Cerebral Blood Flow Reactivity in Spontaneously Breathing, Preterm Infants Shortly after Birth

ABSTRACT. In 18 spontaneously breathing, preterm infants (mean gestational age 30.3 weeks) cerebral blood flow (CBF) was investigated twice, 2 and 3 hours after birth when spontaneous changes in arterial carbon dioxide tension (P_aCO₂) and mean arterial blood pressure (MABP) were expected. Transcutaneous oxygen tension (TcO₂) was kept normal by adjusting the inspiratory oxygen fraction. In 12 infants, plasma adrenaline and noradrenaline were constant throughout the study. Changes in CBF infinity (CBF_∞) were significantly related to changes in P_aCO₂ (p=0.0001) whereas neither changes in MABP nor TcO₂ reached a significant association to changes in CBF (p=0.67 and p=1.0, respectively). The calculated CBF-CO₂ reactivity of 28.9% per kPa P_aCO₂ (95% confidence interval 16.1–43.0) is comparable to findings in older newborns and healthy adults. Only one of 18 infants developed germinal layer haemorrhage (grade I) in spite of the hypercapnic state which was observed during the first hours of life. Periventricular leucomalacia was not detected. It is suggested that the cerebral blood flow is well regulated within physiological variations of P_aCO₂ and MABP in the healthy, preterm newborn even shortly after birth.     

Effect of PaCO2 and Haemoglobin Concentration on Day to Day Variation of CBF in Preterm Neonates

Pryds, O. and Greisen, G. (Department of Neonatology, Rigshospitalet, Copenhagen, Denmark). Effect of P_aCO₂ and haemoglobin concentration on day to day variation of CBF in preterm neonates. Acta Paediatr Scand, Suppl 360: 33, 1989.
The CBF was measured on the first three days of life in 22 mechanically ventilated, preterm neonates (mean gestational age 29.5 weeks) with simultaneous recordings of arterial carbon dioxide tension (P_aCO₂), arterial oxygen tension (P_aO₂), haemoglobin concentration (Hgb), haemoglobin oxygen saturation and mean arterial blood pressure (MABP). CBF ± tended to increase slightly with age. The intra-individual variation of CBF ± was positively related to changes in P_aCO₂ (p=0.0004) and inversely related to changes in Hgb (p=0.029). Neither P_aO₂ nor MABP achieved a significant relation to changes in CBF ± Thus, the mean CBF ±-CO₂ reactivity was calculated to 22.1 % per kPa whereas CBF increased by a mean of 11.9% per mM decrease of Hgb thereby providing a constant oxygen delivery to the brain. It is concluded that P_aCO₂ and Hgb have the expected effect on CBF ± in preterm neonates even during respiratory distress shortly after birth.     

TRANSCUTANEOUS Po2MONITORING IN NEONATAL INTENSIVE CARE

ABSTRACT. The transcutaneous Po₂ monitoring technique was applied in 20 newborns. The method proved reliable during hypoxemia, normoxemia and hyperoxemia, with a high correlation between Ptco₂ and Pao₂ simultaneously obtained arterial samples. Although Ptco₂ reliably reflects changes in Pao₂ occasional arterial samples are still required for establishing the relationship between Ptco₂ and Pao₂, especially in patients with impaired circulation. When this relationship has been determined, the therapist may rely on the recorded Ptco₂ level for hours, given that the energy supply required to maintain the electrode at a preset temperature level remains constant. A considerable difference between Ptco₂ and Pao₂ or a change in the energy supply level to the electrode may alert the therapist to check the patient's circulatory status. The Pao₂ technique is now fully developed and can be recommended for use in neonatal intensive care.     

Evaluation of a Transcutaneous Oxygen and Carbon Dioxide Monitor in a Neonatal Intensive Care Department

Transcutaneous-Po₂; (tc-Po₂ (tc-Pco₂) at 44^oC and transcutaneous-Pco₂) at 38, 42, 43 and 44^oC were measured with a currently available monitoring system (TCM222, Radiometer, Copenhagen) in 64 newborn infants with severe respiratory insufficiency during the first five days of life. Tc-Pco₂ at all four temperatures correlated better with arterial blood-Pco₂ (aB-Pco₂)> than tc-Po₂ with aB-Po2. However, the sensitivity and specificity of tc-Po₂ and tc-Pco₂ were similar with regard to maintaining aB-Po₂, and aB-Pco₂ within specified limits. Tc-Pco₂ increased relatively with increasing electrode temperature by a factor which was similar to the anaerobic temperature coefficient of Po₂, in blood. The coefficient of variation of duplicate measurements was 10 % for tc-Po₂ and 5 % for tc-Pco₂. Electrode drift after an average of 3 hours patient monitoring was 2%±6% (1SD) for tc-Pco₂, and -3 %±6 % for tc-Pco₂- We conclude that tc-Po₂ and tc-Pco₂ are a valuable supplement to arterial blood gas measurements, but the variable correlation with arterial blood gas values and the electrode drifts which may occur, mean that they cannot fully replace arterial sampling.     

Acute Effects of Acetazolamide on Cerebral Blood Flow Velocity and pCO2 in the Newborn Infant

ABSTRACT. Twelve infants with hydrocephalus were treated with acetazolamide. In those treated intravenously middle cerebral artery blood flow velocity increased by a median of 86% (range 54-150%). Maximum increase was reached within 2-20 min. The effect lasted as long as 3.5 hours. Intracranial pressure rose by a median of 4 mmHg (range 0–10 mmHg). There was no significant alteration in blood pressure or heart rate. Respiratory rate increased by approximately 10 breaths/min and the tcpCO₂, rose by a median 0.2 kPa in infants with normal lungs. In infants treated orally, blood velocity rose by 35-40% at 60-80 min with no increase in intracranial pressure. In four infants with lung disease pCO₂, rose by a median of 2.0 kPa (range 0.6 to 3.4 kPa). Acetazolamide was well tolerated in infants with normal lungs but should be used with caution in the presence of lung disease.     

EFFECTS OF AN ANTENATAL LOAD OF PYRIDOXINE (VITAMIN B6) ON THE BLOOD OXYGEN AFFINITY AND PROLACTIN LEVELS IN NEWBORN INFANTS AND THEIR MOTHERS

ABSTRACT. The effects of a loading dose of pyridoxine (100 mg) given intramuscularly or per os to 24 earlier non-supplemented pregnant women at term was investigated. The in vitro oxygen affinity (P₅₀) and the prolactin level in both maternal and newborn blood was sampled. The blood P₅₀ values were measured by a variant of "mixing method". Blood prolactin levels were determined by RIA. After pyridoxine administration, the maternal P₅₀ values increased moderately and the newborns' cord blood P₅₀ values increased significantly when compared with the control group's (number of cases 12) values. The decrease of blood oxygen affinity was most pronounced in the supplemented groups in newborns' capillary blood at the age of five days. The pyridoxine supplementation had no effect on the maternal and the newborns' cord blood prolactin level or on the daily amount of breast milk. Pyridoxine supplementation of the mother at labour may influence favourably the oxygen transport function of the newborn's blood and it may be especially advantageous in early postnatal adaptation disturbances of newborns.     

Postnatal development of the cerebral blood flow velocity response to changes in CO2 and mean arterial blood pressure in the piglet

Cerebral blood flow velocity was studied during changes (haemorrhage) in mean arterial blood pressure or P _aCO₂ in 56 (aged 0–26 days) anaesthetized and ventilated piglets. The CO₂ reactivity increased with age from 6.5% kPa⁻'(< 1 day) to adult levels of 25% kPa⁻¹ for piglets over 4 days old. The mean arterial blood pressure reactivity was reduced from 1.3% mmHg⁻¹ (< 1 day old) to 0.0%/ mmHg (> 4 days old). The reactivities were similar with two different anesthetics: chloralose/urethane or pentobarbital. To validate the cerebral blood flow velocity data, both electromagnetic flow and precerebral Doppler ultrasound velocity were recorded from the same common carotid artery with extracranial branches tied off. There were no differences between the results with these two methods nor between these results and those obtained when the cerebral blood flow velocities were recorded from an intracerebral artery and the electromagnetic flowmeter recorded from the carotid artery. The vessel diameter appears stable during these interventions. In conclusion, the autoregulatory response and the reaction to P _aCO₂ appear poorly developed in the newborn piglet, but rapidly mature during the first 4 days of life.     

Cerebral Blood Flow, PaCO2 Changes, and Visual Evoked Potentials in Mechanically Ventilated, Preterm Infants

ABSTRACT. Two estimations of global cerebral blood flow (CBF) using 133-Xenon clearance were done with an interval of about one hour in 16 mechanically ventilated, newborn infants, of less than 33 weeks gestational age. In eight infants CBF was estimated just before a change in ventilator settings, and again when the Pa_co2 was stable. In the remaining eight infants small spontaneous changes in Pa_co2 occurred. The CBF-CO₂ reactivity was similar in the two groups (+67%/kPa (95% confidence interval 13–146) and 52%/kPa (24–86)) and considerably higher than the CBF-CO₂ reactivity estimated from the interindividual variation of flow and Pa_co2 (+19%/kPa (4–36)). There were no significant relations between CBF and arterial blood pressure. Flash evoked potentials (VEP) were recorded during the 133-Xenon clearances in 8 of the infants. VEP showed no relation to changes in CBF, even when the blood flow rose from the lowest levels. CBF and VEP were obtained once in 9 other infants. Among the 17 infants, the latency of the first negative wave of the VEP was not related to the CBF level. Mean CBF in the 25 infants was 12.3 ml/100 g/min (range 4.3 to 18.9), mean Pa_co2 was 4.2 kPa (range 2.3 to 6.4). Thus, CBF-CO₂ reactivity appeared to be normal in these clinically stable, mechanically ventilated, preterm infants, suggesting that their low cerebral blood flow was well regulated. The absence of a relation of CBF with VEP suggested that cerebral blood flow was not critically decreased.     

Low-dose inhaled nitric oxide for neonates with pulmonary hypertension

Objective : Inhaled nitric oxide (iNO) has been shown to cause selective pulmonary vasodilatation and improve ventilation-perfusion matching and may be an important therapeutic option for the treatment of persistent pulmonary hypertension of the newborn (PPHN). We report our experience on the use of iNO in neonates with severe PPHN.
Methodology : Inhaled NO was administered to 10 infants with PPHN and persistent hypoxaemia (meconium aspiration syndrome, n = 9; pneumonia, n = 1) after failure of conventional therapy to improve oxygenation. With the exception of one infant, iNO was commenced at 10 ppm.
Results : After 30 min exposure to iNO, the arterial oxygen tension (PaO₂) rose from a median of 49 mmHg (6.5 kPa) [range 12-82 mmHg (1.6-10.9 kPa)] to 75 mmHg (10 kPa) [range 17-450 mmHg (2.3-60 kPa)] ( P = 0.005), while the median oxygenation index fell (pre-iNO of 37 vs post-iNO 20) ( P = 0.005) and median systemic arterial pressure rose (pre-iNO 46.5 mmHg (6.2 kPa) [range 32-63 mmHg (4.3 to 8.4 kPa vs post-iNO 54.5 mmHg (7.3 kPa) [range 36-74 kPa]) P = 0.005). All infants subsequently continued to receive iNO with the duration of exposure to iNO ranging from 12 to 168 h (median duration 100 h). Three infants died despite showing an initial beneficial response to iNO. The mean duration of intubation for survivors was 11.9 ± 2.6 days. Methaemoglobinaemia and toxic levels of nitrogen dioxide were not seen during iNO administration. Of the seven survivors, 12 month follow up in two infants and 4 month follow up in four infants showed age-appropriate neurodevelopmental skills, with one infant having very mild hearing loss.
Conclusions : Inhaled NO reduces the oxygenation index by improving the PaO₂ and decreasing ventilation pressures, and appears to be clinically useful in severely hypoxaemic infants with PPHN refractory to conventional treatment.     

Cerebral blood flow and plasma hypoxanthine in relation to surfactant treatment

We have previously reported reduction in EEG activity in preterm babies after tracheal instillation of Curosurf. To elucidate the cause of EEG depression, we have examined cerebral blood flow (CFB), amplitude-integrated EEG (aEEG), mean arterial blood pressure (MABP) and plasma hypoxanthine (Hx) concentration in a group of preterm babies before and immediately after administration of surfactant. No change occurred in CBF immediately after surfactant treatment despite a significant decrease in MABP. At 60 min after surfactant administration, a significant reduction in CBF occurred ( p < 0.05). However, when CBF values were corrected for changes in PaCO₂, no reduction in CBF was observed. Mean plasma Hx concentration was 11.6 (SD 7.3) μmol/l before surfactant therapy, which decreased significantly to 8.1 (5.8) μmol/l ( p < 0.05) 15–30 min after treatment. No correlations were found between plasma Hx concentration and FiO₂, a/A pO₂, PaCO₂, SaO₂, arterial blood pressure, CBF or the degree of EEG depression. This study indicates that EEG depression observed after surfactant instillation is not caused by cerebral ischemia.     

Serum lecithin: cholesterol acyltransferase activity and HDL2 and HDL3 composition in small for gestational age newborns

The aim of this study was to determine serum lecithin: cholesterol acyltransferase (LCAT) activity in parallel with HDL₂ and HDL₃ composition in cord sera of small for gestational age (SGA) newborns, and to compare them with those obtained from appropriate for gestational age (AGA) newborns. LCAT activity was assayed by conversion of [³H]cholesterol to labelled cholesteryl ester. HDL₂ and HDL₃ were separated by ultracentrifugation. Serum cholesteryl ester, apolipoprotein (apo) A-I concentrations and LCAT activity were significantly lower (-47%, -18% and -56%, respectively), whereas serum triglyceride amounts were twofold higher in SGA newborns than in AGA newborns. In SGA newborns, HDL₂ and HDL₃ levels were low, and HDL₃ and HDL₂ phospholipid and HDL₂-cholesteryl ester contents were diminished. HDL₃-apo A-I, A-fl, C-III and E values were lower in SGA newborns. In HDL₂, apo A-I, A-II and E concentrations were decreased. Therefore, in SGA newborns, the reduced LCAT activity was associated with quantitative and qualitative changes in HDL₂ and HDL₃ particles.     

PHOTOSENSITIZED SHIFT IN THE O2 DISSOCIATION CURVE OF FETAL BLOOD

Abstract. Ostrea, E. Jr., and Odell, G. (Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA). Photosensitized shift in the O₂ dissociation curve of fetal blood. Acta Paediatr Scand, 63: 341, 1974.–The exposure of fetal erythrocytes to blue light in the presence of bilirubin was associated with a significant decrease in the affinity of fetal cells for O₂, (δP₅₀) at pH 7.4=+3.17± 0.68 mmHg. This change was not observed with either adult erythrocytes or hemolysates of fetal and adult red cells. Associated with the shift in P₅₀, there was a decrease in the Na⁺, K+ -ATP'ase of the irradiated erythrocytes and no electrophoretic evidence of alteration in the fetal hemoglobin. The results suggest that the shift in the O₂ dissociation curve represents an additional manifestation of photodynamic membrane injury and the stroma of fetal erythrocytes influence their oxygen affinity.     

FUNCTION AND DIMENSIONS OF THE CIRCULATORY SYSTEM IN ANOREXIA NERVOSA

ABSTRACT. The functional and dimensional components of the oxygen transporting system was studied in 17 female and 11 male patients suffering from anorexia nervosa. Both groups were 14.9 years old, on average, and had lost about 25% of their weight. Measurements at rest included blood and heart volume, heart rate, blood pressure, oxygen uptake ( V o₂), RQ, blood lactate (LA) and in 6 of the patients cardiac output. During bicycle ergometry the determinations of heart rate, blood pressure, LA, V o₂ and cardiac output were repeated and maximal aerobic power was determined. A low metabolic rate with bradycardia and hypotension was apparent at rest. Blood and heart volume was decreased proportionally to the weight loss. On a given work load V o₂ was lowered to the same extent as the resting metabolic rate. At maximal effort V o₂ was reduced out of proportion to the circulatory dimensions and maximal heart rate was low. During exercise cardiac output was normally related to V o₂ and stroke volume was maintained, indicating a normokinetic circulation and an unimpaired myocardial function. The main cause of the low maximal aerobic power seems to be the reduced muscle mass.     

Arachidonic acid metabolites in CSF in hypoxic-ischaemic encephalopathy of newborn infants

The aim of this study was to evaluate the cerebral synthesis of eicosanoids in the asphyctic newborn and to investigate the relation between the prostanoid profiles in cerebrospinal fluid (CSF) and the appearance and severity of hypoxic-ischaemic encephalopathy (HIE). Levels of 6-keto-PGF _1-α, TXB₂, PGE₂ and PGF_2-α in CSF were measured in 40 full term newborns during the first day of life. Thirty of these newborns had birth asphyxia and were divided into three groups: 10 without HIE, 12 with mild HIE and 8 with moderate-severe HIE. They were compared to a control group of 10 non-hypoxic newborns. Determinations of the metabolites in CSF were performed by RIA and expressed as pg/ml (mean ± SD). The CSF TXB₂ (thromboxane A₂ metabolite) in asphyxiated newborns was always higher than in the control group (28.12 ± 10.6), and related to the severity of HIE ( p = 0:005): without HIE (50.84 ± 16.4; p = 0:02), mild HIE (80.65 ± 12.64; p ± 0:01) and moderate-severe HIE (178.14 ± 20.5; p < 0:01). The CSF 6-keto-PGF _1-α (prostacyclin metabolite) in asphyxiated newborns was always higher than in the control group (80.55 ± 12.56), but indirectly related to the severity of HIE: without HIE (240.95 ± 28.12; p < 0:01), mild HIE (183.65 ± 30.1; p < 0:01) and moderate-severe HIE (140.55 ± 25.12; p < 0:01). In the moderate-severe HIE group, the increase in TXB₂ was higher than the rise in 6-keto-PGF _1-α.     

Concentrations of LTB4, LTC4, LTD4 and LTE4 in bronchiolitis due to respiratory syncytial virus

Fifty-five infants with bronchiolitis due to respiratory syncytial virus were evaluated for the presence of leukotriene B₄, C₄, D₄ and E₄ in nasopharyngeal secretions. An attempt was made to correlate concentrations of leukotrienes to arterial oxygen tension. Forty participants received conventional therapy consisting primarily of aerosolized albuterol and occasional aminophylline therapy. The other 15 individuals received ribavirin therapy in addition to conventional therapy, and leukotriene concentrations were compared among individuals in these groups. RSV infection was documented by standard methods, and leukotrienes were measured by reverse-phase high pressure liquid chromatography. The leukotriene detected most commonly was LTC₄ (up to 83% of subjects); LTD₄ and LTB₄ were present in approximately 30% of individuals. The mean partial pressure of oxygen was found to be lower in those individuals with detectable LTB₄ than in those without detectable LTB₄ (p < 0.025), and an overall inverse correlation of LTB₄ concentrations with initial pO₂ values was observed (r = 0.318, p < 0.05). The presence and quantity of other leukotrienes did not correlate with the severity of illness. During the first week of illness, the concentration of leukotrienes declined sharply in ribavirin recipients. Individuals receiving conventional therapy during the same time interval exhibited stable or increasing leukotriene concentrations. These observations suggest that LTB₄ may be important in the pathogenesis of bronchiolitis, and that ribavirin therapy may inhibit leukotriene release in the respiratory tract.     

A comparison of P02 monitoring techniques in newborn infants

Abstract This study is an evaluation of different methods of Po₂ monitoring in newborn infants. These were an intra-vascular Pb₂ electrode (Searle Life Support Systems); transcutaneous monitoring (Kontron and Hewlett-Packard); and arteriatized capillary blood samples. Values of each were compared with simultaneous aortic sample values and their correlation compared.
The Searle electrode and TCM were found to be of equivalent accuracy overall, although the Searle was less reliable. Searle catheters were more difficult to insert than normal catheters, with a high wastage. Arterialized capillary Po₂ values did not correlate with arterial.
Transcutaneous monitoring is the most reliable and cheapest method.     

Effects of volume expansion on cardiac output in the preterm infant

Clinical and echocardiography haemodynamic evaluations of response to volume expansion are described in 12 preterm neonates aged < 7days presenting without cardiac dysfunction and with a low cardiac output. They received 10% albumin solution (20 ml kg^-1) for 3h. Measurements were made before infusion, at volumes 5, 12. 5 and 20 ml kg^-1 and 1 h later. All infants increased significantly their cardiac output (CO) (from a median of 177 to 283 ml kg^-1 min^-1). The rise of CO decreased with the volume infused. The index of systemic vascular resistance (SVR = ratio of mean arterial pressure to the CO) decreased for the six patients without PDA (from 272 to 193 mmHg 1^-1 kg^-1 min^-1, p < 0. 05) showing that the hypovolemic preterm infant is able to shut down peripherally in response to hypovolemia. The four hypotensive infants responded by increasing mean arterial blood pressure (from 29 to 44 mmHg). Cutaneous refilling time decreased during infusion (from 6. 7 to 3. 8 s, p < 0. 01). One infant had an haemodynamically significant ductus arteriosus revealed by volume expansion, another one developed myocardial dysfunction.     

Effect of sustained inflations applied directly after cord clamping on lung function in premature newborn lambs

We studied the possibility of improving lung volume and therefore clinical outcome in premature newborn lambs by increasing the inspiratory volumes during the first minute after birth. Sixteen lambs from eight were delivered by hysterotomy after 130–131 days' gestation. In eight lambs the lungs were inflated with a bag with a sustained inspiratory inflation (SI) of 5 s and expiratory time of 5 s during the first four inflations after cord clamping and then mechanically ventilated. Their siblings did not receive SI and served as a control group. At 8 h postnatally, the SI and control groups showed the following results (mean ± SEM): mean airway pressure 14.8 ± 1.8 cmH₂O versus 11.9 ± 1.1 cmH₂O, PaO₂ 41.5 ± 7.3 kPa versus 31.3 ± 7.7kPa, alveolar-arterial oxygen gradient 359 ± 55 mmHg versus 437 ± 58 mmHg. Clinical course, incidence of pneumothorax, oxygenation index, total static compliance, parenchymal-alveolar air area ratio or mortality rate were not different. There was no significant difference between the two groups at this time or at any other time during the experiments.     

Neonatal plasma vitamin K1 levels following oral and intramuscular administration of vitamin K1

Vitamin K₁ levels were measured by high performance liquid chromatography in cord blood ( n = 33) and at the age of 97–120 h after administration of 2 mg of vitamin K_l orally ( n = 88) or 1 mg of vitamin K₁ by im injection ( n = 88). Vitamin K₁ levels were less than 0.05 μg/l in cord blood. The mean (range), SEM, mode and median values (μg/l) for the infants given oral vitamin K₁ were 17.99 (1–56), 1.25, 8 and 15.5 and those for the infants given im vitamin K_l 15.83(2–57), 1.01, 11and 14, respectively. The t- test showed no significant difference in the mean values ( p = 0.09) in the infants given oral or im vitamin K.     

Trials of High Frequency Jet Ventilation in Preterm Infants with Severe Respiratory Disease

ABSTRACT. Nine preterm newborn infants who were maintained on conventional mechanical ventilation for respiratory diseases were given high frequency jet ventilation in the same inspired FiO₂ for short periods (10-120 min). Lower mean airway pressures were used in high frequency jet ventilation (0.70±0.2 kPa versus 0.96±0.2 kPa in intermittent positive pressure ventilation), and peak inspiratory pressures were reduced from 2.06±0.4 to 1.38±0.24 kPa. Respiratory and haemodynamic data were compared with those obtained in intermittent positive pressure ventilation, Pa₀₂ and P_c02 were similar, while an increase in pH and reduction of central venous pressure were observed during high frequency jet ventilation. This preliminary study indicates that high frequency jet ventilation provides good ventilatory support, at least for short periods, with reduced airway pressures, and could be a promising technique for prevention of acute and chronic pulmonary barotrauma.