Effects of Obstructive Sleep Apnea on Heart Rate Variability and Sleep Quality in Infants and Children

Project location: Italy, Rome
Project start date: September 2010 - Project end date: August 2012
Project number: 2010-54
Beneficiary: La Magia di un Sorriso ONLUS

Obstructive sleep apnea syndrome (OSAS) is characterized by repetitive episodes of upper airway collapse during sleep. The obstruction of inspiratory airflow results in asphyxia and subsequent vigorous efforts to breathe, leading eventually to transient arousal and restoration of upper airway patency. These dramatic events exert a profound acute influence on the cardiovascular system. It is believed that long-term exposure to episodic apnea and arousal constitutes an independent risk factor for systemic hypertension, heart failure, myocardial infarction, and stroke. In particular, the evidence suggests that abnormal autonomic control is likely a key factor in the causal pathway linking OSAS to these cardiovascular diseases.

Time-domain and spectral analyses of heart rate variability (HRV) have been employed as noninvasive methods of assessing cardiovascular autonomic function in patients with OSAS. Spectral analysis of the RR tachogram is typically used to estimate the effect of the sympathetic and parasympathetic modulation of the RR-intervals. The two main frequency bands of interest are referred to as the Low-Frequency (LF) band (0.04 to 0.15 Hz) and the High-Frequency (HF) band (0.15 to 0.4 Hz) . Sympathetic tone is believed to influence the LF component whereas both sympathetic and parasympathetic activity have an effect on the HF component. The ratio of the power contained in the LF and HF components has been used as a measure of the sympathovagal balance.
Polysomnography (PSG) is the most commonly used test in the diagnosis of OSAS. It is often considered the standard criterion for diagnosing OSAS, determining the severity of the disease, and evaluating various other sleep disorders that can exist with or without OSAS. PSG consists of a simultaneous recording of multiple physiologic parameters (brain electrical activity, eye and jaw muscle movement, leg muscle movement, airflow, respiratory effort, ECG, oxygen saturation) related to sleep and wakefulness.
PSG can directly monitor and quantify the number of respiratory events (ie, obstructive, central, or complex) and the resultant hypoxemia and arousals related to the respiratory events or even independent of the respiratory events.
Through the application of PSG and time-domain and spectral analyses of HRV, the organization seeks 1) to estimate and quantify the severity of OSAS in infants and children with upper airway obstruction and 2) to determine the cardiac autonomic dysfunction before and after treatments to restore airway patency.

This will be a prospective study including children suspecting of having severe OSAS (apnea-hypopnea index > 10 episodes per hour) and matched healthy control children.

PSG will be performed in OSAS patients to confirm severity. Controls will be selected on the following criteria: absence of snoring, nocturnal pulse oximetry values > 96%, no underline disease, good clinical condition at the time of HRV study and matched age with cases.
Patients with severe OSAS will be referred to surgical treatment. Before and one month after surgery these patients will undergo HRV studies. Six and 12 months after surgery HRV and polysomnographic studies will be repeated to identify possible reoccurrence of apnea.
Patients with severe OSAS will be admitted to the Pediatric Intensive Care Unit (PICU) before surgery and afterwards until the resolution of the clinical symptoms. In case of severe apnea with profound Sat O2 desaturations, non invasive ventilation will be applied during sleep to relieve apnea. In this case HRV will be performed before and after each treatment.
Surgery of the upper airway will include soft (adenotonsillectomy, mass removal, etc.) and bone (mandibular distraction) surgery.
Control infants will be studied only once by HRV and nocturnal pulse oximetry.

The Research Team plans to enroll 10 patients with severe apneas and 20 age and weight matched control children (1:2). Patients screened for severe OSAS, who will be found to have moderate OSAS, will be analyzed separately.
Polysomnographic studies will be performed by the Embla Titanium (technical information is attached to this document).
HRV studies will be performed by HRV Norav Medical version 5.31
This will be a multidisciplinary study involving:
Maxillofacial surgeons
ENT surgeons
PICU physicians
Neurophysiology technicians

The grant received from the Nando Peretti Foundation  will be used for the purchasing of the Polysonnography and to cover the costs for the human resources necessary to undertake the research (2 PICU doctors for one year, who will be involved in data collection and analysis of polysomnographic and HRV studies, already working at the PICU of "La Sapienza" University of Rome; 1 technician for two years, who will be performing the PGV and HRV examinations under the responsibility of the PICU physician).

Infants and children with severe OSAS will present an impaired cardiovascular autonomic regulation as compared to control subjects as shown by increased sympathetic tone (> LF on HRV). Noninvasive ventilation or upper airway surgery will eliminate sleep apneas and will restore the sympathovagal balance.
The findings of this study will be relevant to the care of children with OSAS in terms of timing of surgery and prevention of cardiovascular complications.

The charitable organization "La Magia di un Sorriso - The Magic of a Smile" was born in Rome 2007 from the wish of the parents of little Liam to support the activities of the Paediatric Intensive Care Unit in Rome's Policlinico Umberto I, where Liam spent the majority of his life.
The desire to improve the care a critically ill child receives is at the centre of all the charity's activities. What Liam's parents dreamt of was a paediatric intensive care unit that was more than a simple structure that provided healthcare, but was also a place that united healthcare with a welcome for the whole family, somewhere where pain could be relieved with happiness, attention and treatment; a place that offered the chance to share worries and hopes with the staff and the families of other patients, thus overcoming the sense of isolation that often accompanies illness. In this wish, Liam's parents found an affinity with the doctors of the paediatric intensive care unit with whom they formed a strong bond right from the time when their son Liam was admitted.
The charity has built up contacts with numerous benefactors, thanks to whom it has been possible to finance projects in support of the activities of the paediatric intensive care unit. The projects to be carried out are chosen on the basis of the needs of the unit with particular attention being paid to those that aim to increase the humanisation of treatment. Funds raised by the charity are used to buy equipment and/or materials or for financing projects.
The charity has the following aims:
• promoting and encouraging care for the critically ill child in every way as the expression of a human and social undertaking, facilitating the exchange of opinions between experts in the field as well as between doctors and parents;
• encouraging help for critically ill children after they have left hospital, through the promotion of a support network in collaboration with other specialists;
• carrying out educational activities through courses and meetings, supporting research projects, publicising and promoting its initiatives through its website.
The charity undertakes to create a direct link with those who sign up for its projects, proving feedback through the website in such a way as to guarantee a concrete and trustworthy use of funds that are raised.

The no profit association "La magia di un sorriso" ONLUS includes several academic pediatricians who have produced publications relevant to the field of the project.

Nasal flow-synchronized intermittent positive pressure ventilation to facilitate weaning in very low-birthweight infants: unmasked randomized controlled trial.
Moretti C, Giannini L, Fassi C, Gizzi C, Papoff P, Colarizi P.
Pediatr Int. 2008 Feb;50(1):85-91.

Comparing the effects of nasal synchronized intermittent positive pressure ventilation (nSIPPV) and nasal continuous positive airway pressure (nCPAP) after extubation in very low birth weight infants.
Moretti C, Gizzi C, Papoff P, Lampariello S, Capoferri M, Calcagnini G, Bucci G.
Early Hum Dev. 1999 Dec;56(2-3):167-77.

Modulazione del SNA del cuore in bambini con OSAS di grado severo: effetti del trattamento chirurgico per il ripristino della pervietà delle vie aeree.
Ferro V, Caresta E, Papoff P, Moretti C
Pneumologia pediatrica (in press)

Autonomic cardiac modulation in severe OSAS children undergoing surgical treatment to restore airway patency
Caresta E, Papoff P, Ferro V, Moretti C
Eur Resp J (in press)

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