Congenital Central Hypoventilation Syndrome (CCHS) is a rare and serious condition affecting breathing control. Effective diagnosis and comprehensive management are crucial for improving the quality of life and long-term outcomes for individuals with CCHS. This article provides an in-depth overview of the respiratory assessment, diagnosis, and various management strategies for CCHS, focusing on ensuring optimal ventilation and patient care.
Understanding Respiratory Assessment in CCHS
Patients with CCHS present a unique challenge as they often lack typical signs of hypoventilation. They may not experience dyspnea, hypoxia, or hypercapnia sensations and might not exhibit increased respiratory rate or effort even when oxygen levels are low. Therefore, regular and thorough respiratory assessments are vital throughout their lives.
The primary goal of respiratory assessment is to evaluate ventilation and blood gas status during both spontaneous and assisted breathing, in both awake and sleep states. Comprehensive measurements should include continuous recordings over extended periods using polysomnography or alternative cardio-respiratory monitoring systems. These recordings must incorporate PCO2 measurement and ensure sufficient sleep and wake cycles are captured. Annual check-ups are recommended as a minimum, with more frequent evaluations for younger children due to age-related physiological changes.
Alt: Follow-up program table outlining recommended check-up frequency and assessments for patients with Congenital Central Hypoventilation Syndrome (CCHS) based on age, emphasizing regular monitoring of respiratory function.
The Lifeline of Ventilatory Support in CCHS
Currently, there are no pharmacological interventions that can reliably and sustainably improve ventilation in CCHS patients to the extent that they can avoid assisted ventilation. Therefore, ventilatory support is the cornerstone of management, aimed at preventing the detrimental effects of even mild hypoventilation, particularly on neurocognitive development.
Ventilatory support must be tailored to each patient’s individual needs, ensuring adequate ventilation at all times – during sleep, wakefulness, growth phases, varying activity levels, and during acute illnesses. A patient initially requiring only nighttime ventilation might need 24-hour support during an acute illness. Increased monitoring and ventilatory support are crucial following sedation or anesthesia, even if the patient appears awake. It is essential to understand that ventilatory support for CCHS is a lifelong commitment, and weaning from ventilation is not the goal.
During assisted ventilation, maintaining optimal oxygenation (SpO2 ≥ 95%) and a normal PCO2 range (ideally 35–45 mmHg or 4.6–6.0 kPa) is crucial. However, due to variations in ventilatory needs across different sleep stages, achieving perfectly stable PCO2 levels can be challenging. While some clinicians have explored mild hyperventilation during sleep (PCO2 30-35 mmHg or 4.0–4.6 kPa) to potentially improve daytime gas exchange, this approach lacks comprehensive investigation in CCHS and carries the risk of cerebral vasoconstriction.
It is critically important to note that oxygen therapy alone, while improving oxygenation, can worsen hypoventilation, leading to acidosis and potentially coma. Oxygen supplementation should never be used as a substitute for adequate ventilatory support in CCHS.
Understanding Ventilatory Support Requirements for CCHS Patients
CCHS patients typically exhibit reduced tidal volume and respiratory rate during sleep. They often struggle to generate sufficient spontaneous breaths to effectively trigger ventilators.
Pressure-controlled ventilation is generally favored over volume-controlled ventilation, particularly when leaks are present, such as with uncuffed tracheostomy cannulas or mask ventilation. Pressure-controlled modes ensure consistent and adequate ventilation for CCHS patients of all ages, regardless of cannula type or ventilation interface. In pressure-controlled ventilation, inspiratory positive pressure and expiratory positive pressure are independently adjusted to achieve optimal tidal volume, while respiratory rate and inspiratory time are set according to the patient’s age.
Modern home ventilators often incorporate mixed ventilation modes, combining pressure-controlled ventilation with a guaranteed minimum tidal volume or minute ventilation. These advanced devices can help minimize PCO2 variability across different sleep stages. Pressure support ventilation with a back-up rate and minimum inspiratory time, when appropriately set for age, has demonstrated efficacy in children aged four years and older, and even in infants as young as ten months.
However, pressure support mode without back-up rate and minimum inspiratory time settings, as well as continuous positive airway pressure (CPAP) mode, should be avoided in CCHS. These modes can lead to inconsistent breathing patterns and potentially inadequate ventilation.
Home ventilators for positive pressure ventilation must meet stringent safety standards. They should be certified as suitable for the patient’s age and weight, especially critical for infants and young children. Essential features include visual and audible alarms for disconnection, and pressure/volume irregularities, and sufficient battery power for extended use. For tracheostomy ventilation, the ventilator must be certified for invasive use. Portability is also vital; ventilators should be compact, lightweight, and equipped with internal and external batteries, as well as car battery connection options to maximize patient mobility. Ease of operation is paramount, enabling parents and caregivers to adjust settings as prescribed. Many ventilators offer pre-programmed settings for various conditions, such as different circuits, day/night use, and illness management.
Ventilator noise level is another important consideration. Ideally, ventilators should operate quietly or silently to minimize disruption for the patient and family. The specific brands and models of home ventilators used for CCHS vary across centers and countries and are subject to ongoing advancements in technology. Having a second, back-up ventilator available is highly recommended. If a backup is not feasible, 24-hour access to technicians who can provide a replacement ventilator promptly is essential.
Respiratory monitoring at home is crucial to prevent both hypo- and hyperventilation. Overnight pulse oximetry with alarms is recommended for all CCHS patients. Periodic recordings of end-tidal or transcutaneous PCO2 should also be performed. The reliability of home medical equipment is a significant concern for patients and families, highlighting the need for robust and dependable devices. Transthoracic impedance monitors are not recommended as they are ineffective in detecting hypoventilation or obstructive apneas in CCHS. In some regions, continuous nocturnal observation by trained caregivers is available, particularly during mask ventilation.
Four Primary Types of Ventilatory Support for CCHS
There are four main types of ventilatory support utilized in CCHS management:
- Positive pressure ventilation via tracheostomy (Tracheostomy Ventilation)
- Positive pressure ventilation via mask (Mask Ventilation)
- Phrenic Nerve Pacing
- Negative Pressure Ventilation
The choice of ventilation type, and transitions between methods, is influenced by several factors, including patient age, age of CCHS onset, duration of ventilator dependence, medical center experience with each technique, and patient and family preferences. The decision-making process must be individualized, carefully weighing the benefits and risks of each option alongside local resource availability. Some patients may utilize different ventilation types concurrently (e.g., pacing during the day and ventilator at night) or at different stages of life (e.g., transitioning from tracheostomy to mask ventilation).
Alt: Table outlining the benefits and risks associated with different types of ventilatory support for Congenital Central Hypoventilation Syndrome (CCHS), including tracheostomy ventilation, mask ventilation, phrenic nerve pacing, and negative pressure ventilation.
Positive Pressure Ventilation (PPV) via Tracheostomy: A Common Approach
Tracheostomy ventilation is a widely used method for CCHS patients of all ages, and is often considered the most common type across the CCHS population. It is frequently recommended for neonates and young children with CCHS, based on the assumption that it provides superior gas exchange and supports optimal neurocognitive development during early life. Only home ventilators meeting all safety requirements are suitable for tracheostomy ventilation.
Tracheostomy is typically performed as soon as technically feasible after diagnosis in newborns and young infants. Uncuffed cannulas are generally recommended for infants and children to minimize the risk of tracheomalacia and facilitate speech development using speaking valves or plugs. Cuffed cannulas may be used temporarily in children during severe lower respiratory infections when lung compliance is reduced. Cannula size should be adjusted as the child grows to ensure adequate ventilation at baseline and during respiratory infections. Smaller cannulas are preferred as long as effective ventilation is maintained. Adult patients are more likely to utilize cuffed cannulas to prevent air leaks during assisted ventilation.
Routine surveillance bronchoscopy has been suggested to facilitate early detection of granulomas and to assess cannula size and position. However, the optimal frequency of bronchoscopy remains undefined. Bronchoscopy should be considered in CCHS patients in specific situations: (i) prior to decannulation; (ii) in the presence of symptoms such as airway bleeding, breath-holding spells, pain, cyanosis or desaturation during cannula changes, wheezing, recurrent infections, speaking valve or plug intolerance, or voice quality changes; (iii) in infants and young children within the first two years after tracheostomy creation; and (iv) after cannula size or type changes, to verify position using simple fiber-optic tracheoscopy.
Mask Ventilation: A Less Invasive Option
Mask ventilation is a viable option for cooperative patients with normal airways who require ventilatory support primarily during sleep or who use phrenic nerve pacing during the day. It is often the initial choice for children and adults with late-onset CCHS who only need nighttime ventilation. For patients needing daytime support, mask ventilation can be used in conjunction with respiratory pacing during wakefulness. Notably, some infants with neonatal CCHS presentation have successfully received mask ventilation without ever requiring tracheostomy. However, there is currently a lack of comparative data on outcomes between tracheostomy and early mask ventilation in children with CCHS.
Mask ventilation requires vigilant supervision by caregivers, particularly for infants and young children, due to the potential for mask displacement or upper airway obstruction, which can have serious consequences.
Transitioning from tracheostomy to mask ventilation may be considered at various ages, primarily for patients demonstrating adequate ventilation while awake. While some clinicians suggest older children (e.g., 10 years and older) as the optimal transition age, some younger children (e.g., 5–8 years), especially before starting school, may be cooperative and benefit from this transition. The transition process can vary between medical centers. Prior to decannulation, downsizing the tracheostomy cannula can be beneficial. Inspection of the trachea using a fiberscope by an ENT specialist and a sleep study with mask ventilation while the tracheostomy is capped can help assess the feasibility of transitioning to mask ventilation. Close monitoring is essential following decannulation.
Ventilation can be delivered via nasal masks, oro-nasal masks, nasal prongs, or total face masks. Advances in mask design and manufacturing have made mask ventilation a more viable first-line option, even for young infants. While total face masks have been discouraged by some due to discomfort and aspiration concerns, they can be useful in reducing facial pressure or preventing oral air leaks. Close maxillofacial follow-up is recommended for all patients using mask ventilation, as it has been linked to mid-face deformation, particularly when initiated in early childhood or with prolonged or tight mask application. Newer total face mask designs and alternating mask types, along with avoiding overly tight fittings, may mitigate this complication.
Home ventilators are recommended for mask ventilation, although not all bi-level devices meet the comprehensive safety requirements of dedicated ventilators.
Respiratory Pacing: Stimulating Natural Breathing
How Respiratory Pacing Works
Phrenic nerve pacing is the most common form of respiratory pacing. It involves surgically implanting bilateral electrodes around the phrenic nerves. Lead wires connect these electrodes to subcutaneous radio receivers. An external, battery-powered transmitter with antennas sends radio waves to the implanted receivers, which convert these waves into stimulating pulses delivered to the phrenic nerves via the electrodes.
This stimulation of the phrenic nerves causes the diaphragm to contract, initiating inspiration. When the stimulation ceases, passive expiration follows. This method closely mimics physiological breathing, as inspiration is driven by negative pressure within the chest. While unilateral pacing can be effective in adults, bilateral pacing is usually necessary in children to ensure adequate ventilation. Two phrenic nerve pacing systems are currently commercially available: the monopolar electrode system from Avery® Biomedical Devices Inc. and the quadripolar electrode system from Atrotech® Ltd.
Indications, Benefits, and Risks of Phrenic Nerve Pacing
Phrenic nerve pacing requires functional phrenic nerves and diaphragms. Functionality can be assessed by observing diaphragm movement during voluntary deep breathing using sonography or fluoroscopy, or through transcutaneous phrenic nerve stimulation at the neck combined with diaphragm sonography. Phrenic nerve pacing is considered for daytime ventilatory support in CCHS patients needing ventilation for more than 16 hours per day and who are at least one year old. Relative contraindications include chronic lung or airway disease, including obstructive sleep apnea, severe behavioral disorders, and obesity.
In children under six years old, pacing combined with a tracheostomy provides greater stability in tidal volume, oxygen saturation, and PCO2 compared to pacing without tracheostomy. Tracheostomy closure in this age group is often complicated by recurrent obstructive apneas during sleep. Between 6 and 12 years of age, successful decannulation becomes more feasible, but requires careful monitoring for obstructive apneas. Prior to decannulation, downsizing the tracheostomy cannula for a few weeks and conducting sleep studies with the tracheostomy capped while the patient is paced can help assess for obstructive sleep apnea and optimize pacing settings. Upper airway obstruction issues post-decannulation can be managed by increasing inspiratory time and reducing inspiratory force. Caregiver repositioning of the head and neck can also help minimize obstructive apneas. Mask ventilation may be required as a last resort.
The primary benefit of phrenic nerve pacing is for patients needing 12–24 hours of daily ventilatory support. Pacing offers daytime ventilator freedom, allowing greater mobility and participation in activities using a small, portable transmitter. Nighttime ventilation with positive pressure is still necessary. Pacing for more than 12–16 hours daily is generally not recommended.
The risk of post-surgical implant infection is approximately 6%, requiring surgical removal and replacement. Mechanical nerve injury occurs in about 2% of cases, often resulting in transient phrenic paralysis.
Pacer malfunctions on one side are commonly due to antenna defects. Spare antennae should always be readily available at home. Transmitter defects are less frequent, but a backup transmitter is also advisable. Over time, implant defects can occur, most often due to wire breakage or insulation issues. Receiver damage from external trauma is also possible. Rarely, wire breakage can result from children manipulating the receivers. Receiver defects require subcutaneous replacement, allowing pacing to resume within 1–2 days. Electrode or wire defects necessitate thoracic surgery, potentially delaying pacing resumption for 2–6 weeks.
Technical Procedure for Phrenic Nerve Pacing
Implanting electrodes and receivers requires a surgical procedure. While some centers prefer a cervical approach, most utilize intrathoracic implantation of phrenic nerve electrodes, performed via open thoracotomy or less invasive thoracoscopic techniques under general anesthesia. Receivers are implanted subcutaneously in the lower thorax or abdomen below the 12th rib and connected to the electrode wires.
Regular pacing typically begins 10–14 days post-implantation to allow for wound healing and edema resolution. Some recommend waiting 4–6 weeks for tissue stabilization around the electrodes. Pacing initiation and management require medical monitoring, appropriate settings, and patient training. Initial pacing duration should be short (1–2 hours/day), gradually increasing by 30–60 minutes weekly. A 2–4 month training period is usually needed to reach full pacing of 12–16 hours per day. Phrenic nerve pacing requires thorough caregiver and patient training and at least annual follow-up at a specialized center. The goal is to “minimize electrical stimulation to the phrenic nerves while achieving adequate ventilation and oxygenation.”
Follow-up Care for Phrenic Nerve Pacing
Successful pacing relies on both surgical and pacing expertise, particularly for setting adjustments and managing malfunctions. The first in-hospital evaluation should occur six months post-implantation, followed by annual in-hospital checks. Continuous SpO2 and PCO2 monitoring during sleep and daytime activities over 24 hours is essential for setting adjustments. Additional monitoring includes ECG during pacing to analyze inspiration time and diaphragmatic muscle potentials, and phrenic nerve conduction studies in case of malfunction.
Negative Pressure Ventilation (NPV): Less Common Today
Negative pressure ventilation utilizes a rigid cuirass, wrap, or tank ventilator that encloses the body below the neck. A pump creates negative pressure within the device, expanding the ribcage and promoting inspiration. NPV is now less commonly used due to limitations like air leaks, upper airway obstruction, reduced portability, lack of battery operation, supine sleeping requirement, and skin irritation. However, some CCHS patients, particularly in England and Germany, still utilize NPV. The RTX® cuirass (Hayek Medical®) is one currently available device.
This comprehensive overview provides essential information for the diagnosis and management of CCHS, emphasizing the critical role of respiratory assessment and tailored ventilatory support strategies in improving patient outcomes.
