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A Comparison of Pulse Oximetry and Near Infrared Spectroscopy (NIRS) in the Detection of Hypoxaemia Occurring With Pauses in Nasal Airflow in Neonates
Abstract
Objective:
The aim of this study was to compare the ability of NIRS and pulse oximetry to detect changes in cerebral oxygenation occurring in response to a pause in nasal airflow (PNA).
Methods:
Twenty-one recordings of cerebral oxygenation index by NIRS together with oxyhemoglobin saturation by pulse oximetry were measured on 17 preterm infants with a history of apnoea. Photoplethysmography was used to confirm the accuracy of the pulse oximetry data. PNA events were defined as pauses of greater than 4 seconds in a thermistor trace measuring nasal air flow.
Results:
Baseline variability in oxygenation index (Hbdiff) was found to be from -0.12 to +0.13 micromol 100 g brain(-1). A fall in Hbdiff or SpO2 was defined as a decrease of greater magnitude than 2 standard deviations from the baseline, i.e., -0.12 micromol 100 g brain(-1) and 3% respectively. In 68% of 468 PNA events a fall in oxyhemoglobin saturation (SpO2) was detected and in 56% a fall in Hbdiff was detected. In 20% of events there was no fall in cerebral oxygenation despite a fall in SpO2. In 8% of PNA episodes we recorded a fall in cerebral oxygenation but no fall in SpO2. When a fall in cerebral oxygenation was recorded, the fall was greater when the event was also associated with a fall in SpO2 (median (interquartile range (IQR)) 0.32 (0.21-0.69) vs. 0.25 (0.16-0.43) micromol 100 g brain(-1), p < 0.05). When all the PNA episodes were reviewed no close correlation was shown between the magnitude of change in cerebral oxygenation and the change in SpO2 for small changes in both indices. However, large falls (>1.5 micromol 100 g brain(-1)) in cerebral oxygenation were closely associated with large changes in SpO2.
Conclusions:
We conclude that both techniques are sensitive to changes in oxygenation during PNA. Small changes in cerebral Hbdiff and arterial SpO2 do not always correlate for physiological reasons. A change in Hbdiff of >0.3 micromol 100 g brain(-1) is likely to be physiologically significant and is associated with a change in SpO2 of 12%.
... As an indicator of peripheral capillary oxygen saturation detected by pulse oximeter and an indicator of cerebral oxygenation assessed by NIRS, the relationships between SpO 2 and NIRS during apneic episodes attracted the attention of the researchers. Both techniques are sensitive to hypoxia induced by the pause of respiration, and the changes in SpO 2 and cerebral oxygenation were found to be weakly correlated with small changes but strongly correlated in the case of for larger changes and severity SDB (77,82,94). The changes in SpO 2 were several seconds later than NIRS (76,77). ...
... A SpO 2 threshold was found in preterm infants during apneic episodes, where SpO 2 lowered to <85% would trigger a decrease in cerebral blood volume (95). Researchers have also quantified the changes in SpO 2 and StO 2 , which reported that the desaturation of SpO 2 was twice the reduction in StO 2 (92,94). There was no significant difference in CBV change for apnea with the same degree of desaturation at different durations of apnea. ...
Investigating cerebral hemodynamic changes during regular sleep cycles and sleep disorders is fundamental to understanding the nature of physiological and pathological mechanisms in the regulation of cerebral oxygenation during sleep. Although sleep neuroimaging methods have been studied and have been well-reviewed, they have limitations in terms of technique and experimental design. Neurologists are convinced that Near-infrared spectroscopy (NIRS) provides essential information and can be used to assist the assessment of cerebral hemodynamics, and numerous studies regarding sleep have been carried out based on NIRS. Thus, a brief historical overview of the sleep studies using NIRS will be helpful for the biomedical students, academicians, and engineers to better understand NIRS from various perspectives. In this study, the existing literature on sleep studies is reviewed, and an overview of the NIRS applications is synthesized and provided. The paper first reviews the application scenarios, as well as the patterns of fluctuation of NIRS, which includes the investigation in regular sleep and sleep-disordered breathing. Various factors such as different sleep stages, populations, and degrees of severity were considered. Furthermore, the experimental design and signal processing, as well as the regulation mechanisms involved in regular and pathological sleep, are investigated and discussed. The strengths and weaknesses of the existing NIRS applications are addressed and presented, which can direct further NIRS analysis and utilization.
... Several studies have analysed the association between TOI and SpO 2 during apneas in preterm infants (Schmid et al., 2015;Watkin et al., 1999;Yamamoto et al., 2003) or adults with moderate-to-severe OSAHS (Hausser-Hauw et al., 2000;Matsuo et al., 2011;Pizza et al., 2010;Valipour et al., 2002). Yamamoto et al. (2003) found that preterm infants had a tendency towards a parallel decrease in SpO 2 and cerebral oxygenation, represented by a parameter called 'haemoglobin oxygenation index', calculated as DO 2 Hb + DHHb. ...
... They observed that during the apneic attacks occurring at SpO 2 ≤ 85%, the reduction in cerebral oxygenation and the change in cerebral blood volume were greater than during attacks occurring at SpO 2 > 85%. However, it is not possible to compare their findings with ours or with those of Schmid et al. (2015) or Watkin et al. (1999), as they did not use the same parameters to assess cerebral oxygenation. ...
Near infrared spectroscopy (NIRS) has been used to assess the impact of obstructive sleep apnea-hypopnea syndrome (OSAHS) on cerebral oxygenation. However, the relationship between the variations in the cerebral tissue oxygen saturation (ΔTOI) and pulse oximetry (ΔSpO2 ) has not been assessed in children with OSAHS. Consecutive clinically stable children with severe OSAHS [apnea-hypopnea index (AHI) >15 events h(-1) ] diagnosed during a night-time polygraphy with simultaneous recording of cerebral oxygenation with NIRS (NIRO-200NX, Hamamatsu Photonics KK) were included between September 2015 and June 2016. Maximal ΔSpO2 (SpO2 drop from the value preceding desaturation to nadir) and concomitant variations in transcutaneous carbon dioxide (ΔPtcCO2 ), maximal ΔTOI and maximal variations in cerebral oxygenated (O2 Hb) and deoxygenated (HHb) haemoglobin were reported. The relationships between ΔSpO2 , ΔPtcCO2 and ΔTOI, ΔO2 Hb and ΔHHb were investigated. The data from five children (three boys, aged 9.6 ± 6.7 years, AHI 16-91 events h(-1) ) were analysed. Strong correlations were found between ΔSpO2 and ΔTOI (r = 0.887, P < 0.001), but also with ΔO2 Hb and ΔHHb with a particular pattern in the youngest child with a dark skin pigmentation. Mean ΔSpO2 was 20 ± 17% and mean ΔTOI was 8 ± 7%. Maximal ΔSpO2 of approximately 70% were coupled with ΔTOI of no more than 35%. ΔPtcCO2 correlated only weakly with the cerebral oxygenation indexes. This pilot study shows a strong relationship between pulse oximetry and cerebral oxygenation in children with OSAHS, with lower changes in TOI compared to SpO2 . Future studies should address the clinical impact of respiratory events on cerebral oxygenation and its consequences.
... In the search for noninvasive, continuous modalities for monitoring ischemia, electrical bioimpedance cardiac output monitoring has been proposed but shown to be incompatible with the thermodilution methods [65,66]. Again, while near-infrared spectroscopy (NIRS) [67] is shown to respond to both hypoxemia [68,69] and ischemia [70][71][72], its clinical use has been limited to large organs, such as the brain [73,74,[85][86][87] with its broad normal ranges reported to be between 48% and 88% [75,76]. Similarly, wide normal ranges are reported for sublingual capnography [77][78][79]. ...
... Visible light spectroscopy (VLS) appears to be similar to NIRS on some counts [81] with its mean VLS StO2 shown to be not significantly different from NIRS StO2 reported in human studies [67][68][69][70][71][72][73][74][75][76]. Again, the fractional contribution of venous blood to the cerebral NIRS signal has been reported to be 0.84 ± 0.21 ranging from 0.60 to 1.00 [82][83][84]. ...
Measurement of tumor hypoxia is required for the diagnosis of tumor and the evaluation of therapeutic outcome. Currently, invasive and noninvasive techniques being exploited for tumor hypoxia measurement include polarographic needle electrodes, immunohistochemical (IHC) staining, magnetic resonance imaging (MRI), radionuclide imaging (positron emission tomography [PET] and single-photon emission computed tomography [SPECT]), optical imaging (bioluminescence and fluorescence), and hypoxia imaging endoscopy. This review provides a summary of the modalities available for assessment of tissue oxygenation as well as a discussion of current arguments for and against each modality, with a particular focus on noninvasive hypoxia imaging with emerging agents and new imaging technologies intended to detect molecular events associated with tumor hypoxia.
... Near-infrared spectroscopy (NIRS) is a non-invasive method that is suitable for the continuous, in vivo monitoring of regional tissue oxygenation [78,79]. Similarly, to pulse oximetry, NIRS is based on the modified Beer-Lambert law which relates the attenuation of light to the characteristics of the material through which the light passes [79][80][81]. Since Hb displays different absorption of near-infrared light in response to changes in oxygen levels, changes in tissue oxygenation can be detected with NIRS [82]. ...
The majority of potentially preventable mortality in trauma patients is related to bleeding; therefore, early recognition and effective treatment of hemorrhagic shock impose a cardinal challenge for trauma teams worldwide. The reduction in mesenteric perfusion (MP) is among the first compensatory responses to blood loss; however, there is no adequate tool for splanchnic hemodynamic monitoring in emergency patient care. In this narrative review, (i) methods based on flowmetry, CT imaging, video microscopy (VM), measurement of laboratory markers, spectroscopy, and tissue capnometry were critically analyzed with respect to their accessibility, and applicability, sensitivity, and specificity. (ii) Then, we demonstrated that derangement of MP is a promising diagnostic indicator of blood loss. (iii) Finally, we discussed a new diagnostic method for the evaluation of hemorrhage based on exhaled methane (CH4) measurement. Conclusions: Monitoring the MP is a feasible option for the evaluation of blood loss. There are a wide range of experimentally used methodologies; however, due to their practical limitations, only a fraction of them could be integrated into routine emergency trauma care. According to our comprehensive review, breath analysis, including exhaled CH4 measurement, would provide the possibility for continuous, non-invasive monitoring of blood loss.
... Near-infrared spectroscopy (NIRS) uses an infrared light emitter and a sensor to measure blood flow and oxygen percentage in the tissue, which is determined by the amount of light absorbed. 3,[6][7][8][9][10][11] Hemoglobins absorb these near-infrared lights in different wavelengths depending on whether they are deoxygenated (660 nm) or oxygenated (940 nm). 12 The literature has extensive revisions on many devices and applications for medicine. ...
Free-flap monitoring is challenging to perform in some centers. It requires the availability of trained health care personnel for 24 hours a day and seven days a week. Many methods had been proposed for flap monitoring, and none of them are superior to clinical evaluation. This study aimed to present a murine model to evaluate the accuracy (sensitivity, specificity, and the positive or negative predictive values) of a device. Wistar rats weighing 240–490 g were included for intervention and data collection. A murine model of left inferior epigastric vessel flaps was implemented. Intermittent pedicle clamping was performed to calculate the accuracy of the device that detects flow obstruction. The general variables studied were age, weight, and gender. The sensitivity, specificity, and negative or predictive values were calculated. The results showed a sensitivity of 97%, a specificity of 95% with a positive predictive value of 95%, and negative predictive value of 97%. The sensitivity and specificity showed excellent results within the range of clinical security. We require more data to analyze the multiparameter monitoring to see if it is feasible and cost-effective
... Variations exist due to in-vivo chromophores (hemoglobin and cytochrome-aa3) whose absorption characteristic vary by oxygenation status. This technique has been shown to accurately measure changes in neonatal cerebral blood volume, Watkin, et al. [54] but a Cochrane systematic review concluded that it fails to bear clinical value [55]. However 'Intensity-Modulated' NIR spectroscopy (IMNIRS) may permit measurement of cerebral saturation between contractions, potentially detecting relevant changes in fetal oxygen status. ...
... The authors concluded that both techniques are sensitive to changes in cerebral oxygenation. A fall of Hbdiff >0.3 mmol/100 g brain is likely to be clinically significant and is associated with DSaO2 of about 12% [5]. ...
The feasibility of non-invasive analysis of brain activities was studied in the attempt to overcome the major limitation of actual in vivo methodologies i.e. invasiveness. Optic fibre probes were used as optical head of a novel, highly sensitive near infrared continuous wave spectroscopy (CW-NIR) instrument. This prototype was designed for non-invasive analysis of the two main forms of haemoglobin: oxy-haemoglobin (HbO2) and deoxy-haemoglobin (Hb), chromophores present in biological tissues. It was tested in peripheral tissue (human gastrocnemius muscle) and then reset to perform measurement on rat brain. In animal studies, the optical head was firmly placed using stereotaxic apparatus upon the sagittal line of anaesthetised adult rat's head, without any surgery. Then pharmacological treatments with saline (300μl s.c.) amphetamine (2mg/kg) or nicotine (0.4mg/kg) were performed. Within 10-20 min amphetamine substantially increased HbO2 and reduced Hb control levels. Nicotine produced a rapid initial increase followed by a decrease of HbO2. In contrast to amphetamine, nicotine treatment also reduced Hb and blood volume. These results support the capacity of our CW-NIR prototype to measure non-invasively HbO2 and Hb levels in the rat brain, markers of the degree of tissue oxygenation, index of blood level then of the state of brain metabolism.
... Physiologic baseline variability of cHbD in humans has been described to range from −0.12 to +0.13 μmol 100 g −1 . 28 In the same study, a decrease in cHbD of >0.3 μmol 100 g −1 reflects the effect of reducing saO 2 by approximately 12%. Compared with these values, mean changes in cHbD of −1.0 μmol 100 g −1 could be physiologically important. ...
In order to explore the influence of decreasing flow rate on cerebral hemodynamics during veno-arterial extracorporeal membrane oxygenation (va-ECMO) six normoxemic and six hypoxemic piglets were put on va-ECMO. The ECMO flow rate was decreased from the maximal achievable level to 50 ml.min-1 with steps of 50 ml.min-1 every 2 minutes. Changes in mean arterial blood pressure (MABP), left common carotid artery blood flow (Qcar) and other physiologic variables were continuously measured. Changes in concentrations of oxyhemoglobin and deoxyhemoglobin were measured using near infrared spectrophotometry. Changes in difference between cerebral oxygen hemoglobin and deoxyhemoglobin concentration ([DELTA]cHbD) and total hemoglobin concentration ([DELTA]ctHb) were calculated. [DELTA]cHbD represents changes in cerebral blood flow (CBF), [DELTA]ctHb reflects changes in cerebral blood volume (CBV). Data analysis was performed using mixed models and demonstrated a significant positive correlation between ECMO flow and respectively MABP (r=0.7, p<.001), Qcar (r=0.7, p<.001), cHbD (r=0.8, p<.001) and ctHb (r=0.7, p<.001). There was no significant relation between oxygenation state preceding ECMO and Qcar, cHbD and ctHb during decreasing ECMO flow rate. We conclude that decreasing ECMO flow rate ultimately leads to concurrent decrease in MABP, CBF and CBV.
... The effect of cerebral autoregulation has already been shown in neonates during short periods of apnea. Watkin et al. [25] have investigated cerebral rSO 2 and SpO 2 measurements during apnea in neonates with apnea defined as a pause in nasal flow of [4 s. The authors found that small changes in SpO 2 or cerebral rSO 2 showed no correlation. ...
In this study we investigated the responsiveness of near-infrared spectroscopy (NIRS) recordings measuring regional cerebral tissue oxygenation (rSO2) during hypoxia in apneic divers. The goal was to mimic dynamic hypoxia as present during cardiopulmonary resuscitation, laryngospasm, airway obstruction, or the "cannot ventilate cannot intubate" situation. Ten experienced apneic divers performed maximal breath hold maneuvers under dry conditions. SpO2 was measured by Masimo™ pulse oximetry on the forefinger of the left hand. NIRS was measured by NONIN Medical's EQUANOX™ on the forehead or above the musculus quadriceps femoris. Following apnea median cerebral rSO2 and SpO2 values decreased significantly from 71 to 54 and from 100 to 65 %, respectively. As soon as cerebral rSO2 and SpO2 values decreased monotonically the correlation between normalized cerebral rSO2 and SpO2 values was highly significant (Pearson correlation coefficient = 0.893). Prior to correlation analyses, the values were normalized by dividing them by the individual means of stable pre-apneic measurements. Cerebral rSO2 measured re-saturation after termination of apnea significantly earlier (10 s, SD = 3.6 s) compared to SpO2 monitoring (21 s, SD = 4.4 s) [t(9) = 7.703, p < 0.001, r(2) = 0.868]. Our data demonstrate that NIRS monitoring reliably measures dynamic changes in cerebral tissue oxygen saturation, and identifies successful re-saturation faster than SpO2. Measuring cerebral rSO2 may prove beneficial in case of respiratory emergencies and during pulseless situations where SpO2 monitoring is impossible.
... between changes in peripheral oxygen saturation and rcSO 2 on a group of 17 infants with history of apnoea, as measured by peripheral saturation monitor and NIRS respectively (20). Petrova et al went on to demonstrate that, in a group of mechanically ventilated infants, the cerebral and renal tissue oxygenation associated with short periods of arterial desaturations did not significantly compromise oxygen utilisation in the cerebral tissue but increased TOE in renal tissue (21). ...
Brain injuries remain a significant problem for preterm infants, despite extensive physiological monitoring. Near infrared spectroscopy (NIRS) monitoring in the neonatal intensive care unit has to date remained limited to research activities.Conclusion
This review highlights the increasing clinical application of NIRS in delivery suites and neonatal units. Four randomised controlled trials incorporating NIRS monitoring suggest that the future may indeed be brighter for this technology in the care of very preterm infants.
... Using the incident light with constant intensity, continuous-wave (CW) NIRS [4] is suitable for clinical monitoring because of its convenience. Now CW NIRS has been clinically applied in many areas by some groups [5][6][7][8]. ...
In this paper, the biological tissue oxygen saturation (rSO2) is obtained non-invasively and in real time based on near infrared spectroscopy (NIRS) using two emitting wavelengths and two detectors, where the tissue is covered with overlying tissues. Our group developed an NIRS oximeter based on the above principle independently, and validated it using liquid tissue model calibrations and animal experiments. The results indicate that (1) in the normal range of tissue oxygen saturation (40–70%), the rSO2 measured by NIRS is accurate enough and little influenced by the background absorptions (such as the absorption of water) and overlying tissues (such as fat); (2) during cerebral hypoxia and recovery of three piglets, there is excellent correlation (p
... Since that, further more detailed NIRS investigations were carried out. The screening of cerebral oxygenation of preterm infants with NIRS was introduced by Watkin et al. [63]. A comparative study to conventional pulse oximetry was carried out focussing on the variations of cerebral oxygenation and brain hypoxia related to apnoea. ...
Constant development enabled Infrared (IR) spectroscopy to become a widely used, non-invasive tool for fast sample analyses with less to no pre-preparation. Furthermore, computational data handling is no more a limiting factor and hence, IR measurements are predestined for clinical diagnostics and drug analysis. Within this review the focus was put on clinical topics of high interest. One example is Alzheimer's disease, where the exact metabolism is still not clarified, or blood glucose monitoring for high throughput screening of patients without taking any drop of blood. The second section of this manuscript was focused on the analysis of drugs. The detection of physico-chemical parameters in pharmaceutics and the improvement of industrial proceedings allowed a dramatic increase of quality of produced medicine. In pharmaceutical industries problems with the equable allocation of agents occurs especially in scaling up processes. IR-analyzing-techniques serve as fast and precise indicators for the detection of active components and their distribution in tablets. In combination with statistical factors and medical investigations pharmaceuticals can be improved from their development until their application, and every step can be easily controlled by IR spectroscopy.
... Findings can be used to describe trends in a group of patients and the relevance can only be suspected when compared with studies where known risk factors for the brain are related to changes in NIRS variables. Baseline variability of HbD has been described to range from Ϫ0.12 to ϩ 0.13 mol ⅐ 100 ⅐ g Ϫ1 (33). With a variability of 0.03 Ϯ 0.01, this was lower in our study. ...
To determine the effects of bladderbox alarms during venoarterial extracorporeal membrane oxygenation (va-ECMO) on cerebral oxygenation and hemodynamics, six lambs were prospectively treated with va-ECMO and bladderbox alarms were simulated. Changes in concentrations of oxyhemoglobin (deltacO2Hb), deoxyhemoglobin (deltacHHb), and total Hb (deltactHb) were measured using near infrared spectrophotometry. Fluctuations in Hb oxygenation index (deltaHbD) and cerebral blood volume (deltaCBV) were calculated. Heart rate (HR), mean arterial pressure (MAP), blood flow in the left carotid artery (Qcar), and central venous pressure (CVP) were registered. Bladderbox alarms were simulated by increasing the ECMO flow or partially clamping the venous cannula and resolved by decreasing the ECMO flow, unclamping the cannula, or intravascular volume administration. CBV, HbD, MAP, and Qcar decreased significantly during bladderbox alarms, whereas HR and CVP increased. After the bladderbox alarms, CBV and HbD increased significantly to values above baseline. For HbD, this increase was higher during intravascular volume administration.MAP, Qcar, and CVP recovered to preexperiment values but increased further with volume administration. HR was increased at the end of our measurements. We conclude that Bladderbox alarms during va-ECMO treatment result in significant fluctuations in cerebral oxygenation and hemodynamics, a possible risk factor for intracranial lesions.
... Changes in SaO 2 using pulse oximetry have been compared with changes in Hbdiff using NIRS in preterm infants. 31 During pauses in nasal airflow, a fall in SaO 2 was observed in 68% and a fall in Hbdiff in 56%. Although the degree of concordance was high for large amplitude changes, in 20% no fall in Hbdiff occurred despite a fall in SaO 2 and in 8% the converse was true. ...
Efforts have been made to find new, non-invasive methods for assessing tissue oxygenation and haemodynamics, particularly in the brain of the fetus and the newborn infant. Near infrared spectroscopy (NIRS) is a developmental technique that provides just such a method, allowing calculation of variables such as cerebral blood flow and cerebral blood volume. It can also measure peripheral oxygen consumption. This review is based on our long experience of using NIRS. Basic principles, techniques, validation, and clinical applications are highlighted. Although more than two decades have passed since its introduction, NIRS remains very much a developmental technique, despite technical progression. A great deal more research is required for NIRS to become a routine clinical tool.
... Based on detection of HbO 2 and Hb, the measurement of CBF using NIRS was first described by Edwards et al (1988), who applied HbO 2 as a tracer to assess the cerebral hemodynamics in infants, and then made the observation using NIRS in cerebral hemodynamics of effects of treatment with modified natural surfactant (Edwards et al 1992). Other researchers (Brazy et al 1985, Bucher et al 1993, Watkin et al 1999) assessed the oxygen state of brain tissue and CBF in preterm infants. If occlusion (venous or arterial occlusion) happens, both oxyhemoglobin and hemoglobin would change; there is a clear increase in HbO 2 , Hb as venous occlusion occurs; following arterial occlusion, there is an abrupt decrease in HbO 2 and increase in Hb (Hassan et al 2000). ...
This paper introduces a method of monitoring cerebral oxygenation for healthy neonates and neonates with hypoxic-ischemic encephalopathy (HIE) using near-infrared spectroscopy. The object of this study was to investigate whether or not there were differences between the HIE group and the healthy group in terms of NIRS parameters. The subjects were all term neonates, their age ranging from 2 to 18 days. The healthy group included 25 subjects while the HIE group consisted of 16 patients. A prototype NIRS instrument, which provides the data of tissue oxygenation including regional oxygen saturation (rSO2), the increment of oxyhemoglobin concentration and hemoglobin (deltaHbO2 and deltaHb) was used, and the data of rSO2 was compared with the data from the blood gas analyzer. The result shows that: (1) the mean+/-SD of rSO2 for the healthy group was 62 +/- 4% in the frontal region under the quiet sleep condition, but the mean+/-SD of rSO2 for the HIE group was 53 +/- 3%. (2) As all subjects inhaled pure oxygen in 21 min(-1) for a period of 60 s, rSO2 for the healthy group increased rapidly, with the increase in rSO2 (deltarSO2) being 7 +/- 2.3%, but the increase in rSO2 for the HIE neonates was 3 +/- 1.5%. After inhaling oxygen, deltaHbO2 and deltaHb between the two groups were also significantly different. (3) During all the experiments SpO2 was monitored, the value of SpO2 was not significantly different between the two groups. The above observations suggest that the rSO2 in quiet condition and the values of change of rSO2, HbO2 and Hb during the inhalation of oxygen may be used as the parameters to discover and assess the HIE infants.
... The authors concluded that both techniques are sensitive to changes in cerebral oxygenation. A fall of Hbdiff >0.3 mmol/100 g brain is likely to be clinically significant and is associated with DSaO2 of about 12% [5]. ...
Near infrared spectroscopy (NIRS) was first used as a tool for the in vivo monitoring of tissue oxygenation in the late seventies. Today, NIRS instruments are more and more used in clinical environments since they are now easy to use, sensitive, robust, provide rapid analysis and could be complementary to other non invasive methodologies such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). The feasibility of non-invasive analysis of brain activities is studied in the attempt to overcome the major limitation of invasive in vivo methodologies. In the present work, optic fibre probes were used as optical head of a novel, highly sensitive near infrared continuous wave spectroscopy (CW-NIR) instrument adapted for in vivo NIRS measurements in the brain of rodents. This prototype was designed for non-invasive analysis of the 2 main forms of haemoglobin: oxy-haemoglobin (HbO(2)) and deoxy-haemoglobin (Hb), chromophores present in biological tissues as these are markers of the degree of tissue oxygenation, thus providing an index of blood level and therefore of tissue metabolism. It was first tested in peripheral tissue (human gastrocnemius muscle) and then reset to perform measurement on rat brain. In animal studies, the optical head was firmly placed using stereotaxic apparatus upon the sagittal line of anaesthetised adult rat's head, without any surgery. 'Physiologic' (i.e. with exogenous oxygen (O(2)) or carbon dioxide (CO(2)) supplied orally) or pharmacologic (i.e. with drugs of abuse such as cocaine) experiments have been performed to support the effectiveness of the methodology in preclinical studies. In addition, the possibility that changes in brain metabolism as measured by NIRS might be a useful index of brain penetration of new chemical entities has been investigated using different compounds from different chemical classes that were selected on the basis of their known brain penetration and overall pharmacokinetic profile. Finally, the feasibility of coupling NIRS with another although invasive in vivo method such as electrophysiology for concomitant analysis of cerebral cell firing in discrete brain areas was tested in the attempt to study in real time the putative correlation between blood levels, brain metabolism and neuronal activities in rat CNS, i.e. apply NIRS to pharmacodynamic investigations. The data gathered in rat treated with exogenous O(2), indicate an original relationship between NIRS analysis of brain metabolism and electrical changes in this major nucleus of CNS involved in neurophysiologic and pathologic activities.
During infancy sleep is at a lifetime maximum and the maturation of sleep is one of the most important physiological processes occurring during the first year of life, particularly the first 6 months. Sleep has a marked effect on cardiorespiratory control which is also rapidly maturing during infancy. Immaturity of cardiorespiratory control frequently leads to respiratory instability and prolonged pauses in breathing that manifest in apnoea of prematurity and periodic breathing. During infancy central apnoeas are common and obstructive apnoea rare. Although apnoea of prematurity is actively treated whilst preterm infants are in the neonatal intensive care unit (NICU), shorter apnoeas and periodic breathing go largely undetected and untreated. The hypoxia associated with apnoea of prematurity has been associated with adverse developmental outcomes, shorter central apnoeas are currently believed to be benign during this early period of development. However, there is growing evidence that these short central apnoeas may be associated with developmental deficits in neurocognition. Further research is required to optimise treatment of apnoea of prematurity and to identify if shorter central apnoeas also require treatment to improve developmental outcomes.KeywordsApnoea of prematurityPeriodic breathingPreterm infantNeurodevelopment
Sleep disordered breathing (SDB) is a common condition in infants and children. SDB encompasses a spectrum of respiratory disorders, which are defined as either obstructive or central in nature. Obstructive SDB ranges in severity from primary snoring (PS), to obstructive sleep apnea (OSA). There are a number of conditions characterized by central sleep apnea (CSA), including but not limited to periodic breathing in infants, Arnold Chiari malformations, and idiopathic CSA. SDB is associated with adverse cardiovascular and neurocognitive outcomes believed to be the consequence of the repeated cycles of hypoxia followed by reperfusion, hypercarbia, and sleep fragmentation. The peripheral hypoxia in individuals with SDB may not reflect cerebral oxygenation, and near infrared spectroscopy (NIRS) has been used to determine oxygen delivery and uptake in the brain. Neuroimaging in the form of structural and functional magnetic resonance imaging (MRI, fMRI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) have become widely used to determine the structural, functional and chemical changes in the brain associated with SDB. This review will explore the relationship between central and obstructive SDB and changes in cerebral oxygenation together with changes in brain structure and function, in infants and children. It is important to identify any adverse effects so that they can be mitigated as early as possible to minimize any detrimental effects on the developing brain.
Background
The diagnosis of stroke in the prehospital environment is the subject of intense interest and research. There are a number of non-invasive external brain monitoring devices in development that utilize various technologies to function as sensors for stroke and other neurological conditions. Future increased use of one or more of these devices could result in substantial changes in the current processes for stroke diagnosis and treatment, including transportation of stroke patients by emergency medical services.
Aims
The present review will summarize information about 10 stroke sensor devices currently in development, utilizing various forms of technology, and all of which are external, non-invasive brain monitoring devices.
Summary of review
Ten devices are discussed including the technology utilized, the indications for use (stroke and, when relevant, other neurological conditions), the environment(s) indicated for use (with a focus on the prehospital setting), a description of the physical structure of each instrument, and, when available, findings that have been published in peer-reviewed journals or otherwise reported. The review is organized based on the technology utilized by each device, and seven distinct forms were identified: accelerometers, electroencephalography (EEG), microwaves, near-infrared, radiofrequency, transcranial doppler ultrasound, and volumetric impedance phase shift spectroscopy.
Conclusions
Non-invasive external brain monitoring devices are in various stages of development and have promise as stroke sensors in the prehospital setting. Some of the potential applications include to differentiate stroke from non-stroke, ischemic from hemorrhage stroke, and large vessel occlusion (LVO) from non-LVO ischemic stroke. Successful stroke diagnosis prior to hospital arrival could transform the current diagnostic and treatment paradigm for this disease.
The authors evaluated the ability of visible light spectroscopy (VLS) oximetry to detect hypoxemia and ischemia in human and animal subjects. Unlike near-infrared spectroscopy or pulse oximetry (SpO2), VLS tissue oximetry uses shallow-penetrating visible light to measure microvascular hemoglobin oxygen saturation (StO2) in small, thin tissue volumes.
In pigs, StO2 was measured in muscle and enteric mucosa during normoxia, hypoxemia (SpO2 = 40-96%), and ischemia (occlusion, arrest). In patients, StO2 was measured in skin, muscle, and oral/enteric mucosa during normoxia, hypoxemia (SpO2 = 60-99%), and ischemia (occlusion, compression, ventricular fibrillation).
In pigs, normoxic StO2 was 71 +/- 4% (mean +/- SD), without differences between sites, and decreased during hypoxemia (muscle, 11 +/- 6%; P < 0.001) and ischemia (colon, 31 +/- 11%; P < 0.001). In patients, mean normoxic StO2 ranged from 68 to 77% at different sites (733 measures, 111 subjects); for each noninvasive site except skin, variance between subjects was low (e.g., colon, 69% +/- 4%, 40 subjects; buccal, 77% +/- 3%, 21 subjects). During hypoxemia, StO2 correlated with SpO2 (animals, r2 = 0.98; humans, r2 = 0.87). During ischemia, StO2 initially decreased at -1.3 +/- 0.2%/s and decreased to zero in 3-9 min (r2 = 0.94). Ischemia was distinguished from normoxia and hypoxemia by a widened pulse/VLS saturation difference (Delta < 30% during normoxia or hypoxemia vs. Delta > 35% during ischemia).
VLS oximetry provides a continuous, noninvasive, and localized measurement of the StO2, sensitive to hypoxemia, regional, and global ischemia. The reproducible and narrow StO2 normal range for oral/enteric mucosa supports use of this site as an accessible and reliable reference point for the VLS monitoring of systemic flow.
Preterm birth rates are rising, and many preterm infants have breathing difficulty after birth. Treatments for infants with prolonged breathing difficulty include oxygen therapy, exogenous surfactant, various modes of respiratory support, and postnatal corticosteroids. In this Series paper, we review the history of neonatal respiratory care and its effect on long-term outcomes, and we outline the future direction of the research field. The delivery and monitoring of oxygen therapy remains controversial, despite being in use for more than 50 years. Exogenous surfactant replacement has been used for 25 years and has dramatically reduced mortality and morbidity, but more research on when and how it is administered is needed. Methods and techniques of neonatal respiratory support are evolving. Clinicians are moving away from routine intubation and ventilation, and new modes of non-invasive support are being investigated. Postnatal corticosteroids have a limited role in infants with evolving bronchopulmonary dysplasia, but more research is needed to identify the best timing, type, dose, and method of administration. Despite advances in neonatal care in the past 50 years, bronchopulmonary dysplasia, with all its adverse short-term and long-term consequences, is still a serious problem in neonatal care. The challenge remains to support breathing in preterm infants, with special attention to risk factors in the subpopulation of infants that are at highest risk of bronchopulmonary dysplasia, without damaging their lungs or adversely affecting their long-term health.
Objective:
To assess the incidence and impact of persistent apnea on heart rate (HR), oxygen saturation (SpO2), and brain tissue oxygenation index (TOI) over the first 6 months after term equivalent age in ex-preterm infants.
Study design:
Twenty-four preterm infants born between 27 and 36 weeks of gestational age were studied with daytime polysomnography at 2-4 weeks, 2-3 months, and 5-6 months post-term corrected age. Apneas lasting ≥3 seconds were included and maximal percentage changes (nadir) in HR, SpO2, and tissue oxygenation index (TOI, NIRO-200 Hamamatsu) from baseline were analyzed.
Results:
A total of 253 apneas were recorded at 2-4 weeks, 203 at 2-3 months, and 148 at 5-6 months. There was no effect of gestational age at birth, sleep state, or sleep position on apnea duration, nadir HR, SpO2, or TOI. At 2-4 weeks, the nadirs in HR (-11.1 ± 1.2 bpm) and TOI (-4.4 ± 1.0%) were significantly less than at 2-3 months (HR: -13.5 ± 1.2 bpm, P < .05; TOI: -7.5 ± 1.1 %, P < .05) and at 5-6 months (HR: -13.2 ± 1.3 bpm, P < .01; TOI: -9.3 ± 1.2%, P < .01).
Conclusions:
In ex-preterm infants, apneas were frequent and associated with decreases in heart rate and cerebral oxygenation, which were more marked at 2-3 months and 5-6 months than at 2-4 weeks. Although events were short, they may contribute to the adverse neurocognitive outcomes that are common in ex-preterm children.
Near-infrared spectroscopy (NIRS) has several significant advantages over existing radiological techniques in clinical application. Humans do face any accumulation of deleterious x-rays. Unlike ultrasound methods, NIRS does not lead to excess heat, can differentiate between human tissues with varying optical absorption or scatter, can provide functional information, and can measure oxygenation in human tissues without the use of radioisotopes or other contrast agents. However, NIRS has some disadvantages. Quantifying changes with NIRS requires the use of magnetic resonance (MR) or computed tomography (CT) data. Converting measured optical density to Hb/Mb saturation requires the use of complex formulas. Due to their complexity, the formulas will yield inaccurate measurements arising from even small signal interferences.
Background:
Episodes of hypoxemia and bradycardia frequently occur with apnea of prematurity in preterm infants. Little is known about the impact of different event types on the brain.
Objectives:
To describe the influence of hypoxemia and bradycardia, either isolated or in combination, on cerebral oxygenation.
Methods:
In 16 preterm infants with intermittent hypoxemia and/or bradycardia, cerebral tissue oxygen saturation (StO2, as measured by near-infrared spectroscopy), heart rate and pulse oximetric saturation (SpO2) were recorded simultaneously for 16 h. Events were classified as isolated bradycardia (type 1), isolated hypoxemia (type 2) or combined (simultaneous, type 3; bradycardia first, type 4; hypoxemia first, type 5). Primary outcome was a score representing the area below baseline for cerebral StO2 desaturation during an event. Secondary outcomes were duration and depth of cerebral desaturation.
Results:
Patients had a median (range) gestational age of 25.9 (22.6-30.4) weeks and a postnatal age of 32.5 (7-58) days. The median (quartiles) number of events was 49 (34-58). Isolated hypoxemias were the most frequent events (24; 9-36) and isolated bradycardias the least common (0; 0-1). Cerebral StO2 baseline was not different between event types. Cerebral desaturation score, duration of event and depth of cerebral desaturation were smallest for isolated bradycardias and largest for combined events, especially for those starting with hypoxemia followed by bradycardia. Regardless of event type, 12/16 infants maintained cerebral StO2 >60% despite severe SpO2 desaturations.
Conclusions:
Isolated bradycardias had the lowest impact on cerebral desaturation, and combined events had the highest. Most infants preserved cerebral oxygenation >60% during events.
Background
While the use of supplemental oxygen has a long history in neonatal care, resulting in both significant health care benefits and harms, uncertainty remains as to the most appropriate range to target blood oxygen levels in preterm and low birth weight infants. Potential benefits of higher oxygen targeting may include more stable sleep patterns and improved long‐term growth and development. However, there may be significant deleterious pulmonary effects and health service use implications resulting from such a policy.
Objectives
To determine whether targeting ambient oxygen concentration to achieve a lower vs. higher blood oxygen range, or administering restricted vs. liberal supplemental oxygen, effects mortality, retinopathy of prematurity, lung function, growth or development in preterm or low birth weight infants.
Search strategy
The standard search strategy of the Neonatal Review Group was used. An additional literature search was conducted of the MEDLINE and CINAHL databases in order to locate any trials in addition to those provided by the Cochrane Controlled Trials Register (CENTRAL/CCTR). Search updated to week two July 2008.
Selection criteria
All trials in preterm or low birth weight infants utilising random or quasi‐random patient allocation in which ambient oxygen concentrations were targeted to achieve a lower vs. higher blood oxygen range, or restricted vs. liberal oxygen was administered were eligible for inclusion.
Data collection and analysis
The methodological quality of the eligible trials was assessed independently by each review author for the degree of selection, performance, attrition and detection bias. Data were extracted and reviewed independently by the each author. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group.
Main results
In the meta‐analysis of the five trials included in this review, the restriction of oxygen significantly reduced the incidence and severity of retinopathy of prematurity without unduly increasing death rates The one prospective, multicenter, double‐blind, randomized trial investigating lower vs. higher blood oxygen levels from 32 weeks postmenstrual age showed no significant differences in the rates of ROP, mortality or growth and development between the two groups. However, this study did show increased rates of chronic lung disease and home oxygen use.
Authors' conclusions
The results of this systematic review confirm that (the now historical) policy of unrestricted, unmonitored oxygen therapy has potential harms without clear benefits. However, the question of what is the optimal target range for maintaining blood oxygen levels in preterm/LBW infants was not answered by the data available for inclusion in this review.
Plain Language Summary
Restricted versus liberal oxygen exposure for preventing morbidity and mortality in preterm or low birth weight infants
Restricting oxygen supplementation significantly reduces the rate and severity of vision problems (retinopathy) in premature and low birth weight babies. Babies born either prematurely (before 37 weeks) or with a low birth weight often have breathing problems and need extra oxygen. Oxygen supplementation has provided many benefits for these babies but can cause damage to the eyes (retinopathy) and lungs. The review of trials found that unrestricted oxygen supplementation has these potential adverse effects without any clear benefits. Restricted oxygen significantly reduces these risks. More research is needed to find the best level of oxygen supplementation.
Objective To test the hypothesis that a higher pulsoximetric arterial oxygen saturation (SpO2) target range is associated with reduced cerebral tissue oxygen desaturations from baseline during events of hypoxaemia or bradycardia.
Design Randomised crossover trial.
Setting Single tertiary care neonatal intensive care unit.
Patients Sixteen preterm infants with severe intermittent hypoxaemia or bradycardia.
Interventions SpO2 target was set to 80–92% and 85–96% for 4 h each in random sequence. On a subsequent day, the target sequence was reversed and the study was repeated.
Main outcome measures We simultaneously recorded cerebral tissue oxygen saturation (cerebral StO2), SpO2 and heart rate. Cerebral StO2 was measured by near infrared spectroscopy. The primary outcome was the cumulative cerebral StO2 desaturation score representing the area below a cerebral StO2 baseline value before onset of each hypoxaemic or bradycardic event.
Results During low SpO2 target range the median (IQR) cumulative cerebral StO2 desaturation score was higher (27384 (15825–37396) vs 18103 (6964–32946), p=0.011) and the mean (±SD) number of events was higher (29.1 (±15.3) vs 21.1 (±11.4), p=0.001). More time was spent with SpO2 below 80% (57.2 (±24.8) min vs 34.0 (±29.6) min, p=0.006). Total time of hyperoxaemia (defined as SpO2 ≥97% and ≥99%, respectively) and total time with cerebral StO2 <60% and <55% were similar.
Conclusions A lower SpO2 target range was associated with a greater cumulative cerebral StO2 desaturation score, caused by more frequent SpO2 desaturations. However, time at very low cerebral StO2 was not affected. Episodes of hyperoxaemia were not reduced.
Insufflation of carbon dioxide (CO(2)) to the operative field has been used to prevent major organ injury attributed to air embolisms in cardiac surgery. However, it may be preferable to avoid hypercapnia induced by CO(2) insufflation, owing to its potentially harmful effect. To investigate the effectiveness of near-infrared spectroscopy (NIRS) as a possible method for continuous monitoring of arterial CO(2) tension during cardiac surgery, we evaluated the correlation between the change in arterial CO(2) tension and the change in regional cerebral oxygen saturation (rScO(2)) obtained from NIRS in as controlled a condition as possible.
Thirty patients who underwent surgical correction for atrial or ventricular septal defects were enrolled in this study. Patients who had pulmonary hypertension or other intracardiac anomalies were excluded. Anesthetic and cardiopulmonary bypass (CPB) management were conducted according to our standard institutional practice. Data obtained from arterial blood gas analyses and corresponding regional cerebral oxygen saturation (rScO(2)) recorded from NIRS before and after the insufflations of CO(2) during CPB were used for analysis.
The change in arterial CO(2) tension correlated with the change in rScO(2) in the left hemisphere (r = 0.681, p <0.001, y = -1.393 + 0.547x) and right hemisphere (r = 0.690, p <0.001, y = -1.999 + 0.486x). To control the effects of other variables, including hematocrit and temperature, these relationship were not reduced (left hemisphere: r=0.678, p<0.001; right hemisphere: r=0.634, p<0.001).
Since the change in regional cerebral oxygen saturation was correlated with the change in arterial CO(2) tension during mild hypothermic CPB, NIRS might be a possible non-invasive method for monitoring of arterial CO(2) tension without incurring additional cost in this setting.
The microcirculation plays an essential role in health and disease. Microvascular perfusion can be assessed directly using laser Doppler flowmetry and various imaging techniques or indirectly using regional capnometry and measurement of indicators of mismatch between oxygen delivery and oxygen consumption or indices of disturbed cellular oxygen utilization. Assessment of microvascular oxygen availability implies measurement of oxygen pressure or measurement of hemoglobin oxygen saturation. Microvascular function is assessed using other methods, including venous plethysmography. In this paper, I review current knowledge concerning assessment of the microcirculation with special emphasis on methods that could be used at the bedside.
Analysis of cerebral and systemic hemodynamic consequences of ultrasound dilution cardiac output measurements.
: Prospective, experimental piglet study.
Animal laboratory.
Nine piglets.
Ultrasound dilution cardiac output measurements were performed in ventilated, anesthetized piglets. Interventions that are required for ultrasound dilution cardiac output measurement were evaluated for its effect on cerebral and systemic circulation and oxygenation.
DeltacHbD and DeltactHb, representing changes in cerebral blood flow and cerebral blood volume, respectively, were measured with near infrared spectrophotometry. Pulmonary artery (Q) and left carotid artery (Q) blood flow were assessed with transit time flow probes. Starting and/or stopping blood flowing through the arteriovenous loop did not cause relevant hemodynamic changes. Fast injection of isotonic saline caused a biphasic change in DeltacHbD and DeltactHb. After injection of 0.5 mL/kg, the mean (sd) increase in DeltacHbD and DeltactHb was 0.175 (0.213) micromol/L and 0.122 (0.148) micromol/L, respectively, with a subsequent mean decrease of -0.191 (0.299) micromol/L and -0.312 (0.266) micromol/L. Injection of 1.0 mL/kg caused a mean increase in DeltacHbD and DeltactHb of 0.237 (0.203) micromol/L and 0.179 (0.162) followed by a mean decrease of -0.334 (0.407) micromol/L and -0.523 (0.335) micromol/L, respectively. Q and Q changed shortly with a mean increase of 5.9 (3.0) mL/kg/min and 0.23 (0.10) mL/kg/min after injection of 0.5 mL/kg and with 12.0 (4.2) mL/kg/min and 0.44 (0.18) mL/kg/min after injection of 1.0 mL/kg, respectively. The observed changes were more profound after an injection volume of 1.0 mL/kg compared with 0.5 mL/kg for DeltacHbD (p = .06), DeltactHb (p = .09), Q, and Q (p < .01). No relevant changes in mean arterial blood pressure or heart rate were detected in response to the indicator injection.
Cardiac output measurement by ultrasound dilution does not cause clinically relevant changes in cerebral and systemic circulation and oxygenation in a piglet model.
Hypoxia-ischemia constitutes a risk in infants by altering cerebral blood flow regulatory mechanisms and causing loss of cerebral vascular auto-regulation. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation leading to cell death and tissue damage. These dramatic phenomena represent a common repertoire in infants complicated by perinatal acute or chronic hypoxia. To date, despite accurate perinatal and intra-operative monitoring, the post-insult period is crucial, since clinical symptoms and monitoring parameters may be of no avail and therapeutic window for pharmacological intervention (6-12 hours) may be limited, at a time when brain damage is already occurring. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk infants. The present review is aimed at investigating the role as circulating biochemical markers such as adrenomedullin, S100B, activin A, neuronal specific enolase (NSE), glial fibrillary acid protein (GFAP), in the cascade of events leading to ischemia reperfusion injury in infants complicated by perinatal asphyxia.
To assess the effect of the duration of spontaneous hypoxic episodes and variations in haemodynamic parameters on cerebral and renal tissue oxygenation (rSo(2)C and rSo(2)R) in clinically stable preterm infants.
Observational study.
Neonatal intensive care unit of a university-affiliated children's hospital. Patients rSo(2)C and rSo(2)R and haemodynamic parameters were recorded for 2-3 h (once or twice) in clinically stable preterm neonates (n=10) using near-infrared spectroscopy, GE DASH 4000 and Bedmaster Software.
rSo(2)C and rSo(2)R and fractional oxygen extraction (cerebral and renal fractional oxygen extraction: FOE-C and FOE-R, respectively) in association with the duration of pulse oximetry desaturation (pulse oximetry saturations (Sao(2)) < or =84%), bradycardia (heart rate < or =90 beats/min) and hypotension (mean blood pressure (MBP) <30 mm Hg).
Among the 14 sets of recorded measurements, 128 hypoxic episodes with 5-10 (n=41), 15-20 (n=26), 25-30 (n=78), 35-40 (n=14), 45-50 (n=25) and > or =55 s (n=16) duration were identified. Prolongation of hypoxic episodes for more than 30 s was associated with major reductions in Sao(2), rSo(2)C and rSo(2)R without any significant changes in the regional FOE. Bradycardia occurred during 43.8% of hypoxaemic episodes of > or =55 s duration (p<0.01) and impacted the severity of the tissue deoxygenation. Decreased rSo(2)R and increased FOE-R were observed in association with mild hypotension irrespective of the systemic oxygenation status.
Prolongation of hypoxaemia contributes to the severity of the deoxygenation (systemic and regional) and development of bradycardia. In stable preterm neonates, mild decreases in MBP independently affect the renal but not cerebral tissue oxygenation and oxygen utilisation.
We evaluate the utility of near infrared spectroscopy monitoring and its correlation to conventional respiratory monitors during changes in cardiorespiratory characteristics during pediatric procedural sedation.
In this prospective observational study of 100 children, cerebral oxygenation (rSO(2)), pulse oximetry (SpO(2)), and end-tidal carbon dioxide (etco(2)) were monitored continuously. Values were manually recorded at least every 3 minutes from baseline until 30 minutes after sedative administration, resulting in 1,515 triplicate (simultaneous near infrared spectroscopy/etco(2)/SpO(2)) measurements. Correlations between conventional monitoring characteristics (SpO(2) and etco(2)) and rSO(2) were determined, with focus during adverse cardiorespiratory events.
Cerebral oxygenation remained normal in 1,483 of 1,515 measurements (97.9%). rSO(2) decreased significantly during 3 of 13 hypoxic events occurring in 13 patients and during 5 of 17 hypercarbic events occurring in 8 patients, with 15 measurements of greater than 20% decrease from baseline. Cerebral oxygenation increased transiently in 88% of children. During 31 cerebral desaturation recordings, 3 hypoxic recordings (9.3%, always in combination with hypercarbia) and 5 hypercarbic recordings (15.6%) were observed, whereas in 23 (74.2%), cardiorespiratory characteristics were unchanged. There was poor correlation between rSO(2) and both SpO(2) and etco(2), with correlation coefficients of 0.05 (95% confidence interval 0.04 to 0.07) and 0.01 (95% confidence interval -0.01 to 0.02), respectively.
Cerebral oxygenation as measured by near infrared spectroscopy demonstrated few significant negative changes during pediatric procedural sedation. Transient cardiorespiratory events seldom altered rSO(2), with hypercarbia having a greater effect than hypoxemia. However, cerebral desaturations frequently occurred without associated cardiorespiratory changes.
Background:
While the use of supplemental oxygen has a long history in neonatal care, resulting in both significant health care benefits and harms, uncertainty remains as to the most appropriate range to target blood oxygen levels in preterm and low birth weight infants. Potential benefits of higher oxygen targeting may include more stable sleep patterns and improved long-term growth and development. However, there may be significant deleterious pulmonary effects and health service use implications resulting from such a policy.
Objectives:
To determine whether targeting ambient oxygen concentration to achieve a lower vs. higher blood oxygen range, or administering restricted vs. liberal supplemental oxygen, effects mortality, retinopathy of prematurity, lung function, growth or development in preterm or low birth weight infants.
Search strategy:
The standard search strategy of the Neonatal Review Group was used. An additional literature search was conducted of the MEDLINE and CINAHL databases in order to locate any trials in addition to those provided by the Cochrane Controlled Trials Register (CENTRAL/CCTR). Search updated to week two July 2008.
Selection criteria:
All trials in preterm or low birth weight infants utilising random or quasi-random patient allocation in which ambient oxygen concentrations were targeted to achieve a lower vs. higher blood oxygen range, or restricted vs. liberal oxygen was administered were eligible for inclusion.
Data collection and analysis:
The methodological quality of the eligible trials was assessed independently by each review author for the degree of selection, performance, attrition and detection bias. Data were extracted and reviewed independently by the each author. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group.
Main results:
In the meta-analysis of the five trials included in this review, the restriction of oxygen significantly reduced the incidence and severity of retinopathy of prematurity without unduly increasing death rates The one prospective, multicenter, double-blind, randomized trial investigating lower vs. higher blood oxygen levels from 32 weeks postmenstrual age showed no significant differences in the rates of ROP, mortality or growth and development between the two groups. However, this study did show increased rates of chronic lung disease and home oxygen use.
Authors' conclusions:
The results of this systematic review confirm that (the now historical) policy of unrestricted, unmonitored oxygen therapy has potential harms without clear benefits. However, the question of what is the optimal target range for maintaining blood oxygen levels in preterm/LBW infants was not answered by the data available for inclusion in this review.
Near infrared spectroscopy (NIRS) uses light to monitor changes in the concentration of oxyhemoglobin and deoxyhemoglobin in living tissue non-invasively and in real time. Applications of NIRS in urology research and the strengths and limitations of this technology are reviewed.
A Medline and Pub-Med search using "spectroscopy" with heading terms: near infrared (NIR), near infrared spectroscopy (NIRS), urology, kidney, renal, urinary tract, bladder, prostate, testis and penis.
Research incorporating NIRS has investigated a range of urologic conditions where a hemodynamic or vascular etiology is thought to be the underlying pathophysiology: as an aid to diagnosis in cryptorchidism, testicular torsion and vasculogenic erectile dysfunction; to evaluate renal metabolism and bladder dysfunction, and to study skeletal muscle metabolism in end stage renal disease. Strengths and limitations of NIRS relate primarily to the basic physics of how light in the NIR spectrum penetrates tissue and is scattered and absorbed.
NIRS is a non-invasive, portable, real time measure of changes in tissue perfusion and oxygenation. In urology NIRS appears particularly applicable in ischemic conditions, and the evaluation of disorders associated with alterations in regional tissue hemodynamics (local changes in pressure, muscle contraction and urinary tract obstruction). Because the bladder detrusor can be interrogated transcutaneously NIRS may also provide a non-invasive means of evaluating patients with voiding dysfunction. Studies to date warrant further research and specific refinement of instrumentation and algorithm software for urologic applications, as NIRS could provide urologists with new methods of non-invasive physiologic diagnostic evaluation.
Objectives:
To evaluate whether application of a transducer on the anterior fontanelle during cranial ultrasound (US) examination effects cerebral hemodynamics and oxygenation in preterm infants. STUDY DESIGN*: During cranial US examination, changes in cerebral blood oxygenation (cHbD) and cerebral blood volume (CBV) were assessed using near infrared spectrophotometry (NIRS) in 76 infants (GA 30.7 (4.1)wk, BW 1423 (717)g) within two days after birth. Ten of these infants (GA 29.1 (1.6)wk, BW 1092 (455)g) were studied again at a postnatal age of one week. RESULTS*: We obtained stable and consistent NIRS registrations in 54 infants within the first two days after birth. Twenty-eight of these infants showed a decrease in cHbD (0.59 (0.54) micromol/100g) during the scanning procedure while CBV did not change. Twenty-four infants showed no changes in NIRS and 2 infants showed an atypical NIRS response during cranial US examination. At the postnatal age of one week, stable and consistent NIRS registrations were obtained in 7 infants. None of these infants showed changes in NIRS variables during cranial US examination.
Conclusions:
Application of an US transducer on the anterior fontanelle causes changes in cerebral oxygenation and hemodynamics in a substantial number of preterm infants. ( *values are expressed as median (interquartile range)).
Restricting oxygen supplementation significantly reduces the rate and severity of vision problems (retinopathy) in premature and low birthweight babies Babies born either prematurely (before 37 weeks) or with a low birthweight often have breathing problems and need extra oxygen. Oxygen supplementation has provided many benefits for these babies but can cause damage to the eyes (retinopathy) and lungs. The review of trials found that unrestricted oxygen supplementation has these potential adverse effects without any clear benefits. Restricted oxygen significantly reduces these risks. More research is needed to find the best level of supplementation.
To determine whether pulse oximetry-detected episodes of desaturation are associated with impairment of cerebral and somatic (renal) tissue oxygenation in mechanically ventilated preterm neonates.
Observational cross-sectional study.
Neonatal intensive care unit of a university-affiliated children's hospital.
Ten mechanically ventilated preterm (gestational age 24-32 wks) infants.
In addition to the traditional monitoring of hemodynamic variables that included pulse oximetry (Sao2), near-infrared spectroscopy (NIRS) was used to evaluate the cerebral and somatic (renal) tissue oxygen saturation (rSO2C and rSO2R, respectively).
A total of 40 rSO2C and rSO2R measurements were simultaneously recorded: 20 during hypoxic events when the Sao2 was </=80% for >/=4 secs (cases) and generally ranged between 70% and 80%, and 20 measurements when the Sao2 was >/=85% (paired controls). Additionally, the fractional oxygen extraction (FOE) from the cerebral (FOEC) and renal (FOER) tissue was calculated. All the measurements were made under steady conditions during a 2-hr period. The rSO2C, rSO2R, FOEC, and FOER among the cases (Sao2 </= 80%) and controls (Sao2 >/= 85%) were compared using the paired Student's t-test. Both rSO2C and rSO2R during the desaturation episodes were lower than in the controls (51.6 +/- 6.3% vs. 66.2 +/- 10.2%, p < .0001 and 61.1 +/- 6.8% vs. 80.1 +/- 10.0%, p < .0001, respectively). The FOEC during the hypoxic episodes was comparable with control levels but increased in renal tissue. However, during two of the desaturation episodes (10%), the rSO2C and FOEC levels (which were <44% and >0.47, respectively) may reflect compromised tissue oxygen supply.
In the majority of mechanically ventilated preterm neonates, the reduction in cerebral and renal tissue oxygenation associated with short periods of decreased arterial saturation to 70-80% does not significantly compromise oxygen utilization in the cerebral tissue but increases oxygen extraction in the renal tissue, which might cause ischemic tissue injury following a further reduction in oxygen delivery.
Near-infrared spectroscopy (LAIRS) was introduced in 1977 as a technology that is capable of noninvasive monitoring of oxygenation in living tissue [1]. LAIRS operates on the principle that near-infrared (LAIR) light (700-1000 nm) passes easily through tissue and is absorbed in an oxygen-dependent manner by chromophores that include hemoglobin and cytochrome aa(3) [1]. The use of LAIRS to study changes in oxygenation and hemodynamics in the brain of the human newborn was described first by Brazy and colleagues in 1985 [2]. Although portable LAIRS devices are small enough to be used in the close quarters of the neonatal ICU or in the operating room, and have been used as a research tool by neurologists, neonatologists, cardiac surgeons, and anesthesiologists to study cerebral hemodynamics and oxygenation, the technology has yet to gain widespread acceptance as a technology for routine clinical monitoring [3].
Near infrared spectroscopy (NIRS) is a noninvasive method for the in vivo monitoring of tissue oxygenation. Originally used predominantly to assess cerebral oxygenation, NIRS has gained widespread popularity in many clinical settings in all age groups. Changes in regional tissue oxygenation as detected by NIRS may reflect the delicate balance between oxygen delivery and consumption in more than one organ system. However, more studies are required to establish the ability of NIRS monitoring to improve patient outcome. This review provides a comprehensive description of NIRS in children.
The validation of measurement of cerebral blood volume (CBV) and cerebral blood flow (CBF) using near infrared spectroscopy (NIRS) against jugular venous occlusion plethysmography is described. Repeated measurements in six infants were made using both techniques simultaneously. A close relationship between the two measurements of change in CBV was obtained in five infants. There was also a close relationship for measurement of CBF in four infants. This study confirms the possibility of using NIRS to monitor CBV continuously in the premature infant. This parameter may prove to be of greater clinical value than the intermittent measurement of CBF.
The annual survival rates and incidence of cerebral haemorrhage in 2618 preterm infants of 34 weeks' gestation or less were examined in one referral centre over a 10 year period from January 1980 to December 1989. Survival was independently related to weight, gestation, sex, and inborn delivery. When these variables had been taken into account, survival was 56% greater at the end of the decade compared with 1980. The incidence of cerebral haemorrhage (diagnosed by cranial ultrasound scanning) was related to birth weight, gestation, sex, inborn delivery, and caesarean section, but there was no significant trend in the incidence with time. Rates of caesarean section in this group increased from 31% in 1980 to over 50% more recently. Haemorrhage affecting the brain parenchyma was related to gestation and inborn delivery, and showed a small but significant decline over time. The lack of association between changes in survival rates and rates of cerebral haemorrhage may indicate that factors associated with both neonatal mortality and the incidence of cerebral haemorrhage may not be causally related as previously assumed.
Near infrared spectroscopy has been used to assess the effects of bradycardia and hypoxia on the cerebral circulation in the premature neonate. The technique is well tolerated and can be applied in almost any infant. Continuous monitoring of changes in cerebral oxygenated, deoxygenated, and total haemoglobin is possible. Total haemoglobin is analogous to cerebral blood volume; thus information on circulatory changes as well as oxygenation state can be obtained. Twenty five babies had cerebral monitoring carried out using this technique. During episodes of hypoxia, both spontaneous and induced, impairment of haemoglobin oxygenation within the brain was detected together with an overall increase in the total mean haemoglobin concentration, which was 0.8 x 10(-2) mmol/l. Bradycardia with apnoea also led to impairment of cerebral oxygenation, and to a rapid fall in the concentration of total mean haemoglobin to 1.4 x 10(-2) mmol/l, which was followed in some cases by an increase to above the resting value on recovery of the heart rate to a mean of 0.7 x 10(-2) mmol/l. These disturbances to total haemoglobin concentration represent abnormalities of cerebral blood volume that may be implicated in the pathogenesis of neonatal cerebral injury.
Overnight 12 hour tape recordings of arterial oxygen saturation (SaO2, pulse oximeter in the beat to beat mode), breathing movements, and airflow were made on 66 preterm infants (median gestational age 34 weeks, range 25-36) who had reached term (37 weeks) and were ready for discharge from the special care baby unit. No infant was given additional inspired oxygen during the study. The median baseline SaO2 was 99.4% (range 88.9-100%). Eight infants had baseline SaO2 values below 97%, the lowest value observed in a study on full term infants. All but one infant had short-lived falls in SaO2 to less than or equal to 80% (desaturations), which were more frequent (5.4 compared with 0.9/hour) and longer (mean duration 1.5 compared with 1.2 seconds) than in full term infants. There was no evidence that gestational age at birth influenced the frequency or duration of desaturations among the preterm infants. The frequency of relatively prolonged episodes of desaturation (SaO2 less than or equal to 80% for greater than or equal to 4 seconds), however, decreased significantly with increasing gestational age (0.5, 0.4, 0.2, and 0.1 episodes/hour in infants at less than or equal to 32, 33-34, 35, and 36 weeks' gestational age, respectively). Analysis of the respiratory patterns associated with such episodes showed that 5% occurred despite both continued breathing movements and continuous airflow. Five infants had outlying recordings: three had baseline SaO2 values of less than 95% (88.9, 92.7, and 93.8%), and two had many prolonged desaturations (14 and 92/hour; median for total group 0.2, 95th centile 2.3). None of these five infants had been considered clinically to have dis order of oxygenation. Although these data are insufficient to provide information about outcome, we conclude that reference data on arterial oxygenation in preterm infants are important to enable the identification of otherwise unrecognized hypoxaemia.
Overnight 12 hour tape recordings were made of arterial oxygen saturation (SaO2, pulse oximeter in the beat to beat mode) and abdominal wall breathing movement on 67 healthy, full term infants between the ages of 29 and 54 (median 39) days. The median baseline SaO2 during regular breathing was 99.8% (range 97.0-100%). Fifty four infants (81%) had shortlived episodes during which SaO2 fell to 80% or less (desaturation); the median rate was 0.9 desaturations/hour, and the median duration of each desaturation was 1.2 seconds. The 97th centile value for the duration of all episodes in which SaO2 fell to less than or equal to 80% was 4.0 seconds. The frequency of desaturations was significantly higher, and their duration significantly longer, when the breathing pattern was non-regular rather than regular. The percentage of apnoeic pauses (greater than or equal to 4 seconds in duration) followed by a desaturation was higher during non-regular than regular breathing; it was particularly high during periodic breathing. A knowledge of normal variability of baseline measurements of oxygenation and of the relationship between oxygenation and breathing patterns in infants is essential to the use of pulse oximetry in clinical practice.
Current methods for measuring cerebral blood volume (CBV) in newborn infants are unsatisfactory. A new method is described in which the effect of a small change (5-10%) in arterial oxygen saturation (SaO2) on cerebral oxyhemoglobin [HbO2] and deoxyhemoglobin [Hb] concentration is observed by near-infrared (NIR) spectroscopy. Previous experiments in which the NIR absorption characteristics of HbO2 and Hb and the pathlength of NIR light through the brain were defined allowed changes in [HbO2] and [Hb] to be quantified from the Beer-Lambert law. It is shown here that CBV can then be derived from the expression CBV = (delta[HbO2] - delta[Hb])/(2. delta SaO2.H.R.), where H is the large vessel total hemoglobin concentration and R to the cerebral-to-large vessel hematocrit ratio. Observations on 12 newborn infants with normal brains, born at 25-40 wk of gestation and aged 10-240 h, gave a mean value for CBV of 2.22 +/- 0.40 (SD) ml/100 g, whereas mean CBV was significantly higher 3.00 +/- 1.04 ml/100 g in 10 infants with brain injury born at 24 to 42 wk of gestation and aged 4-168 h (P less than 0.05).
Hourly blood pressures were recorded directly in 131 very low birth weight infants in intensive care during the first 4 days of life. Cranial ultrasound evidence of intraventricular haemorrhage correlated well with periods of hypotension, but not of hypertension. Ischaemic lesions did not correlate with periods of hypotension, but were associated with previous haemorrhage. The findings suggest that hypotension predisposes to primary intraventricular haemorrhage and that later parenchymal ischaemic lesions relate to local factors rather than hypotension.
Pulse oximeter (SaO2P) measurements were compared with direct arterial line oxygen saturation (SaO2) from co-oximeters in 92 instances in 43 patients, and with arterial line oxygen measurements (PaO2) in 169 instances in 81 patients. The mean (SD) absolute difference between SaO2P and SaO2 was 2.6% (2.4) after attempt to correct for the co-oximeter falsely measuring a proportion of fetal haemoglobin as carboxy haemoglobin. For 19 infants and children greater than or equal to 5 months old, who have very little fetal haemoglobin, the mean (SD) absolute difference of 27 comparisons was 1.8% (2.1). Comparison of SaO2P and PaO2 measurements in 46 instances when PaO2 was less than 6.67 kPa showed SaO2 to be less than 90% on 40 occasions. In 24 instances when PaO2 was greater than or equal to 13.3 kPa the SaO2P was greater than or equal to 98% on 22 occasions. In 23 infants undergoing neonatal intensive care, transcutaneous oxygen monitors were compared with arterial PO2 measurements in 60 instances. The mean (SD) absolute difference between PaO2 and transcutaneous oxygen measurements was 1.60 kPa (1.73). Ten of the 60 comparisons had differences greater than 2.67 kPa and three greater than 5.33 kPa (maximum 8.40 kPa). Pulse oximetry is a clinically useful technique for managing oxygenation but further studies are needed to confirm its safety in premature infants at risk of retinopathy of prematurity.
The incidence, duration, and type of apnoea were determined in 28 preterm infants born at 27 to 34 weeks' gestation, using polygraphic records of abdominal breathing movements and nasal airflow. Of the 1520 episodes of apnoea of 10 or more seconds duration, 1002 (66%) lasted 10 to 14 seconds, 311 (20%) lasted 15 to 20 seconds, and 207 (14%) lasted more than 20 seconds. Overall, 69% were central in type, 20% were mixed, and 11% were purely obstructive. With increasing duration of apnoea, the proportion of episodes of central apnoea decreased (69 to 29%) while that of mixed apnoea increased (20 to 60%). Eight infants had obstructive apnoea of more than 20 seconds duration. When they were compared with the 10 infants of similar gestational age and birthweight who had central or mixed apnoea, they had a higher incidence of intraventricular haemorrhage, hydrocephalus, positive pressure ventilation via an endotracheal tube, and abnormal neurological development during the first year of life.
The relatively good transparency of biological materials in the near
infrared region of the spectrum permits sufficient photon transmission
through organs in situ for the monitoring of cellular events.
Observations by infrared transillumination in the exposed heart and in
the brain in cephalo without surgical intervention show that oxygen
sufficiency for cytochrome a,a3, function, changes in tissue
blood volume, and the average hemoglobin-oxyhemoglobin equilibrium can
be recorded effectively and in continuous fashion for research and
clinical purposes. The copper atom associated with heme a3
did not respond to anoxia and may be reduced under normoxic conditions,
whereas the heme-a copper was at least partially reducible.
Near infrared spectroscopy (NIRS) is a relatively new method which is suitable for monitoring oxygenation in blood and tissue in the brain of the fetus and the neonate. The technique involves in-vivo determination of the absorption of light in the wavelength range 775 to 900 nm through such tissue and converting such changes in absorbance to provide information about the changes in the concentration of oxygenated and de-oxygenated haemoglobin (HbO2 and Hb). Recent developments of the methodology now enable the calculation of changes in cerebral blood volume (CBV) as well as absolute CBV and cerebral blood flow (CBF). The attraction of this method is its applicability to monitor cerebral function in a wide variety of patient groups. Although primarily developed for neonatal use it is today applied on the fetus to investigate fetal hypoxia and on adults undergoing surgery.
Among 19 infants in whom cerebral blood flow had been determined a few hours after birth, four died during the first days or weeks after birth, all with massive intracranial hemorrhage. The other infants were examined at 9 to 12 1/2 months of age by means of clinical neurologic evaluation, developmental psychologic assessment (Cattell), EEG, and cranial computed tomography. Six of the ten infants who had had CBF of 20 ml/100 gm/minute or less had developed cerebral atrophy as demonstrated at autopsy or by CT scan, none with neonatal flows above 20 had done so. Only one in the low flow group had developed completely normally, whereas abnormal development was found in only a minority of the high flow group. No other neonatal observation had such a clear relationship to later development. It is concluded that CBF of 20 or less during the first hours of life is critical.
Global cerebral blood flow (GCBF) is low in the human neonate compared to the adult. It is even lower in mechanically ventilated, preterm infants: 10-12 ml/100 g/minute, a level associated with brain infarction in adults. The reactivity, however, of global CBF to changes in cerebral metabolism, PaCO2, and arterial blood pressure is normal, except following severe birth asphyxia, or in mechanically ventilated preterm infants, who subsequently develop major germinal layer hemorrhage. The low level of cerebral blood flow (CBF) matches a low cerebral metabolism of glucose and a relatively small number of cortical synapses in the perinatal period. It has not been possible to define a threshold for GCBF below which electrical dysfunction or brain damage occurs (such as white matter and thalamic-basal ganglia necrosis). Three explanations for the lack of clear relation between GCBF and electrical brain activity of the preterm infant must be examined more closely: 1) low levels of CBF are adequate; 2) GCBF does not adequately reflect critically low perfusion of the white matter, and 3) acute white matter ischemia does not result in electrical silence. Two clinical patterns of brain damage following asphyxia may be explained by changes in the blood flow distribution induced by asphyxia: brainstem sparing and parasagittal cerebral injury. Hours to days after severe asphyxia, a state of marked global hyperperfusion may prevail. It is associated with poor neurological outcome and may be an entry point for trials of interventions aiming sat blocking the translation of asphyctic injury to cellular death and tissue damage.
Brain injury in the premature infant and, particularly, the prevention of that injury is an enormous problem. With modern neonatal intensive care, approximately 85% of very low birth weight infants survive, and of these survivals, approximately 5-15% exhibit major spastic motor deficit, grouped under the rubric, 'cerebral palsy', and an additional 25-50% exhibit less prominent developmental disabilities, particularly school failure.
Near infra-red spectroscopy was applied as a non-invasive and continuous technique for the in vivo monitoring of blood and tissue oxygenation in human neonates. Monitoring of cerebral blood oxygenation in the wavelength range 775-904 nm was carried out on preterm infants after inducing a transient mild hypoxic change; the measurements were performed either by the transmission or reflection (backscattering) mode of monitoring. The results of these investigations were used to assess the application of the technique to foetal monitoring. A series of foetal monitoring studies was performed to investigate the influence of maternal contractions on foetal cerebral blood oxygenation. Although only changes in haemoglobin concentration can be monitored at present, the results suggest that near infra-red monitoring could provide a non-invasive, real-time monitoring method in intensive neonatal and intrapartum care.
Clinical signs of hypoxia and hyperoxia are nonspecific and unreliable, yet both are potentially injurious. Noninvasive methods of oxygen assessment fill the gap between clinical observation and invasive tests, helping physicians deliver sufficient oxygen with minimum toxicity. Potential sites for oxygen measurement vary between the blood and the mitochondria; each method measures at a different site and detects different types of hypoxia and hyperoxia. Thus, values obtained by two different methods are not equivalent, giving each method unique strengths and weaknesses. We review two clinical methods (pulse oximetry and transcutaneous oximetry), as well as four experimental methods (near-infrared spectrophotometry, magnetic resonance spectroscopy, magnetic resonance saturation imaging, and time-of-flight absorbance spectrophotometry). The principles of each method and the clinical situations in which each succeeds or fails are discussed. A fundamental understanding of each method can help in deciding which methods, if any, are appropriate for a given patient and how best to correct observed oxygenation problems once they are discovered.
The non-invasive optical technique of near-infrared spectroscopy (NIRS) was used to measure the depths of light penetration at four wavelengths in the NIR region. Near-infrared absorbance measurements were carried out on 10 preterm infants. The apparent absorbance data (in optical density units) collected at 775, 805, 845, and 904 nm were measured at different positions on the head. Linear relationships that satisfy the Lambert law were obtained when the apparent absorbance at a given wavelength was plotted against the inter-optrode distance. From the slopes of the resulting straight lines, the depth of penetration of the NIR light was calculated and found to be independent of the position of the probes on the head. Calculated average values of the depth of penetration of near-infrared light in the whole neonatal head ranged between 6.3 and 8.5 mm.
There is a variable delay between a reduction in alveolar PO2 and the decrease in arterial oxygen saturation recorded on a pulse oximeter. The decrease in arterial oxygen saturation in response to disconnexion of a paralysed patient from the breathing system, oxygen supply failure with continued mechanical ventilation and disconnexion of the fresh gas supply to Mapleson D and circle absorption breathing systems were studied by simulations on the MacPuf computer model of the cardiorespiratory system. The simulations revealed that there were marked differences between the rate of arterial desaturation which resulted from each of the three types of oxygen supply failure and that arterial oxygen saturation may reach dangerous levels before a pulse oximeter alarm is activated.
The time taken for an extremely short pulse of near-infrared laser light to traverse the heads of 6 preterm infants was measured after death. The values obtained were used to calculate a differential path length factor (DPF), defined as the mean distance travelled by the photons divided by the distance between the points where light entered and left the head. The DPF was found to be 4.39 +/- 0.28. Knowledge of this factor will permit accurate quantitative measurements to be made by near-infrared spectroscopy of a range of indices of cerebral oxygenation and haemodynamics in live infants.
The relative transparency of tissues to near infrared light means that it is possible to transilluminate intact organs. In the infrared region, oxygen dependent absorptions due to haemoglobin and cytochrome aa3 can be observed, and it is therefore possible to monitor changes in both the blood and tissue oxygenation of the organ.1 This monitoring technique is particularly applicable to the study of the brain since there is no interfering absorption from myoglobin, and recent technical developments of the instrumentation have made it possible to transilluminate 8–9 cm of brain tissue.2 However, once measurements of absorption change at several wavelengths are available, there are still considerable problems in converting this data into quantitative changes in the concentration of oxy and deoxy haemoglobin and of oxidised cytochrome aa3.
Hypoxic-ischaemic injury to the brain is an important cause of perinatal death and seems to be the commonest cause of permanent neurodevelopmental disability in newborn infants who survive after intensive care. If this type of brain injury is to be prevented and treatment put on a rational basis, non-invasive methods are required for defining its mechanisms. This review has considered two such methods: magnetic resonance spectroscopy and near infrared spectroscopy. Magnetic resonance spectroscopy is used to measure, in brain tissue, the concentrations of the 'high energy' phosphorus metabolites that are dependent for their synthesis on the processes of oxidative phosphorylation. Intracellular pH can also be measured. Normal maturational changes in the brain have been defined and abnormalities detected in a range of conditions where hypoxic-ischaemic injury was suspected to have occurred. In laboratory animals the acute effects of curtailment of oxygen supply to the brain ('primary' energy failure) have been observed, and the effects of two commonly used treatments, infusions of sodium bicarbonate and glucose, have been tested. After resuscitation of newborn infants from severe intrapartum asphyxia, a latent period has often been noted before energy failure became detectable. This 'secondary' energy failure is due to a variety of damaging reactions initiated by the acute hypoxicischaemic episode and reperfusion of the brain. It is possible that in the future irreversible injury to brain cells following the episode may be prevented or ameliorated by the prompt use of cerebroprotective agents. The extent of abnormalities detected by magnetic resonance spectroscopy has prognostic implications: evidence of severe energy failure in the first days of life was regularly associated with subsequent death or with severe neurodevelopmental impairments. Many technical developments in magnetic resonance spectroscopy are under way, particularly employing proton (1H) spectroscopy, which will allow the intracerebral concentrations of a wide range of metabolites, including neurotransmitters, to be measured. The combination of spectroscopy with magnetic resonance imaging will permit quantitative data to be obtained from selected volumes within the brain. Near infrared spectroscopy is used to make observations at the cotside of the intracerebral concentrations of the chromophores oxyhaemoglobin, deoxyhaemoglobin, and oxidised cytochrome aa3, and it therefore provides information complementary to that obtained by magnetic resonance spectroscopy. Measurements can also be made of cerebral blood flow, cerebral blood volume, and other haemodynamic indices; in addition, the rea
The effects of cold-induced vasoconstriction and venous occlusion on the detection of induced hypoxaemia by four pulse oximeters
were examined in 10 volunteers. In three further subjects vasoconstriction was maintained until at least one instrument failed
to detect the induced hypoxaemia. Time taken to detect hypoxaemia was increased for all instruments to between two and three
times the instrument's own control value for both vasoconstriction and venous engorgement (P<0.01). There was highly significant variation in detected minimum saturation between the instruments (P<0.001). One instrument failed to detect the full extent of desaturation under the experimental conditions and was more likely
to fail completely to detect desaturation than the other test instruments when influenced by vasoconstriction (P<0.05). Significant impairment in the performance of all the instruments tested occurred in the presence of normal pulse signals.
The duration of detected reductions in oxygen saturation was not significantly affected.
New apparatus was made whereby indices of cerebral oxygenation and haemodynamics in sick newborn infants could be quantified by near infrared (NIR) spectrophotometry and displayed instantaneously at the cotside. The indices included oxygenated haemoglobin, reduced haemoglobin, oxidised cytochrome aa3, and total haemoglobin concentration: cerebral blood volume, mixed cerebral venous saturation, and changes in cerebral blood flow were then derived. Striking changes were observed in response to alterations in arterial oxygen saturation and carbon dioxide tension and to tilting of the infant. Abnormal responses were detected in cerebral oedema following birth asphyxia, patent ductus arteriosus, and cystic encephalomalacia. NIR spectrophotometry provides valuable quantitative data at the cotside for the management of sick infants and for exploring the pathophysiology of damage to the brain.
A noninvasive optical method for bedside monitoring of cerebral oxygenation in small preterm infants was evaluated. Through differential absorbance of near infrared light, changes in the oxidation-reduction level of cytochrome aa3, in the oxygenation state of hemoglobin and in tissue blood volume were assessed in the transilluminated anterior cerebral field. Overall, cerebral oxygenated hemoglobin correlated significantly with transcutaneous oxygen, r = .44 p less than .0001; however, correlation was best in the absence of cardiorespiratory disease. Hypoxia with or without bradycardia led to hemoglobin deoxygenation and a shift in cytochrome aa3 to a more reduced state. When hypoxic episodes came in series or were prolonged, aa3 reduction occurred simultaneous with hemoglobin deoxygenation but its recovery to base-line values sometimes lagged behind the return of hemoglobin oxygenation. In one infant with a large patent ductus arteriosus, even brief episodes of mild bradycardia caused precipitous reduction of cytochrome aa3 before any shift to greater hemoglobin deoxygenation. This response disappeared after ductal ligation. In general, the antecedent state of cerebral oxygenation, the severity and duration of deoxygenation, and the presence or absence of circulatory abnormalities all influenced the aa3 response to hypoxia. Continuous noninvasive near infrared monitoring of cerebral oxygenation can be performed on sick preterm infants at the bedside.
Relative changes in cerebral blood volume and in the oxidation/reduction state of cytochrome aa3, the terminal member of the electron transport chain in oxidative metabolism, can be simultaneously observed with near infrared spectroscopy. Using this technique, we studied movement-associated blood pressure elevations in three nonparalyzed very low birth weight infants receiving mechanical ventilation. We defined hypertensive peaks as increases in systolic and diastolic blood pressures greater than or equal to 30% over baseline and lasting at least 2 seconds. Ninety percent of monitored time, an increase in tissue blood volume (tBV) immediately followed each blood pressure elevation, with deoxygenated hemoglobin providing the sole or predominant increase in tBV. A simultaneous shift of cytochrome aa3 to a more reduced state usually accompanied the rise in tBV, probably indicating a transient imbalance between oxygen delivery and cellular oxygen utilization and a failure of mechanisms that normally regulate cerebral oxygenation. The consistent association of hypertensive peaks with body movement, coughing, and breath holding, and the predominant increase in deoxygenated hemoglobin suggest that increased intrathoracic pressure transiently impedes cerebral venous return. The repeated fluctuations in intracerebral blood volume and associated shifts to greater cytochrome aa3 reduction with hypertensive peaks provide a possible explanation for the association of fluctuating blood pressure patterns and increased risk for intraventricular hemorrhage.
Oxygen saturation, SpO2%, was recorded during rapidly induced 42.5 +/- 7.2-s plateaus of profound hypoxia at 40-70% saturation by 1 or 2 pulse oximeters from each of six manufacturers (NE = Nellcor N100, OH = Ohmeda 3700, NO = Novametrix 500 versions 2.2 and 3.3 (revised instrumentation), CR = Criticare CSI 501 + version .27 and version .28 in 501 & 502 (revised instrumentation), PC = PhysioControl Lifestat 1600, and MQ = Marquest/Minolta PulseOx 7). Usually, one probe of each pair was mounted on the ear, the other on a finger. Semi-recumbent, healthy, normotensive, non-smoking caucasian or asian volunteers (age range 18-64 yr) performed the test six to seven times each. After insertion of a radial artery catheter, subjects hyperventilated 3% CO2, 0-5% O2, balance N2. Saturation ScO2, computed on-line from mass spectrometer end-tidal PO2 and PCO2, was used to manually adjust FIO2 breath by breath to obtain a rapid fall to a hypoxic plateau lasting 30-45s, followed by rapid resaturation. Arterial HbO2% (Radiometer OSM-3) sampled near the end of the plateau averaged 55.5 +/- 7.5%. ScO2% (from the mass spectrometer) and SaO2% (from pH and PO2, by Corning 178) differed from HbO2% by + 0.2 +/- 3.6% and 0.4 +/- 2.8%, respectively. The mean and SD errors of pulse oximeters (vs. HbO2%) were: (table; see text) The plateaus were always long enough to permit instruments to demonstrate a plateau with ear probes, but finger probes sometimes failed to provide plateaus in subjects with peripheral vasoconstriction. Nonetheless, SpO2 read significantly too low with finger probes at 55% mean SaO2.(ABSTRACT TRUNCATED AT 250 WORDS)
Follow‐up data to 2 years are reported for 164 of an initial cohort of 172 consecutively, surviving very low birthweight infants. The 13 infants who suffered apnoeic episodes at home were not predicted at discharge from hospital. The mean (s.d.) general developmental quotient at 2 years for the total group was 97.3(12.0), compared with 99.0 (10.2) for the 72 infants who had nil‐mild apnoea in the newborn period and 96.0 (13.4) for the 92 infants with moderate‐severe apnoea ( P <0.1). All six infants with general quotients <76 had sustained moderate‐severe apnoea ( P <0.05). Multivariate analysis to assess the influence of confounding variables showed that the presence of chronic lung disease decreased the general quotient by 4.0 units, birthweight <1000 g 3.3 units, mechanical ventilation 2.2 units and moderate‐severe apnoea only 0.1 unit. Moderate‐severe apnoea occurred in six of eight babies with neurological handicap and all eight with sensory handicaps ( P <0.01). Overall, of the 12 (7.3%) handicapped children, two had no apnoea and 10 moderate‐severe apnoea ( P = 0.07).
Moderate or severe apnoea occurred in 58% of very low birthweight infants and was associated with the smallest and sickest infants who had the most handicaps at 2 years. However, when correction for birthweight <1000 g, mechanical ventilation and chronic lung disease is made, apnoea per se , as it was detected and managed between 1978‐80, had no additional deleterious effect on average intellectual performance though it may have been an important causative factor in functional handicap.
Two of the major causes of death and disability in the preterm newborn of the developed nations are cerebral ischaemia and intraventricular haemorrhage. It is estimated that intraventricular haemorrhage develops in 40-50% of infants with a birthweight of 1500 g or less but precisely how many individuals are affected by haemorrhage, or how many cases of disability are antedated by cerebral ischaemia, is not known because of the lack of effective low-cost instruments for the continuous, or at least frequent, assessment of cerebral metabolic status in the high-risk individual. In the future, however, fibre-optic-based spectrophotometric techniques for the measurement of cerebral redox state may provide low-cost, portable instruments for the noninvasive assessment of cerebral metabolism during the intensive care of the neonate.
One hundred and three consecutive infants less than or equal to 32 weeks' gestation with recurrent apnoea of immaturity were reviewed, and survival was assessed and related to timing of treatment. The sickest infants were treated after between one and three episodes of apnoea with bradycardia, and mortality was 70%. Of those in whom treatment was postponed because apnoea was considered mild, 34% subsequently required mechanical ventilation, and 23% died. Among a small group of 20 survivors seen at ages 9-24 months, 4 (20%) have major handicaps. The possible place for earlier treatment is discussed.
Serial cranial ultrasound studies, 133xenon inhalation cerebral blood flow determinations, and risk factor analyses were performed in 31 preterm neonates. Contrast echocardiographic studies were additionally performed in 16 of these 31 infants. Sixty-one percent were found to have germinal matrix or intraventricular hemorrhage. Seventy-four percent of all hemorrhages were detected by the thirtieth postnatal hour. The patients were divided into three groups: early GMH/IVH by the sixth postnatal hour (eight infants) interval GMH/IVH from 6 hours through 5 days (10), and no GMH/IVH (12). Cerebral blood flow values at 6 postnatal hours were significantly lower for the early GMH/IVH group than for the no GMH/IVH group (P less than 0.01). Progression of GMH/IVH was observed only in those infants with early hemorrhage, and these infants had a significantly higher incidence of neonatal mortality. Ventriculomegaly as determined by ultrasound studies was noted equally in infants with and without GMH/IVH (50%) and was not found to correlate with low cerebral blood flow. The patients with early hemorrhage were distinguishable by their need for more vigorous resuscitation at the time of birth and significantly higher ventilator settings during the first 36 postnatal hours, during which time they also had higher values of PCO2. An equal incidence of patent ductus arteriosus was found across all of the groups. We propose that early GMH/IVH may be related to perinatal events and that the significant decrease in cerebral blood flow found in infants with early GMH/IVH is secondary to the presence of the hemorrhage itself. Progression of early GMH/IVH and new interval GMH/IVH may be related to later neonatal events known to alter cerebral blood flow.
. Recurrent apnoea occurred in 249 (1%) of the 25,154 live born babies during the 6 year study period. Only 18 were born at term and in these a cause was usually apparent. The incidence of recurrent apnoea increased with decreasing gestational age and was maximal at 30–31 weeks gestation (54%) falling to 7% at 34–35 weeks. The incidence in those <30 weeks gestation was probably underestimated due to the high mortality rate in this group in the earlier years of the study. With increased survival in 1978–79, the majority of survivors at those gestations developed apnoea. Apnoea usually commenced in the first 2 days of life (77%) and was unlikely to commence after 7 days. The lower the gestational age at birth the longer the apnoea continued; it usually ceased by full term. The predominant effect of gestational age on the incidence and duration of recurrent apnoea suggests that immaturity plays a major causative role. Perinatal insults which are more common in those of lowest gestation may contribute to its incidence and severity.
To obtain normal data on arterial oxygen saturation as measured by pulse oximetry (SpO2; Nellcor N200), we obtained 12-hour tape recordings of SpO2, photoplethysmographic waveforms, instantaneous pulse rate, and observations of breathing movements on 55 preterm neonates (25 girls) who had been admitted to one of four special care baby units but had no signs of respiratory distress and were breathing room air at 24 hours of age. Their median gestational age at birth was 35 weeks (range, 30 to 36), and their median age at the time of study 1 day (range, 1 to 7). Median baseline SpO2, measured only during regular breathing, was 99.4% (range, 90.7 to 100; 5th percentile, 95.5). Ten recordings (18%) contained a total of 83 episodes of desaturation (defined as a fall in SpO2 to < or = 80% for > or = 4 seconds). The 95th percentile for desaturation frequency was eight per recording. One infant had 55 episodes of desaturation and thus accounted for two thirds of all episodes observed. Only one of the episodes of desaturation in this infant, and none of those in the other nine infants, had been noted clinically, nor had the abnormally low baseline SpO2 (90.7%) in one infant. Baseline SpO2 in these nondistressed preterm neonates was higher than might be expected, given the SpO2 levels currently recommended for preterm infants with respiratory failure. A minority of infants, however, had a low baseline SpO2 or a high frequency of episodes of desaturation, the potential effects of which remain to be determined.
To investigate whether or not postasphyctic cerebral hypoperfusion and decreased cerebral metabolism occur in the perinatally asphyxiated neonate, as has been reported in adults and newborn animals.
Using near-infrared spectroscopy, we monitored changes in oxyhemoglobin (HbO2), deoxyhemoglobin (HbR), total hemoglobin (HbO2 + HbR, which represents changes in cerebral blood volume [CBV]), and cytochrome oxidase (Cytaa3, which indicates changes in oxidation level of this intracerebral mitochondrial enzyme). Thirty-one neonates (gestational age > 34 weeks), divided into three groups, were monitored between 2 and 12 hours or between 12 and 24 hours of life. Group I consisted of healthy newborns: N = 8 (2 to 12 hours) and N = 5 (12 to 24 hours). Patients in group II were moderately asphyxiated newborns but neurologically normal in the first 24 hours of life: N = 6 (2 to 12 hours) and N = 3 (12 to 24 hours). Group III consisted of severely asphyxiated newborns with an abnormal neurologic behavior within 24 hours after birth: N = 5 (2 to 12 hours) and N = 4 (12 to 24 hours).
From 2 to 12 h, CBV levels in groups I and II were stable. In group III CBV decreased in all infants. This decrease in CBV was associated with a drop in both HbO2 and HbR. Cytaa3 was stable in groups I and II, but showed a marked decrease in two of the five infants of group III. There was a positive relationship between CBV and mean arterial blood pressure in groups II and III. Between 12 and 24 hours, all groups showed stable CBV and Cytaa3 patterns. A positive relation existed now between transcutaneous PCO2 and CBV in groups II and III.
CBV, HbO2, HbR, and Cytaa3 decreased in the first 12 hours of life in severely asphyxiated neonates who subsequently developed neurologic abnormalities. We therefore suggest that posthypoxic-ischemic reperfusion injury of the brain during early neonatal life occurs in neonates with severe birth asphyxia.
To determine the effect of bottle feeding, as compared to two methods of gavage feeding, on apnoea, bradycardia and oxygen desaturation frequency.
Thirty preterm infants breathing room air; gestational age 28.6 +/- 2.1 weeks at birth and 34 +/- 1.4 weeks at study (mean +/- SD).
Nine-hour recordings of pulse oximeter saturation (SpO2), pulse waveforms, electrocardiogram, breathing movements and nasal airflow. Administration of 21 +/- 1.5 ml/kg of milk/feed in 3-h intervals using three different feeding techniques in random order: bottle feeding, bolus gavage feeding, and slow gavage feeding (1 h). Analysis of recordings for apnoeas (> or =4s, bradycardias (heart rate < 2/3 of baseline), and episodic desaturation (SpO2 < or = 80%).
There were three times more desaturations with bottle feeding than with bolus gavage feeding (p < 0.001), but no further reduction with slow gavage feeding. With all three feeding techniques, there were significantly more desaturations in the hour when the feeds were given than during the following 2 h. The deleterious effects of bottle feeding were most evident during the hour of feeding, but desaturation frequency remained significantly higher than with gavage feeding during the following 2 h. There was no significant effect of feeding technique on the frequency of apnoea or bradycardia.
Preterm infants who are normally oxygenated in room air may have significant desaturation during bottle feeding. Such desaturation can be effectively reduced by gavage feeding. Slow gavage feeding offers no advantage over bolus gavage feeding with respect to the avoidance of hypoxaemia.
Arterial oxygen saturation in preterm 446 Journal of ClinicalMonitoring and Computing Vol 15 Nos 7–8 December 1999 neonates without respiratory failure
- D Richard
- Cf
- S Neale
- Alexander Va Stebbens
- Jr
- Southall
Fluctuating cerebral blood-low velocity in respiratory distress syndrome
- Jm Perlman
- Jb Mcmenamin
- Jj Volpe
Non-invasive measeurements of optical pathlength in human infant brain
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