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Traditional methods of measuring oxygen saturation, e.g. pulse oximetry, depend on an adequate peripheral circulation and have a 20–30 second lag time before readings are obtained. This was a series of evaluations of novel optical probes, designed to measure oxygen saturation using fibreoptic technology directly from internal organs including the brain, oesophagus and organs with splanchnic circulations. A series of pilot studies were proposed and research ethics approval obtained to carry out studies in humans, under general anaesthesia, using these probes. Innovative reflectance probes were designed specifically for each of the four applications, so as to obtain potentially useful signals needed for signal processing, analysis and evaluation. Signals were successfully obtained from the brain, oesophagus and splanchnic region in almost all of the patients recruited. Good quality photoplethysmograph signals were recorded and these were translated into clinically meaningful values of oxygen saturation comparable to traditional methods of pulse oximetry. Overall, the signals were prone to movement artefacts as well as occasional interference from surgical diathermy and other sources. Nonetheless, the probes could prove to be a useful alternative to conventional external transmittance pulse oximetry methods as well as providing useful information regarding regional perfusion and oxygenation. The success of these pilot studies will form the basis of more research in the area and further development of such probes on the medical engineering front.

Sildenafil increases oxygen delivery and maximal exercise capacity at very high altitudes (greater than or equal to 4300 m) and has been shown to improve short-duration exercise performance in some individuals at simulated high altitude (3900 m). It is unknown whether sildenafil improves maximal exercise capacity and longer duration exercise performance at moderate and high altitudes where competitions are more common. Additionally, the effects of sildenafil on women exercising at altitude have not been examined. The purpose of this study was to determine the effects of sildenafil on cardiovascular hemodynamics, arterial oxygen saturation (SaO2), peak exercise capacity (Wpeak), and 15-km time trial performance, in endurance-trained men and women at simulated moderate (MA; 2100 m, 16.2 % FIO2) and high (HA; 3900 m, 12.8% FIO2) altitudes. Eleven male and 10 female subjects completed two HA Wpeak trials following the ingestion of placebo or 50 mg sildenafil in randomized, counterbalanced, and double blind fashion. Subjects then completed four exercise trials (30 min at 55% of Wpeak + 15-km time trial) at MA and HA following the ingestion of placebo or 50 mg sildenafil in randomized, counterbalanced, and double blind fashion. Sildenafil had little influence on cardiovascular hemodynamics for either gender at MA or HA, but did result in higher SaO2 values compared to placebo during steady state and time trial exercise in men at HA only. Sildenafil did not affect Wpeak or 15-km time trial performance in either gender at MA or HA. We conclude that sildenafil is unlikely to exert beneficial effects at altitudes < 4000 m for a majority of the population.

Maintaining adequate and stable blood oxygen level is important for preterm babies to avoid the risk of brain, lung and retinal injury such as retinopathy of prematurity (ROP). However, wide disparities in policies and practices of oxygenation in preterm babies exist among neonatal care providers as it is still unclear which best method of monitoring and what features of oxygen measurements are important to clinician’s interpretations for assessing preterm babies at risk of developing severe ROP or unstable health condition. This thesis consists of two projects: NZ-ROP that examines multiple factors of severe ROP including summary statistics (mean, standard deviation (SD), coefficient of variation (CV) and desaturation) for oxygen saturation (OS) features in very extreme preterm babies, and NZ-LP that investigates the efficacy of some of these statistics for health monitoring of late preterm babies. The OS data in NZ-ROP were recorded using modified oximeters that have offsets and inherent software artefact, both of which mask the actual saturation for certain OS ranges and may complicate the choice of methods in the analyses. Therefore, novel algorithms involving linear and quadratic interpolations are developed, implemented on the New Zealand data, and validated using the data of a UK preterm baby, as recorded from offsets and non-offsets oximeters. For all data sets, the algorithms produced saturation distributions that were very close to those obtained from the non-offset oximeter. The algorithms perform within the recommended standards of commercial oximeters currently used in the clinical practice. ROP is a multifactorial disease, with oxygenation fluctuations as one of the key contributors. The all-subsets logistic regression, robust and generalised additive statistical modelling, along with a model averaging approach, are applied in NZ-ROP to determine the relationship of variability and level of OS with severe ROP, and the extent of contribution of various clinical predictors to the severity of this eye disease. Desaturation, as a measure of OS variability, has the strongest association with severe ROP among all OS statistics, in particular, the risk of severe ROP is almost three times higher in babies that exhibit greater occurrences of desaturation episodes. Additionally, this study identifies longer periods of ventilation support, frequent desaturation events, extreme prematurity and low birth weight as the most important factors that substantially exacerbate the severity of ROP, and therefore signify babies’ underlying condition of being severely ill. Persistent cardiorespiratory instabilities prior to hospital discharge may expose preterm babies to a greater risk of neuro-developmental impairments. In NZ-LP, the statistical summaries of mean, SD and CV are computed from the OS measurements of healthy stable and unstable babies, and the performance of these statistics in detecting the unstable babies is evaluated using an extremeness index for outlying data and a hierarchical clustering technique. With SD and CV, the clinically unstable babies were very well separated from the group of stable babies, wherein, the separation was even more apparent with the use of CV. These suggest that measures of variability could be better than saturation level for highlighting babies’ underlying instability due to immature physiological systems, but the combination of variability and level through the CV are believed to be even better. Identification and summarisation of useful OS features quantitatively hold great promise for improved monitoring of oxygenation instability and diagnosis of severe ROP for preterm babies.

The purpose of this study was to determine if arterial oxygen saturation (SaO2), as measured by a finger pulse oximeter upon rapid arrival to 4260 m, could be predictive of acute mountain sickness (AMS) or summit success on a climb to 5640 m. In total 73 climbers volunteered to participate in the study. After excluding those taking drugs to counteract the effects of AMS and those with missing data, 48 participants (45 male, 3 female) remained. Climbers were transported from 2650 m to the Piedra Grande hut at 4260 m on Pico de Orizaba within 2 hr. After a median time of 10 ± 13 hr at the hut, they climbed toward the summit (5640 m) and returned with a median trip time of 13.3 ± 4.8 hr. The Lake Louise Self-assessment Questionnaire (LLSA) for AMS, heart rate, and SaO2 from a finger pulse oximeter was collected upon arrival at the hut, repeated immediately before the climbers departed for their summit attempts, and immediately upon their return. The presence of AMS was defined as a LLSA score ≥ 3 with a headache and at least one other symptom. Fifty-nine percent of the participants successfully reached the summit. Average SaO2 for all participants at 4260 m prior to their departure for the summit was 84.2 ± 3.8%. Sixty percent of the participants met the criteria for AMS during their ascent. There was not a significant difference (p = .90) in SaO2 between those who experienced AMS (SaO2 = 84.3 ± 3.3%) and those who did not (SaO2 = 84.2 ± 4.2%) during the ascent. Neither was there a significant difference (p = .18) in SaO2 between those who reached the summit (84.8 ± 3.7%) and those who did not (83.3 ± 4.0%). Arterial oxygen saturation does not appear to be predictive of AMS or summit success.

The objectives for the first part of this thesis were to describe changes in oxygen saturation (SpO2) and heart rate (HR) in newly born infants in the delivery room (DR) and to illustrate the changes using centile reference charts. The objective of the second part of the thesis was to investigate whether infants < 29 weeks gestation who receive positive pressure ventilation (PPV), immediately after birth with a T-piece have higher SpO2 measurements at five minutes than infants ventilated with a self inflating bag (SIB). / Study Design. A prospective observational study was used to achieve the first objectives. For the second part of the thesis I coordinated a randomised, controlled trial of two devices used for resuscitation of extremely preterm infants in the DR where the primary outcome measure was SpO2. / Patients and methods. In all studies a Masimo Radical pulse oximeter (PO) was placed on the infant’s right hand/wrist immediately after birth. PO data (oxygen saturation, HR and signal quality) were downloaded every 2 sec and analysed only when the signal had no alarm messages (low IQ signal, low perfusion, sensor off, ambient light). / Results. Observational studies: The dataset to develop the reference range charts included 61,650 data points from 468 infants. Infants had a mean (range) gestational age of 38 (25-42) weeks and birthweight 2970 (625-5135) g. For all 468 infants at one minute the 3rd, 10th, 50th, 90th and 97th centiles were 29%, 39%, 66%, 87% and 92%; at two minutes 34%, 46%, 73%, 91% and 95% and at five minutes 59%, 73%, 89%, 97% and 98%. It took a median of 7.9 (IQR 5.0 to 10) minutes to reach a SpO2 > 90%. SpO2 of preterm infants rose more slowly than that of term infants. At one min the median (IQR) HR was 82 (66 to 138) bpm rising at two min and five min to 151 (112 to 169) bpm and 166 (148 to 176) bpm respectively. In preterm infants, the SpO2 and HR rose more slowly than term infants. / Randomised trial: Forty nine infants were randomly allocated to the T-piece and 50 to the SIB. Ten infants did not receive PPV, 4 (8%) in the T-piece group and 6 (12%) in the SIB group and were not included in the analysis. Forty-one infants received PPV with a T-piece and 39 with a SIB. At 5 minutes after birth there was no significant difference between the mean (SD) SpO2 in the T-piece and SIB groups [50 (31)% vs. 53 (25)%, (p=0.73)]. More T-piece infants received oxygen during DR resuscitation (100% vs. 90%, p=0.04). There was no significant difference between the groups in the use of continuous positive airway pressure (CPAP); endotracheal intubation or administration of surfactant in the DR. Fewer of the T-piece group who left the DR on CPAP were intubated in the first 24 hrs after birth. (7% vs. 23%, p=0.05). / Conclusion. The centile charts developed in this thesis provide a reference range for SpO2 and HR in the first 10 minutes after birth for preterm and term infants. In the randomised trial there was no significant difference in SpO2 at five minutes after birth in extremely preterm infants given PPV with a T-piece or a SIB.

The objectives for the first part of this thesis were to describe changes in oxygen saturation (SpO2) and heart rate (HR) in newly born infants in the delivery room (DR) and to illustrate the changes using centile reference charts. The objective of the second part of the thesis was to investigate whether infants < 29 weeks gestation who receive positive pressure ventilation (PPV), immediately after birth with a T-piece have higher SpO2 measurements at five minutes than infants ventilated with a self inflating bag (SIB). / Study Design. A prospective observational study was used to achieve the first objectives. For the second part of the thesis I coordinated a randomised, controlled trial of two devices used for resuscitation of extremely preterm infants in the DR where the primary outcome measure was SpO2. / Patients and methods. In all studies a Masimo Radical pulse oximeter (PO) was placed on the infant’s right hand/wrist immediately after birth. PO data (oxygen saturation, HR and signal quality) were downloaded every 2 sec and analysed only when the signal had no alarm messages (low IQ signal, low perfusion, sensor off, ambient light). / Results. Observational studies: The dataset to develop the reference range charts included 61,650 data points from 468 infants. Infants had a mean (range) gestational age of 38 (25-42) weeks and birthweight 2970 (625-5135) g. For all 468 infants at one minute the 3rd, 10th, 50th, 90th and 97th centiles were 29%, 39%, 66%, 87% and 92%; at two minutes 34%, 46%, 73%, 91% and 95% and at five minutes 59%, 73%, 89%, 97% and 98%. It took a median of 7.9 (IQR 5.0 to 10) minutes to reach a SpO2 > 90%. SpO2 of preterm infants rose more slowly than that of term infants. At one min the median (IQR) HR was 82 (66 to 138) bpm rising at two min and five min to 151 (112 to 169) bpm and 166 (148 to 176) bpm respectively. In preterm infants, the SpO2 and HR rose more slowly than term infants. / Randomised trial: Forty nine infants were randomly allocated to the T-piece and 50 to the SIB. Ten infants did not receive PPV, 4 (8%) in the T-piece group and 6 (12%) in the SIB group and were not included in the analysis. Forty-one infants received PPV with a T-piece and 39 with a SIB. At 5 minutes after birth there was no significant difference between the mean (SD) SpO2 in the T-piece and SIB groups [50 (31)% vs. 53 (25)%, (p=0.73)]. More T-piece infants received oxygen during DR resuscitation (100% vs. 90%, p=0.04). There was no significant difference between the groups in the use of continuous positive airway pressure (CPAP); endotracheal intubation or administration of surfactant in the DR. Fewer of the T-piece group who left the DR on CPAP were intubated in the first 24 hrs after birth. (7% vs. 23%, p=0.05). / Conclusion. The centile charts developed in this thesis provide a reference range for SpO2 and HR in the first 10 minutes after birth for preterm and term infants. In the randomised trial there was no significant difference in SpO2 at five minutes after birth in extremely preterm infants given PPV with a T-piece or a SIB.

Στη διπλωματική αυτή περιγράφεται η κατασκευή ενός σφυγμοξύμετρου, της ιατρικής συσκευής που προσδιορίζει με μη επεμβατικό τρόπο το επίπεδο οξυγόνου στο αίμα καθώς επίσης και το ρυμό των καρδιακών παλμών. Η γνώση του επιπέδου του Οξυγόνου στο αίμα είναι ιδιαίτερα σημαντική σε ασθενείς που βρίσκονται υπό ειδική ιατρική περίθαλψη, καθώς και σε ασθενείς υπό εγχείρηση, αφού η καλή οξυγόνωση είναι ο βασικότερος παράγοντας διαβίωσης. Η κατάσταση που προκαλει από μειωμένη οξυγόνωση ονομάζεται υποξία. Η αρχή λειτουργίας της συσκευής βασίζεται στον εμπειρικό νόμο απορρόφησης του Beer- Lambert και στα χαρακτηριστικά απορρόφησης του ερυθρού και του υπέρυθρου μήκους κύματος φωτός από τη οξυγονωμένη και μη αιμοσφαιρίνη. Κάποιο σημείο του σώματος –στη δική μας εφαρμογή ο δείκτης του χεριού- τοποθετείται σε ειδικό probe, όπου δυο φωτοεκπέμπουσες δίοδοι εκπέμπουν ενναλάξ ερυθρό και υπέρυθρο φως. Στη συνέχεια το μέρος της ακτινοβολίας που δεν απορροφάται από το ανθρώπινο μέλος ανιχνεύεται από δύο φωτοανιχνευτικές διόδους τοποθετημένες στην κάτω πλευρά του δαχτύλου. Το οπτικό σήμα μετατρέπεται από τις διόδους σε ηλεκτρικό. Ακολουθεί ένα αναλογικό κύκλωμα ενίσχυσης, που συμπεριλαμβάνει δύο ενισχυτές και ένα ψηφιακό ποτενσιόμετρο για τη ρύθμιση του κέρδους των ενισχυτών. Το αναλογικό σήμα μετατρέπεται σε ψηφιακό με τη χρήση του ADC12 μετατροπέα που αποτελει περιφερειακό στοιχείο του msp430F169 μικροεπεξεργαστή που χρησιμοποιήσαμε. Ο μικροεπεξεργαστής αυτός επιλέχτηκε για τις ιδιαίτερες δυνατότητες χαμηλής κατανάλωσης που διαθέτει, καθώς επίσης και για την ποικιλία περιφερειακών συσκευών του. Στη συνέχεια με τη βοήθεια του Software που υλοποιήθηκε σε C γλώσσα προγραμματισμού, τα δείγματα που λαμβάνονται από τον ADC12 αφού φιλτραριστούν ώστε να απορριφθεί ο περιβαλλοντικός θόρυβος, διέρχονται από ένα δεύτερο φίλτρο αποκοπής της DC συνιστώσας, η οποία προκύπτει απο την απορρόφηση διαφόρων τμηάτων του δαχτύλου, όπως οι φλέβες, το δέρμα, ο ιστός και το οστό. Έτσι απομένει η AC συνιστώσα που αντιστοιχεί στην αρτηριακή απορρόφηση, η οποία και μας ενδιαφέρει. Τα δείγματα του ΑC πλέον σήματος αποθηκεύονται σε πίνακες για την περαιτέρω μαθηματική τους επεξεργασία ώστε να διεξαχθούν τα αποτελέσματα που αντιστοιχούν στο ρυθμό των παλμων και στο επίπεδο κορεσμού του Οξυγόνου. Επίσης, αξίζει να σημειωθεί ότι γίνεται εκτεταμένη χρήση του Timer A που διαθέτει ο msp430f169 για τον χρονισμό του προγράμματος και τον έλεγχο της διαδοχής των διεργασιών. Αυτό γίνεται ώστε η MCU να παραμένει όσο το δυνατόν μεγαλύτερο χρονικό διαστήμα σε LPM3 (κατάσταση αναμονής με κατανάλωση μικρότερη των 2μΑ και χόνο αφύπνισης μικρότερο των 6μs), όταν δε λειτουργεί, ώστε να μειώνεται σημαντικά η κατανάλωση της συσκευής και δεύτερον για να μπορέσουμε να υπολογίσουμε το χρόνο δειγματοληψίας του προγράμματος ανεξαρτητοποιώντας τον από το χρόνο εκτέλεσης του κώδικα. Τέλος, οι απαίτησεις τουπρογράμματος σε μνήμη είναι 3860 bytes για μνήμη κώδικα, 1785 bytes για μνήμη δεδομένων και 556 bytes για μνήμη σταθερών. Ακόμα οι απάτησης ισχύος ειναι εξαιρετικά χαμηλές αφού η συσκευή λειτουργεί με μπαταρία των 6V. / Pulseoximetry is the proceedure through which are defined the level of the oxygen saturation and the heart beat ratio.In this paper we examine the theoratical basis on which the device has been developed,we present the basic characteristics of the msp43of169 microproccessor which has been used and we describe the hardware and the software of the developement.Finally we conclude presenting the results and the graphic of the device.

The objectives for the first part of this thesis were to describe changes in oxygen saturation (SpO2) and heart rate (HR) in newly born infants in the delivery room (DR) and to illustrate the changes using centile reference charts. The objective of the second part of the thesis was to investigate whether infants < 29 weeks gestation who receive positive pressure ventilation (PPV), immediately after birth with a T-piece have higher SpO2 measurements at five minutes than infants ventilated with a self inflating bag (SIB). / Study Design. A prospective observational study was used to achieve the first objectives. For the second part of the thesis I coordinated a randomised, controlled trial of two devices used for resuscitation of extremely preterm infants in the DR where the primary outcome measure was SpO2. / Patients and methods. In all studies a Masimo Radical pulse oximeter (PO) was placed on the infant’s right hand/wrist immediately after birth. PO data (oxygen saturation, HR and signal quality) were downloaded every 2 sec and analysed only when the signal had no alarm messages (low IQ signal, low perfusion, sensor off, ambient light). / Results. Observational studies: The dataset to develop the reference range charts included 61,650 data points from 468 infants. Infants had a mean (range) gestational age of 38 (25-42) weeks and birthweight 2970 (625-5135) g. For all 468 infants at one minute the 3rd, 10th, 50th, 90th and 97th centiles were 29%, 39%, 66%, 87% and 92%; at two minutes 34%, 46%, 73%, 91% and 95% and at five minutes 59%, 73%, 89%, 97% and 98%. It took a median of 7.9 (IQR 5.0 to 10) minutes to reach a SpO2 > 90%. SpO2 of preterm infants rose more slowly than that of term infants. At one min the median (IQR) HR was 82 (66 to 138) bpm rising at two min and five min to 151 (112 to 169) bpm and 166 (148 to 176) bpm respectively. In preterm infants, the SpO2 and HR rose more slowly than term infants. / Randomised trial: Forty nine infants were randomly allocated to the T-piece and 50 to the SIB. Ten infants did not receive PPV, 4 (8%) in the T-piece group and 6 (12%) in the SIB group and were not included in the analysis. Forty-one infants received PPV with a T-piece and 39 with a SIB. At 5 minutes after birth there was no significant difference between the mean (SD) SpO2 in the T-piece and SIB groups [50 (31)% vs. 53 (25)%, (p=0.73)]. More T-piece infants received oxygen during DR resuscitation (100% vs. 90%, p=0.04). There was no significant difference between the groups in the use of continuous positive airway pressure (CPAP); endotracheal intubation or administration of surfactant in the DR. Fewer of the T-piece group who left the DR on CPAP were intubated in the first 24 hrs after birth. (7% vs. 23%, p=0.05). / Conclusion. The centile charts developed in this thesis provide a reference range for SpO2 and HR in the first 10 minutes after birth for preterm and term infants. In the randomised trial there was no significant difference in SpO2 at five minutes after birth in extremely preterm infants given PPV with a T-piece or a SIB.