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1.
Pediatr Res ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819656

RESUMO

Apnoea, a pause in respiration, is ubiquitous in preterm infants and are often associated with physiological instability, which may lead to longer-term adverse neurodevelopmental consequences. Despite current therapies aimed at reducing the apnoea burden, preterm infants continue to exhibit apnoeic events throughout their hospital admission. Bedside staff are frequently required to manually intervene with different forms of stimuli, with the aim of re-establishing respiratory cadence and minimizing the physiological impact of each apnoeic event. Such a reactive approach makes apnoea and its associated adverse consequences inevitable and places a heavy reliance on human intervention. Different approaches to improving apnoea management in preterm infants have been investigated, including the use of various sensory stimuli. Despite studies reporting sensory stimuli of various forms to have potential in reducing apnoea frequency, non-invasive intermittent positive pressure ventilation is the only automated stimulus currently used in the clinical setting for infants with persistent apnoeic events. We find that the development of automated closed-looped sensory stimulation systems for apnoea mitigation in preterm infants receiving non-invasive respiratory support is warranted, including the possibility of stimulation being applied preventatively, and in a multi-modal form. IMPACT: This review examines the effects of various forms of sensory stimulation on apnoea mitigation in preterm infants, namely localized tactile, generalized kinesthetic, airway pressure, auditory, and olfactory stimulations. Amongst the 31 studies reviewed, each form of sensory stimulation showed some positive effects, although the findings were not definitive and comparative studies were lacking. We find that the development of automated closed-loop sensory stimulation systems for apnoea mitigation is warranted, including the possibility of stimulation being applied preventatively, and in a multi-modal form.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33963005

RESUMO

OBJECTIVE: To evaluate the performance of a rapidly responsive adaptive algorithm (VDL1.1) for automated oxygen control in preterm infants with respiratory insufficiency. DESIGN: Interventional cross-over study of a 24-hour period of automated oxygen control compared with aggregated data from two flanking periods of manual control (12 hours each). SETTING: Neonatal intensive care unit. PARTICIPANTS: Preterm infants receiving non-invasive respiratory support and supplemental oxygen; median birth gestation 27 weeks (IQR 26-28) and postnatal age 17 (12-23) days. INTERVENTION: Automated oxygen titration with the VDL1.1 algorithm, with the incoming SpO2 signal derived from a standard oximetry probe, and the computed inspired oxygen concentration (FiO2) adjustments actuated by a motorised blender. The desired SpO2 range was 90%-94%, with bedside clinicians able to make corrective manual FiO2 adjustments at all times. MAIN OUTCOME MEASURES: Target range (TR) time (SpO2 90%-94% or 90%-100% if in air), periods of SpO2 deviation, number of manual FiO2 adjustments and oxygen requirement were compared between automated and manual control periods. RESULTS: In 60 cross-over studies in 35 infants, automated oxygen titration resulted in greater TR time (manual 58 (51-64)% vs automated 81 (72-85)%, p<0.001), less time at both extremes of oxygenation and considerably fewer prolonged hypoxaemic and hyperoxaemic episodes. The algorithm functioned effectively in every infant. Manual FiO2 adjustments were infrequent during automated control (0.11 adjustments/hour), and oxygen requirements were similar (manual 28 (25-32)% and automated 26 (24-32)%, p=0.13). CONCLUSION: The VDL1.1 algorithm was safe and effective in SpO2 targeting in preterm infants on non-invasive respiratory support. TRIAL REGISTRATION NUMBER: ACTRN12616000300471.

4.
Arch Dis Child Fetal Neonatal Ed ; 106(1): 81-83, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32796057

RESUMO

BACKGROUND: Nasal continuous positive airway pressure (NCPAP) can be applied via binasal prongs or nasal masks; both may be associated with air leak and intermittent hypoxia. We investigated whether the latter is more frequent with nasal masks or prongs. METHODS: Continuous 24 hours recordings of inspired oxygen fraction (FiO2), pulse rate, respiratory rate, pulse oximeter saturation (SpO2) and CPAP level were made in preterm infants with respiratory insufficiency (n=20) managed on CPAP in the NICU at the Royal Hobart Hospital. As part of routine care, nasal interfaces were alternated 4-hourly between mask and prongs. In each recording, the first two segments containing at least 3 hours of artefact-free signal for each interface were selected. Recordings were analysed for episodes with hypoxaemia (SpO2 <80% for ≥10 s) and bradycardia (pulse rate <80/min for ≥4 s) and for episodes of pressure loss at the nasal interface. Data were compared using Wilcoxon-matched pairs test and are reported as median (IQR). RESULTS: Infants had a gestational age at birth of 26 (25-27) weeks and postnatal age of 17 (14-24) days. There was no difference in %time with interface leak between prong and mask (0.9 (0-8)% vs 1.1 (0-18)%, p=0.82), %time with SpO2 <80% (0.15 (0-1.2)% vs 0.06 (0-0.8)%, p=0.74) or heart rate <80/min (0.03 (0-0.2)% vs 0 (0-0.2)%, p=0.64). Three infants had interface leak for >10% of the time with prongs and 5 with the mask. CONCLUSION: Both interfaces resulted in a similarly stable provision of positive airway pressure, and there was also no difference in the occurrence of intermittent hypoxia.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/instrumentação , Pressão Positiva Contínua nas Vias Aéreas/métodos , Hipóxia/epidemiologia , Feminino , Idade Gestacional , Frequência Cardíaca , Humanos , Lactente Extremamente Prematuro , Recém-Nascido de muito Baixo Peso/fisiologia , Unidades de Terapia Intensiva Neonatal , Masculino , Oxigênio/sangue , Taxa Respiratória
5.
Front Pediatr ; 8: 570, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042915

RESUMO

Apnoea, a pause in respiration, is almost ubiquitous in preterm infants born before completing 30 weeks gestation. Apnoea often begets hypoxemia and/or bradycardia, and has the potential to result in adverse neurodevelopmental consequences. Our current inability to predict apnoeic events in preterm infants requires apnoea to first be detected by monitoring device/s in order to trigger an intervention by bedside (medical or nursing) staff. Such a reactive management approach is laborious, and makes the consequences of apnoeic events inevitable. Recent technological advances and improved signal processing have allowed the possibility of developing prediction models for apnoeic events in preterm infants. However, the development of such models has numerous challenges and is only starting to show potential. This paper identifies requisite components and current gaps in developing prediction models for apnoeic events, and reviews previous studies on predicting apnoeic events in preterm infants.

7.
Pediatr Pulmonol ; 54(11): 1712-1721, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31313528

RESUMO

BACKGROUND: The factors influencing the severity of apnea-related hypoxemia and bradycardia are incompletely characterized, especially in infants receiving noninvasive respiratory support. OBJECTIVES: To identify the frequency and predictors of physiological instability (hypoxemia-oxygen saturation (SpO2 ) <80%, or bradycardia-heart rate (HR) < 100 bpm) following respiratory pauses in infants receiving noninvasive respiratory support. METHODS: Respiratory pause duration, derived from capsule pneumography, was measured in 30 preterm infants of gestation 30 (24-32) weeks [median (interquartile range)] receiving noninvasive respiratory support and supplemental oxygen. For identified pauses of 5 to 29 seconds duration, we measured the magnitude and duration of SpO2 and HR reductions over a period starting at the pause onset and ending 60 seconds after resumption of breathing. Temporally clustered pauses (<60 seconds separation) were analyzed separately. The relative contribution of respiratory pauses to overall physiological instability was determined, and predictors of instability were sought in regression analysis, including demographic, clinical and situational variables as inputs. RESULTS: In total, 17 105 isolated and 9180 clustered pauses were identified. Hypoxemia and bradycardia were more likely after longer duration and temporally-clustered pauses. However, the majority of such episodes occurred after 5 to 9 second pauses given their numerical preponderance, and short-lived pauses made a substantial contribution to physiological instability overall. Birth gestation, hemoglobin concentration, form of respiratory support, caffeine treatment, respiratory pause duration and temporal clustering were identified as predictors of instability. CONCLUSIONS: Brief respiratory pauses, especially when clustered, contribute substantially to hypoxemia and bradycardia in preterm infants.


Assuntos
Apneia/fisiopatologia , Bradicardia/etiologia , Hipóxia/etiologia , Doenças do Prematuro/fisiopatologia , Recém-Nascido Prematuro/fisiologia , Apneia/complicações , Frequência Cardíaca , Humanos , Hipóxia/fisiopatologia , Recém-Nascido , Estudos Prospectivos , Respiração
8.
Arch Dis Child Fetal Neonatal Ed ; 102(1): F31-F36, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27634820

RESUMO

OBJECTIVE: To assess the performance of a novel algorithm for automated oxygen control using a simulation of oxygenation founded on in vivo data from preterm infants. METHODS: A proportional-integral-derivative (PID) control algorithm was enhanced by (i) compensation for the non-linear SpO2-PaO2 relationship, (ii) adaptation to the severity of lung dysfunction and (iii) error attenuation within the target range. Algorithm function with and without enhancements was evaluated by iterative linking with a computerised simulation of oxygenation. Data for this simulation (FiO2 and SpO2 at 1 Hz) were sourced from extant recordings from preterm infants (n=16), and converted to a datastream of values for ventilation:perfusion ratio and shunt. Combination of this datastream second by second with the FiO2 values from the algorithm under test produced a sequence of novel SpO2 values, allowing time in the SpO2 target range (91%-95%) and in various degrees of hypoxaemia and hyperoxaemia to be determined. A PID algorithm with 30 s lockout after each FiO2 adjustment, and a proportional-derivative (PD) algorithm were also evaluated. RESULTS: Separate addition of each enhancing feature to the PID algorithm showed a benefit, but not with uniformly positive effects. The fully enhanced algorithm was optimal for the combination of targeting the desired SpO2 range and avoiding time in, and episodes of, hypoxaemia and hyperoxaemia. This algorithm performed better than one with a 30 s lockout, and considerably better than PD control. CONCLUSIONS: An enhanced PID algorithm was very effective for automated oxygen control in a simulation of oxygenation, and deserves clinical evaluation.


Assuntos
Algoritmos , Automação/métodos , Doenças do Prematuro/terapia , Recém-Nascido Prematuro , Oxigenoterapia/métodos , Oxigênio/administração & dosagem , Respiração Artificial/métodos , Feminino , Humanos , Recém-Nascido , Masculino , Oximetria
9.
Neonatology ; 109(1): 37-43, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26554825

RESUMO

BACKGROUND: Oxygen saturation (SpO2) targeting in the preterm infant may be improved with a better understanding of the SpO2 responses to changes in inspired oxygen (FiO2). OBJECTIVE: We investigated the first-order FiO2-SpO2 relationship, aiming to quantify the parameters governing that relationship, the influences on these parameters and their variability. METHODS: In recordings of FiO2 and SpO2 from preterm infants on continuous positive airway pressure and supplemental oxygen, we identified unique FiO2 adjustments and mapped the subsequent SpO2 responses. For responses identified as first-order, the delay, time constant and gain parameters were determined. Clinical and physiological predictors of these parameters were sought in regression analysis, and intra- and inter-subject variability was evaluated. RESULTS: In 3,788 h of available data from 47 infants at 31 (28-33) post-menstrual weeks [median (interquartile range)], we identified 993 unique FiO2 adjustments followed by a first-order SpO2 response. All response parameters differed between FiO2 increments and decrements, with increments having a shorter delay, longer time constant and higher gain [2.9 (1.7-4.8) vs. 1.3 (0.58-2.6), p < 0.05]. Gain was also higher in less mature infants and in the setting of recent SpO2 instability, and was diminished with increasing severity of lung dysfunction. Intra-subject variability in all parameters was prominent. CONCLUSIONS: First-order SpO2 responses show variable gain, influenced by the direction of FiO2 adjustment and the severity of lung disease, as well as substantial intra-subject parameter variability. These findings should be taken into account in adjustment of FiO2 for SpO2 targeting in preterm infants.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Recém-Nascido Prematuro , Oximetria/métodos , Oxigenoterapia/métodos , Oxigênio/análise , Humanos , Recém-Nascido
10.
Arch Dis Child Fetal Neonatal Ed ; 100(5): F436-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26054970

RESUMO

Oxygen saturation (SpO2) signal dropout leaves caregivers without a reliable measure to guide oxygen therapy. We studied SpO2 dropout in preterm infants on continuous positive airway pressure, noting the SpO2 values at signal loss and recovery and thus the resultant change in SpO2, and the factors influencing this parameter. In 32 infants of median gestation 26 weeks, a total of 3932 SpO2 dropout episodes were identified (1.1 episodes/h). In the episodes overall, SpO2 decreased by 1.1%, with the SpO2 change influenced by starting SpO2 (negative correlation), but not dropout duration. For episodes starting in hypoxia (SpO2 <85%), SpO2 recovered at a median of 3.2% higher than at SpO2 dropout, with a downward trajectory in a quarter of cases. We conclude that after signal dropout SpO2 generally recovers in a relative normoxic range. Blind FiO2 adjustments are thus unlikely to be of benefit during most SpO2 dropout episodes.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Hiperóxia/prevenção & controle , Hipóxia/prevenção & controle , Doenças do Prematuro/prevenção & controle , Oximetria/instrumentação , Falha de Equipamento , Humanos , Recém-Nascido , Recém-Nascido Prematuro
11.
J Pediatr ; 164(4): 730-736.e1, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24433828

RESUMO

OBJECTIVE: The precision of oxygen saturation (SpO2) targeting in preterm infants on continuous positive airway pressure (CPAP) is incompletely characterized. We therefore evaluated SpO2 targeting in infants solely receiving CPAP, aiming to describe their SpO2 profile, to document the frequency of prolonged hyperoxia and hypoxia episodes and of fraction of inspired oxygen (FiO2) adjustments, and to explore the relationships with neonatal intensive care unit operational factors. STUDY DESIGN: Preterm infants <37 weeks' gestation in 2 neonatal intensive care units were studied if they were receiving CPAP and in supplemental oxygen at the beginning of each 24-hour recording. SpO2, heart rate, and FiO2 were recorded (sampling interval 1-2 seconds). We measured the proportion of time spent in predefined SpO2 ranges, the frequency of prolonged episodes (≥30 seconds) of SpO2 deviation, and the effect of operational factors including nurse-patient ratio. RESULTS: A total of 4034 usable hours of data were recorded from 45 infants of gestation 30 (27-32) weeks (median [IQR]). When requiring supplemental oxygen, infants were in the target SpO2 range (88%-92%) for only 31% (19%-39%) of total recording time, with 48 (6.9-90) episodes per 24 hours of severe hyperoxia (SpO2 ≥98%), and 9.0 (1.6-21) episodes per 24 hours of hypoxia (SpO2 <80%). An increased frequency of prolonged hyperoxia in supplemental oxygen was noted when nurses were each caring for more patients. Adjustments to FiO2 were made 25 (16-41) times per day. CONCLUSION: SpO2 targeting is challenging in preterm infants receiving CPAP support, with a high proportion of time spent outside the target range and frequent prolonged hypoxic and hyperoxic episodes.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Recém-Nascido Prematuro , Oxigênio/administração & dosagem , Feminino , Humanos , Hiperóxia/metabolismo , Hipóxia/metabolismo , Recém-Nascido , Masculino , Oxigênio/metabolismo , Estudos Prospectivos
12.
Leuk Res ; 34(12): 1622-6, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20427086

RESUMO

The c-kit receptor is expressed in 95% of relapsed acute myeloid leukemias (AMLs) and mediates leukemic proliferation. We conducted a Phase 1 study of the c-kit inhibitor, imatinib mesylate (IM), in combination with cytarabine and daunorubicin (7+3) in c-kit+ relapsed AML. IM was dose escalated using a 3 by 3 design. Phosphorylated STAT5 was absent to minimally present in residual blasts on day 14 bone marrows. The maximum tolerated dose of IM was 300 mg. The dose-limiting toxicity was Grade 3-4 hepatic toxicity. The CR/CRp rate was 57%. Cytotoxic therapy that includes IM for relapsed AML is well-tolerated and effective.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia Mieloide Aguda/prevenção & controle , Proteínas Proto-Oncogênicas c-kit , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzamidas , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Daunorrubicina/administração & dosagem , Daunorrubicina/efeitos adversos , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mieloide Aguda/metabolismo , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Recidiva , Fator de Transcrição STAT5/metabolismo
13.
Leuk Lymphoma ; 51(4): 606-12, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20141429

RESUMO

OCT-2 and its co-activator, BOB.1, are B-cell associated transcription factors expressed in a subset of patients with acute myeloid leukemia (AML). We evaluated OCT-2 and BOB.1 expression by immunohistochemistry in patients with newly diagnosed AML. The median overall survival (OS) for patients with varying levels of OCT-2 expression was statistically different (p = 0.03) (OCT-2 <10%: 21.7 months; OCT-2 10-50%: 18.4 months; OCT-2 >50%: 11.6 months). On multivariate analysis, co-expression of OCT-2/BOB.1 remained predictive for achievement of complete remission (HR 0.44, p = 0.010) and increased risk of relapse (HR 2.30, p = 0.047). OCT-2 (per 10% increase) was associated with a decreased progression-free survival (HR 1.10, p = 0.036) and a trend toward a worse OS (HR 1.10, p = 0.063). OCT-2 may act as a cell survival factor in AML by mediating expression of downstream targets, such as BCL-2. These results will need to be validated prospectively.


Assuntos
Leucemia Mieloide Aguda/diagnóstico , Fator 2 de Transcrição de Octâmero/metabolismo , Transativadores/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/fisiologia , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Imuno-Histoquímica , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Fator 2 de Transcrição de Octâmero/genética , Fator 2 de Transcrição de Octâmero/fisiologia , Prognóstico , Recidiva , Indução de Remissão , Análise de Sobrevida , Transativadores/genética , Transativadores/fisiologia , Adulto Jovem
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