Forehead reflectance photoplethysmography to monitor heart rate: preliminary results from neonatal patients

Around 5%–10% of newborn babies require some form of resuscitation at birth and heart rate (HR) is the best guide of efficacy. We report the development and first trial of a device that continuously monitors neonatal HR, with a view to deployment in the delivery room to guide newborn resuscitation. The device uses forehead reflectance photoplethysmography (PPG) with modulated light and lock-in detection. Forehead fixation has numerous advantages including ease of sensor placement, whilst perfusion at the forehead is better maintained in comparison to the extremities. Green light (525 nm) was used, in preference to the more usual red or infrared wavelengths, to optimize the amplitude of the pulsatile signal. Experimental results are presented showing simultaneous PPG and electrocardiogram (ECG) HRs from babies (n = 77), gestational age 26–42 weeks, on a neonatal intensive care unit. In babies ≥32 weeks gestation, the median reliability was 97.7% at ±10 bpm and the limits of agreement (LOA) between PPG and ECG were +8.39 bpm and −8.39 bpm. In babies <32 weeks gestation, the median reliability was 94.8% at ±10 bpm and the LOA were +11.53 bpm and −12.01 bpm. Clinical evaluation during newborn deliveries is now underway

Tidal Breathing Measurements at Discharge and Clinical Outcomes in Extremely Low Gestational Age Neonates

Rationale: The relationship between respiratory function at hospital discharge and the severity of later respiratory disease in extremely low gestational age neonates is not well defined. Objectives: To test the hypothesis that tidal breathing measurements near the time of hospital discharge differ between extremely premature infants with BPD or respiratory disease in the first year of life compared to those without these conditions. Methods: Study subjects were part of the Prematurity and Respiratory Outcomes Program (PROP) study, a longitudinal cohort study of infants born <29 gestational weeks followed from birth to 1 year of age. Respiratory inductance plethysmography was used for tidal breathing measurements before and after inhaled albuterol 1 week prior to anticipated hospital discharge. Infants were breathing spontaneously and were receiving ≤1 liter per minute (lpm) nasal cannula flow at 21-100% FiO2. A survey of respiratory morbidity was administered to caregivers at 3, 6, 9, and 12 months corrected age to assess for respiratory disease. We compared tidal breathing measurements in infants with and without bronchopulmonary dysplasia (BPD, oxygen requirement at 36 wk) and with and without respiratory disease in the first year of life. Measurements were also performed in a comparison cohort of term infants. Results: 765 infants survived to 36 weeks post-menstrual age, with research-quality tidal breathing data in 452 out of 564 tested (80.1%). Among these 452 infants, the rate of post-discharge respiratory disease was 65.7%. Compared to a group of 18 term infants, PROP infants had abnormal tidal breathing patterns. However, there were no significant differences in tidal breathing measurements in PROP infants who had BPD or who had respiratory disease in the first year of life compared to those without these diagnoses. Bronchodilator response was not significantly associated with respiratory disease in the first year of life. Conclusions: Extremely premature infants receiving <1 lpm nasal cannula support at 21-100% FiO2 have tidal breathing measurements that differ from term infants, but these measurements do not differentiate those preterm infants who have BPD or will have respiratory disease in the first year of life from those who do not

Sedative and Neurotoxic Properties of Brexanolone Compared to Midazolam in the Developing Rodent Brain

The developing brain is susceptible to extensive neurotoxicity following exposure to sedative/anesthetic drugs (SADs). Every year hundreds of thousands of children around the world are exposed to SADs with no viable non-neurotoxic agents approved for clinical use. Allopregnanolone (AlloP) has well-established sedative effects in adults and neonates. AlloP and many SADs produce sedation/anesthesia through allosteric modulation of GABAA receptors, which is one of two principal mechanisms behind SAD-induced neurotoxicity. Evidence suggests AlloP has the unique capacity to regulate key apoptotic factors in adults and is widely involved with critical stages of neurodevelopment, indicating this neurosteroid might serve as a less neurotoxic sedative. Here, I showed the brexanolone (BRX) formulation of AlloP is more sedative than midazolam (MDZ). Lower doses of BRX had minimal impact on vital signs and produced no significant neurotoxic effect. Conversely, higher doses of BRX produced neurotoxicity, suggesting the apoptogenicity of BRX is dose dependent. Results for MDZ show far milder levels of sedation were obtainable until high doses. A significant neuroapoptotic response was induced at all sedative doses of MDZ. Prolonged light sedation similar to MDZ was obtained using BRX during continuous infusion. Although BRX appeared qualitatively less deleterious to heart and breath rate over time, 6-hour infusion of BRX induced a similar neurotoxic response compared to MDZ. These findings suggest low, sedative doses of BRX can be administered without gross impact to vital signs or neurotoxic consequences

Oxygen Saturation among Newborn Infants and the Decrease Occurring During Feeding in Various Populations

Pharyngeal and laryngeal structural movements coordinate respiration and swallowing functions, hence eliminating simultaneous execution. This research aims to document levels of oxygen saturation during rest and feeding among various newborn populations. Hypothesized is that an increase in oxygen alterations during feeding will be exhibited by infants of younger gestational age and, further, by those with the presence of respiratory anomalies. Thirty newborns in the nurseries at Medical University of South Carolina, free of cardiac and genetic maladies, were divided into three groups. Subjects of group 1 are healthy, full-term newborns; within groups 2 and 3, preterm infants (\u3c37 weeks gestation). Subjects of groups 1 and 2 have no diagnosed respiratory disorders; those within group 3 have diagnoses of respiratory illness. Nellcor pulse-oximeters monitor infants during sleep and feeding sessions. ANOVA data analysis revealed no statistical difference within this sample. A pattern of increased changes suggests clinical significance. Future studies may find it beneficial to use a larger sample size powered to detect a smaller effect size

Clinical investigation of plethysmographic variability index: A derivative index of pulse oximetry in anesthetized dogs

Plethysmographic Variability Index (PVI) is a derivative index of pulse oximetry that allows evaluating an individual\u27s intravascular volume status. Perfusion Index (PI) represents the strength of pulse signal at the anatomic site of measurement from which PVI is calculated using changes in PI over respiratory cycles. Plethysmographic Variability Index has been used to detect hypovolemia and predict fluid responsiveness in mechanically ventilated human patients however, fewer studies are available in spontaneously breathing patients. The use of PVI has not been explored extensively in dogs so far. The goals of this study were to establish a common range for PVI and assess relationship of the PVI, PI and various clinical variables in the anesthetized spontaneously breathing dogs. Values of PVI and PI derived from Masimo pulse oximetry were obtained at 5, 10, 15 and 20 minutes after anesthetic induction but before surgical stimulation together with cardiorespiratory variables that included heart rate, blood pressures (systolic, mean and diastolic blood pressures), respiratory rate and hemoglobin saturation of oxygen (SpO2) in 73 dogs with ASA 1-3 status admitted to the Purdue Teaching Hospital.^ Other clinical variables like body temperature, anesthetic protocol used, pre-induction packed cell volume (PCV) and total protein (TP) values, recumbency positions (sternal, lateral or dorsal recumbency) and rate of crystalloid fluids administration (5 vs 10 ml/kg/hr) were also obtained. Data were analysed using non-parametric Spearman\u27s rho coefficient and Kruskal Wallis one-way ANOVA by ranks to assess temporal relationship of PVI with all the clinical variables and with significant level set at P\u3c0.05. A common range of PVI was 5-43% with a median 18%. There was no significant correlation found between PVI and PI. Plethysmographic Variability Index positively correlated with the systolic blood pressure (rs=0.25; P\u3c0.001), mean blood pressure (rs=0.26; P\u3c0.001), diastolic blood pressure (rs=0.36; P\u3c0.001) and body temperature (rs=0.166; P=0.004). The other cardiorespiratory variables, recumbency positions, rate of crystalloid fluid administration, pre-operative PCV and TP values had no relationship with PVI. Premedication containing dexmedetomidine resulted in higher PVI (Kruskal-Wallis Test; P=0.001) and lower PI values (Kruskal-Wallis Test; P=0.004) and the opposite was true with protocols that contained acepromazine. It was concluded that while evaluating PVI for fluid response in the anesthetized dogs, various clinical factors should be taken into consideration

Role of Pulse Oximetry and Perfusion Index in Screening for Critical Congenital Heart Disease in Asymptomatic Newborn Babies

INTRODUCTION: Congenital heart disease (CHD) is the commonest group of congenital malformations and affects 7–8/1000 newborns. It contributes to 3% of all infant mortality and 46% of deaths from congenital malformations, with most deaths occurring in the first year of life. One of the major contributors to increased infant mortality and morbidity is clinical deterioration and collapse prior to diagnosis and treatment. Early detection of CHD in the asymptomatic period immediately after birth will reduce clinical deterioration by instigation of appropriate, timely management. Currently infants are screened to detect congenital heart disease by physical examination after birth and another examination at six to eight weeks. However, this method of screening fails to detect up to 50% of CHDs at birth. Several studies have reported the use of pulse oximetry as a screening tool for the detection of CHD. However the detection of left sided obstructive heart diseases remains a problem area with pulse oximetry screening alone. Pulse oximeter sometimes does not detect left heart obstructive lesions which represented 75% of the false negative cases in study by Reide et al.2 With this background, we planned a study to find out the utility of newer generation pulse oximeters with perfusion index in screening for congenital heart diseases. AIM OF THE STUDY: To study the role of pulse oximetry and perfusion index in screening for critical congenital heart disease in asymptomatic newborn babies at 24-72 hrs of life. METHODOLOGY: STUDY DESIGN: Prospective descriptive study. STUDY PLACE: Postnatal and post caesarean wards of Institute of Obstetrics & Gynecology and Hospital for women & children (IOG), Egmore, Chennai. STUDY PERIOD: October 2011- January 2012 (4 months period). INCLUSION CRITERIA: All babies born during the study period and are asymptomatic at 24- 72 hrs of life, being nursed with their mother in the postnatal and post caesarean wards of IOG. EXCLUSION CRITERIA: Asymptomatic babies under evaluation for early onset sepsis. RESULTS: A total of 1,011 babies out of 1,059 eligible babies were screened over a period of four months. Forty eight babies were not screened due to early discharge of mother before 24 hrs of life due to various reasons. There were almost equal number of male and female babies (Male to female ratio= 1.03:1). CONCLUSION: Several studies have proved the role of hemoglobin saturation measurement by pulse oximeter screening in identifying critical Congenital heart diseases. The challenge in identifying left side obstructive heart diseases can be tackled by including perfusion index measurement in the screening protocol. Thus the routine screening of all asymptomatic newborn babies at 24- 72 hours of life with pulse oximeter measurement of hemoglobin saturation and perfusion index may help in early identification of more number babies with critical congenital heart disease

Non-invasive optical monitoring of free and bound oxygen in humans

Background: Possibilities of detecting oxygen - both in its free form, as gas in the lungs, and in its bound form, as oxygenated hemoglobin - have been explored in this thesis. Perfusion and oxygenation of vital organs (e.g., heart, brain and kidneys) may be severely compromised in critical illness or major trauma, which is why blood is rapidly diverted to those organs to improve chances of survival. Blood vessels in less important organs (e.g., skin, skeletal muscles and intestines) are constricted, leading to reduced regional perfusion and oxygenation in these organs. Non-invasive measurements of changes in tissue perfusion and oxygenation, in e.g., the forearm, might give an early indication of clinical deterioration. Preterm infants are very vulnerable patients. Their organs, in particular the lungs, are not fully developed, and the respiratory distress syndrome (RDS) frequently occurs. The intestines may be affected by necrotizing enterocolitis (NEC). Complementary diagnostic and surveillance methods of RDS and NEC are desirable. Aims: The overall aim of this thesis, which includes Studies I-IV, was to develop and evaluate non-invasive optical techniques, based on light at different wavelengths, to complement future bedside surveillance in critically illness or severe injury, for adults as well as for infants. Methods: Changes in tissue oxygenation by near-infrared spectroscopy (I-II), blood perfusion by laser Doppler imaging (I) and blood volume by tissue viability imaging (I) in skeletal muscle and skin were studied, and continuous-wave and timeresolved near-infrared spectroscopy were compared (II) in healthy volunteers subjected to various defined regional physiological perturbations. For the first time, gas in scattering media absorption spectroscopy (GASMAS) was used to detect alveolar water vapor (III-IV) and oxygen gas (IV), as well as intestinal water vapor (III) in newborn infants. Main results: Near-infrared spectroscopy, laser Doppler imaging and tissue viability imaging provided valuable information on physiological changes in the microcirculation (I). Continuous-wave and time-resolved near-infrared spectroscopy techniques were both able to determine changes in tissue oxygenation, but the time-resolved technique provided more realistic values with smaller inter-individual differences (II). Alveolar (III-IV) and intestinal signals of water vapor (III), were readily detected, together with alveolar signals of oxygen gas (IV), non-invasively in newborn infants. Conclusions: Optical techniques, being non-invasive and providing data in real-time, are attractive as potential tools for surveillance in critical illness or severe injury, in particular concerning the oxygenation. As an overall conclusion, we believe, that fully developed time-resolved near-infrared techniques have the potential to become an additional monitoring method of choice for surveillance of critically ill or severely injured patients. Likewise, GASMAS has great potential for future monitoring of critically ill preterm or full-term infants, and might, ultimately, reduce the current use of X-ray imaging in these most vulnerable patients

Frequency-Modulated Orocutaneous Stimulation Promotes Non-nutritive Suck Development in Preterm Infants with Respiratory Distress Syndrome or Chronic Lung Disease

Background—For the premature infant, extrauterine life is a pathological condition which greatly amplifies the challenges to the brain in establishing functional oromotor behaviors. The extent to which suck can be entrained using a synthetically patterned orocutaneous input to promote its development in preterm infants who manifest chronic lung disease is unknown. Objective—To evaluate the effects of a frequency-modulated orocutaneous pulse train delivered through a pneumatically-charged pacifier capable of enhancing non-nutritive suck (NNS) activity in tube-fed premature infants. Methods—A randomized trial to evaluate the efficacy of pneumatic orocutaneous stimulation 3x/day on NNS development and length of stay (LOS) in the NICU among 160 newborn infants distributed among 3 subpopulations, including healthy preterm infants (HI), respiratory distress syndrome (RDS), and chronic lung disease (CLD). Study infants received a regimen of orocutaneous pulse trains through a PULSED pressurized silicone pacifier or a SHAM control (blind pacifier) during gavage feeds for up to 10 days. Results—Mixed modeling, adjusted for the infant’s gender, gestational age, postmenstrual age, and birth weight, was used to handle interdependency among repeated measures within subjects. A significant main effect for stimulation mode (SHAM pacifier vs PULSED orosensory) was found among preterm infants for NNS Bursts/minute (p=.003), NNS events/minute (p=.033), and for Total Oral Compressions/minute [NNS+nonNNS] (p=.016). Pairwise comparison of adjusted means using Bonferroni adjustment indicated RDS and CLD infants showed the most significant gains on these NNS performance indices. CLD infants in the treatment group showed significantly shorter LOS by an average of 2.5 days

Frequency-Modulated Orocutaneous Stimulation Promotes Non-nutritive Suck Development in Preterm Infants with Respiratory Distress Syndrome or Chronic Lung Disease

Background—For the premature infant, extrauterine life is a pathological condition which greatly amplifies the challenges to the brain in establishing functional oromotor behaviors. The extent to which suck can be entrained using a synthetically patterned orocutaneous input to promote its development in preterm infants who manifest chronic lung disease is unknown. Objective—To evaluate the effects of a frequency-modulated orocutaneous pulse train delivered through a pneumatically-charged pacifier capable of enhancing non-nutritive suck (NNS) activity in tube-fed premature infants. Methods—A randomized trial to evaluate the efficacy of pneumatic orocutaneous stimulation 3x/day on NNS development and length of stay (LOS) in the NICU among 160 newborn infants distributed among 3 subpopulations, including healthy preterm infants (HI), respiratory distress syndrome (RDS), and chronic lung disease (CLD). Study infants received a regimen of orocutaneous pulse trains through a PULSED pressurized silicone pacifier or a SHAM control (blind pacifier) during gavage feeds for up to 10 days. Results—Mixed modeling, adjusted for the infant’s gender, gestational age, postmenstrual age, and birth weight, was used to handle interdependency among repeated measures within subjects. A significant main effect for stimulation mode (SHAM pacifier vs PULSED orosensory) was found among preterm infants for NNS Bursts/minute (p=.003), NNS events/minute (p=.033), and for Total Oral Compressions/minute [NNS+nonNNS] (p=.016). Pairwise comparison of adjusted means using Bonferroni adjustment indicated RDS and CLD infants showed the most significant gains on these NNS performance indices. CLD infants in the treatment group showed significantly shorter LOS by an average of 2.5 days