Current problems and potential techniques in in vivo glucose monitoring.

Accurate in vivo monitoring of glucose concentration would be a valuable asset, particularly for management of diabetes and preterm infants during critical care. In vivo glucose monitoring devices can be divided into two categories: implanted and non-invasive. Extensive research into in vivo glucose monitoring over recent decades has not resulted in the widespread use of clinically reliable monitoring systems. For implanted devices, poor biocompatibility of the materials used for fabrication remains a major challenge, whilst progress in the commercial development of non-invasive devices is hampered by the problem of multiple interference between the detected signals and the biological components. In this review, the methods available for in in-vivo glucose monitoring are described and the associated problems are discussed.

The light still shines, but not that brightly? The current status of perinatal near infrared spectroscopy.

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.

Effect of limb cooling on peripheral and global oxygen consumption in neonates.

AIM: To evaluate peripheral oxygen consumption (VO(2)) measurements using near infrared spectroscopy (NIRS) with arterial occlusion in healthy term neonates by studying the effect of limb cooling on peripheral and global VO(2). SUBJECTS AND METHODS: Twenty two healthy term neonates were studied. Peripheral VO(2) was measured by NIRS using arterial occlusion and measurement of the oxyhaemoglobin (HbO(2)) decrement slope. Global VO(2) was measured by open circuit calorimetry. Global and peripheral VO(2) was measured in each neonate before and after limb cooling. RESULTS: In 10 neonates, a fall in forearm temperature of 2.2 degrees C (mild cooling) decreased forearm VO(2) by 19.6% (p < 0.01). Global VO(2) did not change. In 12 neonates, a fall in forearm temperature of 4 degrees C (moderate cooling) decreased forearm VO(2) by 34.7% (p < 0.01). Global VO(2) increased by 17.6% (p < 0.05). CONCLUSIONS: The NIRS arterial occlusion method is able to measure changes in peripheral VO(2) induced by limb cooling. The changes are more pronounced with moderate limb cooling when a concomitant rise in global VO(2) is observed. Change in peripheral temperature must be taken into consideration in the interpretation of peripheral VO(2) measurements in neonates.

Effect of a change in global metabolic rate on peripheral oxygen consumption in neonates.

AIM: To evaluate the effect of an induced change in global metabolic rate on peripheral oxygen consumption (VO(2)) in healthy full term neonates. SUBJECTS AND METHODS: Twenty four healthy full term neonates were studied. Peripheral VO(2) was measured by near infrared spectroscopy (NIRS) using arterial occlusion and measurement of the oxyhaemoglobin (HbO(2)) decrement slope. Global VO(2) was measured by open circuit calorimetry. Global and peripheral VO(2) were measured in each neonate before and after a routine bath. Abdominal and forearm skin temperatures were also recorded. RESULTS: Nineteen neonates completed the study. Global VO(2) increased by 30.7% (p = 0.001), and peripheral VO(2) by 23.1% (p = 0.001). A correlation between the fractional changes in global and peripheral VO(2) was apparent (r = 0.76, p = 0.001). Abdominal skin temperature decreased by 0.8 degrees C (p = 0.001), and forearm skin temperature by 0.6 degrees C (p = 0.04). CONCLUSIONS: Measurement of peripheral VO(2) using NIRS with arterial occlusion is responsive to conditions that increase global metabolic rate. Any change in global VO(2) must be taken into consideration during the interpretation of peripheral VO(2) measurements in neonates.

An essential 'health check' for all medical devices.

In order to safeguard patient safety, all new or modified medical devices must be assessed for their safety and performance before they are used routinely in clinical practice. Most devices will carry a CE (Confirmity European) mark to demonstrate their safety, but many devices will require an alternative method of assessment. In this article, we discuss the procedures already in place, the significant gaps that exist in the system and the risk management issues. We consider the impact on research and clinical practice, and describe our comprehensive risk management system for objectively assessing the safety of any medical device.

Comparative clinical evaluation of a prototype non-electric transport incubator and an electrical infant incubator in a neonatal unit.

A new non-electric transport incubator has been developed for transferring babies between health facilities in developing countries. The temperature performance of this prototype was compared with a commercial electric incubator. The warm-up time for the prototype was 51.8 min, compared with 48.1 min for the electric incubator. Forty-five non-distressed premature babies, aged 24-72 h, with a gestational age of less than 37 weeks, were continuously evaluated for a 2 h period. Twenty-five babies, with a mean weight of 2073 g (range 1500-2500 g), were studied in the prototype, and 20 babies, with a mean weight of 2076g (range 1550-2500 g), were studied in the electrical incubator. The rectal and abdominal skin temperature, heart rate, oxygen saturation and respiratory rate of the babies were recorded. The temperature, oxygen and humidity level of the canopy and the room temperature were also measured. The SaO2, heart rate and respiratory rate were within the normal range (in the prototype: 96.5%, 130.5 beats min(-1) and 43 breaths min(-1), respectively; and, in the electric incubator: 96.5%, 128.5 beats min(-1) and 40 breaths min(-1), respectively). No evidence of carbon dioxide narcosis, hypoxia, acidosis or adverse thermoregulatory behaviour were observed in the two groups. The mean rectal temperature for both groups was within the range 36.5 degrees C-37.5 degrees C. There was no significant difference between the measurements of the two groups. The level of oxygen inside the canopy was 21%, and no decrease was observed. The new nonelectric transport incubator confirmed its safety and efficiency in providing a warm environment for non-distressed premature babies over a 2 h period.

New prototype NIRS instrument [corrected] to investigate multi-regional cerebral blood and tissue oxygenation and haemodynamics.

Near infra-red spectroscopy (NIRS) is a non-invasive optical technique used to assess blood and tissue oxygenation and haemodynamics in living tissue. It is presently used as a semi-continuous monitoring technique on a research basis. Multi-regional NIRS information could be beneficial for a better understanding of the development of cerebral injuries and the reduction of neurodevelopmental abnormalities in the human newborn. The paper presents the conversion of the continuous wave NIRS single-channel instrument (NIRDCU) into a prototype four-channel instrument which can be used to provide continuous multi-regional information regarding the cerebral blood oxygenation and haemodynamics in the frontal, left parietal, right parietal and occipital region of the neonatal brain. This has been achieved by attaching an optical multiplexing system to the NIRDCU to select different transmitting and receiving fibres, thus addressing different regions in the brain. Preliminary laboratory tests on a phantom and on the adult forearm are presented, illustrating the practicality of regional monitoring.

Measurement of peripheral oxygen utilisation in neonates using near infrared spectroscopy: comparison between arterial and venous occlusion methods.

The aim of this study was to develop an arterial occlusion method and compare it with the venous occlusion method for measurement of peripheral oxygen utilisation in neonates using near infrared spectroscopy (NIRS). Twenty healthy neonates were studied. Arterial occlusion was produced by inflating a neonatal blood pressure cuff to 100 mmHg for 30-40 s and oxygen utilisation (VO(2)) was calculated using the HbO(2) decrement slope following occlusion. Venous occlusion was produced by inflating the cuff to 30 mmHg for 15-20 s and VO(2) was calculated by: VO(2)=HbTx4x(SaO(2)-SvO(2)), where SaO(2) is the arterial oxygen saturation measured by pulse oximetry and SvO(2) is the venous oxygen saturation measured by NIRS. Each baby had a minimum of three arterial and three venous occlusions. Criteria were developed for acceptance/rejection of an occlusion. Using the arterial method, the mean VO(2) was 1.12 mM cm(-1) O(2)/min (S.D.=0.25), (95% CI=1.00-1.24 mM cm(-1) O(2)/min). The coefficient of variation was 6.6+/-4.1%. Using the venous method, the mean VO(2) was 1.60 mM cm(-1) O(2)/min (S.D.=0.48), (95% CI=1. 38-1.82 mM cm(-1) O(2)/min). The coefficient of variation was 12. 6+/-5.7%. The correlation between the two methods was weak (r=0.28 and r(2) was 0.08). The mean difference between the two methods was 0. 47 mM cm(-1) O(2)/min (S.D.=0.51). The limits of agreement were -0. 53 to 1.47 mM cm(-1) O(2)/min. The arterial method gives more consistent results.

A comparison of pulse oximetry and near infrared spectroscopy (NIRS) in the detection of hypoxaemia occurring with pauses in nasal airflow in neonates.

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%.

Blood perfusion of subcutaneous tumours in mice following the application of low-level direct electric current.

Electrotherapy with low-level direct electric current has been proved to be an effective local treatment of solid tumours. In the presented study an attempt was made to evaluate the effect of a single treatment with electrotherapy on blood perfusion of solid subcutaneous fibrosarcoma Sa-1 tumours in A/J mice. The tissue-staining method with Patent blue-violet dye, the rubidium extraction technique, and the noninvasive near-infrared spectroscopy method were used for this purpose. Results of all methods indicate that perfusion and subsequently oxygenation of tumours were reduced due to application of electrotherapy.

Fast algorithm to determine optical properties of a turbid medium from time-resolved measurements.

After analytical expressions for the time-resolved reflectance are introduced from the diffusion approximation under the three most commonly used boundary conditions, a novel algorithm is demonstrated for determining the reduced scattering and the absorption coefficients from time-resolved reflectance (or backscatter) measurements at two positions on the surface of biotissue. The algorithm is straightforward and fast and involves only some simple mathematical operations, avoiding complicated iterative nonlinear fitting to the time-resolved curve. The derived reduced scattering coefficient is not affected by whatever boundary condition is applied. The algorithm was verified with time-resolved data from the Monte Carlo model. Both a semi-infinite medium and a turbid slab medium were tested. In contrast to the nonlinear fitting method, this algorithm allows both the scattering and the absorption coefficients to be determined to a high accuracy.

Investigation of neonatal brain cytochrome redox by NIRS.

Near Infrared Spectroscopy (NIRS) has been used to detect changes in cerebral blood and tissue oxygenation. Redox state of enzyme cytochrome aa3 (Cyt aa3 is thought to give an indication of tissue oxygenation. This information would be of value in exploring the aetiology of cerebral ischaemic lesions in preterm infants. However we have found that the change in cerebral cytochrome redox in infants following desaturation was inconsistent and insignificant.

Fibre-optical sensor based on fluorescent indicator for monitoring physiological pH values.

A fibre-optical sensor has been developed based on the fluorescent indicator 8-hydroxyl-1,3,6-pyrene trisulphonic acid trisodium salt (HOPSA) for monitoring physiological pH values. Dowex-1 strongly basic anion exchange resin is used as the medium to immobilise the indicator on the end of an optical fibre. Polyurethane is coated on the sensor as the permeable membrane for H+. The properties of HOPSA in solution, as well as when immobilised on the sensor, are studied and found to have the potential for monitoring physiological pH values.

Is allopurinol beneficial in the prevention of renal ischaemia-reperfusion injury in the rat?: evaluation by near-infrared spectroscopy.

1. The role of allopurinol in the protection of kidney function following ischaemia-reperfusion injury has been investigated using the novel technique of near-infrared spectroscopy. 2. An in vivo model of rat kidney ischaemia was used, with the expected falls in blood and tissue oxygenation seen and confirmed by near-infrared spectroscopy. 3. Allopurinol infusion increased the rate of reperfusion of oxygenated blood seen in control rats (P < 0.05). 4. Allopurinol enhanced the rate of tissue oxygenation during early reperfusion (P < 0.01). 5. This study provides further evidence for the proposed benefits of allopurinol in ischaemia-reperfusion injury. Furthermore, the potential of near-infrared spectroscopy as a technique of value in interventional studies of this nature is confirmed.

Effects of positive and negative pressure ventilation on cerebral blood volume of newborn infants.

The effects of intermittent positive airway and continuous negative extrathoracic pressure ventilation on cerebral blood volume in preterm infants were studied using near infrared spectroscopy. In 12 infants continuous negative extrathoracic pressure caused a median decrease in cerebral blood volume of 0.14 ml/100 ml brain (95% confidence intervals (CI) 0.035-0.280) compared with no respiratory support. Oxygenated and deoxygenated haemoglobin also decreased, implying increased venous drainage as the main effect. In 17 infants intermittent positive pressure ventilation also caused a median reduction in cerebral blood volume of 0.06 ml/100 ml brain (95% CI 0.010-0.115) compared with endotracheal positive airway pressure. Deoxygenated haemoglobin increased by 0.07 ml/100 ml brain (95% CI 0.010-0.100) while oxygenated haemoglobin decreased by 0.10 ml/100 ml brain (95% CI 0.005-0.175). The increase in deoxygenated haemoglobin implies decreased venous drainage and the decrease in oxygenated haemoglobin implies that other factors may also be significant. Heart rate, blood pressure and oxygen saturation were monitored continuously and remained stable.

A non-invasive optical technique for intrapartum fetal monitoring: preliminary clinical studies.

A relatively new optical method based on near infra-red spectroscopy was evaluated in preliminary clinical trials for noninvasive intrapartum fetal monitoring. The measurements were performed using mainly the light reflection mode of monitoring. Continuous monitoring of changes in the concentrations of oxygenated and deoxygenated haemoglobin and thus changes in total haemoglobin concentration in the fetal brain was achieved. It was found that uterine contractions can influence in a distinctive manner the near infra-red derived cerebral haemoglobin concentration changes in the fetus. The results indicate that near infra-red spectroscopy could offer a non-invasive real-time monitoring method for in vivo monitoring of blood oxygenation in the fetal brain. We conclude that this technique may be useful for intrapartum fetal monitoring and in predicting fetal cerebral hypoxia.