen and performed in 8 random-bred lambs. A Gore-Tex® shunt was placed between the left pulmonary artery and the descending aorta. This aortopulmonary shunt was intermittently opened and closed, while cardiac output was manipulated by creating hemorrhagic hypotension. Cardiac output measurement with the mCO2F method (QmCO2F) was compared with pulmonary blood flow obtained by a transit time ultrasonic flow probe positioned around the common pulmonary artery (QAPC). Results: Bias, defined as QmCO2F – QAPC, was calculated for each measurement. With an open shunt there was a significant left-to-right shunt (mean Qp/Qs ratio 2.26; range 1.56–3.69). Mean bias (SD) was –12.3 (50.4) ml·kg–1·min–1 and –12.3 (42.7) ml·kg–1·min–1 for measurements with a closed and open shunt, respectively (no statistical significant difference). Conclusions: Cardiac output measurement with the mCO2F method is reliable and easily applicable in ventilated newborn lambs, also in the presence of a significant left-to-right shunt.

Contains fulltext : 88270.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Analysis of cerebral and systemic hemodynamic consequences of ultrasound dilution cardiac output measurements. DESIGN: : Prospective, experimental piglet study. SETTING: Animal laboratory. SUBJECTS: Nine piglets. INTERVENTIONS: Ultrasound dilution cardiac output measurements were performed in ventilated, anesthetized piglets. Interventions that are required for ultrasound dilution cardiac output measurement were evaluated for its effect on cerebral and systemic circulation and oxygenation. MEASUREMENTS AND MAIN RESULTS: DeltacHbD and DeltactHb, representing changes in cerebral blood flow and cerebral blood volume, respectively, were measured with near infrared spectrophotometry. Pulmonary artery (Q) and left carotid artery (Q) blood flow were assessed with transit time flow probes. Starting and/or stopping blood flowing through the arteriovenous loop did not cause relevant hemodynamic changes. Fast injection of isotonic saline caused a biphasic change in DeltacHbD and DeltactHb. After injection of 0.5 mL/kg, the mean (sd) increase in DeltacHbD and DeltactHb was 0.175 (0.213) micromol/L and 0.122 (0.148) micromol/L, respectively, with a subsequent mean decrease of -0.191 (0.299) micromol/L and -0.312 (0.266) micromol/L. Injection of 1.0 mL/kg caused a mean increase in DeltacHbD and DeltactHb of 0.237 (0.203) micromol/L and 0.179 (0.162) followed by a mean decrease of -0.334 (0.407) micromol/L and -0.523 (0.335) micromol/L, respectively. Q and Q changed shortly with a mean increase of 5.9 (3.0) mL/kg/min and 0.23 (0.10) mL/kg/min after injection of 0.5 mL/kg and with 12.0 (4.2) mL/kg/min and 0.44 (0.18) mL/kg/min after injection of 1.0 mL/kg, respectively. The observed changes were more profound after an injection volume of 1.0 mL/kg compared with 0.5 mL/kg for DeltacHbD (p = .06), DeltactHb (p = .09), Q, and Q (p < .01). No relevant changes in mean arterial blood pressure or heart rate were detected in response to the indicator injection. CONCLUSIONS: Cardiac output measurement by ultrasound dilution does not cause clinically relevant changes in cerebral and systemic circulation and oxygenation in a piglet model. 01 september 2010

Contains fulltext : 69467.pdf (Publisher’s version ) (Closed access) OBJECTIVE: This study was undertaken to validate the transpulmonary thermodilution cardiac output measurement (CO(TPTD)) in a controlled newborn animal model under various hemodynamic conditions with special emphasis on low cardiac output. DESIGN: Prospective, experimental, pediatric animal study. SETTING: Animal laboratory of a university hospital. SUBJECTS: Twelve lambs. INTERVENTIONS: We studied 12 lambs under various hemodynamic conditions. Cardiac output was measured using the transpulmonary thermodilution technique with central venous injections of ice-cold saline. An ultrasound transit time perivascular flow probe around the main pulmonary artery served as the standard reference measurement (CO(UFP)). During the experiment, animals were resuscitated from hemodynamic shock using fluid boluses. Cardiac output measurements were performed throughout the experiment. MEASUREMENTS AND MAIN RESULTS: The correlation coefficient between CO(TPTD) and CO(UFP)was .97 (95% confidence interval .94-.98, p < .0001). Bland-Altman analysis showed a mean bias of 0.19 L/min with limits of agreement of -0.04 and 0.43 L/min (12.0% and +/-14.7%, respectively). The correlation coefficient between changes in CO(TPTD) and CO(UFP) during volume loading was .95 (95% confidence interval .91-.96, p < .0001). There was a significant correlation between changes in global end-diastolic volume and changes in stroke volume (r = .59) but not between changes in central venous pressure and changes in stroke volume (r = .03). CONCLUSIONS: The transpulmonary thermodilution technique is a reliable method of measuring cardiac output in newborn animals. It is also capable of tracking changes in cardiac output.

Objectives: We investigated the accuracy of left-to-right shunt detection using transpulmonary ultrasound dilution (TPUD) and compared the agreement between pulmonary over systemic blood flow (Qp/Qs) ratio measured by TPUD [Qp/Qs(tpud)] and ultrasonic flow probes [Qp/Qs(ufp)]. Methods: Seven newborn lambs under general anesthesia were connected to the TPUD monitor (COstatus™) after insertion of arterial and central venous catheters. A Gore-Tex® shunt, inserted between the descending aorta and left pulmonary artery, was intermittently opened and closed while cardiac output was varied by blood withdrawals. Flow probes were placed around the main pulmonary artery (Qufp) and the descending aorta proximal (Qpre) and distal (Qpost) to the shunt insertion. Qp/Qs(ufp) was calculated as (Qufp+Qpre–Qpost)/Qufp. Results: Seventy-two paired measurement sessions were analyzed. Shunts were detected by TPUD with a positive predictive value of 86%, a negative predictive value of 100%, a sensitivity of 100% and a specificity of 83%. The Bland-Altman analysis comparing Qp/Qs(tpud) and Qp/Qs(ufp) showed an overall mean bias (SD) of 0.1 (0.3), limits of agreement (LOA) of ±0.6 and a percentage error of 34.8%. Conclusions: The qualitative diagnostic accuracy of TPUD for shunt detection is high. Modification of the algorithm seems required as shunt quantification by TPUD is accurate, but not yet very precise.

Background: Insufficient cerebral O2 supply leads to cellular energy failure and loss of brain cell function. The relationship between the severity of cellular energy failure due to hemorrhagic hypotension and the loss of electrocortical brain activity (ECBA), as a measure of brain cell function, is not yet fully elucidated in near-term born lambs. Objectives: To study the relationship between cerebral purine and pyrimidine metabolism, as a measure of brain cell energy failure, and brain cell function after hemorrhagic hypotension in near-term born lambs. Methods: Eight near-term lambs (term 147 days) were delivered at 131 days of gestation. After a stabilization period, mean arterial blood pressure was reduced till 30% of baseline by withdrawal of blood. Cerebrospinal fluid (CSF) was obtained at the end of the hypotensive period (2.5 h). CSF from 8 siblings was used for comparison. HPLC was used to determine purine and pyrimidine metabolites in CSF, as a measure of cellular energy failure. ECBA was calculated as the root mean square value of a band-filtered (2–16 Hz) one-channel EEG. Results: Values of guanosine, inosine, hypoxanthine, xanthine and uridine were significantly higher, while ECBA was significantly lower after hemorrhagic hypotension than control values. The concentrations of inosine, hypoxanthine, xanthine and uridine were significantly negatively linearly related to ECBA. Conclusions: Brain cell function is negatively related to concentrations of inosine, hypoxanthine, xanthine and uridine in the CSF after hemorrhagic hypotension in near-term born lambs.

Item does not contain fulltext The fetal brain develops rapidly during the last trimester of pregnancy. Therefore, the brain of infants who are born preterm is vulnerable to changes in oxygen and nutrient supply in the neonatal period. The objective was to determine the effect of gestational age (GA) on the cerebral O2 supply threshold level for preservation of brain function during hypotension in near-term-born lambs. Lambs were delivered at 141 or 127 d of gestation. Hypotension was induced by stepwise withdrawal of blood. Mean arterial blood pressure (MABP) baseline levels were 63.2 (6.4) in 141-d and 54.4 (15.5) mm Hg in 127-d lambs. The MABP threshold below which MABP and blood flow in the left carotid artery were linearly related was 36.1 (13.1) mm Hg in 141-d lambs. In 127-d lambs, MABP and blood flow in the left carotid artery were linearly related over the whole range of recorded MABP values. Electrocortical brain activity (ECBA) was used as a measure of brain function. Thresholds of MABP for maintenance of ECBA were reached at, respectively, 31.6% (4.9%) of baseline in 141-d and 61.9% (13.0%) of baseline MABP in 127-d lambs. However, thresholds of cerebral O2 supply for maintenance of ECBA were similar in both GA groups. We conclude that thresholds of cerebral O2 supply for maintenance of brain cell function are independent of GA but are reached at higher MABP levels in 127-d than in 141-d lambs and therefore places the sick preterm infant easily at risk for ischemic cerebral injury.

Objectives: in vitro assessment of the reproducibility and the optimal separation and position of the optodes in continuous wave (CW-) NIRS measurement of local inhomogeneities in absorption and/or scattering. Methods: a CW- NIRS system (OXYMON) was used with laser diodes at wavelengths of 767 nm, 845 nm, 905 nm, 945 nm and 975 nm. For practical considerations (dimensions of neonatal head) the measurements were performed on a cylindrical tissue-equivalent phantom (70 mm diameter of base material with µa = 0.01 mm-1 (800 nm) and µ's = 1.00 mm-1 (800 nm)), containing rods with 10 × absorption, or 10 × scattering, and 5 × both Monte Carlo simulations were carried out of a cylinder with transport scattering coefficient µ'e = 0.525 mm-1 and absorption coefficient µa = 0.075 mm-1 and two optode positions. Results: reproducibility of repeated measurements (n = 10) was ± 0.005 OD. Maximum OD in case of absorbing rod, and of absorbing + scattering rod was measured with optodes separated by 90° and rod position angle symmetrically (45°) in between. Minimum OD for these rods was obtained with optodes at 150° angle and rod position at 240° (i.e. relative to transmitting optode position at 0°). A second maximum OD was obtained at an optode angle 180° and rod position at 180°. Maximum OD (i.e. attenuation) for the scattering rod was at optode separation angle of 90° and rod at 0°. Minimum OD for this case was obtained with optode angle of 180° and rod positions around 80° and 280°. Maximum OD changes by absorbing rod were in the order of + 0.12 OD and -0.04 OD, respectively. Simulations at an optode separation angle of 90° showed a spatial sensitivity path enclosing the rod position at maximum absorption found experimentally. Conclusions: when considering the phantom as a realistic geometrical model for the neonatal head, it can be concluded that the optode position at 90° angle would be optimal for detecting an inhomogeneity at 15 mm depth, i.e. the location of the periventricular white matter. Since the rods are relatively strongly different from the base material the question remains to be answered whether local ischemia, which might lead to irreversible brain damage, can be detected by CW-NIRS.

Item does not contain fulltext Adequate cerebral perfusion is necessary to preserve cerebral O(2) supply in order to maintain brain cell function. Our aim was to assess the influence of gestational age on the response of cerebral hemodynamics to hypoxemia and to determine thresholds of cerebral O(2) supply for preservation of brain cell function in preterm born lambs. Lambs were delivered by hysterotomy at 141 (n=5), 134 (n=5) or 127 (n=7) days of gestation. Decreases in arterial oxygen content (CaO(2)) were induced by stepwise reduction of the fraction of O(2) in inspired air (FiO(2)). Mean arterial blood pressure (MABP), carotid artery blood flow (Qcar), and electrocortical brain activity as a measure of brain cell function, were continuously recorded. Cerebral arterial blood gases were analyzed at the end of each hypoxemic level to calculate CaO(2) and cerebral O(2) supply. In contrast to 141-day lambs, MABP could not be maintained in 134-day and 127-day lambs at levels of severe hypoxemia. Increases in Qcar were observed at levels of moderate hypoxemia in all gestational age-groups. Albeit Qcar increased further at levels of severe hypoxemia in the 141-day lambs, Qcar declined under these conditions in the 134-day and 127-day lambs. The threshold of cerebral O(2) supply for the preservation of brain cell function was however similar in all gestational age-groups (1.7 ml/min). It is concluded that the ability to maintain cerebral function during hypoxemia depends upon the ability to preserve cerebral O(2) supply by means of cerebral hemodynamic compensatory mechanisms, which are not fully matured until 96% of gestation.

Contains fulltext : 152964.pdf (Publisher’s version ) (Closed access) To analyze changes in cardiac output and hemodynamic volumes using transpulmonary ultrasound dilution (TPUD) in a neonatal animal model under different hemodynamic conditions. 7 lambs (3.5-8.3 kg) under general anesthesia received arterial and central venous catheters. A Gore-Tex((R)) shunt was surgically inserted between the descending aorta and the left pulmonary artery to mimic a patent ductus arteriosus. After shunt opening and closure, induced hemorrhagic hypotension (by repetitive blood withdrawals) and repetitive volume challenges, the following parameters were assessed using TPUD: cardiac output, active circulating volume index (ACVI), central blood volume index (CBVI) and total end-diastolic volume index (TEDVI). 27 measurement sessions were analyzed. After shunt opening, there was a significant increase in TEDVI and a significant decrease in cardiac output with minimal change in CBVI and ACVI. With shunt closure, these results reversed. After progressive hemorrhage, cardiac output and all volumes decreased significantly, except for ACVI. Following repetitive volume resuscitation, cardiac output increased and all hemodynamic volumes increased significantly. Correlations between changes in COufp and changes in hemodynamic volumes (ACVI 0.83; CBVI 0.84 and TEDVI 0.78 respectively) were (slightly) better than between changes in COufp and changes in heart rate (0.44) and central venous pressure (0.7). Changes in hemodynamic volumes using TPUD were as expected under different conditions. Hemodynamic volumetry using TPUD might be a promising technique that has the potential to improve the assessment and interpretation of the hemodynamic status in critically ill newborns and children.

Objective : This study was meant to obtain insight in the inter- and intra-individual range of neonatal cerebral blood flow velocity and the factors which determine this range. Methods : The blood flow velocity in the internal carotid artery was followed during 5 days in fourteen healthy, appropriate for date preterm newborns, using Doppler ultrasound. Results : It was found that cerebral blood flow velocity varies more between than within the infants, and that this is partially attributable to an inverse relation between cerebral blood flow velocity and weight-for-gestational-age, and a positive relation between cerebral blood flow velocity and postnatal age. The relation with postnatal age could be explained in part by closure of the ductus arteriosus. The effects of weight-for-gestational-age and patent ductus arteriosus were greater for end-diastolic than for peak-systolic velocity. Postnatal age showed an opposite effect. Conclusion : Thus, weight-for-gestational-age, postnatal age and patent ductus arteriosus contribute to the inter-and intra-individual variation of cerebral blood flow velocity.

Objective. To investigate the cerebrovascular response to changes in arterial CO2 tension during extracorporeal membrane oxygenation (ECMO) in normoxaemic and hypoxaemic piglets. Methods. Four groups of six anaesthetized, paralysed and mechanically ventilated piglets: group 1 - normoxaemia without ECMO, group 2 - ECMO after normoxaemia, group 3 - hypoxaemia without ECMO, and group 4 -ECMO after hypoxaemia, were exposed successively to hypercapnia and hypocapnia. Changes in cerebral concentrations of oxyhaemoglob in (cO2Hb), deoxyhaemoglobin (cHHb), (oxidized - reduced) cytochrome aa3 (cCyt. aa3) and blood volume (CBV) were continuously measured using near infrared spectrophotometry. Heart rate, arterial O2 saturation, arterial blood pressure, central venous pressure, intracranial pressure (ICP) and left common carotid artery blood flow (LCaBF) were measured simultaneously. Results. Hypercapnia resulted in increased CBV, cO2Hb and ICP in all groups, while cHHb was decreased. No changes in LCaBF were found. Hypocapnia resulted in decreased cO2Hb and increased cHHb except in group 3. LCaBF decreased in all groups except group 2. CBV decreased only in groups 2 and 4. No effect on ICP was observed in any of the groups. The other variables showed no important changes either during hypercapnia or hypocapnia. ECMO after hypoxaemia resulted in a greater response of cO2Hb and cHHb during hypocapnia. The effect of hypercapnia on CBV while on ECMO was greater than without ECMO. Conclusion. Since cerebrovascular reactivity to CO2 remains intact during ECMO in piglets, it is important to keep arterial CO2 tension stable and in normal range during clinical ECMO.

The purpose of this study was to investigate whether the preference of periventricular hemorrhage (PVH) for the left hemisphere is due to asymmetry of cerebral blood flow (CBF) and, if so, whether this asymmetry is due to patent ductus arteriosus (PDA). Thirty-three preterm newborns at risk for PVH were followed during their first 5 days after birth. Internal carotid CBF velocity (CBFV) and the flow direction in the common pulmonary artery, both determined by ultrasound Doppler, served as measures of CBF and PDA, respectively. The difference between right and left CBFV was analyzed statistically, with outcome, PDA, capillary Pco 2 , behavior, heart rate, and the average of right and left CBFV as covariates. Infants who developed PVH (n = 7) exhibited CBFV asymmetry to the disadvantage of the left side. This finding was partially attributable to PDA. Without PVH there was no significant CBFV asymmetry. Because all hemorrhages were bilateral, a relationship with the side of the hemorrhage could not be explored. In conclusion, asymmetry of CBFV is not normal, but is associated with PVH and PDA.

The effect of interruption of positive end expiratory pressure (PEEP) on cerebral blood flow velocity (CBFV) and CBF fluctuation (CBFF) in the internal carotid arteries and on heart rate, restlessness and wakefulness has been studied in 17 mechanically ventilated neonates with RDS. A decrease in CBFV was found, but no significant change in CBFF. Multiple regression analysis showed that the decrease in CBFV is less pronounced if the PEEP interruption is accompanied by restlessness. It further appeared that the decrease in CBFV is more pronounced if CBFV is high, the ductus arteriosus is patent, or RDS follows a complicated course. These findings indicate that PEEP supports CBF, probably by a decrease in ductal stealing from the brain. Therewith PEEP protects against cerebral hypoperfusion which is one of the major risks in RDS and immaturity. Furthermore, our findings suggest that the decrease in CBF during PEEP interruption is moderated by restlessness and accentuated by brain damage.

Contains fulltext : 110488.pdf (Publisher’s version ) (Closed access) BACKGROUND: Cardiac output (CO) monitoring remains complex in newborns as most of the current technologies fail to accurately measure systemic blood flow in the presence of shunts. We validated CO measurements using transpulmonary ultrasound dilution (TPUD) in a neonatal lamb model with a left-to-right shunt. METHODS: Regular arterial and central venous catheters were inserted into seven lambs (3.5-8.3 kg). A surgically constructed left-to-right aorto-pulmonary Gore-Tex((R)) shunt was intermittently opened and closed, while CO was manipulated by creating haemorrhagic hypotension. CO measurements with TPUD (COtpud) were compared with those obtained by an ultrasonic transit-time flow probe positioned around the main pulmonary artery (COufp). RESULTS: We performed 72 sessions of three paired CO measurements. The mean COufp was 1.00 litre min(-1) (range 0.47-1.75 litre min(-1)) and mean COtpud 1.05 litre min(-1) (range 0.54-1.87 litre min(-1)). With an open shunt, the mean Qp/Qs ratio was 1.8 (range 1.3-2.6). A comparison between COufp and COtpud showed a mean bias (sd) of 0.03 (0.09) and 0.07 (0.10) litre min(-1), respectively, for measurements with a closed and an open shunt. The percentage error was 18% and 20% for measurements with a closed and an open shunt. Polar plot analysis showed good trending ability for both closed and open shunt groups. CONCLUSIONS: TPUD is a reliable technology to measure CO in the presence of a left-to-right shunt. 01 maart 2012

The influence of maturation, sleep state and respiration on heart rate variability was studied in 16 spontaneously breathing preterm infants (< 33 weeks). ECG, respiratory impedance curve and movements were recorded four times a day, during the first three days of life. The power content of selected frequency bands of the R-R interval power spectrum, as well as respiratory frequency and breath amplitude oscillation frequency, were calculated for 3-min periods. An increase in low-frequency heart rate variability with gestational age was found. High-frequency variability increased during early postnatal life. Sleep state influenced very low-frequency heart rate variability. The amount of respiratory sinus arrhythmia and breath amplitude sinus arrhythmia was determined mainly by respiratory rate and breath amplitude oscillation frequency, respectively. The influences of gestational and postnatal age on heart rate variability might be due to an increase in sympathetic tone before birth and a change in parasympathetic-sympathetic balance after birth. Respiration has an important influence on heart rate variability, even in very preterm infants.

Item does not contain fulltext BACKGROUND: The transpulmonary thermodilution (TPTD) technique for measuring cardiac output (CO) has never been validated in the presence of a left-to-right shunt. METHODS: In this experimental, paediatric animal model, nine lambs with a surgically constructed aorta-pulmonary left-to-right shunt were studied under various haemodynamic conditions. CO was measured with closed and open shunt using the TPTD technique (CO(TPTD)) with central venous injections of ice-cold saline. An ultrasound transit time perivascular flow probe around the main pulmonary artery served as the standard reference measurement (CO(MPA)). RESULTS: Seven lambs were eligible for further analysis. Mean (sd) weight was 6.6 (1.6) kg. The mean CO(MPA) was 1.21 litre min(-1) (range 0.61-2.06 l min(-1)) with closed shunt and 0.93 litre min(-1) (range 0.48-1.45 litre min(-1)) with open shunt. The open shunt resulted in a mean Q(p)/Q(s) ratio of 1.8 (range 1.6-2.4). The bias between the two CO methods was 0.17 litre min(-1) [limits of agreement (LOA) of 0.27 litre min(-1)] with closed shunt and 0.14 litre min(-1) (LOA of 0.32 litre min(-1)) with open shunt. The percentage errors were 22% with closed shunt and 34% with open shunt. The correlation (r) between the two methods was 0.93 (P

Contains fulltext : 88152.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To assess agreement between a new method of cardiac output monitoring, using ultrasound dilution technology and ultrasound transit time-based measurement of pulmonary blood flow in a piglet model. DESIGN: Prospective, experimental juvenile animal study. SETTING: Animal laboratory of a university hospital. SUBJECTS: Nine random-bred piglets. INTERVENTIONS: After the animals received general anesthesia, we placed intravascular arterial and central venous catheters with the tip positioned in the abdominal aorta and the right atrium, respectively. The catheters were connected to the ultrasound dilution cardiac output monitor. An ultrasound transit time perivascular flow probe was positioned around the common pulmonary artery and served as the standard reference measurement. Cardiac output was manipulated during the experiment by creating hemorrhagic hypotension. Ultrasound dilution cardiac output was measured intermittently with injection volumes of 0.5 mL/kg and 1.0 mL/kg of isotonic saline at body temperature. MEASUREMENTS AND MAIN RESULTS: Ultrasound dilution cardiac output (Q) measurement was compared with pulmonary blood flow (Q). Bias, defined as Q minus Q, was calculated for each measurement. Mean bias with standard deviation was calculated for measurements with volumes of injected saline, 0.5 mL/kg and 1.0 mL/kg, and compared using the Mann-Whitney U test. Mean bias (sd) between Q and Q was 0.040 (0.132) and 0.058 (0.136) L/min for measurement with 0.5 mL/kg and 1.0 mL/kg of isotonic saline, respectively (no statistically significant difference). CONCLUSIONS: Ultrasound dilution cardiac output measurement is reliable in piglets with the use of a small volume of a nontoxic indicator (isotonic saline). 01 januari 2010

For adequate development and functioning of the neonatal brain, sufficient oxygen (O2) should be available. With a fast sampling (f(s) > 50 Hz) continuous wave NIRS device, arterial (SaO2) and venous (SvO2) saturation can be measured using the physiological fluctuations in the oxyhemoglobin (O2Hb) and total hemoglobin (tHb) concentrations due to heart action and respiration. Before using this technique in a neonatal setting, the method was verified on adult volunteers (n=7) by decreasing inspired oxygen down to an arterial saturation of 70% using a pulse oximeter as reference. NIRS optodes were placed on the left forehead; the pulse oximeter sensor was placed on the right forehead. The experiments were repeated with different optode spacings. SaO2 and SvO2 were determined using the ratio between the O2Hb and tHb value in the amplitude spectrum at the heart rate and respiration rate, respectively. A good agreement between calculated SaO2 and reference SaO2 from pulse oximetry was found (bias range -3.5% to 5.2%, SD of the residuals 1.3% to 3.5%). Optode spacing of 15 mm yielded a negative bias compared to optode spacing of 45 mm. It was not always possible to calculate SvO2 because the respiration peak could not always be detected.

To investigate the influence of maturational and physiological factors on heart rate variability in spontaneously breathing very preterm infants (n = 29) a multiparametric study was performed during the first 3 days of life in infants born at a gestational age below 33 weeks. Four times a day, RR-intervals, respiration curve and rate, transcutaneously measured blood gases and observed body movements were recorded while the infants were asleep. All data were stored simultaneously in a micro-computer. Non-invasively measured blood pressure and patency of the ductus arteriosus were documented as well. Four sets of short- (STV) and long term variability (LTV) indices were calculated. Both STV and LTV appeared to be significantly influenced by conceptional and postnatal age in the appropriate for gestational age infants. LTV was influenced by the behavioural state and body movements. During state coincidence 2 ('active sleep') LTV was influenced by respiratory rate and the variations in transcutaneous PO2. An effect of blood pressure or ductus patency could not be demonstrated.

Measurement of cardiac output within the great arteries of infants by non-invasive Doppler echocardiographic techniques is limited. This paper describes a simple method, based on dual beam Doppler, that is capable of measuring the pulmonary and systemic blood flows independently of the vessel diameter and beam-blood flow angle. In 27 babies (12 of them were premature born) without intracardial shunts the accuracy of this method in measuring cardiac output was evaluated. The mean difference between pulmonary and systemic blood flow measurements was 0.02 (SD 0.06) l min−1. This study demonstrates a good agreement between the pulmonary and systemic blood flow measurements using dual beam Doppler ultrasound in babies.

Continuous wave Near Infrared Spectroscopy is a well known non invasive technique for measuring changes in tissue oxygenation. Absorption changes (DO2Hb and DHHb) are calculated from the light attenuations using the modified Lambert Beer equation. Generally, the concentration changes are calculated relative to the concentration at a starting point in time (delta time method). It is also possible, under certain assumptions, to calculate the concentrations by subtracting the equations at different wavelengths (delta wavelength method). We derived a new algorithm and will show the possibilities and limitations. In the delta wavelength method, the assumption is that the oxygen independent attenuation term will be eliminated from the formula even if its value changes in time, we verified the results with the classical delta time method using extinction coefficients from different literature sources for the wavelengths 767nm, 850nm and 905nm. The different methods of calculating concentration changes were applied to the data collected from animal experiments. The animals (lambs) were in a stable normoxic condition; stepwise they were made hypoxic and thereafter they returned to normoxic condition. The two algorithms were also applied for measuring two dimensional blood oxygen saturation changes in human skin tissue. The different oxygen saturation levels were induced by alterations in the respiration and by temporary arm clamping. The new delta wavelength method yielded in a steady state measurement the same changes in oxy and deoxy hemoglobin as the classical delta time method. The advantage of the new method is the independence of eventual variation of the oxygen independent attenuations in time.

Contains fulltext : 80099.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To evaluate whether application of a transducer on the anterior fontanelle during cranial ultrasound (US) examination effects cerebral hemodynamics and oxygenation in preterm infants. STUDY DESIGN*: During cranial US examination, changes in cerebral blood oxygenation (cHbD) and cerebral blood volume (CBV) were assessed using near infrared spectrophotometry (NIRS) in 76 infants (GA 30.7 (4.1)wk, BW 1423 (717)g) within two days after birth. Ten of these infants (GA 29.1 (1.6)wk, BW 1092 (455)g) were studied again at a postnatal age of one week. RESULTS*: We obtained stable and consistent NIRS registrations in 54 infants within the first two days after birth. Twenty-eight of these infants showed a decrease in cHbD (0.59 (0.54) micromol/100g) during the scanning procedure while CBV did not change. Twenty-four infants showed no changes in NIRS and 2 infants showed an atypical NIRS response during cranial US examination. At the postnatal age of one week, stable and consistent NIRS registrations were obtained in 7 infants. None of these infants showed changes in NIRS variables during cranial US examination. CONCLUSIONS: Application of an US transducer on the anterior fontanelle causes changes in cerebral oxygenation and hemodynamics in a substantial number of preterm infants. ( *values are expressed as median (interquartile range)).

Contains fulltext : 53100.pdf (Publisher’s version ) (Closed access) The aim of our study was to assess consecutive changes in cerebral oxygenation and hemodynamics after serial cerebrospinal fluid (CSF) drainage from a subcutaneous ventricular catheter reservoir (SVCR) in infants with PHVD. Infants with PHVD were studied during CSF drainage from a SVCR on the day of SVCR placement, half a week and one week after SVCR placement. Changes in cHbD and CBV were assessed using near infrared spectrophotometry. Time averaged peak flow velocity (TAPFV), end diastolic flow velocity (EDFV), peak systolic flow velocity (PSFV) and pulsatility index (PI) were measured before (baseline) and after CSF drainage using Doppler ultrasound. Longitudinal data analysis was performed using linear mixed models. Seven patients (GA 26.7-40.4 weeks, BW 800-4575 g) were studied. CSF drainage resulted in a statistically significant increase in CBV during each measurement. The change in CBV was maximal on the day of SVCR placement. A significant increase in cHbD and EDFV, and decrease in PI was observed after CSF drainage only on the day of SVCR placement. Baseline values of all Doppler variables improved consecutively after serial CSF removal in the first week after SVCR placement. Frequent CSF drainage results in consecutive improvement of cerebral perfusion and oxygenation in infants with PHVD.

Contains fulltext : 52992.pdf (Publisher’s version ) (Closed access) Cardiac output can be measured using a modified carbon dioxide Fick (mCO2F) method. A validation study was performed comparing mCO2F method-derived cardiac output (Q(mCO2F)) with invasively measured pulmonary blood flow. In seven randomly bred ventilated newborn lambs, cardiac output was manipulated by creating hemorrhagic hypotension. When steady state was reached, Q(mCO2F) was measured. Gas analysis was performed in simultaneously obtained arterial and venous blood samples (right atrium [RA], superior vena cava [SVC], and inferior vena cava [IVC]). Carbon dioxide exchange and pulmonary blood flow was measured continuously using a CO2SMO Plus monitor and a pulmonary ultrasonic flow probe (Q), respectively. Mean bias, defined as Q(mCO2F) - Q(ufp), was small (respectively, -0.082 L.min, -0.085 Lx min(-1) and -0.183 Lxmin(-1) for venous sampling from RA, SVC, and IVC). The limits of agreement were -0.328 to 0.164 Lxmin(-1) (RA), -0.335 to 0.165 Lxmin(-1) (SVC), and 0.415 to 0.049 Lxmin(-1) (IVC). In conclusion, measurement of cardiac output with the mCO2F method is reliable and easily applicable in ventilated newborn lambs. For clinical use, the site of venous blood sampling is of minor importance.

Contains fulltext : 49871.pdf (Publisher’s version ) (Closed access) Hypotension reduces cerebral O(2) supply, which may result in brain cell damage and loss of brain cell function in the near-term neonate. The aim is to elucidate 1) to what extent the functional disturbance of the cerebral cortex, as measured with electrocortical brain activity (ECBA), is related to cerebral cortical tissue damage, as estimated by MAP2; and 2) whether there is a relationship between the glutamate, nitric oxide (NO), cGMP pathway and the development of cerebral cortical tissue damage after hemorrhagic hypotension. Seven lambs were delivered at 131 d of gestation. Hypotension was induced by withdrawal of blood until mean arterial blood pressure was reduced to 30% of normotension. Cerebral O(2) supply, consumption, and ECBA were calculated in normotensive conditions and after 2.5 h of hypotension. Concentrations of glutamate and aspartate in cerebrospinal fluid (CSF), NO(2) and NO(3) (NOx) in plasma, and cGMP in cortical brain tissue were determined in both conditions. CSF and brain tissue from siblings were used to determine normotensive values. Cortical neuronal damage was detected after 2.5 h of hypotension. ECBA was negatively related to the severity of the cortical damage. ECBA was related to respectively glutamate, NOx, and cGMP concentrations. In conclusion, cortical neuronal damage is detected after 2.5 h of hemorrhagic hypotension in the near-term born lamb. The damage is reflected by a reduction of ECBA. The glutamate, NOx, cGMP pathway is likely to be involved in the pathogenesis of cerebral cortical damage.

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.

The influence of skin on the bias and reproducibility of regional cerebral oxygenation measurements is investigated using cw near-infrared spectroscopy (NIRS). Receiving optodes are placed over the left and right hemispheres of a piglet (C3, C4 EEG placement code) and one transmitting optode centrally (Cz position). Optical densities (OD) are measured during stable normo, mild, and deep hypoxemia. This is done for skin condition 1: all optodes on the skin; skin condition 2: transmitting optode on the skin and one receiving optode on the skull; and skin condition 3: all optodes on the skull. Absolute changes of oxy- (cO2Hb), deoxyhemoglobin (cHHb), and total hemoglobin (ctHb) concentrations [micromolL] are calculated from the ODs. These absolute changes are calculated for each skin condition with respect to normoxic condition. Additionally, for skin condition 2, the difference of concentration changes between receiver 1 (skull) and receiver 2 (skin) is calculated. The effect of skin removal is an average increase of attenuation changes by a factor of 1.66 (=0.51 OD) and of the concentration changes due to the arterial oxygen saturation steps by 23%. We conclude that skin significantly influences regional oxygenation measurements. Nevertheless, it is hypothesized that the estimated concentration changes are dominated by changes of the oxygenation in the brain.

Background: Midazolam sedation and morphine analgesia are commonly used in ventilated premature infants. Objectives: To evaluate the effects of midazolam versus morphine infusion on cerebral oxygenation and hemodynamics in ventilated premature infants. Methods: 11 patients (GA 26.6–33.0 weeks, BW 780–2,335 g) were sedated with midazolam (loading dose 0.2 mg/kg, maintenance 0.2 mg/kg/h) and 10 patients (GA 26.4–33.3 weeks, BW 842–1,955 g) were sedated with morphine (loading dose 0.05 mg/kg, maintenance 0.01 mg/kg/h). Changes in oxyhemoglobin (ΔcO2Hb) and deoxyhemoglobin (ΔcHHb) were assessed using near infrared spectrophotometry. Changes in cHbD (= ΔcO2Hb – ΔcHHb) reflect changes in cerebral blood oxygenation and changes in concentration of total hemoglobin (ΔctHb = ΔcO2Hb + ΔcHHb) represent changes in cerebral blood volume (ΔCBV). Changes in cerebral blood flow velocity (ΔCBFV) were intermittently measured using Doppler ultrasound. Heart rate (HR), mean arterial blood pressure (MABP), arterial oxygen saturation (saO2) and transcutaneous measured pO2 (tcpO2) and pCO2 (tcpCO2) were continuously registered. Statistical analyses were carried out using linear mixed models to account for the longitudinal character study design. Results: Within 15 min after the loading dose of midazolam, a decrease in saO2, tcpO2 and cHbD was observed in 5/11 infants. In addition, a fall in MABP and CBFV was observed 15 min after midazolam administration. Immediately after morphine infusion a decrease in saO2, tcpO2 and cHbD was observed in 6/10 infants. Furthermore, morphine infusion resulted in a persistent increase in CBV. Conclusions: Administration of midazolam and morphine in ventilated premature infants causes significant changes in cerebral oxygenation and hemodynamics, which might be harmful.

Background: Energy failure due to insufficient cerebral O2-supply leads to excess accumulation of calcium ions in presynaptic neurons, followed by excess release of excitatory amino acids, which are potent neurotoxins, into the synaptic cleft. Aim:To investigate whether electrocortical brain activity (ECBA) can provide an adequate measure for excitatory amino acid release due to hemorrhagic hypotension. Methods: Ten near-term lambs were delivered at 127 days of gestation (term: 147 days). After a stabilization period, hypotension was induced by stepwise withdrawal of blood. Cerebral microdialysis was used to measure the concentrations of glutamate and aspartate. Results:During hypotension, mean arterial blood pressure, cerebral O2-supply and ECBA decreased and the extracellular concentration of glutamate increased significantly. ECBA was significantly related to glutamate (R2: 0.67, p < 0.001) and aspartate (R2: 0.57, p < 0.001) concentrations. Conclusion:The extracellular release of glutamate and aspartate in the cerebral cortex increases after hemorrhagic hypotension in near-term born lambs. The extracellular overflow of glutamate and aspartate were significantly inversely related to ECBA.

Contains fulltext : 48350thijssen.pdf (Publisher’s version ) (Closed access) The objective of this study is to correlate regional cerebral blood concentration measurements made with near infrared spectroscopy to simultaneous local measurements of ultrasound contrast agent (CA) densitometry. Experiments were performed with piglets (7 kg) under general anesthesia. The cerebral blood flow (CBF) and volume (CBV) were changed by inducing various degrees of hypercapnia. NIRS measurements were performed with a quasi-continuous wave system, using an optode distance of 3-6 cm. The concentration changes in oxygenated and deoxygenated hemoglobin and their sum and difference (cO2Hb, cHHb, ctHb, cHbD) were continuously calculated. Ultrasound contrast agent (SF6) was administered as a short intra-venous bolus. Ultrasound equipment was used in pulse inversion second harmonic gray scale imaging mode at low transmit power setting. Three regions-of-interest (0.25 cm2) were analyzed in each image. Wash-in curves were constructed as spatial mean gray level vs. time. The variables collected with both methods changed according to the induced changes in the physiological condition. Changes in the PaCO2, pH and carotid flow induced highly correlated changes in cO2Hb, cHHb, ctHb and cHbD, and in the variables derived from CA analyses. NIRS and CA methods measure regional, respectively, local changes in CBV and CBF. Moreover, NIRS can yield complementary information about the cerebral oxygenation.

Goal: To investigate the influence of skin on the accuracy and precision of regional cerebral oxygenation measurements using CW-NIRS and to reduce the inter individual variability of NIRS measurements by normalization with data from an extra wavelength. Method: Three piglets (7.8-9.3 kg) were anesthetized, paralyzed and mechanically ventilated. Receiving optodes were placed over the left and right hemisphere (C3, C4 EEG placement code) and one emitting optode on C z position (optode distance=1.8cm). Optical densities (OD) were measured for 3 wavelengths (767, 850, 905 nm) (OXYMON) during stable normoxic, mild and deep hypoxemic conditions (SaO 2 =100%, 80% and 60%) of one minute in each region. This was repeated 3 times: all optodes with skin (condition 1); one receiving optode directly on the skull (2); emitting and also receiving optode on the skull (3). The absolute cO 2 Hb, cHHb, ctHb concentrations (μmol/L) were calculated from the OD's and changes with respect to the SaO 2 =100% condition were estimated. Because ODs varied over a large range, the light intensity was externally attenuated to adapt to the range of the spectrophotometer. The data were then corrected for these attenuation effects and for pathlength changes caused by skin removal using the OD at the independent wavelength (λ=975nm). Results: Removal of the skin resulted in an increase of the absorption values (average 0.25 OD in condition 2 and 0.42 OD in condition 3 with respect to condition 1). The change from normoxic to medium, and to deep hypoxic conditions produced a decrease of cO2Hb (-15, and -29 μmol/L, respectively), an increase in cHHb (+16, and +35 μmol/L) and in ctHb (+1, and +5 μmol/L). Total skin removal yielded an extra change in cO 2 Hb (-5, -1 μmol/L), cHHb (+8, +9 μmol/L), and ctHb (+3, +8 μmol /L). The coefficient of variability of the absolute concentration changes was considerably decreased by the normalization of densities by the density obtained at 795 nm. Conclusion: Skin and subcutaneous layers influence the regional oxygenation measurements but the estimated concentration changes are dominated by changes of the oxygenation levels in the brain. Inter individual variability can be considerably reduced by the normalization.

Background: Sufficient O2 supply to the brain is necessary for adequate cerebral energy metabolism, function and growth. Objectives: To elucidate the relation between changes in cerebral arterial O2 content and cerebral O2 supply and changes in the oxygenation state of cerebral hemoglobin, and to determine whether concentration changes in oxyhemoglobin (ΔcO2Hb), deoxyhemoglobin (ΔcHHb), and cerebral arterial oxygenation (ΔcHbD; the difference between ΔcO2Hb and ΔcHHb), and cerebral blood volume (ΔCBV) can be used to assess the decline in brain cell function during hypoxemia in lambs born near term. Methods: 17 preterm lambs were delivered at a mean gestational age of 133 days. Decreases in cerebral arterial oxygen content were induced by a stepwise reduction in inspired oxygen concentration. Mean values of all continuous variables were calculated over the last 180 s of each hypoxemic level. Cerebral arterial blood gases were analyzed at the end of each level to calculate cerebral arterial O2 content and cerebral O2 supply. Results: Changes in cerebral arterial O2 content and cerebral O2 supply were positively linearly related with ΔcO2Hb and ΔcHbD, and negatively with ΔcHHb and the concentration changes in total hemoglobin. Electrocortical brain activity remained stable until the cO2Hb and cHbD decreased to >3.0 ± 0.9 and >8.1 ± 1.9 (mean ± SD) µmol/100 g, respectively, and cHHb and CBV increased to >4.3 ± 1.7 and 1.37 ± 0.48 ml/100 g, respectively, as compared to baseline. Conclusions: Changes in cerebral arterial O2 content and cerebral O2 supply are adequately reflected by changes in the oxygenation state of cerebral hemoglobin. Concentration changes in ΔcO2Hb, ΔcHHb, ΔcHbD and ΔCBV can be used to assess the decline in brain cell function during hypoxemia in lambs born near term.

Contains fulltext : 57562thijssen.pdf (Publisher’s version ) (Closed access) A double-ring sensor was applied in photoacoustic tomographic imaging of artificial blood vessels as well as blood vessels in a rabbit ear. The peak-to-peak time (tau(pp)) of the laser (1064 nm) induced pressure transient was used to estimate the axial vessel diameter. Comparison with the actual vessel diameter showed that the diameter could be approximated by 2ctau(pp), with c the speed of sound in blood. Using this relation, the lateral diameter could also precisely be determined. In vivo imaging and monitoring of changes in vessel diameters was feasible. Finally, acoustic time traces were recorded while flushing a vessel in the rabbit ear with saline, which proved that the main contribution to the laser-induced pressure transient is caused by blood inside the vessel and that the vessel wall gives only a minor contribution.

Contains fulltext : 58013.pdf (Publisher’s version ) (Closed access) Insufficient cerebral O(2) supply leads to brain cell damage and loss of brain cell function. The relationship between the severity of hypoxemic brain cell damage and the loss of electrocortical brain activity (ECBA), as measure of brain cell function, is not yet fully elucidated in near-term newborns. We hypothesized that there is a strong relationship between cerebral purine and pyrimidine metabolism, as measures of brain cell damage, and brain cell function during hypoxemia. Nine near-term lambs (term, 147 d) were delivered at 131 (range, 120-141) d of gestation. After a stabilization period, prolonged hypoxemia (fraction of inspired oxygen, 0.10; duration, 2.5 h) was induced. Mean values of carotid artery blood flow, as a measure of cerebral blood flow, and ECBA were calculated over the last 3 min of hypoxemia. At the end of the hypoxemic period, cerebral arterial and venous blood gases were determined and CSF was obtained. CSF from 11 normoxemic siblings was used for baseline values. HPLC was used to determine purine and pyrimidine metabolites in CSF, as measures of brain cell damage. Concentrations of purine and pyrimidine metabolites were significantly higher in hypoxemic lambs than in their siblings, whereas ECBA was lower in hypoxemic lambs. Significant negative linear relationships were found between purine and pyrimidine metabolite concentrations and, respectively, cerebral O(2) supply, cerebral O(2) consumption, and ECBA. We conclude that brain cell function is related to concentrations of purine and pyrimidine metabolites in the CSF. Reduction of ECBA indeed reflects the measure of brain damage due to hypoxemia in near-term newborn lambs.

Contains fulltext : 59018.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Oxygenation and hemodynamics in the left and right cerebral hemispheres were measured during induction of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). STUDY DESIGN: Using near infrared spectrophotometry, effects of right common carotid artery (RCCA) and right internal jugular vein (RIJV) ligation and start of VA-ECMO on concentrations of oxyhemoglobin, deoxyhemoglobin, and cerebral blood volume (CBV) were evaluated in 10 newborn infants. Mean cerebral blood flow velocity (CBFV) in the major cerebral arteries was compared before and after the start of VA-ECMO (pulsed Doppler ultrasonography). RESULTS: RCCA ligation caused a decrease in oxyhemoglobin concentration and an increase in deoxyhemoglobin concentration. RIJV ligation caused no changes. Sixty minutes after the start of VA-ECMO, oxyhemoglobin concentration and CBV had increased, and deoxyhemoglobin concentration had decreased. There were no differences between the hemispheres. Mean CBFV had increased in the left internal carotid artery, and it increased equally in both middle cerebral arteries. Flow direction was reversed in the right internal carotid artery. Three patients had asymmetric cerebral lesions, not related to differences in the measurements between the cerebral hemispheres. CONCLUSION: The initiation of VA-ECMO causes changes in cerebral oxygenation and hemodynamics but without a difference in effect on left and right cerebral hemispheres.

Item does not contain fulltext This study tested the hypothesis that changes in the blood concentration, and possibly in the perfusion, of different areas in the brain can be assessed by the use of ultrasound contrast agent (CA) and (linear) echo densitometry. The experiments were performed with piglets (n=3) under general anesthesia and artificial ventilation. Ultrasound CA was administered through a femoral vein as a short bolus. First passage wash-in curve was measured from image gray level during continuous low level (mechanical index

OBJECTIVE: To investigate the effect on cerebral oxygenation and hemodynamics of a patent ductus arteriosus with left-to-right shunt during venoarterial extracorporeal membrane oxygenation in a lamb model. DESIGN: Prospective intervention study in animals. SETTING: Animal research laboratory of a university medical center. SUBJECTS: Six anesthetized newborn lambs with patent ductus arteriosus and left-to-right shunt, installed on venoarterial extracorporeal membrane oxygenation. INTERVENTIONS: Six lambs of 140 days gestational age were prepared to keep the ductus arteriosus open by infiltration of the vessel wall with formaline 10%. The animals were installed on standard venoarterial extracorporeal membrane oxygenation. With a mechanical occluder, the ductus was closed. MEASUREMENTS AND MAIN RESULTS: Changes of mean arterial blood pressure and carotid artery blood flow were measured simultaneously. Using near infrared spectrophotometry, we calculated changes in cerebral concentration of oxyhemoglobin and deoxyhemoglobin (reflecting changes in cerebral oxygen supply) and total hemoglobin (reflecting changes in cerebral blood volume). Also, cerebral oxygen delivery before and after ductus closure was calculated. Before ductus closure there was a left-to-right shunt with a mean +/- SEM of 41 +/- 20% of total body blood flow. Closure of the ductus resulted in an immediate increase in mean arterial blood pressure and carotid artery blood flow. The concentration of oxyhemoglobin increased and the concentration of deoxyhemoglobin decreased, representing increased cerebral oxygen supply. The concentration of total hemoglobin was unchanged, representing unchanged cerebral blood volume. There was an increase in cerebral oxygen delivery. CONCLUSIONS: In this lamb model, a considerable left-to-right shunt over the ductus during venoarterial extracorporeal membrane oxygenation reduced cerebral circulation and oxygenation.

Item does not contain fulltext This paper describes the simultaneous use of two, noninvasive, near-infrared techniques near-infrared spectroscopy (NIRS) and a continuous wave NIR laser Doppler flow system (LDF) to measure changes in the blood oxygenation, blood concentration and blood flow velocity in the brain. A piglet was used as animal model. A controlled change in the arterial CO2 pressure (PaCO2) was applied for achieving changes in the listed cerebrovascular parameters. The time courses of blood concentration parameters (NIRS) and RMS blood flow velocity (LDF) were found to correspond closely with those of carotid blood flow and arterial carbon dioxide pressure (PaCO2). This result shows the additional value of LDF when combined with NIRS, preferably in one instrument. Development of pulsed LDF for regional blood flow measurement is indicated.

The present study addressed the hypotheses that cerebral ischemia and/or excessive cerebral blood pulsation contribute to periventricular hemorrhage in preterm newborns with respiratory distress and that the pulse width is a valuable tool to estimate the contribution of cerebral blood pulsation. These hypotheses were tested by following preterm newborns at risk for respiratory distress and periventricular hemorrhage. We monitored for cerebral blood flow velocity (CBFV), cerebral pulse width, and cerebral pulsatility index; for patent ductus arteriosus, capillary Pco2, heart rate (HR) and behavior; and for the occurrence of respiratory distress and periventricular hemorrhage (PVH). The data obtained were analyzed with linear regression with the mode of respiration (spontaneous or supported) and postnatal age as additional covariates. We observed that (a) respiratory distress, either uncomplicated or complicated by PVH, correlates with a low CBFV and a high cerebral pulsatility index; (b) PVH also correlates with a high cerebral pulse width; (c) the increased pulse width precedes the onset of the hemorrhage; and (d) these CBF alterations can be partly attributed to ductal shunting and are ameliorated by mechanical ventilation.

Noninvasive determination of pulmonary hemodynamics is important for the management of congenital heart disease complicated by pulmonary hypertension. Flow deceleration is less influenced by right ventricular function and would allow more accurate estimation of pulmonary hemodynamics than acceleration. Respiratory influences on pulmonary blood flow are exaggerated by mechanical ventilation. Doppler-derived pulmonary artery (PA) blood flow velocity characteristics were therefore compared with pulmonary hemodynamic parameters in 42 mechanically ventilated children, aged 0.2 to 14.8 years (mean +/- SD 6.7 +/- 4.9). Mean PA pressure ranged from 11 to 47 mm Hg (21 +/- 9 mm Hg). Pulmonary hypertension was present in 14 patients. Significant differences were found between patients with and without pulmonary hypertension in maximal velocity (1.03 +/- 0.22 vs 0.88 +/- 0.18 m/s), acceleration time (119 +/- 39 vs 136 +/- 29 ms), maximal acceleration (17.6 +/- 6.4 vs 13.1 +/- 4.0 m/s2), mean acceleration (9.3 +/- 2.6 vs 6.7 +/- 2.0 m/s2), and mean deceleration (4.5 +/- 1.0 vs 3.8 +/- 0.8 m/s2). In contrast to our hypothesis of the deceleration phase-derived parameters, only maximal deceleration correlated with PA pressure. Acceleration parameters showed closer relations with PA pressures, but correlations were generally low and did not permit accurate prediction of PA pressure (SEE 5 to 11 mm Hg), PA resistance (SEE 1.14 U. m2) or PA driving force (SEE 7 mm Hg). An analysis that took respiratory phase into account did not improve correlations. Measurement of mean acceleration, maximal deceleration, and rate-corrected preejection period permitted for accurate discrimination between the presence or absence of pulmonary hypertension, with positive and negative predictive values being 92% and 90%. In mechanically ventilated children with congenital heart disease, accurate noninvasive PA pressure assessment is not possible. Accurate predictions for the presence of pulmonary hypertension can be made by measurement of both acceleration and deceleration parameters.

Objective: This prospective study determines reproducibility of measurements derived from the pulmonary arterial (PA) blood flow velocity waveform in infants and children with congenital heart disease by performance of the Doppler echocardiographic examination by different echocardiographers. Additionally, the effect of respiration on reproductibility is investigation. Methods: In group I consisting of 44 consecutive patients (aged 0.1–16.2 years) admitted for echocardiography, the PA blood flow velocity waveform was independently determined by two equally experienced echocardiographers. To obtain intra-operator variability, one performed the examination again. In 38 mechanical ventilated patients (aged 0.2–15.6 years), PA blood flow velocity was examined twice by the same echocardiographer to investigate the effects of respiration on reproducibility (group II). Results: In both groups, no systematic difference between examinations could be shown for all Doppler measurements. In group I, the percentage of absolute difference between echocardiographers ranged from 6.0% to 26.4%. Maximal acceleration and deceleration were least reproducible. In group II, the percentage of absolute difference between successive PA bloodflow velocity waveform determinations ranged from 9.2% to 28.6%. No significant difference in reproducibility between respiratory phases was present for all Doppler measurements. Reproducibility was best in end-expiratory beats. Conclusions: reproducibility of measurements derived from the PA blood flow velocity waveform is low and might explain the conflicting results in non-invasive PA pressure determination. To overcome effects of respiration, selection of end-expiratory beats is reccommended.

To study the influence of artificial ventilation rate on neonatal heart rate variability (HRV), ECG and respiratory impedance curves were recorded four times a day in 20 preterm infants (< 3 3 wk) during the first 3 d after birth while the infants were ventilated at a wide range of ventilator rates. The contents o f selected frequency bands within the R-R interval power spectrum were calculated for 3-min periods. Respiratory distress syndrome severity was assessed at each measurement. Respiratory sinus arrhythmia (RSA) induced by the ventilator appeared to mimic spontaneous RSA. As in spontaneous respiration, the amount of RSA (power in a frequency band around the respiratory rate) increases as the ventilation rate decreases. This phenomenon is most probably due to entrainment with baroreflex-related fluctu­ ations in the heart rate. Although the artificial ventilation rate influences RSA and thus high-frequency HRV ? an increase in respiratory distress syndrome severity results in a decrease in low-frequency HRV. Thus, the attenuation of low-frequency HRV by respiratory distress syndrome is not likely to be due to artificial ventilation. (Pediatr Res 37: 124-130, 1995)

In 810 schoolchildren (aged 5-14 years) the prevalence of a grade 1-3/6 vibratory innocent heart murmur (VIHM) is 41%. Restricted to a grade 2 or 3 VIHM, the prevalence is 14%, decreasing from 21% in the age-class 5-6 years to 8% for children 13-14 years of age. The prevalence of a grade 3 VIHM is 1%. Together with a matched control, 84 children with a grade 2 or 3 VIHM underwent further cardiologic examination including electrocardiography, phonocardiography, and Doppler echocardiography. A positive correlation was found between the presence of a VIHM and higher left ventricular voltages on the ECG, but within the normal range; lower heart rate; smaller diameter of the ascending aorta (AAO); and higher blood flow velocity and higher maximal acceleration of the blood flow in the LVOT and the AAO. In 40% of the children with a VIHM, a systolic aortic valve vibration was seen with a frequencyor = 100 Hz and an amplitudeor = 1 mm, whereas this type of vibration was present in only one case control. No significant difference was found concerning the prevalence of false tendons in the left ventricle, systolic and diastolic diameter of the left ventricle, systolic time intervals, and shortening fraction of the left ventricle. The VIHM is strongly associated with a smaller AAO, with higher velocity and acceleration of the blood flow in the LVOT and AAO, and with a vibratory phenomenon of the aortic valve, pointing towards the LVOT-aortic valve region as the site of origin of the VIHM.

The objectives of this study were to evaluate the effect of repeated indomethacin administration on cerebral oxygenation in relation to changes in cerebral blood flow velocity (CBFV) and other relevant physiological variables. Fourteen preterm infants with patent ductus arteriosus were studied during three subsequent indomethacin bolus administrations with intervals of 12 and 24 h. Changes in concentration of oxyhaemoglobin (cO2Hb), deoxyhaemoglobin (cHHb) and oxidized cytochrome aa3 (cCyt.aa3) in cerebral tissue and changes in cerebral blood volume (CBV) were measured by near infrared spectrophotometry; changes in mean CBFV in the internal carotid artery were measured by pulsed Doppler ultrasound. Simultaneously heart rate, transcutaneous pO2 and pCO2, arterial O2 saturation and blood pressure were measured. All variables were continuously recorded until 60 min after indomethacin administration. Within 5 min after each indomethacin administration, significant decreases in CBFV, CBV and cO2Hb and cCyt.aa3 were observed which persisted for at least 60 min, while cHHb increased or did not change at all. There were no changes in the other variables recorded. These data demonstrate that indomethacin administration is accompanied by a reduction in cerebral tissue oxygenation due to decreased cerebral blood flow. Therefore, low arterial oxygen content, either caused by low arterial O2 saturation or by low haemoglobin concentration, may be a contraindication for indomethacin treatment in preterm infants.

The relationship of cerebral blood flow fluctuation (CBFF) with periventricular haemorrhage (PVH) and respiratory distress syndrome (RDS) was studied in 35 preterm newborns. CBFF was defined as the interquartile range in the ensemble of pulses of a 20-s Doppler recording of CBF velocity (CBFV) in the internal carotid artery. We found a statistically significant increase in end diastolic CBFF in PVH and RDS. This increase was related to the mode of respiration (spontaneous or mechanically supported), the state of the ductus arteriosus, and the level of end diastolic CBFV. Differences before and after the onset of PVH were not found. In view of this, we conclude that RDS increases CBFF, that this increase is related to pleural pressure fluctuations, that these can be damped by mechanical ventilation, and that their propagation to the CBF is promoted by patency of the ductus arteriosus and foramen ovale. Whether the CBFF increase causes PVH, or is merely an expression of coincident RDS, remains a question that needs further investigation.

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.