(a) Patients with chronic respiratory failure and sleep-related hypoventilation syndromes with at least one criterion:
Frequent SpO2 <90% in continuous 8-hour observation
FVC <50%; PiMax <40 cm H2O; Cough Peak Flow <150 L/min
PaCO2 >50 mmHg; BE>4 mEq /L
(b) Patients with compromised control of ventilation and OSAS
Frequent SpO2 <90% in continuous 8-hour observation
Apnea-Hypopnea Index>5; TcCO2 >50 mmHg for more than 50%
Selection criteria for home non-invasive ventilation
NIV selection criteria
Stable clinical condition that allows respiratory autonomy outside non-invasive ventilation
NIV requirements in less than 12 hours
Hypercapnia without respiratory acidosis; oxygen requirement <2 L/min to maintain SpO2 >93%
Socioeconomic status that allows having appropriate facilities and basic amenities. Level of education that allows compliance with the indications
Caregivers committed to monitoring and controls
Equipment for NIV Delivery: Technical Considerations
Non-invasive ventilation uses pressure-controlled ventilation, which involves setting inspiratory and expiratory pressure limits. There are exclusive flow generators for this, less expensive than conventional positive pressure respirators. Among them the bi-level equipment stands out, which is transportable, electric, and of continuous flow, using a turbine connected to a compressor.
Bi-Level Positive Airway Pressure
It delivers a positive airway pressure in two levels with independent adjustment: inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP). The difference between the two is the pressure support level.
Inspiratory positive airway pressure (IPAP) : Sets the inspiratory pressure limit and controls ventilation. The higher the IPAP is, the higher the tidal volume during inspiratory phase. The percentage of inspiratory time will determine the IPAP duration.
Expiratory positive airway pressure (EPAP) : Sets the expiratory pressure limit above atmospheric pressure. It improves functional residual capacity and oxygenation.
Pressure support (IPAP–EPAP): The difference between IPAP and EPAP generates a pressure gradient called pressure support. Ventilation occurs as a consequence of the difference between these pressures.
Two pressure levels are useful in restrictive disorders that require increasing the functional residual capacity and decreasing the work of the respiratory muscles. For example, in patients with neuromuscular diseases (Duchenne muscular dystrophy, congenital muscular dystrophy, congenital myopathy, congenital spinal muscular atrophy), severe cases of kyphoscoliosis, and in diseases that compromise the central nervous system, such as myelomeningocele and type I and II Chiari malformations. It could also be used in alterations of the respiratory center (central hypoventilation syndromes).
Bi-level positive airway pressure can be used in different modes, with differences between available options by the different existing equipment.
Household equipment usually does not have an internal battery, which limits non-invasive ventilation in transport or in the event of a power outage. This can be solved with optional external batteries appropriate for the equipment which allows its operation, although this usually only works for the flow generator and not the associated humidifier. New equipment comes with lithium-ion batteries that deliver a minimum of 4 hours of autonomy.
Flow generators allow recognizing and compensating involuntary leaks in the system; more traditional equipment triggers inspiratory flow to deliver programmed IPAP when they sense in the system a flow generated by the patient of 40 ml/s for more than 30 ms. Inspiration ends when it lasts for more than 3 s or the flow has dropped to a quarter of the maximum flow. The VPAP II, III, Stellar 100 and 150, and VS lll (Resmed) equipment can be programmed to deliver a minimum and maximum inspiratory time (Ti Control). Equipment, such as S/T-D 30, Vision, Harmony, Synchrony (Respironics), and currently Trilogy, A30 and A-40 (Philips), have a sensitivity algorithm defined as Auto-Trak, which detects patient flow pattern, automatically adjusting sensitivity thresholds through three algorithms: (1) Inspiratory trigger threshold of 6 ml/s in a period of 30 ms; (2) Triggering algorithm determined by the flow curve shape from IPAP to EPAP and EPAP to IPAP; (3) Trigger according to spontaneous expiratory threshold to cycle to EPAP.
Conventional microprocessor-based mechanical ventilators, which have a pressure support and built-in non-invasive mode (New Port Wave or New Port E500, Evita XL or Savina by Dräger, Vela and Aveas by Vyasis, I-Vent by Versamed, Servo I Maquet and Galileo, G1 and G5 of Hamilton, among others), can be used for non-invasive ventilation in patients in pediatric intensive care units. Its administration through a conventional ventilator allows to determine the inspired oxygen concentration (the new generation of hybrid equipment has internal oxygen mixers), to prevent rebreathing due to use of double tubing, and to use the ventilator monitors and alarms. The vast majority of these ‘heavy’ mechanical or institutional-use ventilators have non-invasive ventilation modes. For this, it is necessary to change the active exhalation option, through an exhalation valve, to passive exhalation (in the mask or in the proximal exhalation port), or to maintain the exhalation through the exhalation valve of the ventilator, requiring in these cases non-vented masks (they are indicated by their light blue elbow). The disadvantage of using these ventilators is that they do not produce good leak compensation, which creates a strong adjustment pressure of the mask to the face, causing discomfort, poor tolerance, and complications such as pressure ulcers.
The choice of the ventilator for the administration of non-invasive ventilation will depend on the variety and particular characteristics of the available equipment, the type of patient, the circumstances in which it is applied, and the operator experience.
Non-invasive Ventilation Modes with Bi-level Flow Generators
These devices regulate a constant flow of air and have the capacity to change that flow to achieve certain pressures chosen by an operator. The exhalation is usually established passively through the interface (masks with exhalation port) in the units that work with tubing for inspiration and exhalation, as is the case in the vast majority of flow generators marketed for home use. Regardless of the method to establish non-invasive ventilation, a device capable of correcting the leakage flow (Q leak) is required; some equipment even requires a minimum Q leak of 13 LPM. The turbine establishes accelerated flows that decline once the IPAP is achieved, with cycle times and inspiratory duration determined by the percentage of the total time of the chosen cycle for inspiration, by direct programming of the inspiratory time, and by the maximum fixed flow percentage; traditionally, this last parameter is established in a quarter of the maximum Q.
In sum, flow generators work with pressure programming and are usually limited by flow (to prevent undesirable prolongation of inspiration when there is a leak in the interface or an obstructive pathology) or by inspiratory time (to prevent short Ti in patients with decreased compliance). At present, there is equipment that, while cycling by pressure, deliver an “assured” tidal volume in the range of 2 IPAP, maximum and minimum. This feature decreases the risk of hypoventilation: these methods may have tidal volume targets (AVAPS™, Philips Respironics), or alveolar ventilation targets (iVAPS™, ResMed Inc).
Rise Time regulates the air entry speed during inspiratory time: the higher the Rise Time, the longer it will take to reach the set IPAP within a cycle, improving tolerance in some patients. This time should be minimal in patients with dyspnea due to restrictive lung diseases. The values oscillate between 0.1 and 0.9 s. It is important to note that Rise Time should not exceed 40% of the total inspiratory time, since it has a direct implication on the final tidal volume delivered.
Ramp time refers to a characteristic that some equipment has, in which there is a latency expressed in minutes for the pressures selected by an operator to be achieved. In general, the minimum EPAP to start ramp time is 4 cm H2O and the time to reach planned pressures is 5–30 minutes. This method of progressive delivery of expiratory pressure in the airway is particularly useful and comfortable in patients with sleep apnea, giving them enough time to fall asleep.
Volume Assist-Control Ventilation (ACV)
Volume assist-control ventilation (ACV) is defined as a time or patient-triggered, flow-limited, and volume-cycled mode. A constant flow waveform is used, although a decelerating flow waveform can be used if the ventilator software allows it. The latter is recommended for the application of non-invasive ventilation (NIV), since it is the most comfortable one for the patient.
The ventilator delivers a predetermined tidal volume in response to the patient’s inspiratory effort (assisted mechanical ventilation or AMV). If the patient does not trigger the respirator, it will give him the tidal volume added to a predetermined respiratory frequency (controlled mechanical ventilation or CMV) or the combination of both (ACMV). In the case of long-term home non-invasive ventilation, this method is the first choice in those patients with neuromuscular disorders with advanced symptoms, mainly for cough assistance (increase in inspiratory capacity and consequent increase in peak cough flow (PCF) or because there is no other ventilator available that offers more sophisticated or comfortable options for the patient (PSV, Bilevel, iVAPS)
Pressure-Control Ventilation (PCV)
In pressure-control ventilation (PCV) all breaths are time- or patient-triggered (in assisted mode), pressure-limited (inspiratory pressure), and time-cycled (inspiratory time). The flow waveform is decelerating.
The tidal volume will depend on the patient’s thoraco-pulmonary impedance: the greater the latter, maximal inspiratory pressure will be obtained more quickly and with a smaller volume of alveolar ventilation.
With pressure ventilation, the maximal inspiratory pressure is the variable to be programmed instead of the Vt as in the volumetric mode. In addition, the operator must place a minimum respiratory rate, an inspiratory time (Ti) or I:E ratio, and the sensitivity level of the trigger.
The main differences between the pressure and the volumetric modes are the tidal volume consistency and the peak inspiratory pressure (PIP): the PIP is constant with the control pressure, but the tidal volume can vary. Its main advantage over NIV is that the flow is variable and can be adjusted to the patient’s flow demand, within the framework of a pre-established pressure delta: the higher the delta, the greater the capacity to generate higher flows. This mode is chosen when the patient does not achieve an adequate ventilator adaptation in the pressure support ventilation (PSV) mode due to a leak around the mask: in PCV, since inspiratory time is fixed, the cycle to expiration will be according to the patient’s demand, despite the system leak. Thus, the operator will determine the ventilator inspiratory time according to the patient inspiratory time (usually between 0.6 and 1.2 sec, depending on age and underlying pathology).
There are a wide variety of interfaces that adjust to the age and the morphology of the face of the patient. This choice is essential to achieve an adequate pressure transfer to the airway, which translates into proper ventilation and no unwanted side effects such as injuries where the pressure points are.
The interfaces must be made of soft, flexible, silicone material, transparent, with a smooth and padded adaptation surface (inflatable or gel-like material), and latex-free.
The nasal mask is the one that is better tolerated and is generally the choice for patients using home non-invasive ventilation. The naso-buccal mask is preferred in mouth breathers and in patients with acute respiratory failure and high ventilatory parameters. Full face mask is rarely used in pediatrics, although it is an alternative for children with craniofacial morphology variations or with lesions where the pressure points are. An alternative to masks is the high-flow nasal cannula. It is recommended for use at low pressures or for daytime use in patients with long-term non-invasive ventilation.
Interfaces must be fixed through elastic systems, minimizing involuntary leaks and at the same time allowing the patient to be as comfortable as possible, avoiding ocular occlusion, buccal movements, or excessive compression. It must be remembered that equipment designed for non-invasive ventilation compensates for leaks, and what matters is that they do not cause discomfort to patients.
To avoid lesions, it is recommended to install the interface on a clean face, do rotatory massages at the pressure points, and wash the interface daily.
Conditioning respiratory gas is essential to treat patients who need medical gases, oxygen therapy, invasive mechanical ventilation, and non-invasive ventilation.
Mucociliary clearance is probably the respiratory function most sensitive to changes in humidity and temperature of inspired gas. Dried up secretions can lead to alterations in ciliary activity, inflammatory changes, and respiratory epithelium necrosis, retained thick and adherent secretions with secondary impactation, bacterial colonization, atelectasis, and pneumonia.
In cases of acute respiratory failure, ineffective or insufficient humidification would be directly related to failed non-invasive ventilation. For this reason, in patients who require non-invasive ventilation for more than 12 consecutive hours, it is necessary to provide an efficient airway humidification, either with traditional systems as passover humidification or with those compatible with flow generators.
Use of passive humidification delivered by a heat and moisture exchanger (HME) is not recommended for non-invasive ventilation with a flow generator, because it increases system resistance and dead space, alters trigger response, and delivers insufficient conditioning of inspired air. It is reserved only for transportation.
In patients with motor neuron disease (MND) who present desaturation, oxygen administration is a mistake if there is not a proper management with assisted cough and proper ventilation protocols.
In patients with chronic lung damage, O2 necessary for SpO2 greater than or equal to 93% will be provided. Flow generators, except for most modern hybrid equipment, do not have an internal mixer. For this reason, the FiO2 will vary depending on flows delivered by programmed pressures and on gas leak. The best alternative to deliver O2 is by means of a T-connection placed at the exit of the BiPAP, prior to connection to the tubing, which can serve as a reservoir and determine a more stable FiO2. This will depend on the mixture produced during the inspiratory and expiratory cycle between O2 flow from its administration source (concentrator, cylinder, or network) and the flow created by the bi-level, with less than 3 L/min O2 flows. In general, only a bubble type humidifier is required. In case of larger flows, it may be required to use traditional humidifiers, such as passover or those compatible with flow generators. Leaks through the interface are frequent causes of desaturation, which will not be corrected with an increase in O2 concentration but repositioning and adapting the mask to the patient’s face. It must also be ruled out that the desaturation cause is not excess of secretions, which are treated by applying assisted cough protocols.
The use of antibacterial filters is not recommended, since they increase resistance, affect the operation of triggers, and there is no evidence that these prevent infections associated with health care.
NIV as a 24 Hours per Day Prolonged Mechanical Ventilation Method
Patients with nocturnal non-invasive ventilation (NIV) who have dyspnea during daytime hours, respiratory infections despite assisted cough, and CO2 >45 mmHg or SpO2 <95% with room air, require daytime NIV. This happens naturally in children, adolescents, and adults with NMD.
Nocturnal and diurnal non-invasive ventilation is preferably performed with bi-level flow generators plus nasal masks. It is recommended to have two different mask models to vary the pressure points. The advantages offered by the bi-level in nocturnal hypoventilation prevention by using pressure-limited equipment (30 or 40 cm H2O maximum delivery) with high differential pressure, not less than 7 cm H2O, and that allow leak compensations and even average volume assured pressure support (AVAPS™, IVAPS™) are increased in patients who require continuous non-invasive ventilation due to a greater dependence.
Those patients with greater ventilatory demand, with little ventilatory autonomy and with NIV requirements greater than 16 hours per day should be evaluated for continuous assisted ventilation. Continuous NIV is defined as the use of it for more than 20 hours per day, as an alternative more effective than mechanical ventilation by TQT. This strategy is carried out with volume-controlled ventilators, with active exhalation valves in assist/control mode (S/T-PCV) and with pressure trigger to avoid auto-trigger. To avoid alarms, a minimum respiratory rate of 1–2 per minute is set and an angled 15 mm mouthpiece is used.
As there is always a leak flow around the nozzle, higher tidal volumes should be used than if a TQT was used, on 500 ml (700–1.200 ml) and inspiratory times of 1–1.5 s that generate inspiratory flows > at 40 L/m. When these flows pass through a system with specific resistance (angled mouthpiece), they generate an opposing pressure that prevents the activation of the low-pressure alarm. Currently, there are ventilators that include the option of a mouthpiece that allows delivering breathing cycles when they are needed and performing air-stacking maneuvers, optimizing complementary assisted cough protocols, impossible to achieve with continuous flow equipment such as bi-levels. To achieve efficient ventilation, it is necessary that the patient has sufficient control of the bulbar muscles and cervical mobility. This alternative is for daytime use. During sleep, conventional non-invasive ventilation with interfaces is used. Another alternative is volume-cycled ventilation via mask, as previously mentioned.
Indication of TQT should be reserved for patients without respiratory autonomy with subglottic stenosis, a vocal cord dysfunction due to severe bulbar involvement, which produces secretion or saliva aspiration that prevents maintaining a SpO2 >95%.
Survival of patients with NMD and technology dependent has improved, among other things, by specialized respiratory care, such as prolonged mechanical ventilation and assisted cough protocols. This also means an improvement in the HRQoL of the patient and their family environment. However, expected results are not always achieved, and psychological, social, and financial burdens constitute topics that require developing assessment criteria in the bioethics domain. The therapeutic challenges, which are possible thanks to the new applied technologies, require including bioethical principles considered as the sum of knowledge that orient in a rational sense the human action of promoting good and avoiding evil. These can be summarized as autonomy, beneficence, equity (justice), and non-maleficence.
The development of non-invasive ventilation has allowed improving the natural history of some NMD, especially DMD. However, in some neuromuscular diseases with progressive deterioration, such as spinal muscular atrophy type 1, characterized by its fatal evolution without ventilatory support, there is controversy about the technical feasibility of non-invasive ventilation support during the early stages of life (<6 months) and on the bioethical implications of the decision. This is especially true with infants with swallowing disorder due to bulbar compromise within the first 3 months of life that prevents holding SpO2 stable above 95%. However, the rest of children whose bulbar involvement is not severe can benefit from non-invasive ventilation, assisted cough protocols, and gastrostomy feeding, regardless of their ventilatory autonomy level. Thus, without tracheostomy it is possible to maintain language and positively impact on HRQoL.
Bioethical aspects involved in managing patients with chronic, progressive, and potentially lethal diseases must be considered strongly when deciding together with patients and their families on mechanical ventilation therapies. It is essential to communicate all possible alternatives, such as non-invasive ventilation, ventilation through TQT or only accompaniment. Treatment decisions must consider not only technical feasibility aspects, but the aforementioned bioethical principles. Respecting the principle of justice, it is essential that healthcare systems understand the importance of addressing the necessary reimbursements for home care services that include such cost-effective and cost-efficient coverage.
Non-invasive ventilation is an alternative to invasive mechanical ventilation in patients who evolve with acute and chronic respiratory failure, who meet selection criteria. As the patient will be at home, it is necessary to organize activities there that include monitoring of clinical parameters, supervision of professionals, and continuing education to the patient and their family. Within the group of children with chronic respiratory diseases, it is useful in particular in NMD, kyphoscoliosis, obstructive sleep apnea syndrome, and cystic fibrosis, being able to alter the beginning of the natural history of the disease when identifying hypoventilation at night, without waiting until functional clinical deterioration is already obvious in wakefulness.
Respiratory compromise in neuromuscular diseases is a frequent cause of morbidity and mortality and ventilatory insufficiency of premature mortality. Over the past 10 years, we have gone from the consideration of the natural history of these diseases to both anticipatory and comprehensive recommendations in respiratory care.
The most substantial change in these recommendations is the routine inclusion of non-invasive ventilation and complementary protocols of assisted cough. Consequently, not only has the role of non-invasive ventilation been consolidated when it is initiated in a timely manner after confirming nocturnal hypoventilation but it has also been consolidated as the best strategy for delivering prolonged mechanical ventilation to those patients who require total ventilatory support or for more than 20 hours a day, reserving the indication of TQT exclusively for those who have a severe compromise of the bulbous muscles that prevent the SpO2 from being continuously maintained over 95%. These strategies have allowed survival, with good HRQoL, in patients with DMD for more than 20 years and in patients with spinocerebellar ataxia type one for more than 10 years, avoiding tracheostomy.