Ventilatory drive and the apnea-hypopnea index in six-to-twelve year old children

Ralph F Fregosi, Stuart F Quan, Andrew C Jackson, Kris L Kaemingk, Wayne J Morgan, Jamie L Goodwin, Jenny C Reeder, Rosaria K Cabrera, Elena Antonio, Ralph F Fregosi, Stuart F Quan, Andrew C Jackson, Kris L Kaemingk, Wayne J Morgan, Jamie L Goodwin, Jenny C Reeder, Rosaria K Cabrera, Elena Antonio

Abstract

Background: We tested the hypothesis that ventilatory drive in hypoxia and hypercapnia is inversely correlated with the number of hypopneas and obstructive apneas per hour of sleep (obstructive apnea hypopnea index, OAHI) in children.

Methods: Fifty children, 6 to 12 years of age were studied. Participants had an in-home unattended polysomnogram to compute the OAHI. We subsequently estimated ventilatory drive in normoxia, at two levels of isocapnic hypoxia, and at three levels of hyperoxic hypercapnia in each subject. Experiments were done during wakefulness, and the mouth occlusion pressure measured 0.1 seconds after inspiratory onset (P0.1) was measured in all conditions. The slope of the relation between P0.1 and the partial pressure of end-tidal O2 or CO2 (PETO2 and PETCO2) served as the index of hypoxic or hypercapnic ventilatory drive.

Results: Hypoxic ventilatory drive correlated inversely with OAHI (r = -0.31, P = 0.041), but the hypercapnic ventilatory drive did not (r = -0.19, P = 0.27). We also found that the resting PETCO2 was significantly and positively correlated with the OAHI, suggesting that high OAHI values were associated with resting CO2 retention.

Conclusions: In awake children the OAHI correlates inversely with the hypoxic ventilatory drive and positively with the resting PETCO2. Whether or not diminished hypoxic drive or resting CO2 retention while awake can explain the severity of sleep-disordered breathing in this population is uncertain, but a reduced hypoxic ventilatory drive and resting CO2 retention are associated with sleep-disordered breathing in 6-12 year old children.

Figures

Figure 1
Figure 1
Expired minute ventilation (VE) corrected for body surface area (BSA), as a function of the partial pressure of end-tidal CO2 (PETCO2) (top panel) or end-tidal O2 (PETO2) (bottom panel). Each data point represents the average value computed during room air breathing and at each of three levels of hypercapnia and two levels of hypoxia in each of the subjects (see Methods).
Figure 2
Figure 2
Mouth occlusion pressure (P0.1) as a function of the partial pressure of end tidal CO2 (PETCO2) (top panel) or end-tidal O2 (PETO2) (bottom panel). Each data point represents the average value computed during room air breathing and at each of three levels of hypercapnia and two levels of hypoxia in each of the subjects (see Methods).
Figure 3
Figure 3
Relation between the partial pressure of end tidal CO2 (PETCO2) measured under resting, baseline conditions and the obstructive apnea-hypopnea index (OAHI). The top panel represents data from all subjects, and the bottom panel shows that the relation is strengthened when the outlier with the very high OAHI is removed from the data set (see Text for details). Measurements were made while the subjects respired room air, and after they were given several minutes to become accustomed to the breathing mask and associated measurement equipment.
Figure 4
Figure 4
Sample records from two subjects showing VE and mouth occlusion pressure (P0.1) responses to room air breathing, and severe hypoxia and hypercapnia. The top panel shows records from a subject with a low OAHI, and the bottom panel from the subject with the highest OAHI observed in our population.
Figure 5
Figure 5
Correlation between each subject's OAHI and the slope of the P0.1/PETCO2 curve. The top panel represents data from all subjects, and the bottom panel shows that the relation is strengthened when the outlier with the very high OAHI is removed from the data set (see Text for details). The slope of the P0.1/PETCO2 curves were obtained for each subject during the response tests, as described in Methods.
Figure 6
Figure 6
Correlation between each subject's OAHI and the slope of the P0.1/PETO2 curve. The top panel represents data from all subjects, and the bottom panel shows that the relation is strengthened when the outlier with the very high OAHI is removed from the data set (see Text for details). The slope of the P0.1/PETO2 curves were obtained for each subject during the response tests, as described in Methods.

References

    1. Marcus CL. Sleep-disordered breathing in children. Am J Respir Crit Care Med. 2001;164:16–30.
    1. Gold AR, Schwartz AR, Wise RA, Smith PL. Pulmonary function and respiratory chemosensitivity in moderately obese patients with sleep apnea. Chest. 1993;103:1325–1329.
    1. Lopata M, Onal E. Mass loading, sleep apnea, and the pathogenesis of obesity hypoventilation. Am Rev Respir Dis. 1982;126:640–645.
    1. Marcus CL, Lutz J, Carroll JL, Bamford O. Arousal and ventilatory responses during sleep in children with obstructive sleep apnea. J Appl Physiol. 1998;84:1926–1936.
    1. Marcus CL, Gozal D, Arens R, Basinski DJ, Omlin KJ, Keens TG, Ward SL. Ventilatory responses during wakefulness in children with obstructive sleep apnea. Am J Respir Crit Care Med. 1994;149:715–721.
    1. Honda Y, Ohyabu Y, Sato M, Masuyama H, Nishibayashi Y, Maruyama R, Tanaka Y, Nakajo I, Shirase H, Hayashida K. Hypercapnic and hypoxic ventilatory responses during growth. Jpn J Physiol. 1986;36:177–187.
    1. Whitelaw WA, Derenne JP, Milic-Emili J. Occlusion pressure as a measure of respiratory center output in conscious man. Respir Physiol. 1975;23:181–199. doi: 10.1016/0034-5687(75)90059-6.
    1. Marcus CL, Lutz J, Hamer A, Smith PL, Schwartz A. Developmental changes in response to subatmospheric pressure loading of the upper airway. J Appl Physiol. 1999;87:626–633.
    1. Schmidt-Nielsen Knut. Scaling-why is animal size so important? London, Cambridge University Press; 1984. p. 241.
    1. Xie A, Skatrud JB, Dempsey JA. Effect of hypoxia on the hypopnoeic and apnoeic threshold for CO(2) in sleeping humans. J Physiol. 2001;535:269–278.
    1. Robbins PA. Possible mechanisms that may determine the set point and sensitivities of the chemoreflexes. Adv Exp Med Biol. 2001;499:237–239.
    1. Meza S, Mendez M, Ostrowski M, Younes M. Susceptibility to periodic breathing with assisted ventilation during sleep in normal subjects. J Appl Physiol. 1998;85:1929–1940.
    1. Reeves JT, McCullough RE, Moore LG, Cymerman A, Weil JV. Sea-level PCO2 relates to ventilatory acclimatization at 4,300 m. J Appl Physiol. 1993;75:1117–1122.
    1. Waters KA, McBrien F, Stewart P, Hinder M, Wharton S. Effects of OSA, inhalational anesthesia, and fentanyl on the airway and ventilation of children. J Appl Physiol. 2002;92:1987–1994. doi: 10.1063/1.1494127.
    1. Kerbl R, Zotter H, Schenkeli R, Hoffmann E, Perrogon A, Zotsch W, Kurz R. Persistent hypercapnia in children after treatment of obstructive sleep apnea syndrome by adenotonsillectomy. Wien Klin Wochenschr. 2001;113:229–234.
    1. Ruboyianes JM, Cruz RM. Pediatric adenotonsillectomy for obstructive sleep apnea. Ear Nose Throat J. 1996;75:430–433.
    1. Goodwin JL, Enright PL, Kaemingk KL, Rosen GM, Morgan WJ, Fregosi RF, Quan SF. Feasibility of using unattended polysomnography in children for research--report of the Tucson Children's Assessment of Sleep Apnea study (TuCASA) Sleep. 2001;24:937–944.
    1. Rechtshaffen A, Kales A. UCLA Brain Information Service/Brain Research Institute. Los Angeles, CA; 1968. A manual of standardized terminology: Techniques and scoring systems for sleep stages of human subjects.
    1. Tang JP, Rosen CL, Larkin EK, DiFiore JM, Arnold JL, Surovec SA, Youngblut JM, Redline S. Identification of sleep-disordered breathing in children: variation with event definition. Sleep. 2002;25:72–79.
    1. Fregosi RF, Seals DR. Hypoxic potentiation of the ventilatory response to dynamic forearm exercise. J Appl Physiol. 1993;74:2365–2372.
    1. White DP, Douglas NJ, Pickett CK, Weil JV, Zwillich CW. Sexual influence on the control of breathing. J Appl Physiol. 1983;54:874–879.
    1. American Thoracic Society. Standards and indications for cardiopulmonary sleep studies in children. Am J Respir Crit Care Med. 1996;153:866–878.
    1. American Thoracic Society. Cardiorespiratory sleep studies in children. Establishment of normative data and polysomnographic predictors of morbidity. Am J Respir Crit Care Med. 1999;160:1381–1387.
    1. Schechter MS. Technical report: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2002;109:e69.
    1. Goodwin JL, Kaemingk KL, Fregosi RF, Rosen GM, Morgan WJ, Sherrill DL, Quan SF. Clinical Outcomes Associated with Sleep-Disordered Breathing in Caucasian and Hispanic Children-the Tucson Children's Assessment of Sleep Apnea Study (TuCASA) Sleep. 2003;26:587–91.
    1. Carskadon MA, Harvey K, Dement WC, Guilleminault C, Simmons FB, Anders TF. Respiration during sleep in children. West J Med. 1978;128:477–481.
    1. Gaultier C. Cardiorespiratory adaptation during sleep in infants and children. Pediatr Pulmonol. 1995;19:105–117.
    1. Schafer T. Variability of vigilance and ventilation: studies on the control of respiration during sleep. Respir Physiol. 1998;114:37–48. doi: 10.1016/S0034-5687(98)00070-X.
    1. Poets CF, Southall DP. Noninvasive monitoring of oxygenation in infants and children: practical considerations and areas of concern. Pediatrics. 1994;93:737–746.
    1. Weitzenblum E, Hirth C, Parini JP, Roeslin N, Ravault MC, Oudet P. Comparative study of the ventilatory responsiveness to CO2 in bronchitic and emphysematous patients with chronic respiratory failure. Respiration. 1976;33:188–198.
    1. Gozal D, Arens R, Omlin KJ, Ben-Ari JH, Aljadeff G, Harper RM, Keens TG. Ventilatory response to consecutive short hypercapnic challenges in children with obstructive sleep apnea. J Appl Physiol. 1995;79:1608–1614.
    1. Berkenbosch A, Bovill JG, Dahan A, DeGoede J, Olievier IC. The ventilatory CO2 sensitivities from Read's rebreathing method and the steady-state method are not equal in man. J Physiol. 1989;411:367–377.
    1. Shi YX, Seto-Poon M, Wheatley JR. The breathing route dependence of ventilatory responses to hypercapnia and exercise is modulated by upper airway resistance. Respirology. 1999;4:331–338. doi: 10.1046/j.1440-1843.1999.00201.x.
    1. Whitelaw WA, Derenne JP. Airway occlusion pressure. J Appl Physiol. 1993;74:1475–1483.
    1. Radwan L, Koziorowski A, Maszczyk Z, Plywaczewski R, Boros P, Franczuk M, Kowalski J, Zielinski J. [Respiratory response to inspiratory resistive load changes in patients with obstructive sleep apnea syndrome] Pneumonol Alergol Pol. 2000;68:44–56.
    1. Garcia-Rio F, Racionero MA, Pino JM, Martinez I, Ortuno F, Villasante C, Villamor J. Sleep apnea and hypertension. Chest. 2000;117:1417–1425. doi: 10.1378/chest.117.5.1417.
    1. Garcia-Rio F, Pino JM, Ramirez T, Alvaro D, Alonso A, Villasante C, Villamor J. Inspiratory neural drive response to hypoxia adequately estimates peripheral chemosensitivity in OSAHS patients. Eur Respir J. 2002;20:724–732. doi: 10.1183/09031936.02.00250102.
    1. Osanai S, Akiba Y, Fujiuchi S, Nakano H, Matsumoto H, Ohsaki Y, Kikuchi K. Depression of peripheral chemosensitivity by a dopaminergic mechanism in patients with obstructive sleep apnoea syndrome. Eur Respir J. 1999;13:418–423. doi: 10.1183/09031936.99.13241899.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir