Is One Fixed Level of Assist Sufficient to Mechanically Ventilate Spontaneously Breathing Patients?

Ventilate Spontaneously Breathing Patients?

C. Sinderby, L. Brander, and J. Beck

Synchronous versus Asynchronous Assist

Mechanical ventilation delivers pressure, flow, and/or volume to the patient with the aim of improving ventilation and reducing inspiratory work. Depending on various circumstances, such as the level of sedation, paralysis, or if the ventilator support is patient triggered or not, the goals of mechanical ventilation (improved ventilation and reduced work of breathing) may be achieved in different ways.

In its simplest form, the mechanical ventilator delivers assist according to a preset level of assist, ventilator frequency, and duty cycle (controlled mode). If the patient is not breathing (i.e., no neural inspiratory effort) the ventilator must assume all the work of breathing to overcome inspiratory loads, and the tidal volume and the fre- quency of breath delivery is adjusted to maintain adequate blood gases. When no neural inspiratory effort is present, unloading is achieved by sedation and manda- tory ventilation keeping CO

levels lower than what is necessary to breathe sponta- neously. Figure 1 (left panel) illustrates a patient ventilated in the volume control mode who is not triggering any inspirations or showing any electrical activity of the diaphragm (EAdi), i.e., the patient is not performing neural inspiratory efforts. The right panel of Figure 1 shows the same patient on volume control 40 minutes later, and at this time the diaphragm is very active and the patient tries to inspire, how- ever, since the volume delivered to the patient is fixed, and not adaptable, all the patient’s inspiratory efforts are performed in vain.

It is reasonable to assume that patients who are not paralyzed, although sedated, are likely to have changes in respiratory drive and that modes that deliver fixed fre- quencies and volumes are not ideal in this situation. Modes of mechanical ventila- tion where inspiratory efforts trigger and cycle the ventilator have, therefore, been introduced to better meet patient requirements by attempting to deliver assist in synchrony to patient effort. Patient-ventilator interaction has two dimensions: The first dimension relates to ventilator timing in relation to a patient’s neural timing and the second relates to how the magnitude of the assist level adapts with neural inspiratory effort [1].

Timing of Assist Delivery

When mechanical ventilation is applied in a patient who is breathing, the ventilator

assist could either be delivered at the same time as the patient’s inspiratory effort (so

called patient-ventilator synchrony) or the assist could be delivered asynchronously

with the patient’s inspiratory effort (i.e., not delivered at the same time as the

Fig. 1. From top to bottom: Diaphragm electrical activity (EAdi), flow, volume and airway pressure (Paw) in a patient with respiratory failure ventilated on volume control. The left and right panels illustrate mea- surements in the same patient 40 minutes apart. As indicated in the left panel, the diaphragm is neurally apneic. Forty minutes later the diaphragm is very active, indicating increased inspiratory efforts; however the ventilator mode does not allow the patient to change his tidal volume regardless of whether he makes inspiratory efforts or not.

patient is inspiring). Examples of mild forms of asynchrony in terms of timing include late triggering of assist as well as early or delayed off-cycling of the assist.

Severe forms of asynchrony can involve inspiratory efforts that do not trigger the ventilator at all, so called wasted inspiratory efforts [2] or the inability to cycle-off the assist, so called hang-ups [3].

Magnitude of Assist

The second dimension of patient-ventilator interaction relates to the adjustment of the assist level in relation to the magnitude of the patient’s neural inspiratory effort.

Today, mechanical ventilation is typically associated with delivery of one fixed level of assist (i.e., targeted pressure or volume) to the patient, where the frequency of adjustment is arbitrarily determined and the level of assist is adjusted according to changes in the patient’s clinical status.

Regardless of whether the patient is breathing or not, there are a number of fac-

tors that may vary with time and which can influence the need for an adjustment in

the assist. For example, respiratory mechanics, i.e., elastance and resistance of the

respiratory system, can alter. Insufficient exhalation time in relation to the expira-

tory time constant of the respiratory system may induce dynamic hyperinflation so called intrinsic positive end-expiratory pressure (iPEEP), a threshold load that must be overcome to initiate the inspiration. Altered metabolism, e.g., fever, may increase CO

production and, thus, the need for increased ventilation.

If a patient is breathing spontaneously, and if the mechanisms controlling the respiratory drive are functional, he/she can compensate for the above changes in respiratory status. If the settings of the ventilator are inadequate to meet the altered respiratory demand, the patient will need to compensate when changes in respira- tory status occur, something that a patient with respiratory failure may not be pre- pared for if the demand is high (e.g., respiratory muscles are weak and inspiratory load is high). Recent studies indicate that patients with high inspiratory load [4] as well as patients who fail weaning [5] have marked reductions in the variability of their breathing pattern, whereas patients who wean successfully demonstrate more variable breathing patterns [5].

In order to avoid respiratory failure, it is, therefore, likely that the assist level has to be set to a level where the patient can sustain ventilation when demand is at its highest. Consequently, this level of assist may be too high during periods when the patient’s respiratory demand for assist is lower.

How do Synchrony and Asynchrony Affect Unloading of the Respiratory Muscles?

One example of severe asynchrony in terms of both timing and magnitude is when a fixed level of ventilatory assist is delivered during the neural exhalation period.

This means that the ventilator would provide a more or less fixed tidal volume dur- ing the period when the patient is not making an inspiratory effort. Thus, the venti- lator cannot aid the patient’s inspiratory effort in terms of sharing the work of inspi- ration and, with most modes currently used, the patient’s inspiratory efforts would be performed against closed inspiratory valves. Despite such wasted inspiratory efforts, the ventilator will deliver tidal volume at a breathing frequency that could be sufficient or even excessive with regards to satisfying the patient’s ventilatory requirements. If the asynchronous ventilation provokes the patient to recruit expira- tory muscles to interrupt the assist delivered by the ventilator, which is not uncom- mon [6], work of breathing may actually increase [7], it becomes difficult to ensure that appropriate assist is delivered, and sedation may be required.

If the ventilator’s assist period coincides with the inspiratory effort of the patient, this will act to unload the patient’s inspiratory muscles since the ventilator will assume a part of the work to reduce the respiratory system load. The combination of the patient’s inspiratory effort, which increases the distending pressure around the lungs (pleural pressure, Ppl), and the pressure delivered by the ventilator, which increases the airway pressure (Paw), will increase the transpulmonary pressure (Ptrans = Paw-Ppl), and hence increase the tidal volume.

If the ventilator’s assist is delivered at the same time as the patient is inspiring,

i.e., the ventilator’s trigger and cycling off is synchronized to neural inspiratory

effort, the ventilator and the patient will share the work of breathing to overcome

inspiratory loads. However, truly synchronized assist occurs when the sharing of

load between the ventilator and patient adapts in relation to patient effort, i.e., both

the timing and magnitude of the assist delivered by the ventilator are synchronized

to the patient’s inspiratory effort.

Typical features of asynchronous assist could thus be identified as maintenance of ventilation without aiding the patient’s inspiratory efforts while maintaining patient comfort through sedation. In other words, asynchronous ventilation of a patient involves suppression of respiratory drive through ventilation and sedation. On the other hand, synchronous assist delivery will aid the patient to overcome inspiratory loads, i.e., the ventilator is ‘pushing’ when the patient is ‘pulling’. If optimal patient- ventilator synchrony is present, the ventilator should provide assist and share the patient’s inspiratory effort, i.e., the ventilator should act as an inspiratory muscle prosthesis which can deliver support in proportion to inspiratory demand, allowing the patient to control both timing and depth of inspiration.

Sedation is another factor that helps unload respiratory muscles (by inhibiting respiratory drive) but also affects control of breathing. Breathing is controlled by multiple feedback loops including neural networks and chemical reflexes as well as by direct voluntary control. The central chemoreflex (i.e., the ventilatory response to carbon dioxide mediated by the central chemoreceptors), and the peripheral chemo- reflex (i.e., the ventilatory response to carbon dioxide and hypoxia mediated by the peripheral chemoreceptors) are the key components of models describing the con- trol of breathing [8]. Sedation not only suppresses voluntary control of breathing but may also alter the sensitivity of chemoreceptors for their specific stimuli (e.g., hypercapnia or hypoxia).

Ideally, a comfortable level of analgesia and sedation should be achieved that allows the patient to control respiratory drive while the ventilator unloads the respi- ratory muscles by overcoming elastance and resistance of the respiratory system.

However, in clinical practice, a variety of reasons necessitate that the level of seda- tion is increased, including difficulties to achieve synchrony between the patient and the ventilator, especially when the respiratory drive is high [9]. Most of the com- monly used sedative drugs and opioids depress the response of the respiratory cen- ters to breathing stimuli in a dose-dependent manner, although differences between substance groups may exist [10 – 12].

Increasing the level of sedation reduces the load on the respiratory muscles and reduces the production of CO

, but also deprives the patient of the control over the respiratory drive. For example, Grasso and colleagues [13] increased the sedation level stepwise to achieve a Richmond agitation-sedation scale (RASS) of -1 (drowsi- ness), to -2 (light sedation), and to -3 (moderate sedation). These investigators found that an increase in the sedation level resulted in a monotonous breathing pat- tern (i.e., a progressive loss in variability of tidal volume, respiratory rate, and inspi- ratory time) [13].

According to the above discussion, factors that influence unloading can be sum- marized to:

a) unloading by delivering a fixed level of assist asynchronous to the patient’s demand, which is in essence maintaining ventilation but not assisting patient efforts. Unloading thus takes place by only ventilating the patient, reducing CO

levels, and reducing the central respiratory drive

b) increasing sedation, which reduces the respiratory drive and the sensitivity to respiratory stimuli and hence reduces the load on respiratory muscles, but also deprives the patient of the control over the respiratory drive

c) Unloading by delivering assist in synchrony and in proportion to the patient’s

demand overcoming inspiratory loads while allowing the patient to maintain

control over his/her breathing pattern.

Fig. 2. Different ways of unloading respiratory muscles in breathing patients are indicated by the three circles. Unsynchronized mechanical ventilation suggests that the patient is being ventilated, which satisfies the ventilatory demand without assisting during the patients inspira- tory efforts. Agitation often increases respiratory muscle efforts whereas sedation can reduce the respiratory drive (i.e. decreases respiratory mus- cle effort) and thus unloads respira- tory muscles. Combination of asyn- chronous mechanical ventilation and sedation likely acts to unload the respiratory muscles through suppres- sion of respiratory drive not necessar- ily assisting to overcome inspiratory loads during the patient’s inspiratory effort; moreover, it may hinder the patient in maintaining control of ven- tilaton. Synchronized mechanical assist + ventilation suggests that assist is delivered to overcome inspiratory loads, aiding inspiratory muscles dur- ing inspiration while allowing ventila- tion to be controlled by the patient.

Today’s clinical practice of mechanical ventilation in spontaneously breathing patients likely involves a combination of all these factors as indicated by Figure 2.

Introducing changes in respiratory demand would certainly add complexity to this model increasing the likelihood that patients will alter between the different types of unloading described in Figure 2.

Patient-ventilator Interaction and Adaptation to Changes in Respiratory Demand with Frequently used Modes of Ventilation

In order to adapt the assist to changes in respiratory demand, modes of mechanical

ventilation must adapt to both changes in respiratory timing and magnitude of

inspiratory effort. Few studies comment on how current modes perform with

respect to timing of assist in relation to patient effort. For example, synchronized

intermittent mandatory ventilation (SIMV) is actually poorly synchronized to a

patient’s neural inspiratory effort [14]. Increasing pressure support causes off-

cycling to be prolonged into the neural exhalation period [2, 15]. Asynchronous off-

cycling interferes with breathing pattern [14 – 16]. Furthermore, it appears that

delayed off-cycling also has a negative impact on pneumatic triggering of ventilatory

assist [6]. In fact, the Cochrane review on synchronized mechanical ventilation in

neonates remarked on limited evidence that modes that are considered to deliver

assist synchronously to patient effort actually are doing what they are intended to do

[17].

A recent modification of mechanical ventilation to overcome wasted inspiratory efforts during asynchronous ventilation is by using two levels of continuous pressure, allowing the patient to breathe freely regardless of the pressure level. Though this eliminates the negative impact of occluded inspiratory/expiratory efforts, the assist delivery could still be asynchronous in terms of timing and is asynchronous in terms of magnitude of assist for the same reasons as during pressure support. Moreover, the assist is not adjusted in response to changes in patient inspiratory effort.

Today, there are few modes that deliver patient-triggered assist that adapts the level of assist in relation to the patient’s inspiratory effort. The first mode to be introduced was proportional assist ventilation (PAV) [1]. During PAV, the ventilator delivers positive pressure throughout inspiration in proportion to the air flow and volume generated by the patient where the magnitude of unloading is based upon measurements of elastance and resistance [1]. Unlike other modes assisting sponta- neous breathing, air flow, tidal volume, and airway pressure are not preset. PAV has been shown to be effective in unloading the respiratory muscles [18].

Neurally adjusted ventilatory assist (NAVA) [19] is directly driven by the neural output to the diaphragm. During NAVA, positive pressure is instantaneously applied

Fig. 3. From top to bottom: Diaphragm electrical activity (EAdi), flow, volume, and airway pressure (Paw)

in a patient with respiratory failure on pressure support ventilation (PSV, left panel) and neurally adjusted

ventilatory assist (NAVA, right panel). All delivered breaths were triggered during PSV period and, as indi-

cated by the arrows, there were also indications of wasted inspiratory efforts in the flow and pressure trac-

ings. The EAdi, however, indicated that the diaphragm was not active at all during PSV. After switching the

patient to NAVA, diaphragm activity was restored (right panel), suggesting that the patient ventilator asyn-

chrony was because of overassist during PSV and that waveform analysis of flow and pressure without EAdi

may be misleading.

to the airway opening in proportion to the measured amplitude of the EAdi. The EAdi constitutes the temporo-spatial summation of the phrenic nerve activity from the brain’s respiratory centers to the diaphragm motor units [20] and is influenced by both facilitatory and inhibitory feedback loops controlling respiratory drive. EAdi provides a reliable estimate of inspiratory timing [21] and drive [20, 22]. Hence, during NAVA, the ventilator support is synchronous with and proportional to the respiratory drive and, therefore, acts as an external ‘respiratory muscle pump’ controlled by mechano- and chemo-receptors as well as by voluntary and behavioral inputs [23, 24].

To emphasize the importance of a patient driven assist, the left panels of Figure 3 shows EAdi and airway pressure, flow, and volume during pressure support venti- lation (PSV). The patient is receiving inspiratory assist at a frequency of 24 breaths per minute and each breath is triggered by the patient. The flow tracing in the left panel of Figure 3 also indicates that the patient suffers from wasted inspiratory efforts (indicated by arrows). However, the EAdi tracing does not reveal that the dia- phragm is active, i.e., with regards to EAdi the patient is not using his diaphragm to breathe. In the right panel of Figure 3, the patient has been switched to NAVA, i.e., no assist is delivered unless the diaphragm is electrically active. With NAVA the patient is making noticeable inspiratory effort as indicated by the EAdi, confirming the possibility that the patient was over-assisted during PSV.

Fig. 4. Diaphragm electrical activity (EAdi) and airway pressure (Paw) in a patient with respiratory failure

on triggered pressure control ventilation (PCV, top panel) and neurally adjusted ventilatory assist (NAVA,

lower panel). Despite a strong EAdi signal, the delivered ventilator breaths are poorly synchronized to the

EAdi as indicated by the shaded areas in the upper panels. Moreover, arrows indicate a high frequency of

wasted inspiratory efforts. When switching to NAVA (lower panels), all EAdi efforts are synchronized with

the ventilatory assist.

In this case it appeared that the flow trigger was so sensitive that the patient was able to trigger the ventilator with other muscles than the diaphragm and then received a full breath without using the diaphragm. In contrast to PSV, NAVA would not deliver assist if the patient is not making inspiratory efforts with the diaphragm. Since the diaphragm normally is recruited in every breath in healthy subjects, one would assume that a patient with respiratory failure should recruit the diaphragm to breathe.

Absence of EAdi during PSV hence suggests that the patient was either over-assisted or too sedated and that NAVA restored the normal activation of the diaphragm.

From one extreme to another, Figure 4 (upper panel) shows poor patient ventila- tor synchrony with numerous wasted inspiratory efforts during pressure control ventilation despite significant levels of diaphragm activity in every breath. When switching to NAVA, the ventilatory assist becomes synchronized to the patient’s demand and every inspiratory effort of the patient is shared by the ventilator’s pres- sure delivery.

Finally, as an example about adaptation of assist level over time, Figure 5 top panel illustrates how highly variable neural inspiratory efforts over time are not met by alteration in assist during pressure support whereas during NAVA (lower panel) each inspiratory effort is shared by the ventilator both in time and magnitude.

Fig. 5. Diaphragm electrical activity (EAdi) and airway pressure (Paw) in a patient with respiratory failure

on pressure support ventilation (PSV, top panel) and NAVA (lower panel). During PSV assist is constant at

one level despite large variability in the EAdi. During NAVA, the pressure delivery is in proportion to EAdi

such that low pressure is delivered during low neural inspiratory efforts (low EAdi) and high pressures are

delivered during high inspiratory efforts (high EAdi). In other terms, PSV delivers monotonous assist

regardless of patient needs, whereas during NAVA the mechanical ventilator is sharing the work with the

patient.

Conclusion

One fixed level of assist may be insufficient to satisfy a patient’s ventilatory demand and there is a need for ventilator modes that deliver assist in time and in proportion to patient inspiratory effort. However, modes of mechanical ventilation used today are poorly evaluated with respect to timing of assist and the majority do not adapt to changes in patient respiratory demand. Moreover, there is a lack of monitoring devices to evaluate respiratory drive and determine if the assist is delivered in syn- chrony with patient effort.

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