Estimation of extravascular lung water using the transpulmonary ultrasound dilution (TPUD) method: a validation study in neonatal lambs.

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.

Influence of lung injury on cardiac output measurement using transpulmonary ultrasound dilution: a validation study in neonatal lambs.

BACKGROUND: 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: 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: 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: The accuracy and precision of CO measurement using TPUD is not influenced in the presence of heterogeneous lung injury in an animal model.

Cardiac output measurement with transpulmonary ultrasound dilution is feasible in the presence of a left-to-right shunt: a validation study in lambs.

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(®) 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.

Cardiac output can be measured with the transpulmonary thermodilution method in a paediatric animal model with a left-to-right shunt.

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<0.001) with closed shunt and 0.86 (P<0.001) with open shunt. The correlation (r) between the two methods in tracking changes in CO (ΔCO) during the whole experiment was 0.94 (P<0.0001). CONCLUSIONS: The TPTD technique is a feasible method of measuring CO in paediatric animals with a left-to-right shunt.

Effects of midazolam and morphine on cerebral oxygenation and hemodynamics in ventilated premature infants.

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 (Delta cO2Hb) and deoxyhemoglobin (Delta cHHb) were assessed using near infrared spectrophotometry. Changes in cHbD (= Delta cO(2)Hb - Delta cHHb) reflect changes in cerebral blood oxygenation and changes in concentration of total hemoglobin (Delta ctHb = Delta cO2Hb + Delta cHHb) represent changes in cerebral blood volume (DeltaCBV). Changes in cerebral blood flow velocity (DeltaCBFV) 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.

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

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

Monitoring cerebral perfusion using near-infrared spectroscopy and laser Doppler flowmetry.

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.

Assessment of local changes of cerebral perfusion and blood concentration by ultrasound harmonic B-mode contrast measurement in piglet.

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<0.2) ultrasound imaging. This curve was obtained from 1-cm2 areas of the cortex (surface), the brain stem (inner) and the left carotid artery (vessel). Cerebral hemoglobin concentration changes were measured with near-infrared spectroscopy (NIRS). This approach enabled a cross-validation of these techniques. The measurements were repeated under conditions of normocapnia, mild hypercapnia and deep hypercapnia. Several physiologic signals, as well as the carotid blood flow, were measured simultaneously and related to gray level by linear regression analysis. The most significant results found were a high R2-statistic of the regression of the percentage change of the peak of the surface and inner wash-in curves with the arterial carbon dioxide pressure (R2=0.63 and R2=0.70, respectively), the blood pH (R2=0.79 and R2=0.81), the carotid flow (R2=0.75 and R2=0.72) and the partial arterial oxygen pressure (R2=0.47 and R2=0.55). Finally, a high correlation of peak gray level with total hemoglobin concentration change, independently measured by NIRS, was found (R2=0.69). In conclusion, these experiments show a reasonable intersubject variability of various relative measures derived from gray level ultrasound wash-in curves. High sensitivity to physiologic changes related to hypercapnia was observed for the peak contrast of wash-in curves. For up-slope and area-under-the-curve (first passage) this was lower but still highly significant. The gray-level ultrasound measures are highly correlated to changes in regional hemoglobin concentration in brain tissue assessed by NIRS.

Experimental verification of conditions for near infrared spectroscopy (NIRS).

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 mua = 0.01 mm(-1) (800 nm) and mu's = 1.00 mm(-1) (800 nm)), containing rods with 10 x absorption, or 10 x scattering, and 5 x both Monte Carlo simulations were carried out of a cylinder with transport scattering coefficient mu's = 0.525 mm(-1) and absorption coefficient mua = 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 degrees and rod position angle symmetrically (45 degrees ) in between. Minimum OD for these rods was obtained with optodes at 150 degrees angle and rod position at 240 degrees (i.e. relative to transmitting optode position at 0 degrees ). A second maximum OD was obtained at an optode angle 180 degrees and rod position at 180 degrees. Maximum OD (i.e. attenuation) for the scattering rod was at optode separation angle of 90 degrees and rod at 0 degrees. Minimum OD for this case was obtained with optode angle of 180 degrees and rod positions around 80 degrees and 280 degrees. 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 degrees 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 degrees 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

The effect of blood transfusion and haemodilution on cerebral oxygenation and haemodynamics in newborn infants investigated by near infrared spectrophotometry.

UNLABELLED: The objective of this study was to investigate the influence of blood transfusion and haemodilution on cerebral oxygenation and haemodynamics in relation to changes in cerebral blood flow velocity (CBFV) and other relevant physiological variables in newborn infants. Thirteen preterm infants with anaemia (haematocrit < 0.33) and ten infants with polycythaemia (haematocrit > 0.65) were studied during blood transfusion and haemodilution respectively using adult red blood cells and partial plasma exchange transfusion. Changes in cerebral concentrations of oxyhaemoglobin (cO2Hb), deoxyhaemoglobin (cHHb), total haemoglobin (ctHb), (oxidized-reduced) cytochrome aa3 (cCyt.-aa3) were continuously measured using near infrared spectrophotometry throughout the whole procedure. Simultaneously, changes of mean CBFV in the internal carotid artery were continuously measured using pulsed Doppler ultrasound. Heart rate, transcutaneous partial pressure of oxygen and carbon dioxide, and arterial O2 saturation were continuously and simultaneously measured. Blood transfusion resulted in increase of cO2Hb, cHHb, ctHb and red cell transport (product of CBFV and haematocrit), whereas CBFV decreased. The increase of cO2Hb exceeded that of cHHb, reflecting improvement of cerebral O2 supply. Haemodilution resulted in a decrease of cO2Hb, cHHb and ctHb, whereas CBFV increased. Red cell transport was unchanged. The decrease of cO2Hb exceeded that of cHHb, reflecting decreased cerebral O2 supply. cCyt.aa3 decreased after blood transfusion and remained unchanged after haemodilution, but the reliability of these results is uncertain. With the exception of a small, but significant increase in transcutaneous partial pressure of oxygen after blood transfusion, the other variables showed no changes. Each blood withdrawal during exchange transfusion resulted in only a significant increase in heart rate without changes in the other variables measured, suggesting unchanged cerebral perfusion. CONCLUSION: In newborn infants blood transfusion in anaemia results in improvement of cerebral oxygenation, but haemodilution in polycythaemia does not improve cerebral oxygenation despite possible improvement of cerebral perfusion.

Cerebral blood flow velocity and pulsation in neonatal respiratory distress syndrome and periventricular hemorrhage.

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.

Is noninvasive determination of pulmonary artery pressure feasible using deceleration phase Doppler flow velocity characteristics in mechanically ventilated children with congenital heart disease?

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.

Asymmetry of the cerebral blood flow: an ultrasound Doppler study in preterm newborns.

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 PCO2, 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.

Cerebral oxygenation and hemodynamics during induction of extracorporeal membrane oxygenation as investigated by near infrared spectrophotometry.

OBJECTIVE: To investigate cerebral oxygenation and hemodynamics in relation to changes in some relevant physiologic variables during induction of extracorporeal membrane oxygenation (ECMO) in newborn infants. METHODS: Twenty-four newborn infants requiring ECMO were studied from cannulation until 60 minutes after starting ECMO. Concentration changes of oxyhemoglobin (cO2Hb), deoxyhemoglobin (cHHb), total hemoglobin (ctHb), and (oxidized-reduced) cytochrome aa3 (cCyt.aa3) in cerebral tissue were measured continuously by near infrared spectrophotometry. Heart rate (HR), transcutaneous partial pressures of oxygen and carbon dioxide (tcPO2 and tcPCO2), arterial O2 saturation (saO2), and mean arterial blood pressure (MABP) were measured simultaneously. Intravascular hemoglobin concentration (cHb) was measured before and after starting ECMO. In 18 of the 24 infants, mean blood flow velocity (MBFV) and pulsatility index (PI) in the internal carotid and middle cerebral arteries were also measured before and after starting ECMO using pulsed Doppler ultrasound. RESULTS: After carotid ligation, cO2Hb decreased whereas cHHb increased. After jugular ligation, no changes in cerebral oxygenation were found. At 60 minutes after starting ECMO, the values of cO2Hb, saO2, tcPO2, and MABP were significantly higher than the precannulation values, whereas the value of cHHb was lower. There were no changes in cCyt.aa3, tcPCO2, and HR, whereas cHb decreased. The MBFV was significantly increased in the major cerebral arteries except the right middle cerebral artery, whereas PI was decreased in all measured arteries. Cerebral blood volume, calculated from changes in ctHb and cHb, was increased in 20 of 24 infants after starting ECMO. Using multivariate regression models, a positive correlation of delta ctHb (representative of changes in cerebral blood volume) with delta MABP and a negative correlation with delta tcPO2 were found. CONCLUSIONS: The alterations in cerebral oxygenation after carotid artery ligation might reflect increased O2 extraction. Despite increase of the cerebral O2 supply after starting ECMO, no changes in intracellular O2 availability were found, probably because of sufficient preservation of intracellular cerebral oxygenation in the pre-ECMO period despite prolonged hypoxemia. The increase in cerebral blood volume and cerebral MBFV may result from the following: (1) reactive hyperperfusion, (2) loss of autoregulation because of prolonged hypoxemia before ECMO and/or decreased arterial pulsatility, or (3) compensation for hemodilution related to the ECMO procedure.

The influence of artificial ventilation on heart rate variability in very preterm infants.

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 (< 33 wk) during the first 3 d after birth while the infants were ventilated at a wide range of ventilator rates. The contents of 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 fluctuations 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.

Influence of end expiratory pressure on cerebral blood flow in preterm infants.

The effect of interruption of positive and 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.

The influence of arterial carbon dioxide on cerebral oxygenation and haemodynamics during ECMO in normoxaemic and hypoxaemic piglets.

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 oxyhaemoglobin (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 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.

Effects of repeated indomethacin administration on cerebral oxygenation and haemodynamics in preterm infants: combined near infrared spectrophotometry and Doppler ultrasound study.

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.

Cerebral blood flow fluctuation in neonatal respiratory distress and periventricular haemorrhage.

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.

Heart rate variability.

PURPOSE: To present an overview of the applicability of heart rate variability measurements in medicine. DATA SOURCES: During a 4-year period all new papers concerning heart rate variability were collected. A selection of the most recent publications in the presented research area was used for this review. DATA SYNTHESIS: The amount of short- and long-term variability in heart rate reflects the vagal and sympathetic function of the autonomic nervous system, respectively. Therefore heart rate variability can be used as a monitoring tool in clinical conditions with altered autonomic nervous system function. In postinfarction and diabetic patients, low heart rate variability is associated with an increased risk for sudden cardiac death. A sympathovagal imbalance is also detectable with heart rate variability analysis in coronary artery disease and essential hypertension. Besides diabetic neuropathy, in many other neurologic disorders, such as brain damage, the Guillain-Barré syndrome, and uremic neuropathy, heart rate variability analysis can provide insight into which division of the autonomic nervous system is most affected. Heart rate variability can be influenced by various groups of drugs, but it can also shed light on the mode of action of drugs. The protective effect of cardiovascular drugs in postinfarction patients has been investigated. CONCLUSIONS: Heart rate variability analysis is easily applicable in adult medicine, but physiologic influences such as age must be considered. The most important application is the surveillance of postinfarction and diabetic patients to prevent sudden cardiac death. With heart rate variability analysis, individual therapy adjustments to achieve the most favorable sympathetic-parasympathetic balance might be possible in the future.