Section 1 Modes of Ventilation

## **Chapter 1** High-Flow Nasal Cannula

*Amal Francis Sam and Anil Yogendra Yadav*

### **Abstract**

Conventionally, oxygen is given at 4 to 6 L/min through nasal cannula for supplementation of oxygen. The FiO2 achieved through this can be up to 0.4. Flows more than this can cause dryness to the nasal mucosa without much increase in the FiO2. High-flow nasal cannula (HFNC) uses flow up to 60 L/min. Positive endexpiratory pressure is created in the nasopharynx and it is also conducted to the lower airways. Studies have shown HFNC improves washout of CO2 and decreases respiratory rate. Patient compliance also improves due to the comfort of the cannula compared to the non-invasive ventilation through a mask.

**Keywords:** non-invasive ventilation, high-flow nasal cannula, positive end-expiratory pressure, humidification

#### **1. Introduction**

Typically, respiratory support devices fit into three major categories: conventional oxygen delivery devices, non-invasive respiratory support, and invasive respiratory support. High-flow nasal cannula (HFNC) comes under a new category between conventional oxygen delivery device and non-invasive respiratory support. High-flow oxygen *via* non-rebreather mask can supplement oxygen at high concentration, provided the flow is around 10–15 L/min. At this rate, the medical gas is not humidified efficiently and this unwarmed and dry gas causes mask discomfort, and eye, oral, and nasal irritation [1]. Non-invasive ventilation is conventionally administered with a tight-sealing face mask, which might cause discomfort to the patient. Hence, it is associated with poor compliance when compared to other oxygen delivery systems. A device with better compliance with some added advantages of positive end-expiratory pressure (PEEP) and humidification would be a blessing to the patients and the caregivers.

In 1987, for the first time, oxygen therapy at a maximum flow rate of 20 L/min, with heated humidification system, was used in oxygen therapy for patients with bronchiectasis and cystic pulmonary fibrosis to promote the removal of lower respiratory tract secretions. It is still being extensively studied in respiratory distress syndrome, in apnea of prematurity in the neonate and pediatric units [2]. In adults, it has been used to treat acute respiratory failure, high-risk extubations in ICU, and many other clinical scenarios.

#### **2. Mechanism**

HFNC has an air/oxygen blender, which delivers the gas at desired FiO2 regardless of the flow rate. The heated humidifier is an inline system and actively humidifies the inspiratory gas. Other conventional oxygen therapy (COT) devices mostly through bubble humidification deliver non-humidified or under-humidified gas to the patient. Additionally, the nasal cannula of HFNC differs from the conventionally used nasal prongs by being loose, larger, and softer, which improves tolerance (**Figure 1**).

#### **2.1 Mucociliary clearance and humidification**

Epithelial cells of the respiratory tract when exposed to dry gas for 4 to 8 h have been shown to have reduced function and increased inflammation. The mucociliary clearance was studied with saccharin transit times, and there was 40% delay in the transit when patients were supplemented with dry non-humidified or under-humidified oxygen. Hence, adequate humidification is vital in maintaining the functions of respiratory epithelial cells [3]. Breathing unwarmed dry gas can increase resistance and decrease pulmonary compliance as well [4]. This is also partly attributed to receptors in the nasal mucosa, which results in muscarinic receptors-mediated bronchoconstriction in the lower airways [5].

During spontaneous breathing of room air, humidification is actively done by the nasal mucosa and nasopharynx. As per Dalton's law, the warmer the gas, the more water vapor is held. In this process of heating, some energy expenditure occurs in the human body. Supplementation of heated and humidified air reduces energy expenditure and can reduce CO2 production and decrease oxygen consumption. This mechanism is also supported by the study in infants, which showed increased weight gain in patients treated with HFNC [6, 7].

#### **2.2 Washout of dead space**

About 30% of the tidal volume does not participate in gas exchange. This is due to the anatomical dead space from the nose to the terminal bronchiole. The volume of this dead space is fixed and when the tidal volume reduces, the proportion of dead space ventilation increases. The effect of this dead space is higher in shallow breathing in a patient with respiratory insufficiency. In acute respiratory distress syndrome (ARDS), this dead space ventilation can go above 60% above the tidal volume (i.e., VD/VT ≥ 0.6) [8]. In a spontaneously breathing patient, HFNC

**Figure 1.** *Components and effects of HFNC.*

#### *High-Flow Nasal Cannula DOI: http://dx.doi.org/10.5772/intechopen.101311*

washes out the exhaled gas in the nasopharynx and replaces this dead space with a lower CO2 and higher oxygen air mixture, and this oxygen-rich air is breathed in by the patient at the next cycle, which helps in washing out the CO2. It was evident by the reduction in minute ventilation at a constant arterial CO2 tension and pH, in the studies [9].

#### **2.3 Patient acceptance**

Non-invasive ventilation (NIV) has a low acceptance rate from the patient point of view due to the discomfort of tight-fitting mask and variable levels of humidification according to the type of humidification used. Studies have shown that HFNC is better tolerated than NIV [10]. Also, when compared with face mask (FM), oxygen supplementation with a bubble humidifier HFNC is shown to be better tolerated. In a study involving oxygen supplementation at 15 L/min through FM with bubble humidifier and HFNC, patients on HFNC had greater overall comfort level, lower dyspnea scores, and reduced mouth dryness [11].

In "do not intubate" scenario, there is no change in outcome observed between NIV and HFNC, but the patients who were on HFNC had better diet intake, who conversed until just before their death. People like to eat by themselves and to talk with their friends and family at the end of their life, and HFNC favored patients in these requirements [12].

#### **2.4 Work of breathing**

The peak inspiratory flow in patients with respiratory failure is around 60 L/min and HFNC can match this flow, when compared with COT devices, and hence helps in reducing the work of breathing during the inspiration. The reduction in work of breathing was also evident in the form of lower inspiratory esophageal pressure swing, better compliance (Vt/ΔPes), and lower PTP and PTPmin in HFNC group compared with face mask and oxygen [9].

#### **2.5 PEEP effect**

At higher flow rates through the nasal cannula, positive pressure is created in the nasopharynx. The effect of positive pressure is higher when the patient is breathing with the mouth closed as it creates a seal. Some amount of airway pressure is lost if the patient opens the mouth.

The mean pressure generated with flows between 10 and 15 L/min was 1.7 to 5.3 cm H2O. Anatomical differences in the nares' size and variability in the airway among the patients, varying leak around the bores of the HFNC, might have led to this wide variation in the pressure created in the airway [13]. The positive pressure created in the airway is maximum at the end of expiration. For each increase of 10 L/ min of flow, there is an increase in mean airway pressure of 0.69 cm H2O, in patients breathing with mouth closed. It decreases to 0.35 cm H2O if the patient is breathing with mouth open [14]. These studies have measured the pressure changes by placing a catheter through the nasopharynx and placing the tip of the catheter at the level of uvula. Whether this pressure created in the nasopharynx is conducted down to the respiratory system is the next question. There is an increase in functional residual capacity when electrical impedance tomography is used to study the effect of HFNC. The pressure created in the nasopharynx by the high flow is transmitted down to the lower airways and there is an increase in the lung volume. The increase in lung volume is much homogenous in the prone position when compared to supine position. In the supine position, the expansion of lung is predominant in the ventral region [15].

#### **3. Clinical use**

#### **3.1 Difficult intubation**

In case of difficult intubation, HFNC can be given to patients as a method of pre-oxygenation and can be continued during induction, relaxation, and laryngoscopy. Clinicians should note that a jaw thrust is necessary to keep the airway in continuum with the nasopharynx. This method is called Trans-nasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE), which has improved the apneic time up to 17 min with PaCO2 levels around 60–75 mm Hg [16]. It is a potential alternative to high-flow intra-tracheal oxygen insufflation for apneic oxygenation. Patients could maintain oxygen saturations for a longer time during the apneic oxygenation and this could change the nature of difficult intubations from a hurried stop-start event to a smooth event.

#### **3.2 Hypoxemia**

The mechanisms of action of HFNC and its comfort make it a first-line oxygen delivery device for adult patients with hypoxemia. The beneficial effects of HFNC are evident by reduction in respiratory rate and improvement in oxygen saturation [17]. It not only improves the numbers in arterial blood gas, but also improves the patient clinically in terms of dyspnea score, supraclavicular retraction, and thoraco-abdominal asynchrony. All these benefits can be seen as early as 15–30 min [18]. When compared with COT devices, HFNC has shown to have reduced requirement of NIV for rescue [19].

However, the results were not the same in other studies. In a study involving patients presenting with respiratory failure to the emergency department, HFNC was not superior to COT devices in terms of escalation to mechanical ventilation, length of hospital stay, and 90-day mortality. Similar results were seen in FLORALI trial, except for reduced mortality at 90 days in patients treated with HFNC [20]. Authors attributed this benefit to degree of comfort, the heating and humidification of inspired gases, which prevented thick secretions, low levels of PEEP generated by a high gas flow rate, and reduction in dead space.

In a meta-analysis, authors concluded that, in hypoxemic patients with respiratory distress, HFNC was not better than COT devices in terms of mortality, but when compared with initiation of mechanical ventilation and escalation of therapy, HFNC was associated with risk reduction [21]. In immunocompromised patients with respiratory failure, HFNC was associated with reduction in the rate of intubation and mechanical ventilation when compared with the COT devices and NIV [22]. HFNC is also useful in treating patients with stable hypercapnic COPD and obstructive sleep apnea [23, 24].

#### **3.3 Extubation in ICU**

Extubation in intensive care unit is associated with 12–14% of re-intubation mostly within 72 h. NIV is advised in high-risk patients to prevent early re-intubation [25]. HFNC can be an alternative to NIV in patients with high risk of re-intubation. However, the results were contradictory. Compared with conventional oxygen delivery devices, HFNC has reduced the incidence of re-intubation in high-risk patients in few studies and it has not, in few other studies [26–29].

#### **3.4 Postoperative management**

In cardiothoracic postoperative patients, HFNC is equal to NIV in preventing postoperative pulmonary complications. Patients treated with HFNC and NIV had

#### *High-Flow Nasal Cannula DOI: http://dx.doi.org/10.5772/intechopen.101311*

similar rates of treatment failure and mortality. But for the ease of nursing care and better acceptance from the patients, HFNC can be an alternative to NIV in postoperative cardiac surgeries [30]. In case of major abdominal surgeries, the incidence of hypoxemia in the postoperative period is 10–50% according to various studies. Pulmonary complications are due to loss of functional alveolar units because of de-recruitment and basal atelectasis. In this subset of postoperative patients, HFNC was inferior to NIV in preventing hypoxemia and in terms of length of stay [29].

#### **3.5 Pediatrics**

There is a lack of guidance of flow in the pediatric population. About 1–2 L/min, for less than 24 months, is advised and sometimes a flow of 0.5 L/min is used in neonates. Regarding cannula size for the pediatric patients, the manufacturers recommend that the cross-sectional area of the cannula should not be more than 50% of the cross-sectional area of the nares and the outer diameter of the cannula should not be more than two-thirds than that of the nares. Discrepancies in size might lead to unexpected elevations in airway pressure or excess air leak.

In optimum conditions, the pressure created by the HFNC is comparable to nasal CPAP. But with increasing leak, the pressure effect diminishes and varies between patients. A pressure release valve is necessary in neonatal HFNC as the flow is fixed and directly delivered to the infant, to prevent over distension and injury [31]. In a retrospective study involving premature infants with neonatal respiratory disease, there were no differences in incidence of bronchopulmonary dysplasia, and no difference in rate of infection and death. But more infants were intubated for failing early nasal CPAP compared with early HFNC [32]. In another study involving nasal CPAP and HFNC as a prophylaxis to prevent re-intubation in high-risk preterm infants, HFNC failed to maintain the extubation status of the preterm infants [33]. When compared with COT, HFNC has shown to reduce extubation failures in pediatric population [34].

In addition to respiratory failure, post-extubation, and pre-oxygenation, acute bronchiolitis is the main indication for HFNC in pediatric patients. In studies, there were no differences in length of stay, intubation rate, respiratory rate (RR), SpO2, or adverse events in patients treated with HFNC versus COT devices and nasal CPAP groups. But treatment failure was higher in the HFNC group when compared with nasal CPAP group and lower in the HFNC group when compared with COT devices group [35]. In status asthmaticus, HFNC when compared with COT devices had better pCO2 levels, pH, improvement in SpO2, and reduction in respiratory rate [36]. In children who do not tolerate CPAP for OSA, HFNC has proved to be a better alternative. In a study involving children not tolerating CPAP, use of HFNC has reduced obstructive apnea-hypopnea index by 9 events/h and desaturation episodes by 13 events/h on an average [37]. HFNC stands between COT devices and CPAP in bronchiolitis and for prophylaxis after extubation. Better designed, larger studies are needed for other indications and comparisons with other oxygen delivery and ventilating systems.

#### **3.6 Initiation and titration**

In a patient with acute respiratory distress, first the eligibility of the patient for non-invasive support is to be assessed. Whoever it does not fit in the criteria should be intubated to protect the upper airway and mechanical ventilated. Patients who can be given a trial of HFNC are started at 40 L/min flow, 100% FiO2, and 31°C temperature. Temperature of 31°C is more comfortable to patients than temperature of 37°C. FiO2 is titrated down for a SpO2 target of 90%. Patient is assessed after 1–2 h and in case of respiratory rate > 35/min or the FiO2 requirement is more than

45%; then, the flow is increased by 5–10 L/min. Once the maximum recommended flow of 60 L/min is reached, FiO2 is gradually increased for the desired targets. The targets are SpO2 just above 90% and respiratory rate less than 35/min (**Figure 2**).

In case of clinical improvement, first the FiO2 is titrated down to 40–50%, and then, the flow is titrated down 5–10 L/min per session. The frequency at which the flow is adjusted depends on the clinical situation. Once the flow reaches less than 20 L/min, the patient can be weaned from HFNC and can be put on COT devices [38].

HFNC is being attributed to delay in intubation and studies have shown increased mortality in such situations. Failure of HFNC might cause delayed intubation and worse clinical outcomes in patients with respiratory failure [39]. Roca et al. derived an index to predict the success of HFNC in patients with respiratory failure and pneumonia. ROX (Respiratory rate – OXygenation) index with oxygenation as numerator (SpO2/FiO2 ratio) and respiratory rate as denominator is calculated after 12 h of initiation of HFNC therapy. A value less than 4.88 identified patients who will fail HFNC and require intubation (area under curve of 0.74; 95% CI, 0.64–0.84) [40]. This index was also externally validated, and their calculated cutoff was 3.85. A score of more than 4.88 suggests therapeutic success of HFNC and a score of less than 3.85 is suggestive of failure of HFNC and needs intubation as delayed intubation is associated with poor outcomes. There is a gray area between 3.85 and 4.88. In that case, ROX index to be calculated after 1–2 h and in case if it is increasing, then invasive mechanical ventilation is recommended (**Figure 3**).

#### **3.7 Adverse effects**

HFNC is more expensive than COT devices and that limits its widespread use. When compared with COT devices and NIV, administration of HFNC is considered as an aerosol-generating procedure. This might put the health care workers at risk and in case of a communicable disease, this will be an additional burden during an epidemic or a pandemic. The aerosol dispersion can be up to 17 cm from the patient, with the use of HFNC at 60 L/min. This dispersion is higher than the simple face mask delivering oxygen at 6 L/min, but it is lesser than the devices that deliver higher flows such as non-rebreathing face mask (24 cm) and venturi mask (39 cm) [41, 42]. Clinician should make sure the fit and seal of the HFNC is satisfactory, or else the lateral spread of aerosol can be as high as 60 cm in case the interface is loose. In another study involving patients with bacterial pneumonia, who were either on HFNC or on face mask, with settle plates at 0.4 and 1.5 meters from

#### **Figure 2.**

*Initiation and titration of HFNC. FiO2—Fraction of inspired oxygen. SpO2—oxygen saturation in blood. RR—respiratory rate. COT—Conventional oxygen therapy (Adapted from Ischaki et al. [38]).*

#### **Figure 3.**

*Utility of ROX index. ROX—Respiratory rate-OXygenation (adapted from Roca and Messika et al. [40]).*

patients, there was no significant difference in bacterial counts in the air sample between HFNC and face mask [43]. Even though studies do not establish transmission of disease through HFNC, there is uncertainty and fear of aerosol dispersion [44, 45]. Addition of a surgical mask over the HFNC can prevent aerosolization, which is not possible in case of oxygen face masks [46].

Similar to NIV, HFNC also has the potential for delaying intubation when clinically indicated. Patients who got invasively ventilated after 48 h of NIV had higher mortality than those intubated and ventilated within 48-h therapy. Hence, early detection of NIV/HFNC failure is vital for optimum management [38].

One of the beneficial effects of HFNC is the positive pressure created in the airway, but that can be maximum up to 7 cm H2O and there is loss of positive pressure if the patient opens the mouth [14]. When compared with COT devices, HFNC had higher PaO2, but the effect was attributed to higher FiO2 achieved as the PF ratio was unaffected. But when compared with HFNC, NIV not only had higher PaO2, but also higher PF ratio, which was attributed to its higher PEEP effect. The peak inspiratory flow generated by patients with respiratory failure is around 60 L/min, which can increase further, when there can be entrapment of room air, which will affect the FiO2 achieved, whereas the FiO2 delivered to the patient using NIV can reach 100% with proper seal and the higher flow demand of the patient is also matched by the ventilator.

#### **3.8 Complications**

Prolonged use of HFNC may lead to abdominal distension, aspiration, and barotrauma, although the risk of barotrauma is much less as compared with non-invasive or mechanical ventilation. A well-known complication of HFNC is barotrauma such

as air trapping, pneumothorax, and pneumomediastinum. The equipment is costlier and involves more technology and accessories than conventional nasal cannula. There is a learning curve for the caregivers but that is usually quickly achieved.

#### **3.9 Contraindications**

HFNC is contraindicated in patients who are unresponsive or agitated and patients at risk of aspiration. HFNC will be of limited use in patients with airway obstruction due to tumors. Facial anomalies, recent or past facial surgery, or facial trauma might hinder the use of HFNC. It is better avoided in patients with upper airway surgery to avoid the theoretical risk of venous thromboembolism due to the high pressure during its use.

### **4. Conclusion**

HFNC lies in between conventional oxygen delivery devices and NIV. HFNC has been used to treat hypoxemic respiratory failure, cardiogenic pulmonary edema, and post-extubation prophylaxis to decrease pulmonary complications, and in high-risk extubations. However, most of the studies addressing these are of low quality to draw conclusions and strong recommendations. HFNC can be of useful value in a setup where there is continuous monitoring of patients.

### **Author details**

Amal Francis Sam\* and Anil Yogendra Yadav Institute of Liver and Biliary Sciences, New Delhi, India

\*Address all correspondence to: amalfsam@gmail.com

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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#### **Chapter 2**

## Advanced Modes of Mechanical Ventilation

*Carmen Silvia Valente Barbas and Sergio Nogueira Nemer*

#### **Abstract**

Advanced modes of mechanical ventilation emerged from the need for better control of the ventilator by the patient, the possibility of respiratory mechanics and respiratory drive monitoring in assisted modes and a better patient-ventilator synchrony. Volume-assured pressure support ventilation (VAPSV) has the advantage of the variable of flow pressure support ventilation (PSV) assuring tidal volume in each respiratory cycle. Proportional assist ventilation plus (PAV+) delivers assistance in proportion of inspiratory efforts while monitoring work of breathing, respiratory compliance, resistance and auto-PEEP, improving patient-ventilator asynchrony. Neurally adjusted ventilatory assist ventilation (NAVA) provides diaphragmatic electroactivity information and a better inspiratory and expiratory patient-ventilator synchrony. Adaptative support ventilation (ASV) assures a pre-set minute ventilation adjusting Pressure Support according to respiratory rate. Intellivent-ASV adds SpO2 and PETCO2 monitoring to adjust minute ventilation and PEEP/FIO2 according to lung pathology. Smart-Care ventilation provides an algorithm that decreases PSV according to patients tidal volume, respiratory rate and ETCO2 according to lung pathology and performs a spontaneous breathing trial indicating the redness for extubation. Clinical indications of advanced modes are to improve patient-ventilator synchrony and provide better respiratory monitoring in the assisted modes of mechanical ventilation.

**Keywords:** new modes of mechanical ventilation, VAPSV, PAV+, NAVA, ASV, Smart Care®

#### **1. Introduction**

When patients with acute respiratory failure recovery from the respiratory insufficiency, they are transitioned to assisted modes of ventilation to start the weaning process. The most common assisted modes are volume assisted ventilation in which the ventilator delivers the same tidal volume during every inspiration, and Pressure support ventilation (PSV) in which the ventilator delivers the same delta pressure assistance during every inspiration. The fixed deliver tidal volume or pressure assistance are the main reason for the occurrence of patient-ventilator asynchrony in these modes of ventilation. In PSV, the inspiratory flow is variable resulting in less asynchrony than in volume assisted ventilation, however asynchrony can still be present in cases of patients with obstructive lung disease and ineffective efforts or under assistance with insufficient tidal volume, can also occur especially in patients with low respiratory system compliance or high respiratory resistance. In these cases, the patients' tidal volume cannot be guaranteed and the patient can generate a huge inspiratory effort that is often under detected. During PSV, the same assistance is independent of the

patient's demand, allowing under or over-assistance and the occurrence of patientventilator asynchrony [1]. The advanced modes of mechanical ventilation emerged from the need of greater control of the ventilator by the patient, the possibility of better synchrony and monitoring of the respiratory mechanics during the assisted modes of mechanical ventilation [1].

#### **2. Volume assured pressure support ventilation**

Volume assured pressure support ventilation (VAPSV) is a dual mode of mechanical ventilation that associates pressure support ventilation to volume assisted ventilation. This combination optimizes the inspiratory flow, decreasing the patient's work of breathing while assuring the set tidal volume. Compared to volume assisted ventilation, VAPSV can decrease the patient's respiratory drive (a lower measure P0.1), the pressure -time product and the patient's work of breathing. This advanced mode of ventilation extends the benefits of PSV to unstable patients with acute respiratory failure, assuring a pre-set tidal volume (**Figure 1**) [1].

**Figure 1.**

*Volume assisted ventilation (VAV) compared to volume assured pressure support ventilation (VAPSV): note the decrease of the esophageal pressure and the better inspiratory flow synchrony during VAPSV [1].*

#### **3. Proportional assist ventilation (PAV)**

Proportional modes deliver assistance in proportion to the patient's demand, allowing variation of inspiratory pressure and avoiding diaphragm excessive loading and atrophy by disuse. Proportional assist ventilation (PAV) is a form of synchronized ventilator support in which the ventilator generates pressure in proportion to the instantaneous patient effort, or in proportion to flow and volume generated by the same [2–4]. Therefore, the ventilator allows at any time during inspiration, airway pressure in proportion to the pressure generated by inspiratory muscles (Pmus) and respiratory mechanics [4].

*Advanced Modes of Mechanical Ventilation DOI: http://dx.doi.org/10.5772/intechopen.100283*

Initially described by Magdy Younes in 1992, PAV amplifies inspiratory efforts with the goal of the patient comfortably attain whatever ventilation and breathing pattern that the control system desires [2].

There is no target tidal volume, mandatory rate and airway pressure preset [5]. The ventilator is able to automatically adapt to changes in ventilatory demand of the patient. The pressure delivered by the ventilator follows the Pmus profile, usually with a progressive increase from the beginning of inspiration, with gradual pressurization, to the end of inspiration [4]. Maximal assistance is achieved until the end of inspiration [4].

Unlike PSV, in which a constant preset level of pressure assists each inspiration, regardless of the patient's inspiratory effort, PAV allows assistance proportional to the patient's demand, avoiding under-assistance or over-assistance [4], frequently observed during PSV. Under-assistance can induce respiratory distress and overassistance can cause overdistension, and both may generate patient-ventilator asynchrony, that are associated with poor outcomes [5].

Therefore, PAV is designated for patients with stable respiratory drive, and can be used in any patient who is being ventilated under pressure support ventilation (PSV) or during weaning from mechanical ventilation [2, 6]. PAV is also designated to improve synchronism, while generating proportional assistance [2, 6].

#### **3.1 How PAV works**

PAV plus (PAV+) or Proportional Pressure Support (PPS) represent an upgrade to PAV [4] and are the clinically available versions of PAV.

During assisted ventilation, both the patient and ventilator contribute to the pressure required to overcome the elastic and resistive load during tidal breathing, according to the equation of motion [6]:

$$\text{Prms} + \text{Pvent} = \mathbf{V}' \mathbf{x} \, \mathbf{R} + \mathbf{V} \, \mathbf{x} \, \mathbf{E} + \mathbf{P}\_{\text{EE}} \tag{1}$$

where Pmus is the pressure generated by respiratory muscles, Pvent is the pressure provided by the ventilator, V′ is the instantaneous flow, V is the volume, R and E are the resistance and elastance of the respiratory system respectively, and finally, PEE, is the elastic recoil pressure at end-expiration [7].

During PAV+, the ventilator software calculates elastance or compliance of the respiratory system and airway resistance using a brief end-inspiratory occlusion performed randomly every four to ten breaths [7, 8]. During each end-inspiratory occlusion, a 300 ms pause allows the ventilator to measure compliance (Crs) or elastance of the respiratory system (Ers) [9] and airway resistance (Raw). Based on inspiratory effort and respiratory mechanics, the ventilator adjusts inspiratory pressure, according to the equation of motion. As patient demand changes, PAV can also change proportionally inspiratory pressure above positive end-expiratory pressure (PEEP) level.

During Proportional Pressure Support (PPS), a combination of two parameters, generate inspiratory pressure: flow assist (FA) and volume assist (VA).

Airway occlusion pressure (P 0.1) can be monitored during PPS and PAV+, but the work of breathing (WOB) cannot be monitored during PPS.

The transition from inspiration to expiration, or the cycling off criteria occurs when inspiratory flow decreases to a pre-set level between 1 to 10 liters per minute. Cycling of criteria in PAV+ should be adjusted around 10 liters per minute in

obstructive patients, while around 1 liter per minute in restrictive and around 3–5 liters per minute in those without respiratory abnormalities.

If apnea occurs, the apnea ventilation is automatically activated as in other spontaneous modes.

#### **Figure 2.**

*PAV+ adjustments in clinical practice: parameters to set: % of assistance, tube ID, tube type, maximal pressure, maximal spontaneous tidal volume. Monitored parameters: compliance, resistance, auto-PEEP, work of breathing (J/liters). (Obtained from a simulator of the authors laboratory).*

#### **3.2 How to adjust parameters in PAV**

In PAV+, the percentage support can be adjusted between 5 to 95%, usually between 10 and 20 to 70–80%. When percentage support is 50%, ventilator amplifies Pmus by two times, while when in 90%, Pmus is amplified by ten times. When the percentage support is set, patient and ventilator are sharing WOB, as defined by the operator. If the percentage support is 60%, the patient will be responsible by 40% of total WOB. The percentage support can be adjusted according to WOB, that can be kept between 0.3 to 0.7 joules/liter. However, WOB is considered normal between 0.2 to 1.0 J/L [10], and eventually, if others criteria are normal, like respiratory rate and P 0.1, percentage support not necessarily should be changed in case of WOB between 0.7 to 1.0 J/L (**Figure 2**). As the patient improves the percentage support is decreased to 20–30%; if the tidal volume remains 5–6 ml/kg/predicted body weight, respiratory rate less than 28, FIO2 less than 40%, PEEP less than 10 cmH20 and WOB less than 1.0 J/L, the patient can be extubated.

During Proportional Pressure Support (PPS), initially, the flow assistance (FA) should be set around 80% of airway resistance and volume assistance (VA), around 80% of elastance of the respiratory system, and then, changed according to the respective variations in these criteria. As higher FA and VA values, highest will be airway pressure and probably, tidal volume. PEEP and fraction of inspired oxygen (FiO2) should preferably be set in less than or equal to 10 cmH2O and 50% respectively.

#### **3.3 Limitations, advantages and current evidences of PAV**

PAV can also be used during noninvasive ventilation (NIV). As PAV requires clinical estimation of resistance and elastance, and measurements of these criteria with short end-inspiratory occlusions cannot be accurately performed in presence of leaks, it can, however, be of limited reliability [5]. Therefore, PAV as NIV did not present any evidence for daily routine.

Synchronism, proportional assistance and WOB monitoring seem to be the main advantages of PAV as well as to improve the patient-ventilator synchrony. Several studies and reviews evaluated PAV in comparison to PSV [7, 11–14] showing results favorable to PAV regarding synchronism, weaning success, sleep quality, duration of mechanical ventilation, lung and diaphragm protection and lower proportion of patients requiring reintubation [7, 11–14]. Although mortality seems to be generally favorable with PAV [11], this hypothesis has not been confirmed and more studies are necessary for this issue. One systematic review and meta-analysis that evaluated 14 randomized controlled studies, involving 931 patients [15] showed no difference on intubation risk (as noninvasive PAV), weaning time, hospital mortality, reintubation, or tracheostomy.

#### **4. Neurally adjusted ventilatory assist (NAVA)**

Neurally adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation delivering pressure in response to the patient's respiratory drive, measured by the electrical activity of the diaphragm (EAdi) [16–18]. Initially described in 1999, by Christer Sinderby et al. [16], NAVA introduced a new dimension to mechanical ventilation, in which the patient's respiratory center can assume full control of the magnitude and timing of the mechanical support provided, regardless of changes in respiratory drive. This technology helps to decrease the risk of hyperinflation, respiratory alkalosis and hemodynamic impairment [16].

NAVA captures the EAdi, and uses it to assist the patient's breathing in synchrony with, and in proportion to respiratory drive [17–19]. Normal EAdi generally ranges between a few and 10 μV, while patients with chronic respiratory insufficiency may demonstrate signals 5–7 times stronger [17]. Although there is no cutoff for weaning outcome, EAdi above 26 μV can be related to failure [20].

Like PAV, there are no target tidal volume, mandatory rate and airway pressure preset. Ventilator support is proportional to a combination of EAdi, and NAVA level, which defines the magnitude of pressure delivered for a given EAdi [18]. NAVA depends of the captured signal of EAdi via sensing electrodes on a nasogastric tube [17] so, in case of damage on phrenic nerve or alterations on its activity, NAVA cannot be used.

Therefore, NAVA, like PAV, is also designated for patients with stable respiratory drive, and can be used in patients who are ventilated on PSV (as long as EADi is detected), or during weaning from mechanical ventilation. NAVA is also designated to improve synchronism, while generating proportional assistance to EAdi.

#### **4.1 How NAVA works**

A specialized nasogastric feeding catheter with electrodes should be inserted until the electrical activity of the crural diaphragm is observed [17, 21]. Correct positioning of the catheter is checked using the transesophageal electrocardiographies signal recorded by the electrodes as a guide [4], observed on the screen of the ventilator at second and third tracings. The absence of detectable EAdi is a contraindication of NAVA [17].

Ventilator support begins when EAdi starts [18]. As EAdi increases, assistance increases proportionally, and pressure delivered is cycled-off when EAdi is ended by the respiratory center (**Figure 3**) [17]. Application of a respiratory load, agitation, pain, respiratory distress or other causes that increase respiratory drive, can result in an increased EAdi, while over assistance should reduce EAdi [17].

NAVA trigger is not pneumatic as other ventilatory modes, but utilizes EAdi, a reflection of neural respiratory output to the diaphragm, as its primary source to trigger [17]. Pneumatic trigger is available, but electrical trigger of NAVA allows faster response to inspiratory effort than traditional pneumatic trigger.

When NAVA level is changed, the resulting pressure depends on how respiratory afferents modulate neural output to diaphragm [18]. If the response to an increase in NAVA level is not a reduction in EAdi, delivered pressure increases [17, 18]. In the presence of high inspiratory efforts (inspiratory pressures higher than 7 cmH20), when EAdi is at its highest, pressure delivered could reach extreme levels and may cause lung injury [18]. In this situation, NAVA and other spontaneous modes should be avoided.

Inspiratory pressure above PEEP level is adjusted automatically multiplying the EAdi by a proportionality factor, called NAVA level, expressed as cmH2O/μV [17, 22].

$$\text{Inspiratory pressure} \left( \text{above PEEP} \right) = \text{EAd} \ge \text{NAVA level} \tag{2}$$

$$\text{Peak pressure} = \text{EAdi} \ge \text{NAVA level} + \text{PEEP} \tag{3}$$

For example: a NAVA level of 1 cmH2O/ μV will give an inspiratory pressure (above PEEP level) of 7 cmH2O when EAdi is 7 μV. Increasing NAVA level to 2 cmH2O/μV with the same EAdi will give an inspiratory pressure of 14 cmH2O.

The transition from inspiration to expiration, or the cycling off criteria occurs when EAdi decreases automatically to 70–40% of the peak inspiratory flow value observed at the same breath, and cannot be modified by the operator [4, 17]. If apnea occurs, the apnea ventilation is automatically activated as in other spontaneous modes.

#### **4.2 How to adjust parameters in NAVA**

During NAVA, minimal and maximum EAdi are monitored constantly. The NAVA trigger detects increases in EAdi and should be set to a level where random variation in the background noise does exceed the trigger level. The neural inspiratory trigger default of 0.5 μV, or 0.5 μV above the minimal EAdi is adequate in most cases [4]. Auto-triggering is possible due to a too sensitive trigger setting and /or leak. In case of auto-triggering, neural inspiratory trigger can be slightly increased, until this asynchrony disappears.

Frequently, NAVA level is used between 0.5 to 2.0 μV/cmH2O [4, 19]. Initial value can be around 1.0 μV/cmH2O in most cases. There is no consensus as to best approach and no definitive recommendations are available how to set NAVA level." [4, 22]. Even so, some proposals deserve to be highlighted:


When inspiratory pressure reaches around 5 cmH2O, either by decreasing EAdi or decreasing NAVA level, weaning should be considered. PEEP and fraction of inspired oxygen (FiO2) should preferably be set in less than or equal to 10 cmH2O and 50% respectively.

#### **4.3 Limitations, advantages and current evidence of NAVA**

A limitation of NAVA mode is that it requires a specialized nasogastric feeding catheter with electrodes located in the esophagus for its functioning which adds additional costs. The advantages of NAVA mode are that it can monitor the EAdi (eletroactivity of diaphragm), it improves the inspiratory and expiratory synchrony and it can be used as a non-invasive ventilation (NIV) mode too [17]. Since EAdi is a pneumatically independent signal and not affected by leaks, NAVA can deliver assist synchrony during NIV even with leaks [17]. Only a few larger studies [23, 24] compare NIV-NAVA with NIV-PS. No improved clinical outcomes were observed except a decreased incidence of asynchronies in NIV-NAVA.

In a large, multicenter, randomized, controlled clinical trial that included patients with acute respiratory failure (ARF) from several etiologies [19], NAVA was used in 153 patients, while another 153 enrolled in the control group used volume control ventilation, pressure control ventilation, PSV, or pressure-regulated volume control. NAVA decreased duration of mechanical ventilation, although it did not improve survival in ventilated patients with ARF.

#### **5. Adaptative support ventilation (ASV)**

Adaptative Support ventilation (ASV) is a closed- loop controlled ventilatory mode, which is designed to ensure optimization of the patient work of breathing, automatically adjusted according to the patient's requirements. ASV combines passive ventilation with pressure-controlled ventilation with adaptive pressure support if the patient's respiratory effort is present.

ASV delivers pressure- controlled breaths according to the set minute ventilation, resulting in the best combination of tidal volume and respiratory rate. As the patient's inspiratory efforts start, ASV delivers pressure-supported breaths according to the set minute ventilation resulting in the best combination of tidal volume, respiratory rate and the patient's inspiratory effort. In ASV mode FIO2 and PEEP are set manually [25].

#### **6. Intellivent-ASV**

Intellivent ASV is also a closed-loop ventilation that adds the monitoring of SpO2 and Pressure End-tidal CO2 to best manage ventilation and oxygenation. *Advanced Modes of Mechanical Ventilation DOI: http://dx.doi.org/10.5772/intechopen.100283*

In Intellivent ASV mode the clinician sets patients' sex, height and choice the following respiratory mechanics situations: normal, ARDS, chronic hypercapnia and brain injury. Intellivent ASV determines the target PETCO2 and SPO2 according to the patient's condition. The ventilator controller adjusts the best tidal volume and respiratory rate to achieve the minute ventilation and PETCO2 set by the clinician combining pressure-control and or pressure support ventilation according to the patient's inspiratory effort. In Intellivent ASV, FIO2 and PEEP are adjusted according to the patient's SpO2 following a PEEP-FIO2 table [25].

#### **7. Smart-care ventilation**

Smart Care ® is an automatic weaning protocol, designed to stabilize the patient's spontaneous breathing in a comfort zone of a preset defined ventilation and to automatically reduce the ventilatory support. Smart Care ® ventilates the patient with pressure support which levels are adjusted according to respiratory rate, tidal volume and End tidal CO2 to meet the patient's demand. Smart Care ® classifies the patient a minimum of every 5 minutes into one of 8 categories and decreases or increases the pressure support levels accordingly. Smart Care® assesses and indicates the readiness for extubation after a successful automatic spontaneous breathing trial [26].

#### **8. Conclusions**


*Mechanical Ventilation*

### **Author details**

Carmen Silvia Valente Barbas1 \* and Sergio Nogueira Nemer2

1 Pneumology and Critical Care, Albert Einstein Hospital, INCOR-University of São Paulo Medical School, São Paulo, Brazil

2 Pneumology, INCOR-University of São Paulo Medical School, São Paulo, Brazil

\*Address all correspondence to: carmen.barbas@gmail.com

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Advanced Modes of Mechanical Ventilation DOI: http://dx.doi.org/10.5772/intechopen.100283*

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### Section 2
