Noninvasive Ventilation

Anatomy and Physiology

Lung compliance refers to the change in volume that accompanies a change in pressure in the lung. Compliance is calculated according to the formula dV/dP, where V refers to the volume of the lung and P refers to the transpulmonary pressure (TPP), which can be otherwise expressed as alveolar pressure (Palv) – intrapleural pressure (Ppl). TPP can be thought of as the pressure that prevents the inward recoil of the lung, or rather, the pressure that keeps the lung from collapsing on itself.[8] At rest, TPP is slightly positive, and during inspiration, as the diaphragm contracts, Ppl decrease, causing TPP to increase and, subsequently, the lung to expand. Normal lung tissue is based on a compliance curve in which a change in TPP generates a maximum increase in lung volume. Lung diseases can either cause an increase or decrease in the lung's compliance and distortion of the curve, resulting in an increased TPP to generate the appropriate change in lung volume. For example, emphysema causes the compliance curve to be displaced upwards, resulting in the TPP being in a region where increased TPP results in a minimal increase in lung volume.[9] In contrast, acute respiratory distress syndrome and cardiogenic pulmonary edema cause an overall decrease in compliance due to liquid-filled alveoli exerting mechanical stress on air-filled alveoli.[10] NPPV reduces the work of breathing through 3 different methods. By applying positive end-expiratory pressure (PEEP) through expiratory positive airway pressure (EPAP), NPPV allows the body to overcome the dynamic intrinsic positive end-expiratory pressure threshold required to initiate a breath and increase lung compliance.[11] By applying inspiratory positive airway pressure (IPAP), NPPV contributes a more significant portion of the TPP required during inspiration, thus reducing the body's breathing work.[12]

Indications

According to the latest ATS/ERJ guidelines from 2020 for acute respiratory failure, NPPV carries a strong recommendation for the following in the setting of acute respiratory failure (ARF):

• BPAP for acute or acute-on-chronic respiratory acidosis secondary to COPD exacerbation where pH </= 7.35
• BPAP is the prevention of endotracheal intubation and mechanical ventilation in a patient that is not immediately deteriorating
• BPAP or continuous positive airway pressure (CPAP) for cardiogenic pulmonary edema[5]

ATS/ERJ guidelines carry a conditional recommendation for the following in the setting of ARF:

• Early NIV for immunocompromised patients with ARF
• Post-operative ARF
• As palliation to dyspneic patients in the setting of terminal cancer or other terminal conditions
• Chest trauma patients with ARF
• Prevention of post-extubation respiratory failure in high-risk patients

In addition, NPPV has been effective in treating various chronic respiratory diseases. These diseases include chronic stable COPD with hypercapnia, obesity hypoventilation syndrome, obstructive sleep apnea, respiratory failure secondary to neuromuscular disease, and restrictive thoracic disorders.[6][7]

Contraindications

Absolute Contraindications

• Facial trauma/burns
• Fixed upper airway obstruction
• Active vomiting
• Respiratory or cardiac arrest[13]

Relative Contraindications

• A recent facial, upper airway, or upper GI tract surgery
• Inability to protect the airway
• Life-threatening hypoxemia
• Medical or hemodynamic instability (hypotensive shock, myocardial infarction requiring intervention, uncontrolled ischemia or arrhythmias)
• Altered mental status/agitation
• Bowel obstruction
• Copious respiratory secretions
• Focal consolidation
• Undrained pneumothorax
• Severe co-morbidity

Equipment

NPPV Circuit Components

• NIV device: While CPAP is delivered using a continuous flow, BPAP is typically produced using 2 modes: Spontaneous or spontaneous/timed (S/T). Spontaneous mode is where the machine augments the patient's spontaneous breaths, whereas S/T mode includes a backup rate slightly below the patient's respiratory rate. Newer versions of NPPV devices were developed to add more monitoring features and ventilatory assistance, such as averaged volume-assured pressure support (AVAPS). The AVAPS device delivers a constant tidal pressure-volume to patients and uses a specific algorithm that automatically calculates the pressure changes needed to maintain an optimal tidal volume. In addition, AVAPS can be combined with auto–expiratory positive airway pressure (AVAPS-AE) to maintain a patient's upper airway patency.[14]

  BPAP S/T mode vs. AVAPS

• Mask: several types of masks exist, including nose masks, nose-mouth masks, and helmets, each with its own set of advantages and disadvantages[15]
• Tubing
• Oxygen supply
• Power supply
• Humidifier

Personnel

NPPV initiation and titration should be performed by experienced physicians who are trained in its use and monitoring. Qualified physicians typically come from internal medicine, anesthesiology, surgery, emergency medicine, pulmonary medicine, and critical care. Support staff for the procedure includes personnel proficient with the device and complications, and this typically comprises respiratory therapists or registered nurses with an essential care background.

Technique or Treatment

The initiation of NPPV must occur after careful patient, ventilator, and interface selection. As successful NPPV implementation mainly depends on patient cooperation, the goals, process, and complications of this procedure must be explained to the patient in detail before initiation. Following this, mask fitting is started, and the patient should be given time to acclimate to the mask before securing it. The ventilator is then connected to the mask and turned on with oxygen supplementation. Initiation and titration of NPPV must be performed carefully, closely monitored by the clinician, and with nursing and respiratory therapy. Titration protocols often differ by institution and pathology. In addition, few titration protocols have been published in the literature. One such protocol for NPPV titration for OSA has been published in the Journal of Clinical Sleep Medicine.[16] In addition, a recently published review in Annals of ATS details a titration protocol for chronic hypercapnic respiratory failure in COPD.[17]

Titration of NPPV in an Acute Setting

Clinician experience shows that the titration of NPPV in the acute setting in the intensive care unit can be divided into 3 categories. The first category is for patients with simple airway conditions, such as obstructive sleep apnea, needing end-expiratory positive airway pressure, or CPAP alone. The titration of pressure in this situation requires overcoming the collapsing pressure of the upper airway, which can be estimated from the actual body weight. From our experience, using 10% of the patient's actual body weight in kilograms would be the starting point of the EPAP or CPAP.

The second category is for those with hypercapnic or mixed respiratory failures, such as those with acute exacerbation of COPD and no upper airway obstruction (no obesity or suspicion of OSA). In this category of hypercapnic patients, clinicians can use EPAP of 5 cmH₂O and add high-intensity pressure support of 10 to 15 cmH₂O, which can be titrated based on response in reducing CO₂ (measured by arterial blood gas). A third category is when patients hospitalized with hypercapnic respiratory failure are associated with obesity or obstructive sleep apnea. This group of patients is the most challenging as they require careful adjustment for both inspiratory and expiratory pressures to prevent upper airway collapse while maintaining adequate ventilation. Therefore, in this group of patients, one must combine the strategy used in the previous 2 categories of patients, where clinicians can apply sufficient EPAP to overcome the collapsing upper airway pressure using the 10% rule of actual body weight (in kilograms) and add high-intensity pressure support between 10 to 15 cmH₂O to provide adequate ventilation and titrate based on arterial blood gas.

Once pH is normalized, the pressure support can be weaned off slowly to allow a slight decrease in hypercapnia that can be managed in an outpatient setting. Patients with chronic respiratory failure suspected of having OHS should be discharged on NPPV until they undergo outpatient diagnostic polysomnography and laboratory PAP titration. In the meantime, the BPAP S/T mode can be used with empiric settings or auto-titrating NPPV such as VAPS with the auto-expiratory positive airway pressure (VAPS-AE), which can automatically adjust the EPAP to ensure adequate upper airway patency due to OSA. When monitoring to ensure adequate response to NPPV in the acute setting, the clinician must consider the subjective and physiologic responses of the patient. Clinicians should use caution when asking patients about their respiratory status, as some patients minimize or deny discomfort, thus confounding the clinical picture. Patients likely to succeed on NPPV in the acute setting have a drop in their respiratory rate after 1 to 2 hours, a decrease in heart rate, and better ventilator synchrony.[18]  A blood gas should be drawn 1 hour after initiation of BPAP as a decrease in PCO₂ and an increase in pH predict NPPV success. In addition to the parameters above, tidal volume and air leak must be closely monitored as these can contribute to treatment failure if not corrected. The patient's hemodynamics, including blood pressure and heart rate, must be monitored during treatment as intrathoracic pressure right ventricular afterload increases and right ventricular preload decreases. This is consistent with prior studies demonstrating reduced cardiac output after initiating NPPV.[19][20]

Titration of NPPV in a Chronic Setting

1) COPD with chronic hypercapnic respiratory failure: NIV is used for patients with COPD and stable hypercapnia (CO₂ ≥52 mmHg). Prospective randomized controlled trials have significantly improved survival and clinical outcomes (less exacerbation rate and better disease control).[21][22] Contrary to previous studies, the clinical benefits of NIV in stable COPD seem to be due to high-intensity pressure support that targets the normalization of CO₂ (or at least a 20% decrease in CO₂ level).[23] Clinician experience in stable patients with COPD and chronic hypercapnic respiratory failure with no evidence of obstructive sleep apnea or obesity indicates using BPAP S/T mode with IPAP 15-20 cmH₂O. However, when there is obstructive sleep apnea suspicion or obesity (OSA/COPD overlap), EPAP level needs to be adjusted based on their opening pressure (from the PAP titration sleep study when obstructive apnea is eliminated), or if not available, pressure is set empirically based on actual body weight using the above 10% rules (e.g., for a patient whose weight is 70 kg, the EPAP is set at 7 cmH₂O). 

2) Obesity hypoventilation syndrome: OHS is defined as a combination of obesity (body mass index >/=30 kg·m^-2), daytime hypercapnia (arterial CO₂ >/= 45 mmHg), and diagnosis of OSA (apnea-hypopnea index ≥ 5 events/hour) after excluding other causes of alveolar hypoventilation. OHS and coexistent OSA treatment is CPAP; however, when CPAP is not tolerated or fails to correct ventilation (CO₂ >/= 45mmHg), NPPV (BPAP S/T mode or VAPS) is recommended (see prescription parameters below).[24] The pressure selection in OHS associated with OSA requires eliminating apnea and hypopnea (AHI <5 event/hour) and fixing the hypoventilation and sustained hypoxia. Therefore, a dedicated pressure titration in the sleep laboratory is recommended with follow-up in the clinic to measure ABG and adherence to device treatment (usually within 4 to 6 weeks).

3) Thoracic restrictive disorder (TRD) with hypercapnic respiratory failure: TRD is defined as ventilatory defects associated with elevated CO₂ (≥45 mmHg) due to neuromuscular disorders (amyotrophic lateral sclerosis, spinal cord injury, muscular dystrophy, diaphragm paralysis, spina bifida, and congenital central hypoventilation syndrome), chest wall deformity, and other ventilatory drive defects without evidence of interstitial lung disease. The use of NPPV treatment in TRD is similar to other hypoventilation syndromes. It requires careful assessment of OSA and monitoring of CO₂ and oxygenation while the patient is awake and sleeping after initiation of therapy. BPAP S/T or VAPS should be considered without sleep testing in this condition.

Complications

The most common complication of NPPV is mask discomfort. More serious adverse effects include skin rash secondary to hypersensitivity or infection and rarely nasal bridge ulcers. Aerophagia and sialorrhea are also complications that may arise. Patients may experience symptoms related to the pressure, including discomfort, ear and sinus pain, or gastric insufflation. Serious side effects from pressure include pneumothorax, pneumocephalus, and, more recently, pneumomediastinum from NPPV in the setting of SARS-CoV-2 pneumonia.[25][26] Aspiration is a serious complication of NPPV, and steps should be taken during patient selection to ensure that patients on NPPV are at low risk of aspiration. Sedation in NPPV has not been well studied due to the thought process that it can lead to an increased risk of aspiration and hypoventilation. Rarely, when patients co-present with respiratory failure and compromised cardiac output, NPPV causes hemodynamic compromise due to increased intrathoracic pressure, right ventricular afterload, and reduced preload. 

The final complication arises from patient-ventilator dyssynchrony with BPAP. This falls under 2 categories: Failure to trigger and cycle, leading to inadequate gas exchange and unnecessary expiratory muscle use. An example of failure to cycle would be during COPD, where rapid inhalations may not give the BPAP adequate time to cycle from inspiration to expiration. Thus, the patient is expiring against the ventilator’s effort to deliver inspiratory pressure, leading to respiratory discomfort and distress.[2] Failure to trigger can be seen in neuromuscular diseases such as ALS, where the patient cannot generate enough negative pressure during inspiration to trigger the assisted breath.[27]

Clinical Significance

Respiratory failure is a life-threatening condition responsible for around 30% of in-hospital mortality. The definitive treatment for respiratory failure is mechanical intubation and ventilation. However, this process is associated with significant morbidity and mortality.[28] These include complications with intubation, such as laryngospasm, bronchospasm, incorrect tube placement, aspiration, and hypotension, as well as complications from prolonged time on mechanical ventilation, including ventilator-induced lung injury, ventilator-associated pneumonia, and GI complications, including peptic ulcers and colonization of the GI tract by aerobic gram-negative bacteria. NPPV has been shown to reduce intubation in COPD, cardiogenic pulmonary edema, and pneumonia and reduce the need for reintubation in hypercapnic respiratory failure following extubation. However, NPPV is a time-consuming procedure requiring high resource utilization and should only be performed under a clinician and support staff with proficiency in its use.

Clinical Pearls

• Start treatment as early as possible.
• When arterial pH is less than 7.35, and PaCO₂ is elevated, it indicates the presence of acute or acute chronic hypercapnia respiratory failure, which requires admission to the ICU.
• The first goal is to correct arterial pH in acute or chronic hypercapnia respiratory failure.
• High-intensity pressure support is indicated in chronic hypercapnic respiratory failure with arterial PaCO₂ of more than 51 mmHg. It should be targeted to correct CO₂ toward normal or at least reduced by 20% from initial levels.
• When OSA is suspected, the EPAP  should be adjusted empirically (use the 10% rule of actual body weight) if no PAP titration was performed. 

Enhancing Healthcare Team Outcomes

NPPV is initiated at the physician level but requires the cooperation of an interprofessional team to ensure its success. While the physician performs the initial settings and titration, a team usually does subsequent patient monitoring, including nurses with critical care training and respiratory therapists. The patient's mental status and vital signs must be continuously monitored, and any abnormalities must be recognized and reported to the physician expediently. Should hypotension develop, intravenous access should be secured before initiation of NPPV. The patient needs frequent arterial/venous blood gas draws during titration of NPPV. During transfers of care, it is vital to communicate the patient’s prior NPPV settings and changes to ensure optimal adjustment and effectiveness of NPPV.