Laura M. Sterni

Adherence to and Effectiveness of Positive Airway Pressure Therapy in Children With Obstructive Sleep Apnea

OBJECTIVES. Positive airway pressure therapy (PAP) is frequently used to treat children who have obstructive sleep apnea syndrome and do not respond to adenotonsillectomy. However, no studies have evaluated objectively adherence to PAP in children, and few studies have evaluated objectively the effectiveness of PAP. The objective of this study was to determine adherence and effectiveness of PAP (both continuous [CPAP] and bilevel [BPAP] pressure) in children with obstructive apnea. METHODS. A prospective, multicenter study was performed of children who were randomly assigned in a double-blind manner to 6 months of CPAP versus BPAP. Adherence was measured objectively using the equipments computerized output. Effectiveness was evaluated using polysomnography. RESULTS. Twenty-nine children were studied. Approximately one third of children dropped out before 6 months. Of the 21 children for whom 6-month adherence data could be downloaded, the mean nightly use was 5.3 ± 2.5 (SD) hours. Parental assessment of PAP use considerably overestimated actual use. PAP was highly effective, with a reduction in the apnea hypopnea index from 27 ± 32 to 3 ± 5/hour, and an improvement in arterial oxygen saturation nadir from 77 ± 17% to 89 ± 6%. Results were similar for children who received CPAP versus BPAP. Children also had a subjective improvement in daytime sleepiness. CONCLUSIONS. Both CPAP and BPAP are highly efficacious in pediatric obstructive apnea. However, treatment with PAP is associated with a high dropout rate, and even in the adherent children, nightly use is suboptimal considering the long sleep hours in children.

Perioperative management of children with obstructive sleep apnea

Obstructive sleep apnea syndrome (OSA) affects 1%-3% of children. Children with OSA can present for all types of surgical and diagnostic procedures requiring anesthesia, with adenotonsillectomy being the most common surgical treatment for OSA in the pediatric age group. Thus, it is imperative that the anesthesiologist be familiar with the potential anesthetic complications and immediate postoperative problems associated with OSA. The significant implications that the presence of OSA imposes on perioperative care have been recognized by national medical professional societies. The American Academy of Pediatrics published a clinical practice guideline for pediatric OSA in 2002, and cited an increased risk of anesthetic complications, though specific anesthetic issues were not addressed. In 2006, the American Society of Anesthesiologists published a practice guideline for perioperative management of patients with OSA that noted the pediatric-related risk factor of obesity, and the increased perioperative risk associated with adenotonsillectomy in children younger than 3 yr. However, management of OSA in children younger than 1 yr-of-age was excluded from the guideline, as were other issues related specifically to the pediatric patient. Hence, many questions remain regarding the perioperative care of the child with OSA. In this review, we examine the literature on pediatric OSA, discuss its pathophysiology, current treatment options, and recognized approaches to perioperative management of these young and potentially high-risk patients.

Resetting and postnatal maturation of oxygen chemosensitivity in rat carotid chemoreceptor cells

1 Carotid chemoreceptor sensitivity is minimal immediately after birth and increases with postnatal age. In the present study we have investigated the peri‐ and postnatal developmental time course of [Ca2+]i responses to hypoxia in clusters of type I cells isolated from near‐term fetal rats and rats that were 1, 3, 7, 11, 14 and 21 days old, using the Ca2+‐sensitive fluoroprobe fura‐2. 2 In type I cells from all age groups a graded increase in [Ca2+]i occurred in response to lowering the P  O 2 from 150 mmHg to 70, 35, 14, 7, 2 and 0 mmHg. The graded [Ca2+]i response to hypoxia was hyperbolic at all ages. 3 Type I cells from rats near‐term fetal to 1 day old exhibited small [Ca2+]i responses, mainly to the most severe levels of hypoxia. After day 1, an increase in the [Ca2+]i responses to submaximal hypoxia stimulation resulted in a rightward shift in the O2 response curve. Using the Δ[Ca2+]i between 35 and 2 mmHg P  O 2 as an index of O2 sensitivity, type I cell O2 sensitivity increased approximately 4‐ to 5‐fold between near‐term fetal to 1 day old and 11 to 14 days of age. 4 Exposure to elevated extracellular potassium (10, 20 and 40 mm K+) caused a dose‐dependent [Ca2+]i rise in type I cells from all age groups. There were no age‐related changes in [Ca2+]i responses to any level of K+ between near‐term fetal and 21 days. 5 We conclude that the maximal type I cell [Ca2+]i response to anoxia, as well as the sensitivity to submaximal hypoxic stimulation, of rats aged from near‐term fetal to 21 days depends on the level of postnatal maturity. The lack of an age‐related increase in the [Ca2+]i response to elevated K+ during the timeframe of maximal development of O2 sensitivity suggests that resetting involves maturation of O2 sensing, rather than non‐specific developmental changes in the [Ca2+]i rise resulting from depolarization.

Postnatal maturation of carotid body and type I cell chemoreception in the rat

The site of postnatal maturation of carotid body chemoreception is unclear. To test the hypothesis that maturation occurs synchronously in type I cells and the whole carotid body, the development of changes in the intracellular Ca2+ concentration responses to hypoxia, CO2, and combined challenges was studied with fluorescence microscopy in type I cells and compared with the development of carotid sinus nerve (CSN) responses recorded in vitro from term fetal to 3-wk animals. Type I cell responses to all challenges increased between 1 and 8 days and then remained constant, with no multiplicative O2-CO2 interaction at any age. The CSN response to hypoxia also matured by 8 days, but CSN responses to CO2 did not change significantly with age. Multiplicative O2-CO2 interaction occurred in the CSN response at 2-3 wk but not in younger groups. We conclude that type I cell maturation underlies maturation of the CSN response to hypoxia. However, because development of responses to CO2 and combined hypoxia-CO2 challenges differed between type I cells and the CSN, responses to these stimuli must mature at other, unidentified sites within the developing carotid body.The site of postnatal maturation of carotid body chemoreception is unclear. To test the hypothesis that maturation occurs synchronously in type I cells and the whole carotid body, the development of changes in the intracellular Ca2+ concentration responses to hypoxia, CO2, and combined challenges was studied with fluorescence microscopy in type I cells and compared with the development of carotid sinus nerve (CSN) responses recorded in vitro from term fetal to 3-wk animals. Type I cell responses to all challenges increased between 1 and 8 days and then remained constant, with no multiplicative O2-CO2interaction at any age. The CSN response to hypoxia also matured by 8 days, but CSN responses to CO2 did not change significantly with age. Multiplicative O2-CO2interaction occurred in the CSN response at 2-3 wk but not in younger groups. We conclude that type I cell maturation underlies maturation of the CSN response to hypoxia. However, because development of responses to CO2 and combined hypoxia-CO2 challenges differed between type I cells and the CSN, responses to these stimuli must mature at other, unidentified sites within the developing carotid body.

Chronic hypoxia abolished the postnatal increase in carotid body type I cell sensitivity to hypoxia

The O2 sensitivity of carotid chemoreceptor type I cells is low just after birth and increases with postnatal age. Chronic hypoxia during postnatal maturation blunts ventilatory and carotid chemoreceptor neural responses to hypoxia, but the mechanism remains unknown. We tested the hypothesis that chronic hypoxia from birth impairs the postnatal increase in type I cell O2 sensitivity by comparing intracellular Ca2+ concentration ([Ca2+]i) responses to graded hypoxia in type I cell clusters from rats born and reared in room air or 12% O2. [Ca2+]ilevels at 0, 1, 5, and 21% O2, as well as with 40 mM K+, were measured at 3, 11, and 18 days of age with use of fura 2 in freshly isolated cells. The [Ca2+]iresponse to elevated CO2/low pH was measured at 11 days. Chronic hypoxia from birth abolished the normal developmental increase in the type I cell [Ca2+]iresponse to hypoxia. Effects of chronic hypoxia on development of [Ca2+]iresponses to elevated K+ were small, and [Ca2+]iresponses to CO2 remained unaffected. Impairment of type I cell maturation was partially reversible on return to normoxic conditions. These results indicate that chronic hypoxia severely impairs the postnatal development of carotid chemoreceptor O2sensitivity at the cellular level and leaves responses to other stimuli largely intact.The O2 sensitivity of carotid chemoreceptor type I cells is low just after birth and increases with postnatal age. Chronic hypoxia during postnatal maturation blunts ventilatory and carotid chemoreceptor neural responses to hypoxia, but the mechanism remains unknown. We tested the hypothesis that chronic hypoxia from birth impairs the postnatal increase in type I cell O2 sensitivity by comparing intracellular Ca2+ concentration ([Ca2+]i) responses to graded hypoxia in type I cell clusters from rats born and reared in room air or 12% O2. [Ca2+]i levels at 0, 1, 5, and 21% O2, as well as with 40 mM K+, were measured at 3, 11, and 18 days of age with use of fura 2 in freshly isolated cells. The [Ca2+]i response to elevated CO2/low pH was measured at 11 days. Chronic hypoxia from birth abolished the normal developmental increase in the type I cell [Ca2+]i response to hypoxia. Effects of chronic hypoxia on development of [Ca2)]i responses to elevated K+ were small, and [Ca2+]i responses to CO2 remained unaffected. Impairment of type I cell maturation was partially reversible on return to normoxic conditions. These results indicate that chronic hypoxia severely impairs the postnatal development of carotid chemoreceptor O2 sensitivity at the cellular level and leaves responses to other stimuli largely intact.

Obstructive sleep apnea in children: An update

The diagnosis of obstructive sleep apnea in children requires clinical suspicion supplemented with the use of specific diagnostic tests. Polysomnography remains the key to diagnosis, and helps to assess the need for treatment, the risk for perioperative respiratory compromise, and the likelihood of persistent OSAS after treatment. Adenotonsillectomy is the mainstay of treatment, although children with complex medical conditions that affect upper airway anatomy and tone may require additional treatment.

An Official American Thoracic Society Clinical Practice Guideline: Pediatric Chronic Home Invasive Ventilation.

BACKGROUND Children with chronic invasive ventilator dependence living at home are a diverse group of children with special health care needs. Medical oversight, equipment management, and community resources vary widely. There are no clinical practice guidelines available to health care professionals for the safe hospital discharge and home management of these complex children. PURPOSE To develop evidence-based clinical practice guidelines for the hospital discharge and home/community management of children requiring chronic invasive ventilation. METHODS The Pediatric Assembly of the American Thoracic Society assembled an interdisciplinary workgroup with expertise in the care of children requiring chronic invasive ventilation. The experts developed four questions of clinical importance and used an evidence-based strategy to identify relevant medical evidence. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to formulate and grade recommendations. RESULTS Clinical practice recommendations for the management of children with chronic ventilator dependence at home are provided, and the evidence supporting each recommendation is discussed. CONCLUSIONS Collaborative generalist and subspecialist comanagement is the Medical Home model most likely to be successful for the care of children requiring chronic invasive ventilation. Standardized hospital discharge criteria are suggested. An awake, trained caregiver should be present at all times, and at least two family caregivers should be trained specifically for the childs care. Standardized equipment for monitoring, emergency preparedness, and airway clearance are outlined. The recommendations presented are based on the current evidence and expert opinion and will require an update as new evidence and/or technologies become available.

Polysomnographic Values in Adolescents With Ataxia Telangiectasia

Most adolescents with ataxia telangiectasia (A‐T) develop progressive bulbar muscle weakness and decreased pulmonary reserve. The purpose of this study was to define the patterns of sleep and respiration during sleep, and to identify sleep‐related breathing problems in subjects with A‐T. To address these issues, overnight polysomnography was performed on 12 adolescents with A‐T. Eleven of the 12 subjects completed overnight polysomnography. The median age was 16 years (range, 13–20 years). All subjects in the study were wheelchair‐bound and the median forced vital capacity (% predicted of normal) was 44% (range, 16–82%). The mean sleep efficiency was 72.6% with a mean apnea hypopnea index (AHI) of 0.7 events/hr (range, 0–2.2). The majority of apnea/hypopneas were REM related. The mean central apnea index was 0.1 events/hr (range, 0–0.2). The mean oxygen saturation nadir was 92.7% (range, 87–96) and the mean peak end‐tidal carbon dioxide ET  CO 2 value was 53.8 mm Hg (range, 49–60). Two of 11 subjects had ET  CO 2 values ≥50 mm Hg for more than 50% of total sleep time. In this study, the majority of A‐T adolescents had infrequent partial or complete upper airway obstructions during sleep and minimal nighttime hypoxemia. They did, however, have decreased sleep efficiency most likely, due in part, to their underlying neurological condition. This decrease in total sleep time may underestimate hypoventilation. Based on these findings, overnight polysomnography should be considered in adolescents with A‐T, particularly in those in which there is a clinical suspicion of sleep related breathing abnormalities. Pediatr Pulmonol. 2008; 43:674–679.

Mechanisms of Carotid Chemoreceptor Resetting after Birth

The results of these studies are consistent with the hypothesis that carotid chemoreceptor type-I cell resetting occurs, at least in part, at the level of the type-I cell. Furthermore, we have developed an in vitro model of newborn type-I cell resetting, in which freshly isolated glomus cells from newborns exhibit small, immature [Ca2+]i response to anoxia, but-after 72 hours in culture-[Ca2+]i responses convert to adult magnitude and profile. Finally, work so far suggests that glomus cell resetting in this model is modulated by oxygen tension. The mechanisms of glomus cell resetting remain unknown. Resetting of O2 sensitivity could result from withdrawal of tonic inhibitory influences present in vivo, changes in the oxygen sensor itself, changes in ion channel expression, modulation, and function, or other mechanisms occurring around the time of birth. Additional work is needed to determine the mechanisms of glomus cell resetting at the cellular level, and the role of O2 tension and other potential modulators of resetting.

Sleep disordered breathing in bronchopulmonary dysplasia

There are limited data on the effect of bronchopulmonary dysplasia (BPD) on sleep disordered breathing (SDB). We hypothesized that both the severity of prematurity and BPD would increase the likelihood of SDB in early childhood. Our secondary aim was to evaluate the association of demographic factors on the development of SDB.