Ole Pryds

Carbon dioxide-related changes in cerebral blood volume and cerebral blood flow in mechanically ventilated preterm neonates : comparison of near infrared spectrophotometry and 133Xenon clearance

ABSTRACT: Carbon dioxide-induced changes in near infrared spectrophotometry recordings were compared with changes in cerebral blood flow estimated by 133Xenon clearance (global cerebral blood flow (infinity)) at serial measurements in 24 mechanically ventilated preterm infants (mean gestational age 30.2 wk). In all infants, three measurements were taken at different arterial carbon dioxide tension levels (mean 4.4 kPa, range 2.1-7.8) obtained by adjustment of the ventilator settings. Mean arterial blood pressure changed spontaneously, whereas arterial oxygen tension was kept within normal range. At all wavelengths (904, 845, 805, and 775 nm), the OD increased at higher arterial carbon dioxide tension levels, indicating cerebral vasodilation. This conclusion was supported by conversion of the data to changes in oxygenated and deoxygenated Hb concentration. A parallel increase in cerebral blood volume index and global cerebral blood flow (infinity) was found (P < 0.0001). The oxygenation level of cytochrome aa3 increased with increases in oxygen delivery (P < 0.0001). This observation, however, may have been artifactual due to cross-talk between the oxidized cytochrome aa3 and the oxygenated Hb signals, as these signals were closely interrelated in the present experimental design. We suggest that near infrared spectrophotometry may be used for estimation of the cerebral blood volume index/cerebral blood flow-CO2 reactivity within a wide range of arterial carbon dioxide tension. Knowledge of the light path length would put this estimation on a quantitative basis.

Estimating cerebral blood flow in newborn infants: comparison of near infrared spectroscopy and 133Xe clearance.

ABSTRACT: A new method of measuring cerebral blood flow (CBF) in newborn infants by means of near infrared spectroscopy (CBFnirs) was compared with the i.v. 133Xe clearance technique (CBFxe). Forty CBFnirs measurements were obtained during 19 133Xe measurements in 16 infants; 79 other CBFnirs data sets were discarded because the assumptions for their use were not fulfilled. The test-retest variation or repeated near infrared-measurements during each 133Xe clearance was 17.5%. CBFnirs was closely related to CBFxe (r2 = 0.84, p < 0.0001), with a slope of 0.75 (SEM = 0.064) and a intercept of 1.58 mL/100 g/min (SEM = 0.51). The difference between the measurements obtained by the two methods (CBFnirs – CBFxe) was negative in the high range of CBF, whereas the difference was close to zero in the low range. We conclude that CBF measured with near infrared spectroscopy was in good agreement with the CBF measured with the 133Xe method. The near infrared spectroscopy method has the advantage of being noninvasive, and it does not involve ionizing radiation. Because of methodologic constraints, however, it may underestimate CBF in the high range of flow, and it may have limitations of application in clinical research. (Pediatr Res 30: 570–573, 1991)

Estimation of Cerebral Venous Saturation in Newborn Infants by Near Infrared Spectroscopy

ABSTRACT: The purpose of the study was to evaluate the near infrared spectroscopy technique for determination of the cerebral venous oxygen saturation. By tilting the patients head down 15°, changes in OD may be caused by changes in cerebral blood volume. On the assumption that increases in cerebral blood volume consist of venous blood only, cerebral venous oxygen saturation can be calculated as the measured change in oxygenated Hb divided by the change in total Hb. Two groups of mechanically ventilated, newborn infants were investigated: 10 asphyxiated, term infants and another 22 preterm infants with respiratory distress syndrome. All were monitored by near infrared spectroscopy during tilting, and cerebral blood flow was estimated by the 133Xe clearance technique immediately before tilting. Cerebral venous oxygen saturation could not be calculated in 13 preterm infants, as the blood volume remained constant during tilting. In the remaining 19, cerebral venous oxygen saturation averaged 0.67 (SD = 0.09) in asphyxiated infants and 0.53 (SD = 0.15) in preterm infants (p = 0.03). The corresponding values of cerebral blood flow were closely and inversely related to oxygen extraction calculated from cerebral venous saturation as estimated by near infrared spectroscopy.

Changes in cerebral oxygenation and cerebral blood volume during endotracheal suctioning in ventilated neonates

The effect of endotracheal suctioning on cerebral haemodynamics was investigated in 29 newborn infants with a mean gestational age of 31 weeks (range 25‐40 weeks). Prior to one of two suctioning procedures, the inspiratory fraction of oxygen was increased by 10%. Brain oxygenation and total haemoglobin concentration were estimated continuously by near infrared spectroscopy. Mean arterial blood pressure, arterial blood oxygen saturation and carbon dioxide tension were recorded simultaneously. Brain oxygenation decreased in parallel with arterial oxygen saturation during suctioning. Preoxygenation ameliorated the decrease in brain oxygenation and arterial oxygen saturation whereas there was no benefit with regard to the changes in total haemoglobin concentration, carbon dioxide tension or mean arterial pressure. Changes in total haemoglobin concentration were related closely to concomitant changes in carbon dioxide tension (p < 0.0001) but unrelated to changes in mean arterial pressure or arterial oxygen saturation. Our findings suggest that cerebral blood volume may react to changes in carbon dioxide tension during endotracheal suctioning in mechanically ventilated neonates. Apparently, preoxygenation prior to suctioning does not ameliorate the stress in normoxic infants.

Cerebral Pressure Autoregulation and Vasoreactivity in the Newborn Rat

Perinatal brain injury has been associated with impaired cerebral blood flow (CBF) pressure autoregulation. The brain of 3- to 5-d-old rat pups is immature and similar to that of a preterm infant, and therefore we tested cerebral vasoreactivity in that animal. CBF pressure autoregulation was tested in 20 Wistar pups during normocapnia and hypercapnia, respectively. Hypotension was induced by hemorrhage and cerebral perfusion was monitored with laser Doppler flowmetry and near-infrared spectroscopy. Systolic blood pressure was measured noninvasively from the tail. During normocapnia, the autoregulatory plateau was narrow. Resting systolic blood pressure (SBP) was 39.2 mm Hg and CBF remained constant until SBP decreased below 36.0 mm Hg (SE 0.8). Below the lower limit, CBF declined by a mean of 2.7% per mm Hg [95% confidence interval (CI), 2.4–3.0%], and hemoglobin difference (HbD) and total hemoglobin (HbT) changed proportionally to CBF. After inhalation of carbon dioxide, CBF increased significantly by a mean of 17.7% (95% CI, 13.7–22.8%). The CBF-CO2 reactivity was estimated to 13.4% per kPa (95% CI, 2–24.8%), p = 0.026. Over the range of SBP (6–54 mm Hg), a linear relationship between CBF and SBP was found during hypercapnia, indicating abolished pressure autoregulation. A linear correlation between CBF and HbD was found (r = 0.80). CBF pressure autoregulation and reactivity to CO2 operate in the newborn rat. This model may be useful for future investigations concerning perinatal pathophysiology in the immature brain.

Bacillus Calmette-Guérin immunisation at birth and morbidity among Danish children: A prospective, randomised, clinical trial

BACKGROUNDnStudies from low-income countries report positive non-specific effects of early Bacillus Calmette-Guérin (BCG) immunisation on childhood health and survival. Neonatal immunisation with BCG may prime the immune system and offer partial protection against other infectious and possibly allergic diseases. The potential clinical value of these non-specific effects has not yet been examined in a large randomised trial in high-income countries.nnnMETHODSnThe Danish Calmette Study is a multicentre randomised clinical trial conducted between October 2012 and November 2015. Within the first 7 days of life, infants were randomly assigned to intra-dermal vaccination with BCG or no intervention. At 3 and 13 months of age structured telephone interviews and clinical examinations of the children were conducted. In a subgroup of children blood samples were drawn and stool samples collected at age 4 days, 3 and 13 months. Thymus index was assessed by ultrasound in a subgroup at randomisation and at 3 months. The primary study outcome is hospitalisation within the first 15 months of life as assessed in Danish health registers. Secondary outcomes include infectious disease hospitalisations, wheezing, eczema, use of prescribed medication, growth, development, thymus index, T- and B-cell subpopulations assessed by flow cytometry, in vitro cytokine responses and specific antibody responses to other vaccines. Adverse reactions were registered.nnnDISCUSSIONnWith participation of 4184 families and more than 93% adherence to clinical follow-up at 3 and 13 months, this randomised clinical trial has the potential to create evidence regarding non-specific effects of BCG vaccination in a high-income setting.

Cerebral Effects of Commonly Used Vasopressor-Inotropes: A Study in Newborn Piglets

Background Despite widespread use in sick infants, it is still debated whether vasopressor-inotropes have direct cerebral effects that might affect neurological outcome. We aimed to test direct cerebrovascular effects of three commonly used vasopressor-inotropes (adrenaline, dopamine and noradrenaline) by comparing the responses to those of nonpharmacologically induced increases in blood pressure. We also searched for reasons for a mismatch between the response in perfusion and oxygenation. Methods Twenty-four piglets had long and short infusions of the three vasopressor-inotropes titrated to raise mean arterial blood pressure (MAP) 10 mmHg in random order. Nonpharmacological increases in MAP were induced by inflation of a balloon in the descending aorta. We measured cerebral oxygenation (near-infrared spectroscopy), perfusion (laser-Doppler), oxygen consumption (co-oximetry of arterial and superior sagittal sinus blood), and microvascular heterogeneity (side stream dark field video microscopy). Results Vasopressor-inotropes increased cerebral oxygenation significantly less (p≤0.01) compared to non-pharmacological MAP increases, whereas perfusion was similar. Furthermore, cerebral total hemoglobin concentration increased significantly less during vasopressor-inotrope infusions (pu200a=u200a0.001). These physiologic responses were identical between the three vasopressor-inotropes (p>0.05). Furthermore, they induced a mild, although insignificant increase in cerebral metabolism and microvascular heterogeneity (p>0.05). Removal of the scalp tissue did not influence the mismatch (p>0.05). Conclusion We demonstrated a moderate vasopressor-inotrope induced mismatch between cerebral perfusion and oxygenation. Scalp removal did not affect this mismatch, why vasopressor-inotropes appear to have direct cerebral actions. The statistically nonsignificant increases in cerebral metabolism and/or microvascular heterogeneity may explain the mismatch. Alternatively, it may simply reflect a vasopressor-inotrope-induced decrease in the arterial-to-venous volume ratio as detected by near-infrared spectroscopy.

BCG vaccination at birth and early childhood hospitalisation: a randomised clinical multicentre trial

Background The BCG vaccine is administered to protect against tuberculosis, but studies suggest there may also be non-specific beneficial effects upon the infant immune system, reducing early non-targeted infections and atopic diseases. The present randomised trial tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting. Methods Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7u2005days of age. Randomisation was stratified by prematurity. The primary study outcome was number of all-cause hospitalisations analysed as repeated events. Hospitalisations were identified using The Danish National Patient Register. Data were analysed by Cox proportional hazards models in intention-to-treat and per-protocol analyses. Results 4184 pregnant women were randomised and their 4262 children allocated to BCG or no intervention. There was no difference in risk of hospitalisation up to 15u2005months of age; 2129 children randomised to BCG experienced 1047 hospitalisations with a mean of 0.49 hospitalisation per child compared with 1003 hospitalisations among 2133 control children (mean 0.47), resulting in a HR comparing BCG versus no BCG of 1.05 (95% CI 0.93 to 1.18) (intention-to-treat analysis). The effect of BCG was the same in children born at term (1.05 (0.92 to 1.18)) and prematurely (1.07 (0.63 to 1.81), p=0.94). The effect was also similar in the two sexes and across study sites. The results were essentially identical in the per-protocol analysis and after adjustment for baseline characteristics. Conclusions BCG vaccination at birth did not reduce the risk of hospitalisation for somatic acquired disease until 15u2005months of age in this Danish study population. Trial registration number NCT01694108, results.

Nonspecific effect of BCG vaccination at birth on early childhood infections: a randomized, clinical multicenter trial

Background:Childhood infections are common and Bacillus Calmette-Guérin (BCG) vaccination at birth may prevent these via nonspecific effects.Methods:A randomized, clinical multicenter trial. All women planning to give birth (n = 16,521) at the three study sites were invited during the recruitment period. Participating children were randomized to receive BCG within 7 d of birth or to a no intervention control group. Parent-reported infections (events) were collected using telephone interviews at 3 and 13 mo. Data collectors were blinded to allocation.Results:The analyses included 4,224/4,262 (99%) and 4,192/4,262 (98%) children at 3 and 13 mo. From 0 to 3 mo, there were 291 events in the BCG group vs. 336 events in the control group, incidence rate ratio (IRR) = 0.87 (95% confidence interval (CI): 0.72 to 1.05). In this age group, the IRR was 0.62 (95% CI: 0.39 to 0.98) if the mother was BCG vaccinated. From 3 to 13 mo, there were 7,028 vs. 6,791 events, IRR = 1.02 (95% CI: 0.97 to 1.07).Conclusion:This study did not find a nonspecific public health benefit of BCG on parent-reported infections. BCG may have reduced the incidence of infections in children of BCG-vaccinated mothers during the first 3 mo.

Cerebral vascular effects of hypovolemia and dopamine infusions: a study in newborn piglets

Aim:u2002 Despite widespread use, effects of volume boluses and dopamine in hypotensive newborn infants remain controversial. We aimed to elucidate if hypovolemia alone impairs cerebral autoregulation (CA) and if dopamine affects cerebral vasculature.