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C L Marcus

Publications and source records attributed to C L Marcus.

53 records · Page 3Linked to original sources
PubMed1994

Polysomnographic characteristics of patients with Rett syndrome.

During wakefulness, patients with Rett syndrome have disordered breathing. To understand further this ventilatory control disorder, we performed polysomnography in 30 patients with Rett syndrome and 30 control subjects (female subjects with primary snoring). The median age was 7 years (range, 1 to 32 years) for Rett syndrome and 6 years (range, 1 to 17 years) for control subjects. During periods of wakefulness, 67% of patients with Rett syndrome had the characteristic pattern of disordered breathing (i.e., episodes of hyperventilation followed by central apnea and desaturation). No such events occurred during sleep. Sleep efficiency and sleep architecture were similar for both groups. During sleep, there was no difference in duration of periodic breathing, number of episodes of central apnea with desaturation, or number of episodes of obstructive apnea or end-tidal carbon dioxide tension between the two groups. Although arterial oxygen saturation during rapid eye movement (REM) sleep was slightly lower in patients with Rett syndrome (nadir, 94% +/- 2% vs 96% +/- 2%), it remained within the normal range. Parental history reflected the awake respiratory findings in most cases. We conclude that patients with Rett syndrome have normal breathing during non-rapid eye movement (NREM) sleep. We speculate that patients with Rett syndrome have normal brain-stem control of ventilation, and that the disordered breathing seen during wakefulness is due to an abnormality of the cortical influence on ventilation.

Adolescent↗
PubMed1994

Developmental pattern of hypercapnic and hypoxic ventilatory responses from childhood to adulthood.

The developmental pattern of ventilatory responses, through childhood and puberty into adulthood, is not known. Therefore we studied hypercapnic (HCVR) and hypoxic ventilatory responses (HOVR) in 59 subjects (29 males and 30 females) 4-49 yr of age, of whom 35 were children ( < 18 yr old). There was a significant correlation between HCVR and weight (r = 0.33, P < 0.02), vital capacity (r = 0.30, P < 0.05), and body surface area (r = 0.30, P < 0.05) but not height (r = 0.22, NS). There was no correlation between HOVR and any of the correcting factors. To account for disparities in body size, volume-related results were scaled for body weight. The HCVR corrected for weight (HCVR/WT) decreased with age (r = -0.57, P < 0.001). HCVR/WT was significantly higher in children than in adults (0.056 +/- 0.024 vs. 0.032 +/- 0.015 l.kg-1 x min-1. Torr end-tidal PCO2-1, P < 0.001). The (tidal volume/inspiratory duration)/weight, respiratory rate, and heart rate responses to hypercapnia were increased in the children, and the CO2 threshold was lower (36 +/- 5 vs. 40 +/- 6 Torr, P < 0.05). Similarly, the HOVR corrected for weight (HOVR/WT) decreased with age (r = 0.34, P < 0.05), and HOVR/WT was significantly higher in children than in adults (-0.035 +/- 0.017 vs. -0.024 +/- 0.016 l.kg-1 x min-1.% arterial O2 saturation-1, P < 0.02). The respiratory rate and heart rate responses to hypoxia were increased in the children. We conclude that rebreathing HCVR and HOVR are higher during childhood than during adulthood.

Adolescent↗
PubMed1994

Maturational differences in step vs. ramp hypoxic and hypercapnic ventilatory responses.

The influence of the speed of stimulus presentation on hypoxic and hypercapnic ventilatory responses (step vs. ramp) is not known. Furthermore, it is unclear whether children and adults respond similarly. We tested ramp ventilatory responses to hypercapnia and hypoxia with use of rebreathing in 8 prepubertal children and 11 adults. We tested step ventilatory responses to hypercapnia with single vital capacity breaths of 15% CO2 in O2 and to hypoxia with five tidal breaths of 100% N2. For children, slopes of step hypercapnic ventilatory responses were always greater than those of ramp responses (0.85 +/- 0.07 vs. 0.71 +/- 0.07 l.min-1.Torr end-tidal PCO2-1; P < 0.0005). Conversely, for adults, step responses were always less than ramp responses (0.88 +/- 0.19 vs. 2.10 +/- 0.29 l.min-1.Torr end-tidal PCO2-1; P < 0.0007). Similarly, for children, the slopes of step hypoxic ventilatory responses were always greater than those of ramp responses (-0.71 +/- 0.09 vs. -0.45 +/- 0.04 l.min-1.Torr O2 saturation-1; P < 0.02), and for adults, step responses were always less than ramp responses (-0.68 +/- 0.14 vs. -1.85 +/- 0.46 l.min-1.Torr O2 saturation-1; P < 0.04). We conclude that ventilatory responses vary depending on step vs. ramp presentation of hypercapnia or hypoxia and that the ratio of these responses is reversed in children compared with adults. We speculate that the responsiveness of peripheral chemoreceptors is increased in children compared with adults and that it may play a role in the mechanisms leading to increased ventilatory responses observed during childhood.

Adult↗
PubMed1994

Upper airway collapsibility in children with obstructive sleep apnea syndrome.

In adults, the critical nasal pressure (Pcrit) at which the upper airway collapses is higher in patients with the obstructive sleep apnea syndrome (OSAS) than in those with primary snoring. Pediatric OSAS differs clinically from adult OSAS. We therefore compared Pcrit between prepubertal children with OSAS and primary snoring. Pcrit was determined by correlating the maximal inspiratory airflow with the level of positive or negative nasal pressure applied via a nasal mask. As in adults, we found that the maximal inspiratory airflow varied in proportion to the upstream (nasal) rather than the downstream (esophageal) pressure changes. Pcrit was 1 +/- 3 cmH2O in OSAS compared with -20 +/- 9 cmH2O in primary snorers (P < 0.002). In three OSAS patients reevaluated after tonsillectomy and adenoidectomy, Pcrit declined to -7.2 +/- 4.0 cmH2O. We conclude that the pediatric airway behaved as predicted by the Starling resistor model and that Pcrit, a measure of airway collapsibility, correlated with the degree of upper airway obstruction and was reduced postoperatively, consistent with increased upper airway stability.

Adenoids↗
PubMed1994

Ventilatory responses during wakefulness in children with obstructive sleep apnea.

The pathophysiology of the obstructive sleep apnea syndrome (OSAS) is not fully understood. In children, airway obstruction secondary to tonsilloadenoidal hypertrophy is the leading cause of OSAS. However, not all children with tonsilloadenoidal hypertrophy develop OSAS. Thus, other factors, including abnormalities in ventilatory control, may contribute to the etiology of OSAS. To test this, we performed polysomnography and hypercapnic and hypoxic ventilatory response testing in 20 children and adolescents with OSAS (mean age, 8 +/- 3 [SD] yr) and 19 control subjects. Only two children with OSAS were obese. Children with OSAS had an apnea index of 16 +/- 20, peak PETCO2 of 54 +/- 5 mm Hg, and SaO2 nadir of 84 +/- 13% during polysomnography. Ventilatory responses were performed by rebreathing techniques. The slope of the hypercapnic ventilatory responses, corrected for body surface area, was 1.74 +/- 0.79 L/min/m2/mm Hg PETCO2 in children with OSAS and 1.45 +/- 0.58 L/min/m2/mmHg PETCO2 in control subjects (NS). Hypoxic ventilatory responses, corrected for body surface area, were -0.94 +/- 0.49 L/min/m2/% SaO2 in children with OSAS and -0.95 +/- 0.45 L/min/m2/% SaO2 in control subjects (NS); however, the sample size was small. There was a weak inverse correlation between the slope of the hypercapnic ventilatory response and the duration of hypoventilation during polysomnography (r = -0.44, p < 0.05). We conclude that children with OSAS have normal ventilatory responses to hypercapnia, and they may have normal ventilatory responses to hypoxia. We speculate that abnormal central ventilatory drive plays little if any role in the pathogenesis of pediatric OSAS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoids↗
PubMed1993

Peripheral chemoreceptor function in children with the congenital central hypoventilation syndrome.

In children with the congenital central hypoventilation syndrome (CCHS), some patients require mechanical ventilation during sleep, whereas others need respiratory assistance even when awake. The cause of this disparity is unclear. We hypothesized that differences in peripheral chemoreceptor response (PCR) could provide an explanatory mechanism for this disparity in clinical manifestations. PCR was measured in five children with CCHS and five sex- and age-matched controls by measuring the ventilatory responses induced by 100% O2 breathing, five tidal breaths of 100% N2, and vital capacity breaths of 5% and 15% CO2 in O2 and 5% CO2-95% N2. Tidal breathing of 100% O2 resulted in similar ventilatory responses in CCHS patients and controls with various changes dependent on the method of analysis of response used. Acute hypoxia by N2 tidal breathing resulted in a 39.2 +/- 22% increase in respiratory rate in CCHS patients and a 15.1 +/- 11.1% increase in controls (P < 0.05), with similar increases in minute ventilation (VE) of 124 +/- 69% and 85 +/- 11%, respectively. Vital capacity breaths of each of the CO2-containing gas mixtures induced similar increases in VE in CCHS patients and controls. The changes in VE obtained with 15% CO2-85% O2 and with 5% CO2-95% N2 were significantly greater than those with 5% CO2-95% O2, suggesting a dose-dependent response as well as additive effects of hypercapnic and hypoxic stimuli. We conclude that the PCR, when assessed by acute hypoxia, hyperoxia, or hypercapnia, is present and intact in CCHS children who are able to sustain adequate ventilation during wakefulness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Comparison of nap and overnight polysomnography in children.

Overnight polysomnography is the "gold standard" for diagnosing sleep-disordered breathing. However, the limited number of resources for pediatric polysomnography make the availability of a screening test for sleep-disordered breathing highly desirable. Therefore, we compared 1 hour daytime nap polysomnography to overnight polysomnography in 40 children [mean age, 5.4 +/- 0.8 (SE) years] with sleep-disordered breathing; 76% of children were sedated with chloral hydrate for nap polysomnography; none was sedated for overnight polysomnography. Studies were done 26 +/- 4 days apart. Chest wall motion, ECG, end-tidal PCO2 (PETCO2), arterial oxygen saturation (SaO2), and electrooculogram were monitored. Nap studies had a sensitivity of 74%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 17% in predicting sleep-disordered breathing. Significantly more children had obstructive apnea and desaturation (SaO2 less than 90%) during overnight polysomnography. The peak PETCO2 and the SaO2 nadir were significantly worse during overnight polysomnography. However, the percentage of time during which abnormalities were manifested did not differ between nap and overnight polysomnography. Despite the use of sedation, nap polysomnography underestimated sleep-disordered breathing. We conclude that sleep-disordered breathing detected by nap polysomnography is always confirmed by overnight polysomnography and speculate that nap polysomnography may be an effective screening method for sleep-disordered breathing. However, overnight polysomnography should be performed if nap polysomnography is inconclusive. Chloral hydrate may be used effectively to facilitate sleep for nap polysomnography in children.

Adolescent↗
PubMed1992

Hypercapnic and hypoxic ventilatory and cardiac responses in school-aged siblings of sudden infant death syndrome victims.

Siblings of sudden infant death syndrome (SIDS) victims have been shown to have abnormal ventilatory patterns and altered responses to respiratory stimuli during infancy. To evaluate whether these abnormalities persist, we studied ventilatory responses in 20 older SIDS siblings (9.8 +/- 0.9 (mean +/- SEM) years of age) and 20 control subjects (10.2 +/- 0.9 years of age). To evaluate hypercapnic ventilatory responses, we had subjects rebreathe 5% carbon dioxide and 95% oxygen until end-tidal carbon dioxide tension reached 65 mm Hg. Instantaneous minute ventilation, mean inspiratory flow, and respiratory rate were calculated breath by breath. Hypercapnic responses did not differ between SIDS siblings (2.08 +/- 0.14 L/min per mm Hg) and control subjects (1.90 +/- 0.10 L/min per mm Hg; not significant). To assess hypoxic ventilatory responses, we asked subjects to rebreathe 13% oxygen and 7% carbon dioxide, with the balance nitrogen, at mixed-venous end-tidal carbon dioxide tension, until arterial oxygen saturation by pulse oximetry fell to 75%. No differences in hypoxic ventilatory responses were found between the SIDS siblings (-1.39 +/- 0.15 L/min/% saturation) and the control subjects (-1.22 +/- 0.17 L/min/% saturation; not significant). The mean inspiratory flow, tidal volume, respiratory rate, and heart rate responses to hypercapnia and hypoxia were also similar in the two groups. We conclude that there is no difference in hypercapnic and hypoxic ventilatory and cardiac responses, as assessed by rebreathing techniques, between school-aged SIDS siblings and control subjects. We speculate that in SIDS siblings the control of breathing is immature during infancy and that they achieve maturity of control and resolution of breathing abnormalities with time.

Child↗
PubMed1992

Normal polysomnographic values for children and adolescents.

Although polysomnography is routinely performed to evaluate children and adolescents with sleep-disordered breathing, normal polysomnographic values for the pediatric age group have not yet been established. We therefore performed overnight polysomnography in 50 normal children and adolescents (mean age 9.7 +/- 4.6 SD yr, range 1.1 to 17.4 yr). Of the children 56% were male. Chest wall motion, ECG, oronasal airflow, end-tidal PCO2 (PETCO2), arterial oxygen saturation (SaO2), and electrooculogram were monitored. Children had 0.1 +/- 0.5 (range 0 to 3.1) obstructive apneas per hour of total sleep time, with only 18% of children having any obstructive apneas. No child had obstructive apneas > 10 s in duration. Of the children 30% had central apneas > or = 10 s in duration, and one child had a central apnea associated with SaO2 < 90%. Peak PETCO2 was 46 +/- 4 mm Hg (range 38 to 53 mm Hg), and hypoventilation (PETCO2 > 45 mm Hg) occurred for 7 +/- 19% total sleep time (range 0 to 91%). The SaO2 nadir was 96 +/- 2% (range 89 to 98%), with only one child desaturating below 90% in association with a central apnea. We conclude that polysomnographic results in the pediatric age group differ from those in adults. Recommendations for normal polysomnographic criteria are given.

Adolescent↗
PubMed1992

Supplemental oxygen and exercise performance in patients with cystic fibrosis with severe pulmonary disease.

Patients with cystic fibrosis (CF) and advanced pulmonary disease have pulmonary limitation of exercise, often associated with arterial oxygen desaturation. Improving oxygenation during exercise by providing supplemental oxygen may improve exercise performance in these patients. To test this, we performed graded exercise stress tests in 22 CF patients with severe pulmonary disease (mean PaO2, 64 +/- 2 mm Hg [+/- SE]; PaCO2 46 +/- 2 mm Hg; RV/TLC, 57 +/- 4 percent; FEV1, 38 +/- 4 percent of predicted; FEF25-75%, 13 +/- 2 percent of predicted; median age, 26 years) and compared them to 21 controls (RV/TLC, 27 +/- 4 percent; FEV1, 112 +/- 2 percent of predicted; FEF25-75%, 80 +/- 4 percent of predicted; median age, 29 years). Each subject performed graded exercise stress tests while breathing FIO2 of 0.21 and FIO2 of 0.30. Subjects were blinded to the composition of the inspired gas, and the order of testing was randomized. We found that CF subjects exercised longer, had a higher maximal VO2, higher O2 pulse, and less arterial oxygen desaturation when receiving supplemental O2. Control subjects exercised longer when breathing supplemental O2 but had no significant change in maximal VO2, O2 pulse, or SaO2. Both CF and control subjects had increased end-tidal PCO2 when exercising while breathing supplemental O2. We conclude that CF patients with advanced pulmonary disease have increased exercise tolerance and aerobic capacity when exercising while breathing supplemental O2.

Adolescent↗
PubMed1991

Medical and psychosocial outcome of children with congenital central hypoventilation syndrome.

We report the long-term medical and psychosocial outcome of 13 children with congenital central hypoventilation syndrome. One child (8%) died before initial hospital discharge. Of the remaining 12 children, 11 (92%) have been successfully cared for in their natural or foster parents' homes. Home ventilatory support was provided with positive-pressure ventilation, negative-pressure ventilation, or diaphragm pacers. After an initial lengthy hospitalization, children spent little time in the hospital. Severe medical complications were uncommon but included cor pulmonale (one child), poor growth (two children), and seizure disorder (three children). Most children functioned in the slow-learner range of mental processing, with a composite score (Kaufman Assessment Battery for Children) of 78 +/- 20 (SD); two were mentally retarded, and one functioned above the normal range. The children's care givers were assessed as having low levels of psychologic distress (Symptom Checklist 90--Revised) and good coping resources (Coping Resources Inventory) but a high level of marital discord. The children were able to attend school and partake in normal childhood activities. We conclude that with modern techniques for home ventilation, children with CCHS can have a good long-term medical and psychosocial outcome. We speculate that early diagnosis and the prevention of intermittent hypoxia will improve their physical and mental outcome.

Child↗
PubMed1991

Hypercapnic and hypoxic ventilatory responses in parents and siblings of children with congenital central hypoventilation syndrome.

Children with congenital central hypoventilation syndrome (CCHS) have abnormal ventilatory responses to metabolic stimuli. As there is a genetically determined component of chemoreceptor sensitivity, parents and siblings of children with CCHS may also have blunted ventilatory responses to hypercapnea and hypoxia. To test this, we studied hypercapnic ventilatory responses and hypoxic ventilatory responses in six mothers, four fathers, and five siblings (6 to 49 yr of age) of seven children with CCHS and compared them with 15 age- and sex-matched control subjects (5 to 47 yr of age). Pulmonary function tests were not different between relatives of children with CCHS and control subjects. To measure hypercapnic ventilatory responses, subjects rebreathed 5% CO2/95% O2 until PACO2 reached 60 to 70 mm Hg. To measure hypoxic ventilatory responses (L/min/% SaO2), subjects rebreathed 14% O2/7% CO2/balance N2 at mixed venous PCO2 until SaO2 fell to 75%. All tests were completed in less than 4 min. Instantaneous minute ventilation, mean inspiratory flow (tidal volume/inspiratory time), and respiratory timing (inspiratory timing/total respiratory cycle timing) were calculated on a breath-by-breath basis. Hypercapnic ventilatory responses were 1.97 +/- 0.32 L/min/mm Hg PACO2 in children with CCHS relatives and 2.23 +/- 0.23 L/min/mm Hg PACO2 in control subjects. Hypoxic ventilatory responses were -1.99 +/- 0.37 L/min/% SaO2 in the relatives and -1.54 +/- 0.25 L/min/% SaO2 in the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Obstructive sleep apnea in children with Down syndrome.

Children with Down syndrome have many predisposing factors for the obstructive sleep apnea syndrome (OSAS), yet the type and severity of OSAS in this population has not been characterized. Fifty-three subjects with Down syndrome (mean age 7.4 +/- 1.2 [SE] years; range 2 weeks to 51 years) were studied. Chest wall movement, heart rate, electroculogram, end-tidal PO2 and PCO2, transcutaneous PO2 and PCO2, and arterial oxygen saturation were measured during a daytime nap polysomnogram. Sixteen of these children also underwent overnight polysomnography. Nap polysomnograms were abnormal in 77% of children; 45% had obstructive sleep apnea (OSA), 4% had central apnea, and 6% had mixed apneas; 66% had hypoventilation (end-tidal PCO2 greater than 45 mm Hg) and 32% desaturation (arterial oxygen saturation less than 90%). Overnight studies were abnormal in 100% of children, with OSA in 63%, hypoventilation in 81%, and desaturation in 56%. Nap studies significantly underestimated the presence of abnormalities when compared to overnight polysomnograms. Seventeen (32%) of the children were referred for testing because OSAS was clinically suspected, but there was no clinical suspicion of OSAS in 36 (68%) children. Neither age, obesity, nor the presence of congenital heart disease affected the incidence of OSA, desaturation, or hypoventilation. Polysomnograms improved in all 8 children who underwent tonsillectomy and adenoidectomy, but they normalized in only 3. It is concluded that children with Down syndrome frequently in have OSAS, with OSA, hypoxemia, and hypoventilation. Obstructive sleep apnea syndrome is seen frequently in those children in whom it is not clinically suspected. It is speculated that OSAS may contribute to the unexplained pulmonary hypertension seen in children with Down syndrome.

Adenoidectomy↗
PubMed1991

Hypercapneic arousal responses in children with congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS, Ondine's curse) is generally thought to be due to insensitivity of the central chemoreceptors to carbon dioxide. Children with CCHS have absent ventilatory responses to both hypercapnea and hypoxia, suggesting either abnormal central and peripheral chemoreceptor function or abnormal central integration of chemoreceptor input. Because ventilatory and arousal responses to respiratory stimuli are distinct from each other, if children with CCHS have complete chemoreceptor dysfunction, one would predict that both ventilatory and arousal responses to respiratory stimuli would be abnormal. However, if they have abnormal central integration of chemoreceptor input for ventilation, they may still arouse to respiratory stimuli despite the absence of a ventilatory response. Hypercapneic arousal responses were tested in eight children with CCHS, aged 5.8 +/- 1.2 (SEM) years, and seven healthy control subjects, aged 4.4 +/- 1.1 years. Children were studied during sleep while normal ventilation was maintained using their home ventilators. Hypercapneic challenges were performed by rapidly increasing the inspired carbon dioxide tension to 60 mm Hg and maintaining this level until the child aroused or for a maximum of 3 minutes. Of children with CCHS, 87.5% aroused to hypercapnea, compared with 100% of control children. There was no significant difference in arousal between children with CCHS and normal control subjects. It is concluded that most children with CCHS arouse to hypercapnea, indicating the presence of some central chemoreceptor function. It is speculated that because these children do respond to hypercapnea, the most probable mechanism for CCHS is a brainstem lesion in the area where input from both chemoreceptors is integrated.

Arousal↗
PubMed1990

Evaluation of epiglottoplasty as treatment for severe laryngomalacia.

Six patients with severe laryngomalacia underwent epiglottoplasty. Four of these patients had life-threatening episodes of airway obstruction before surgery; of these, two had required tracheal intubation and one had required cardiopulmonary resuscitation. Two patients had failure to thrive and two had cor pulmonale. Patients had required a mean of two hospitalizations related to upper airway obstruction. We performed polysomnography during a daytime nap, both before and after epiglottoplasty, in all patients. Respiratory effort, arterial oxygen saturation, and end-tidal carbon dioxide pressure were monitored with continuous electrocardiograms and electrooculograms. All patients had abnormal polysomnograms preoperatively. Six patients had obstructive apnea, four had hypoxemia (arterial oxygen saturation less than 90% while breathing room air), and four had hypoventilation (end-tidal carbon dioxide pressure greater than 45 mm Hg) before epiglottoplasty. Mean age (+/- SEM) at epiglottoplasty was 10.3 +/- 5.3 months. No patients had surgical complications. An endotracheal tube was in place for 25 +/- 7 hours postoperatively, and patients were discharged 4 +/- 1 days postoperatively. Polysomnography performed 2.8 +/- 1.0 months after surgery showed that all patients had improved. Two patients had residual, mild episodes of obstructive apnea, and one patient had mild hypoventilation and desaturation. No patient had further life-threatening events or required further hospitalizations after epiglottoplasty. We conclude that epiglottoplasty is an effective and safe treatment for a selected group of patients with severe laryngomalacia.

Carbon Dioxide↗