Proportional Assist Ventilation and Neurally Adjusted Ventilatory Assist

Proportional Assist Ventilation

The underling theory of operation for PAV is based on the equation of motion:

which states that the total pressure required to ventilate (P_total) is equal to tidal volume (V) times elastance (E) plus flow (V̇) times airways resistance (R).

and

As noted above, in patients who are actively participating in ventilatory support P_total equals patient-generated muscular effort or pressure (P_mus) plus ventilator-generated pressure (P_vent), so the equation of motion can be rewritten as:

All of today's ventilators can easily measure flow and thus can calculate volume on a moment-to-moment basis.⁴ The problem is to measure, in an ongoing manner, the R and E of the respiratory system. Some ventilator manufacturers have interposed an end-inspiratory pause of about 300 ms every 8 to 15 breaths, and from those measurements during those pauses they estimate the R and E.⁸ Others manufacturers have defined a process for the one-time estimation of R and E, at the time PAV is initiated. Assuming that can be done accurately, the only variable in equation 1 that is not either directly measured or calculated is P_total. Thus, the ventilator can calculate the pressure needed, at any given moment, to provide ventilation. If the clinician has set PAV at 60%, the ventilator would provide 60% of the calculated pressure, the remaining pressure being left to the patient to generate. That is, on a breath-to-breath basis the ventilator applies the calculated amount of pressure needed to meet the flow and volume demand of the patient based on the set PAV percentage, leaving the remaining work to the patient. Exhalation occurs when flow decreases to a preset level. Additionally, as the patient's lung mechanics change, those ventilators that automatically measure R and E can adjust the amount of pressure needed to maintain the set PAV percentage.

Specifically, PAV improves patient-ventilator synchrony during the onset of inspiration, by matching the patient's inspiratory demand. That is, there is no limit to flow delivery, the ventilator responds to the patient's demand up to the capabilities of the ventilator, regardless of the PAV setting. This differs from pressure ventilation, in which flow will decelerate when airway pressure meets the target level. In PAV there is no pressure target; pressure will increase, as will flow, as patient demand increases. Cycling is improved because the ventilator adjusts flow during the end of inspiration the same as it does during the onset. Thus, as patient effort starts to decrease, flow delivery decreases, and when flow decreases to the cycling criterion, the ventilator transitions to exhalation. However, triggering is not directly improved with PAV, compared to conventional ventilation. The patient still has to generate sufficient flow to trigger the ventilator. However, as discussed later, conventional modes may force a larger tidal volume than normal, causing air trapping and thus increasing the number of missed triggers.

Neurally Adjusted Ventilatory Assist

NAVA accomplishes the same goals as PAV but utilizes measurement of the diaphragmatic EMG signal to control gas delivery.⁶ This is accomplished by the placement of a specifically designed nasogastric tube that has a series of EMG electrodes near its distal end, positioned across the diaphragm. As illustrated in Figure 1, supporting ventilation based on the diaphragmatic EMG signal should greatly improve the response of the ventilator and synchrony, since the signal recognized is high up on the neural pathway controlling ventilation.⁷ What is set by the clinician is the pressure applied for each millivolt of EMG activity. Thus, similar to PAV, a portion of the ventilatory effort is proportionally provided by the ventilator, and the remainder by the patient. As EMG activity increases, pressure is applied during the inspiratory phase, and as the diaphragm relaxes, airway pressure decreases. Inspiration ends at a specific percentage of the peak EMG activity. Contrary to PAV, NAVA greatly improves triggering, since gas delivery begins when the diaphragm is simulated, not as a result of flow in the airway. Thus, even in the presence of severe air trapping or large system leaks, triggering is not compromised.

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Fig. 1.

Steps in the process of activating a ventilator breath. Neurally adjusted ventilatory assist ventilation modes are activated and controlled by diaphragm excitation. Proportional assist ventilation modes are activated by a change in airway pressure, flow, and volume. (Adapted from Reference 6.)

PAV in Exercise

Most of the data on PAV in exercise have been from patients with COPD,^9–13 but there are also data from volunteers,^14,15 and patients with idiopathic pulmonary fibrosis¹⁶ and obesity.¹⁷ In all the comparisons, regardless of the subjects' clinical status, PAV improved exercise capacity, compared to no support or to continuous positive airway pressure (CPAP) or pressure support ventilation (PSV). In 15 stable hypercapnic COPD patients undergoing 4 random endurance tests on a cycle ergometer at 80% of the patient's maximum work rate, PAV, PSV, and CPAP all increased endurance, compared to spontaneous breathing. However, the greatest increase was with PAV (P < .05).¹⁰ Similarly, Dolmage et al⁹ observed a doubling of exercise tolerance with PAV plus CPAP, versus sham, in 10 patients with severe but stable COPD (P < .05). In 10 patients with idiopathic pulmonary fibrosis, Moderno et al¹⁶ reported that PAV doubled exercise tolerance, compared to CPAP and sham (P < .05). In 7 healthy volunteers at altitude, PAV reduced inspiratory pressure-time product to a greater extent than did PSV or sham (P < .05). The benefits of PAV, compared to PSV or CPAP, appear to be a direct result of PAV's ability to unload ventilatory work proportionally, regardless of the PAV setting or the load applied to the subject. However, the impact of PAV on synchrony during exercise is unknown.

PAV During Sleep

A number of groups have used PAV to evaluate quality of sleep in patients requiring ventilatory support¹⁸ or the susceptibility of volunteers to periodic breathing.^19–22 Prior data from Meza et al²⁰ and Parthasarathy and Tobin²³ clearly demonstrated that PSV induces arousals and awakenings due to central apneas in healthy volunteers²⁰ and critically ill mechanically ventilated patients.²³ This seems to be in part a result of PSV driving a level of ventilation during sleep that is consistent with that awake, causing a relative hypocapnia and, in the absence of backup control ventilation, apnea. The apnea threshold is a P_CO2 change of 1.5–5.8 cm H₂O.²¹

Bosma et al studied PAV versus PSV during sleep in critically ill patients.¹⁸ In 13 patients weaning from ventilatory support, PAV and PSV were applied randomly on subsequent nights. Each was set to unload 50% of patient work while awake. PAV was more effective in matching the patient's ventilatory requirements, and was associated with significantly less asynchrony and sleep disturbance (Table 1). Specifically, PAV was better able to adjust to the patient's decreased ventilatory drive during sleep and resulted in fewer episodes of periodic breathing.

Critically Ill Pediatric Patients

Although current versions of PAV are not recommended for use in neonates in the United States, there have been comparisons of PAV to other approaches to ventilatory support in these patients.^24–27 Schulze et al²⁴ randomly compared the physiologic efficacy and safety of PAV to pressure assist control ventilation and pressure synchronized intermittent mandatory ventilation in a series of 36 infants of birth weight 600–1200 g. Compared to pressure assist control ventilation and pressure synchronized intermittent mandatory ventilation, PAV maintained similar gas exchange with lower airway pressure and transpulmonary pressure (P < .05), and the oxygenation index decreased 28% during PAV. PAV decreased thoracoabdominal asynchrony and chest-wall distortion, compared to CPAP, in a study by Musante et al,²⁵ with 10 preterm infants. This was accomplished with airway pressure increases of only 3.8–7.6 cm H₂O above CPAP settings. In a more recent study, Schulze et al²⁷ demonstrated that PAV, compared to pressure-targeted ventilation, reduced mean airway pressure and peak airway pressure without a change in gas exchange. Although these positive studies appear in the literature, PAV is currently not recommended for patients less than 20 kg. Part of this recommendation may be due to the inability of today‘s intensive-care ventilators to accurately measure lung mechanics in neonates.²⁸

Noninvasive Ventilation

Numerous studies have evaluated PAV during noninvasive ventilation.^29–39 Most of these comparisons were between PAV and PSV,^{32–35,37–39} and in almost all of these comparisons the patients evaluated suffered from chronic respiratory failure and were in an exacerbation. The first randomized comparison between PAV and PSV enrolled 44 patients with COPD exacerbation.³² This was a physiologic comparison; the small number of subjects prevented comparison of intubation rate, mortality, or stay, but the patients managed with PAV had a lower refusal rate, a more rapid reduction in respiratory rate, and fewer complications. Similar finding were reported by Wysocki et al,³⁴ Serra et al,³⁵ Fernández-Vivas et al,³⁷ and Winck et al.³⁸ In those studies gas exchange and respiratory pattern did not differ between PSV and PAV, but the PAV patients were more comfortable. PAV has also been shown to be essentially equivalent to PSV in stable patients with chronic ventilatory failure³³ and patients with acute cardiogenic pulmonary edema.³⁹ This lack of difference has not been fully explained, but it may be a result of all approaches to the application of noninvasive ventilation being compromised by the varying level of leak, which is still poorly compensated for by most ventilators.⁴⁰

Invasive Mechanical Ventilation

PAV has been most widely studied during invasive mechanical ventilation.^41–55 As with the evaluation of PAV in other settings, most of the comparisons have focused on the physiologic response when PSV is changed to PAV. In general, during invasive ventilation the change from PSV to PAV results in lower tidal volume, more rapid respiratory rate, lower peak airway pressure, and lower mean airway pressure, without significant changes in gas exchange or hemodynamics.^{41,44,45,48–53} A number of studies have evaluated the response of PSV and PAV to changes in the patient's lung mechanics.^43,45,51 Both Ranieri et al⁴³ and Grasso et al⁴⁵ found no difference in patient work and effort between PSV and PAV as ventilatory load was increased, contrary to the finding of Kondili et al.⁵¹ The reason for this difference appears to be the ability of the PAV version used by Kondili to automatically assess lung elastance and resistance. In the Kondili⁵¹ trial the ventilator was able to update these measurements every 8–15 breaths, whereas the PAV version used by Ranieri³⁹ and Grasso⁴⁵ required input of lung mechanics at the onset of ventilation and required interruption of ventilation and clinician remeasurement of lung mechanics if the values were to change. The current ability of some PAV systems to automatically and ongoingly measure lung mechanics ensures PAV's ability to consistently unload lung mechanics when changes occur in the patient's condition.

The best long-term evaluation of PAV versus PSV randomized their application for a 48-hour period in a series of critically ill patients.⁵³ Patients randomized had to be on controlled mechanical ventilation for 36-hours, and had to be able to trigger the ventilator and maintain a minute volume of > 10/min and a P_aO2 of > 60 mm Hg and a pH > 7.30 on an F_IO2 of < 0.65 and a total PEEP of < 15 cm H₂O. In addition, the patients could not have severe hemodynamic instability, severe bronchospasm, or severe neurologic impairment. The percentage of patients who failed the transition to PAV or PSV differed (P = .04): 11% failed PAV, and 22% failed PSV. In addition, the proportion of patients who developed asynchrony was greater with PSV (29%) than with PAV (5.6%) (P < .001). Similar results were observed by Giannouli et al,⁵¹ who compared the impact of different levels of PAV and PSV in a series of 14 ventilator-dependent patients. They found that at the minimum PAV and PSV levels no differences existed between the 2 modes. However, as the level of support for each mode increased, asynchrony increased. At the maximum settings, trigger asynchrony was markedly different: the ventilator response rate with PAV was 27.6 ± 10.5/min, versus 13.2 + 3.9/min with PSV (P < .05). The primary reason for the asynchrony was missed triggers. This difference was a result of PSV forcing a larger tidal volume (0.9 + 0.3 L) than PAV (0.51 + 0.16 L), which caused air trapping and prevented normal triggering. Trigger synchrony is generally better in PAV because a large tidal volume is not forced on the patient. The current data on PAV essentially indicate it can sustain the same patients as PSV: those who can breathe spontaneously and manage their ventilatory drive normally. In addition, PAV can better adjust to changing lung mechanics and provide better synchrony than PSV. However, PAV, like all other conventional forms of ventilation, cannot compensate for nor overcome the effects of intrinsic PEEP. The asynchrony observed with intrinsic PEEP during conventional ventilation is still present in PAV. In addition, the PAV on some ventilators (but not on others) can compensate for leaks, so before use the ventilator's operational capabilities must be careful evaluated.

Animal Data

In 3-kg rabbits, Allo et al⁵⁶ found that NAVA could effectively unload respiratory muscles without increasing tidal volume. NAVA, compared to PSV, also decreased diaphragm electrical activity and transdiaphragmatic pressure-time product (P < .05) in lung-injured rabbits,⁵⁷ and reduced the incidence and severity of ventilator-induced lung injury in rabbits.⁵⁸ However, similar to studies with other ventilation modes, the rabbits in the conventional-ventilation arm were ventilated with volume-controlled ventilation and tidal volumes of 15 mL/kg. Tidal volumes during NAVA were about 5.5 mL/kg. In lung-injured rabbits, NAVA can be delivered noninvasively as effectively as in intubated rabbits despite large and varying leaks.⁵⁹

Critically Ill Adults

A number of investigators have studied NAVA in critically ill adults.^60–66 In a series of 15 adult critically ill patients, all with a P_aO2/F_IO2 < 300 mm Hg, Brander et al determined an “adequate” level of NAVA.⁶⁰ Adequate NAVA was identified by the slope change in airway pressure and tidal volume curves as NAVA was increased. The NAVA level that caused a slope decrease of the airway-pressure and tidal-volume curves was considered adequate. This physiologic response was compared to the response at lower (NAVA-low) and higher (NAVA-high) levels. At NAVA-adequate the medium esophageal pressure-time product and diaphragmatic EMG were decreased 47%, compared to NAVA-low. At NAVA-high those variables were reduced by 74%. Ventilatory parameters during the subsequent 3-hour follow-up period were the same on average as during titration: tidal volume 5.9 mL/kg and respiratory rate 29 breaths/min. Gas exchange and hemodynamics remained unchanged.

Colombo et al⁶³ and Spahija et al⁶⁵ compared NAVA to PSV in series of critically ill patients. Colombo matched the setting during NAVA and PSV by adjusting both to produce a tidal volume of 6–8 mL/kg. They compared NAVA and PSV at these settings and at settings 50% higher and 50% lower. At the initial and lowest settings they found no differences in gas exchange, ventilatory pattern, ventilatory assistance, or respiratory drive between the modes. But at the highest settings, tidal volume significantly increased, and ventilator response rate and peak diaphragmatic EMG significantly decreased during PSV, resulting in air trapping and cycling asynchrony. The asynchrony index was greater than 10% in 5 of the 6 patients studied during PSV, and in zero patients during NAVA. They concluded that even at the high settings NAVA avoided over-assisting, compared to PSV, by avoiding air trapping and cycling asynchrony.

Spahija et al⁶⁵ reported similar finding in a series of 12 patients with COPD exacerbation. They evaluated 2 PSV and NAVA levels: for PSV the lowest pressure tolerated and that level plus 7 cm H₂O; for NAVA the settings resulting in the same average peak pressures. At the lowest settings there were no differences, but at the highest setting tidal volumes were greater and ventilator response rates lower with PSV. The asynchrony index at the highest setting was 23 ± 12% of breaths during PSV, but only 7 ± 2% during NAVA (P < .05). Spahija et al cited air trapping as the cause of the cycling asynchrony during PSV.

The effect of PEEP titration during NAVA was recently reported by Passath et al,⁶⁶ in a series of 20 patients, only one of whom had acute respiratory distress syndrome. Passath et al first adjusted NAVA to an adequate level, as previously defined,⁵⁶ then titrated the PEEP up and down and evaluated the effect on respiratory drive. At adequate NAVA levels, increasing the PEEP reduced the ventilatory drive, and monitoring tidal volume divided by diaphragmatic EMG during PEEP changes identified the PEEP level at which tidal breathing occurs at a minimal EMG cost.

Neonatal Application

In neonates, NAVA has shown similar outcomes to those observed in adults.^67–69 After the change to NAVA, tidal volume tends to decrease, respiratory rate to increase, and peak diaphragmatic EMG to decrease. In addition, despite the open ventilating system, triggering and cycling were still primarily neurally activated. Beck et al⁶⁷ reported that in 936-g, 26-week neonates there were no significant differences between triggering and cycling delays during invasive and noninvasive NAVA. Bengtsson et al⁶⁸ found, in a series of 21 mechanically ventilated children, ages 2 days to 15 years, that neural triggering occurred 68% of the time, and neural cycling 88% of the time. NAVA has only been available for about 18th months, so the literature on its effectiveness is limited, compared to PAV, and essentially no outcome data exist for either PAV or NAVA.