Introduction

Near-infrared spectroscopy (NIRS) has been used to study cerebral blood flow (CBF) in normal and sick newborn infants, and cerebral blood volume (CBV) and its changes (ΔCBV) [1] during conventional [2, 3, 4] or oscillatory ventilation [5]. Previous studies have measured CBF according to the infant's age [6], and both CBF and CBV have been measured according to blood pressure changes [7, 8]. Palmer et al. [2] found increased CBV in the continuous positive airway pressure (CPAP) phase of an on/off ventilation study. Pellicer [4] found no change in CBF but increased ΔCBV (relative CBV) in preterm neonates on 90° rotation of their heads during conventional and oscillatory ventilation. We report the findings of a NIRS study in neonates treated with two different devices for inducing CPAP. Numerous beneficial effects of nasal CPAP have been reported in the literature, particularly a smaller physiological dead space, reduction in breathing effort [9, 10, 11], lower proximal airway resistance [12], fewer apneic spells [13], and chest wall stabilization [14].

A new device (neonatal helmet CPAP) for administering CPAP in preterm infants was recently developed at our unit [15], which leaves the neck free while pressure is maintained by the membrane placed on the patient's shoulders. The primary difference between this and Infant Flow driver (IFD) CPAP is that the latter applies pressure to the nose, with a loss of the applied pressure around the prongs and through the mouth, whereas the helmet device applies pressure to both the nose and the mouth, without any loss.

There is some concern, however, about the cerebral perfusion pressure in the neonates studied [16], due to the outside positive pressure applied to their head, fontanel, neck, and shoulders. We hypothesized that this positive pressure counterbalances the brain perfusion pressure by reducing it. Our main goal was to compare the noninvasive NIRS assessment of absolute CBF and relative CBV using the neonatal helmet CPAP and the IFD CPAP.

Patients and methods

CPAP devices

The neonatal helmet CPAP (StarMed, Mirandola, Modena, Italy) is a prototype device made of transparent polycarbonate (Fig. 1 shows the latest prototype, in which the oximeter and manometer of the devices that we describe have been improved). It is a bed comprising two basic parts: at the top end there is a sealed hood (connected directly to the inspiratory line of the circuit by a dedicated port) where the pressure in the chamber is detected and continuously displayed on an aneroid manometer (Dwyer Instruments, Michigan City, Ind., USA). Another, expiratory outlet port is provided where a positive end-expiratory pressure (PEEP) valve enables the pressure in the system to be adjusted as required. Between the pressure hood and the PEEP valve an oximeter (Criterion OxiCheck, Caradyne, Ireland) continuously monitors FIO2. The pressure chamber is kept separate from the rest of the bed by a transparent latex-free polyurethane membrane. This cone-shaped membrane has a hole in the middle for the patient's head. Due to the pressure in the chamber this soft membrane becomes a loose collar around the neck, adhering to the patient's shoulders with a comfortable sealing effect. A soft strap secures the baby to the bed. The space in the pressure chamber around the patient's head is approx. 2.5 l, but the high, continuous flow of fresh gases being delivered through the chamber (ranging between 8–10 l/min) means that the dead space is negligible.

Fig. 1
figure 1

The neonatal helmet CPAP prototype (StarMed, Mirandola, Modena, Italy)

As a standard nasal CPAP system we used the IFD) (Hamilton Medical, Reno, Nev., USA; Electro Medical Equipment, Brighton, UK). CPAP pressure was adjusted by varying the flow rate, and the largest prongs that could fit easily into the nostrils were used in each infant [17].

Study design and patient selection

The study was conducted at the Neonate Intensive Care Unit of the Pediatric Department, Padua University Medical School, between January 2003 and May 2003. Premature infants with a postnatal age over 24 h receiving nasal CPAP for apnea or mild respiratory distress but otherwise medically stable were eligible for the study (Table 1); 17 infants were enrolled (median age 5 days, range 2–48) with a median gestational age of 26 weeks (range 24–32) and median birth weight of 850 g (599–1440). The neonates were studied while awake or asleep. If necessary, the child was calmed with a glucose-coated pacifier.

Table 1 Patients' characteristics and clinical data at the time of the study (GA gestational age, BW birth weight, HMD hyaline membrane disease, PDA patent ductus arteriosus, BPD bronchopulmonary dysplasia)

A crossover study was conducted to assess CBF and ΔCBV changes in very low birth weight infants (≤ 1500 g) treatment using two CPAP devices with a continuous distending pressure of 4 mbar. Each infant was evaluated for two 60-min periods, one with neonatal helmet CPAP and the other with IFD CPAP. The initial choice of CPAP was randomized by drawing a sealed, numbered envelope. Before each recording a suitable interval was allowed to change the device and stabilize the patient. The CPAP level was kept constant regardless of the type of device being used. The fraction of inspired oxygen (FIO2) was adjusted to keep pulse oximetry saturation (SpO2) in the range of 92–96%. During the assessment the CPAP level, FIO2, breathing rate, heart rate, SpO2 (Agilent Technologies, Böblingen, Germany), and transcutaneous PaO2 (tcPO2) and PaCO2 (tcPCO2) (TCM3, Tina Radiometer Electrode, Copenhagen, Denmark; Linde Medical Sensors, Basel, Switzerland) were monitored continuously. Mean arterial blood pressure (MABP) was obtained using a monitor (Agilent) and an indwelling umbilical or peripheral arterial catheter or an automated oscillometric monitor (Dinamap model 8100, Critikon, Tampa, Fla., USA). The infants were nursed in their incubators in a thermoneutral environment, and care was continued as usual. All infants were lying supine and fed continuously through an orogastric tube. Before the study the patients also underwent brain ultrasound scan (HDI 3000 CV, Advanced Technology Laboratories, Bothell, Wash., USA).

Skin temperature was recorded at the start and end of each recording. At the end of the study the number of significant desaturations (episodes with SpO2 < 85%) while the infant was receiving either neonatal helmet CPAP or IFD CPAP were evaluated. Ethical approval was obtained for the study from the local ethics committee and informed consent was obtained from the parents.

NIRS and physiological measurements

NIRS measurements were obtained using the NIRO-300 oximeter (Hamamatsu Photonics, Japan). The design and features of this device are described elsewhere [18]. The optical probe consisted of one emitter and one detector optode (comprising three separate sensors) placed 5–6 cm apart. The emission and detection probes of the Near-Infrared Oxygenation Monitor (NIRO 300, Hamamatsu) were placed on the child's frontotemporal brain area to study the cerebral cortex and adjacent subcortical white matter. A computer-converted absorption changes at each wavelength recorded every 0.16 s into relative concentration changes in oxyhemoglobin (ΔO2Hb) and deoxyhemoglobin (ΔHHb). The changes are expressed in μmol/l, and the optical path length was calculated by multiplying the interoptode distance by 3.9 (the differential path length factor) [19]. To prevent ambient light from reaching the optodes a piece of dark felt covered the neonate's head when both the devices were used. The NIRO-300, based on the spatially resolved spectroscopy approach, provides relative concentration changes (expressed in μM) of O2Hb, HHb, and the derived total hemoglobin content (tHb = O2Hb+HHb), or tissue oxygenation index (TOI = O2Hb/tHb × 100). O2Hb and HHb concentration changes were calculated using the central sensor alone as a detector, an algorithm incorporating the modified Beer-Lambert law [18] and a differential path length factor. Since the hematocrit did not change during the study, changes in the infant's CBV were determined from the change in tHb, according to the formula ΔCBV = ΔtHb × 0.89/[Hgb], where [Hgb] is the infant's serum Hb concentration (g/dl), and 0.89 is a constant reflecting the large vessel to cerebral hematocrit ratio, brain density (g/ml), and the molecular weight of hemoglobin [1].

Spikes due to movement artifacts were not considered, and we thus analyzed only the NIRS data collected after obtaining a steady recording (averaged over 30 s: baseline) for both O2Hb and HHb, with both returning to the original baseline after each flow measurement. The basal chromophore trace enabled changes in ΔCBV (at least 100 changes) to be calculated after the 10th min from the beginning. The CBF measurements were taken using O2Hb as a tracer [20] as of the 15th min from the beginning. CBF was calculated by applying the Fick principle, i.e., a sharp rise in O2Hb is induced, coupled with a rise in SpO2 up to 100% of FIO2. CBF = k × Δ × (O2Hb-HHb)/(2 × Hgb × ∫ΔSaO2SpO2dt) [8, 21], where k is a constant incorporating the molecular weight of hemoglobin and the brain tissue density. In accordance with Elwell [19] we considered a brain tissue density of 1.05 g/ml, a molecular weight for hemoglobin of 64,500 and a cerebral to large vessels hematocrit ratio of 0.69. At least three CBF measurements were obtained, increasing FIO2 according to Fick's principle, to increase the SpO2 and O2Hb-HHb. CBF (ml 100 g–1 min–1) was calculated from the integral of the rise in saturation and the rate of the rise in O2Hb-HHb at 10 s.

Data analysis and statistics

Data are expressed as median (range). Assuming a symmetrical distribution of the differences, a Wilcoxon matched-pairs test was used to compare averaged NIRS measurements with IFD and helmet CPAP and to compare averaged tcPO2, tcPCO2, SpO2, heart rate, FIO2, breathing rate, MABP, desaturation rate, and skin temperature during the CPAP treatments. CBF measurements were attempted in all infants, but only traces that met the established criteria for stability of Sao2, tcPcO2, MABP, and tHb concentration were considered [19]. The reported data for each infant are the average of the accepted measurements. A repeated-measurements analysis was conducted on all CBF measurements obtained with the two CPAP devices using one-way within-subject analysis of variance. Statistical analysis used the Statistica Program for Windows, release 4.5. A p less than 0.05 was considered statistically significant.

Results

Median (range) CBF (ml 100 g–1 min–1) in helmet CPAP was 27.37 (9.47–48.20) as opposed to 34.74 (13.59–60.10) with the IFD CPAP (p = 0.049); repeated-measurements analysis showed lower values with helmet CPAP (F = 6.87, p = 0.01). Median (range) ΔCBV (ml/100 g) was 0.15 (0.09–0.28) with IFD, and 0.13 (0.07–0.27) with helmet CPAP (NS). During the CBF and CBV assessments our patients showed no changes in tcPCO2, MABP, breathing rate, or heart rate. Likewise there were no differences in their averaged physiological parameters (tcPCO2, tcPO2, SpO2, heart rate, breathing rate, MABP, desaturation rate, axillary temperature) during the 60 min in which each CPAP device was evaluated. Details on the neonates are summarized in Table 1; neonatal cerebral hemodynamic data, FIO2, and physiological variables during the study period are shown in Table 2. The NIRS trace of one neonate is shown in Fig. 2 and the distribution of CBFs in Fig. 3.

Fig. 2
figure 2

Typical time course of O2Hb and HHb changes in a newborn during three oxygen bolus in one of the two devices. Bolus oxygen induced an increase in O2Hb and a decrease in HHb; an increase in the tissue oxygenation index was also observed

Fig. 3
figure 3

Distribution of NIRS CBFs by IFD CPAP vs. helmet CPAP

Table 2 Neonatal cerebral hemodynamic data and physiological variables during the study period: median values (parentheses range)

Discussion

The main finding of this study is that ΔCBV did not change using the helmet vs. the IFD CPAP, although the absolute CBF was lower with helmet CPAP. CPAP is known to increase intrathoracic pressure, and therefore it may also increase central venous and intracranial pressure and reduce cardiac output [22]. Gregory et al. [23] described two CPAP delivery methods for treating respiratory distress syndrome through an endotracheal tube and through a plastic pressure chamber around the infant's head. We used a new delivery device, the neonatal helmet CPAP, that leaves the neck free and the positive pressure is maintained by a membrane lying on the patient's shoulders, a solution very different from the Gregory et al. device where the collar had a “garroting” effect on the baby [15]. Compared to nasal CPAP, the primary difference is that IFD CPAP applies pressure to the nose, with a loss of the applied pressure around the prongs and through the mouth, whereas the helmet device applies pressure to the head without any loss, and therefore a potential bias lies in the fact that the pressure values may not have always been the same. The neonatal helmet CPAP was introduced in our NICU to improve the patient-ventilator interface, a crucial aspect in the management of CPAP therapy according to Trevisanuto et al. [24]. The aim of the present study, however, was to assess the cerebral hemodynamic effects obtained with the new device.

Intraventricular hemorrhage and hydrocephalus [25], pneumothorax, neck ulceration, and 8th nerve damage have been reported [26] using head box CPAP. Studying the effects of positive and negative pressure on CBV in ventilated preterm newborn infants, Palmer et al. [2] found that initiating either positive or negative pressure ventilation produced a drop in CBV. We studied the cerebral hemodynamic effect of outside positive continuous pressure in terms of brain volume and flow as well as in terms of gases and physiological variables. Our CBF values are consistent with the measurements obtained by Greisen [27] using 133Xe clearance during CPAP treatment by comparison with mechanical ventilation. Moreover, Pellicer et al. [4] reported mean CBF and ΔCBV values during mechanical ventilation that are comparable with our findings using NIRS. The London University College group [5] has recently reported a lower CBF in preterm newborn infants subjected to high-frequency oscillatory ventilation. This was due more to hypocapnia than to the preterm infant's skull cap in the early days of life, but CBF seemed to increase over the following 3 days. We performed NIRS assessments of absolute CBF based on a 10-s increase in O2Hb-HHb, as in previous reports [6, 8, 20, 21].

Our main problem was the effect of the continuous distending positive pressure of 4 mbar around the neonate's head, neck, and shoulders and the effect on the cerebral perfusion pressure measured as CBF, assuming that MABP minus intracranial pressure equals the cerebral perfusion pressure. Critical closing cerebral perfusion pressure is affected more by perfusion pressure than by vessel tone or intracranial pressure [28]. A greater intracranial pressure has been found in ventilated infants [29], and it also increases during endotracheal suctioning [30]. Our MABP was around 50 mmHg, and we hypothesized an intracranial pressure below 8 mmHg [31] in our preterm group, and MABP-ICP thus should not in theory be counterbalanced by the outside CPAP, although a lower CBF was noted in helmet CPAP. Cerebral blood flow in neonates is about two-thirds [32] that of normal adults, which is reportedly 64.9 ± 9 ml 100 g–1 min–1 [33]. As far as we know, CBF depends on gestational age, postnatal age, and vascular homeostasis. Its assessment by NIRS includes a wide range of values, from 5 to 33 ml 100 g–1 min–1, averaging around 18 ml 100 g–1 min–1 [7, 34, 35, 36, 37, 38]. Both the different gestational ages and the different ages at evaluation could affect the homogeneity of our group. For instance, we considered each neonate individually and evaluated differences between the two devices. Given the range of CBF values we cannot currently say which of the two devices is safer in terms of brain perfusion and further studies on neonates are warranted. As Altman et al. [39] note, the threshold for brain viability with a normal outcome is around 5 ml 100 g–1 min–1 when measured by positron emission tomography, and this is much lower than the values found in our group. Moreover, although they were deemed clinically stable, our neonates may have been under the hemodynamic effects of drugs (i.e., caffeine) [40], and they may also have experienced two different states of physical well-being with the two different systems well [34]. In a more numerous group of subjects treated with helmet CPAP Trevisanuto et al. [15] demonstrated a lower Neonatal Infant Pain Scale score [41] than with IFD CPAP.

The lower CBF that we found with no concomitant changes in ΔCBV suggests a longer blood transit time [3, 8] with helmet CPAP. An increase in active (e.g., arterial) vasoconstriction and/or passive compression of capillary and/or venous vessel areas seems a most likely underlying mechanism [42] when there is a positive pressure around the head, neck, and shoulders by comparison with the airway pressure. Due to vasoconstriction and/or vasocompression CBF may also decrease in ventilated patients [42], although it decreases more when the newborn breathes against an external pressure than in IFD CPAP breathing. In NIRS studies CBV and CBF changes may be proportional. Adcock et al. [34] suggested that CBV is affected especially by the vascular bed, the diameter, and the recruitment of the vessels. CBF is related both to vascular bed and to mean arterial pressure, intracranial pressure, and blood viscosity, and therefore some conditions can affect CBV and CBF in unrelated ways.

We assessed CBF and ΔCBV as measured by NIRS using two CPAP systems and found no differences in relative blood volume, although CBF was lower during helmet CPAP. This result can be considered scarcely reassuring especially in view of the slightly higher tcPcO2 which would otherwise have raised CBF with no change in heart rate (and presumably in cardiac output). Moreover, both our findings (assessed on averaged data in each single subject) and those of Trevisanuto et al. [15] (assessed on averaged data in each device) revealed no changes in the physiological parameters studied, and in tcPcO2 in particular.

Conclusions

The change in CBF may not be clinically relevant although its correlation with a more comfortable condition warrants further investigation. Moreover, since the values remain within the reportedly normal CBF values for this population, further studies are needed to determine the safety of the new device and the effects of higher continuous pressure values.