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| REVIEW ARTICLE |
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| Year : 2021 | Volume
: 3
| Issue : 1 | Page : 13 |
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Monitoring Respiratory Drive and Effort during Mechanical Ventilation
Irene Telias1, Megan Abbott2, Laurent Brochard3
1 Interdepartmental Division of Critical Care Medicine, University of Toronto; Department of Medicine, Division of Respirology, University Health Network and Sinai Health System; Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada
2 Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada
3 Interdepartmental Division of Critical Care Medicine, University of Toronto; Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada
| Date of Submission | 17-Sep-2021 |
| Date of Acceptance | 12-Oct-2021 |
| Date of Web Publication | 16-Nov-2021 |
Correspondence Address:
Dr. Irene Telias
30 Bond Street, 4th Floor – Donnelly Wing Room 4-079, Toronto, Ontario M5B 1W8
Canada
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2665-9190.330536
During assisted mechanical ventilation, the respiratory system is exposed to the positive pressure from the ventilator and the negative pressure generated by the respiratory muscles. Both excessively high and low respiratory drive and effort can injure the respiratory muscles and lungs resulting in worse patient's outcomes. Monitoring respiratory drive and inspiratory effort are key to prevent harm by adjusting sedation and ventilation to meet safe targets of respiratory drive and inspiratory effort. Based on physiological studies and observational data, it is currently recommended to target an intermediate range of drive and effort in most patients, however, these targets need to be validated prospective and adjusted for different patient populations. The gold standard for measuring inspiratory effort requires the insertion of an esophageal catheter and additional equipment. However, recently, several noninvasive techniques using end-expiratory or end-inspiratory occlusions on the ventilator have been validated to estimate respiratory drive and effort allowing clinicians to monitor drive and effort easily at the bedside. In this narrative review, we discuss potential beneficial and deleterious consequences of breathing effort during assisted ventilation, available monitoring techniques, and propose a structured approach for bedside implementation.
Keywords: Inspiratory effort, mechanical ventilation, monitoring techniques, myotrauma, patient self-inflicted lung injury, respiratory drive, ventilator-induced diaphragm dysfunction
How to cite this article:
Telias I, Abbott M, Brochard L. Monitoring Respiratory Drive and Effort during Mechanical Ventilation. J Transl Crit Care Med 2021;3:13 |
| Why Monitoring Respiratory Drive and Inspiratory Effort Is Important during Mechanical Ventilation? | |  |
During assisted mechanical ventilation, the respiratory system is exposed to the positive pressure from the ventilator and muscular pressure generated by the respiratory muscles. When muscular pressure is either too low (sedation, excessive ventilation) or too high (underassistance, high respiratory drive) these abnormal conditions can injure the respiratory muscles[1] or the lungs[2] by different mechanisms, and negatively impact patient's outcome.[2],[3] On the one hand, a low respiratory drive and effort lead to diaphragmatic disuse atrophy resulting in ventilator-induced diaphragm dysfunction.[4] On the other hand, excessively high respiratory drive and effort can injure the diaphragm referred to as load-induced diaphragm dysfunction[5] and/or result in patient self-inflicted lung injury[6] from increased global and regional lung stress and strain and even negative trans-alveolar pressure.[7] Sustained abnormal high or low drive will prolong the duration of mechanical ventilation due to an imbalance between load and capacity.[8]
Observational studies have shown that an intermediate range of effort during the first three days of mechanical ventilation is associated with the best clinical outcomes and is thus preferable to achieve lung and diaphragm protective ventilation.[4],[9] This gives a strong justification for monitoring these parameters.
The respiratory drive is the neural output from the respiratory centers in the brainstem that determines the magnitude of inspiratory effort, which is the negative pressure generated by the respiratory muscles. Under normal conditions, the chemoreflex control system adapts breathing effort to patients' needs. In mechanically ventilated patients, the respiratory drive is still present and can be modified by independent factors such as cortical stimuli (pain, anxiety), sleep depth, sedation, or lung injury through direct lung receptors stimulation.[8],[10] By definition, if a patient needs to be ventilated, it is because the relationship between drive and effort is 'abnormal' and the ventilator is supposed to “normalize” this relationship but with mixed and variable efficacy which may be relevant to understand.[8]
To avoid potentially injurious consequences of excessively high or low drive and effort because of insufficient or excessive assistance, monitoring its intensity and understanding the mechanisms are key. The respiratory drive is not directly measured, but it can be estimated based on its output.[8],[11] Measures of the respiratory drive (e.g., P0.1) can be used to infer the possible amplitude of inspiratory effort (e.g., esophageal pressure-based-pressure time product).[12] The latter is particularly precise with low drive and effort. However, in case of substantial respiratory muscle dysfunction (frequent in the ICU), there is a dissociation between drive and effort (e.g., patients with high respiratory drive might be dyspneic but generate only modest inspiratory effort). Therefore, in this context, the relationship between drive and effort is more difficult to predict for the high respiratory drive.[12] Different techniques have been validated for estimating both respiratory drive and effort, each one having specific technical and functional characteristics that we will discuss here [Figure 1], [Figure 2], [Figure 3], [Figure 4],[Figure 5] and [Table 1] and [Table 2]. | Figure 1: Simplified anatomical pathway leading to the generation of inspiratory effort and available monitoring techniques to assess respiratory drive and effort. Respiratory drive arises from the respiratory centers in the brain stem (A) stimulating the respiratory muscles. The neural stimulus through the phrenic nerve (B) generates the depolarization of the diaphragm (C) and consequent mechanical activation (D) that, together with the mechanical activation of the accessory muscles (E) results in changes in airway pressure and flow at the airways (F). Each monitoring technique focuses on one portion of this pathway
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 | Figure 2: Esophageal and gastric pressures: Quantification of the muscular pressure generated by the coordinated action of all respiratory muscles. (a) Tracings of esophageal (Peso), gastric (Pga) and transdiaphragmatic (Pdi) pressures (Pdi = Pga − Peso) are displayed with 2 active inspiratory efforts on the left and one passive breath on the right. Parameters calculated to quantify inspiratory effort based on these recordings are shown: Tidal change in Peso (deltaPeso), tidal change in transdiaphragmatic pressure (deltaPdi), pressure-time product of the respiratory muscles (PTPes) and the diaphragm (PTPdia). (b) The schema shows the nasogastric catheter with an air-filled balloon (in blue) located in the lower third of the esophagus
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 | Figure 3: Electrical activity of the diaphragm: The closest signal to the respiratory center. On the left, the schema shows the nasogastric catheter with an array of electrodes positioned close to the crural diaphragm. On the right, respiratory tracings of airway pressure (Paw), flow, tidal volume and electrical activity of the diaphragm are seen as displayed on the ventilator screen
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 | Figure 4: Noninvasive techniques based on occlusions using the ventilator. On the left (a) Measurement of airway occlusion pressure (P0.1) and negative deflection in airway pressure during a whole breath occlusion (Pocc) are shown on flow, airway pressure (Paw), and esophageal pressure (Peso) tracings. On the right (b) Changes in Paw, Flow and Peso over time during an end-inspiratory occlusion together with the calculation of pressure muscle index (PMI) as the difference between plateau pressure (Pplat) and peak pressure (Ppeak). Of note, because of the substantial contribution of muscular pressure to lung inflation in the example shown, Pplat is higher than Ppeak when respiratory muscles are relaxed at the end of inspiration (horizontal line in Paw and Peso)
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 | Figure 5: Diaphragm ultrasound and measurement of diaphragm thickening fraction. On the left, a high frequency probe is positioned between the 9th and 10th intercostal space at the level of the mid-axillary line. On the right, M-mode is applied to calculate diaphragm thickening fraction (Tfdi) in two consecutive breaths (A-B and C-D). The diaphragm is seen as an hypoechogenic structure surrounded by two hyperechogenic layers. Tfdi is calculated using the formula: Tfdi = (Thickness at end-inspiration [B and D for breath 1 and 2] − Thickness at end-expiration [A and C for breath 1 and 2])/Thickness at end-expiration (A and C for breath 1 and 2)
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 | Table 1: Parameters to measure and estimate respiratory drive and inspiratory effort
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 | Table 2: Applications and potential benefits of monitoring respiratory drive and inspiratory effort during mechanical ventilation
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| Esophageal and Transdiaphragmatic Pressure and Electrical Activity of the Diaphragm | | |
The coordinated activation of all inspiratory muscles changes the shape of the ribcage decreasing intrathoracic pressure, more specifically, pleural pressure.[13] Esophageal pressure (Peso) is a precise estimate of the changes in pleural pressure and is considered the gold standard to measure respiratory effort [Figure 2]. It requires the insertion of a naso-or oro-gastric catheter with an air-filled balloon positioned at the lower third of the esophagus connected to a pressure transducer (on the ventilator, specialized device, or multiparametric monitor). A gastric balloon can also record abdominal pressure and allows to measure the transdiaphragmatic (esophageal minus gastric -Pga-) pressure (Pdi). Inspiratory and expiratory effort can be calculated based on Peso and Pga [Figure 1]d.[14] Inspiratory effort generates a negative deflection in Peso; the magnitude of this negative deflection (deltaPeso) is the simplest estimate of the strength of effort. It can easily be measured with any acquisition device. An accurate measure of inspiratory effort (muscular pressure-Pmus) requires measurement or estimation of chest wall compliance (resting position of Peso with lung volume). Inspiratory effort over the duration of inspiration is measured by the pressure-time product (PTPes) which is the integral of Pmus during inspiration. PTPes correlates with the energy expenditure of the respiratory muscles. A software is needed for the online calculation. Moreover, Peso also allows to measure the lung distending pressures and risk of patient self-inflicted lung injury by calculating the driving transpulmonary pressure (deltaPL). Gastric pressure also allows to assess of expiratory abdominal muscle activity.
Electrical activation of the diaphragm can be measured by the insertion a naso-or oro-gastric catheter with an array of electrodes positioned in the esophagus at the level of the crural diaphragm [Figure 3]. The catheter is connected to a ventilator with software for signal processing and online display of the electrical activity of the diaphragm (Eadi). The main parameter used for estimation of respiratory drive and effort based on Eadi is the maximum Eadi during tidal breathing (Eadipeak). Absolute values of Eadipeak vary greatly between subjects[15] (both healthy controls and ICU patients). Normalizing tidal Eadipeak to the changes in airway pressure during an end-expiratory occlusion (neuromechanical efficiency index), can provide a reasonable estimate of muscular pressure during tidal breathing using Eadi.[16] In any case, changes in the absolute Eadipeak value for one individual patient are indicative of changes in respiratory drive and inspiratory effort.
The Eadi and Peso signal also allow to see neural timing of inspiration and expiration and adjust ventilator settings to ensure synchrony.
| Noninvasive Occlusion Techniques | | |
Modern ventilators allow to perform an end-expiratory occlusion during assisted ventilation. When patients breathe against an occluded airway, any change in airway pressure (Paw) follows changes in pleural pressure (ie Peso) in magnitude and timing. This phenomenon permits to measure changes in intrathoracic pressure resulting from the activation of respiratory muscles, without Peso [Figure 4]. In addition, given that there are no changes in volume or flow during the occlusion, respiratory mechanics do not influence the measurements.
The initial drop in Paw during a very short occlusion end-expiratory occlusion is representative of patients' respiratory drive and independent from the patients' reaction to the occlusion. Airway occlusion pressure or P0.1 is the drop in airway pressure during the first 100 msec of the occluded breath.[17] It is a well-validated measure of respiratory drive and directly measured by most modern ventilators either by activating a specific maneuver or estimated based on the drop in Paw during the trigger breath-by-breath. Values displayed on the ventilators' screen have been validated as a measure of respiratory drive and reasonable estimates of changes in the inspiratory effort as discussed above.[12] In addition, extreme values of P0.1 have a great diagnostic performance to detect the potentially injurious magnitude of effort (1.1 cmH2O and 3.5–4 cmH2O for low and high effort, respectively).
The negative deflection in Paw during the whole breath end-expiratory occlusion (Pocc) is a valid estimate of the inspiratory effort during assisted ventilation. A caveat is that the magnitude of Pocc, despite being equal to the negative deflection in pleural pressure during the occlusion is higher than that during un-occluded breaths.[18] For this reason, a correction factor needs to be considered when estimating muscular pressure based on Pocc (Pmus estimated = ¾ × Pocc). Driving transpulmonary pressure can also be estimated based on Pocc by doing a simple calculation (deltaPL estimated = [Ppeak − PEEP] − [2/3 × Pocc]). Values of estimated Pmus and deltaPL higher than 15 cmH2O have been recently validated as reliable estimates of excessive inspiratory effort and dynamic driving transpulmonary pressure.[19] Both calculations can be performed using an online calculator (rtmaven. com).
Performing an end-inspiratory occlusion during assisted ventilation can also be used to estimate static driving pressure and inspiratory effort. However, plateau pressure (Pplat) during assisted ventilation is a reliable estimate of the recoil pressure of the respiratory system only if inspiratory and expiratory muscles are relaxed during the maneuver. When inspiratory or expiratory muscles are active during the occlusion, a negative deviation or continuous increase in the observed airway pressure are often seen.[20] Therefore, it is recommended to carefully assess the shape of the observed Pplat. In contrast to what it is often seen during passive mechanical ventilation, during assisted ventilation, Pplat often exceeds peak pressure (Ppeak). The difference between Pplat and Ppeak is the pressure muscle index, another validated measure of effort.[21]
| Diaphragmatic Ultrasound | | |
Finally, diaphragmatic ultrasound can also be used to measure inspiratory effort [Figure 5]. It requires some training, but it is reproducible between operators.[22] The diaphragm can be visualized by placing a high-frequency probe between the 9th and 10th intercostal space, mid-axillary line. It is seen as a hypo-echogenic structure surrounded by two hyper-echogenic membranes. Tidal thickening fraction (Tfdi) can be calculated using the M-mode as the ratio between the difference in diaphragmatic thickness at end-inspiration (Tdi, ei) and end-expiration (Tdi, ee) and the Tdi, ee. In a large observational study, values of Tfdi obtained daily during the first 3 days of mechanical ventilation similar to those of healthy controls breathing at rest (15%–30%) have been shown to be associated with better outcomes compared to lower and higher Tfdi.[3]
| Future Directions in Monitoring Respiratory Drive and Inspiratory Effort | | |
Not only the strength of respiratory drive and of inspiratory effort are relevant, but also the relationship between the timing of patient's inspiratory effort and the positive pressure provided by the ventilator (i.e., patient-ventilator interactions). The occurrence of frequent patient-ventilator dyssysnchrony has been associated with adverse clinical outcomes[23] and automated techniques for continuous 24-h detection of asynchronies have been developed.[24],[25] However, physiological studies suggest that the presence of patient-ventilator dyssynchrony might have either a beneficial (e.g., preventing disuse) or harmful effect (e.g., injuring the diaphragm or creating pendelluft) for the patient, depending both on the magnitude of inspiratory effort generated during the dyssynchrony and on the specific timing (e.g., eccentric contraction). These two aspects need to be identified and current automated algorithms to quantify synchronous and dyssynchronous efforts are under development (BEARDS study clinicaltrials.gov #NCT03447288).
| How Do We Implement Available Monitoring Tools at the Bedside? | | |
Each monitoring technique has its own strengths and weaknesses. The use of esophageal pressure, despite being the gold standard for measurements of inspiratory effort, is somehow invasive and, despite being well described, requires training for insertion and interpretation together with some additional time and equipment. Importantly, esophageal pressure provides an accurate measurement of inspiratory effort, and also the calculation of driving transpulmonary pressure during assisted ventilation (the true lung distending pressure, and therefore, main risk factor for patient self-inflicted lung injury). However, parameters derived from esophageal pressure measurements can also be poor estimates of respiratory drive in the context of respiratory muscle weakness.
Another invasive technique, the electrical activity of the diaphragm, also requires some training for insertion and interpretation, however, it is of simpler implementation because it is available on one ventilator brand. The main drawback is that absolute values of EAdi are very variable between patients and normalizing EAdi values requires the performance and interpretation of additional maneuvers. An important advantage of using EAdi is that when the catheter is inserted, NAVA mode, a proportional mode of ventilation, can be used. Both EAdi and Peso allow for continuous estimation of respiratory drive, bedside evaluation of patient-ventilator dyssynchronies and can be used for adjustment of ventilator settings and sedation.
The use of diaphragm ultrasound is noninvasive, but is not continuous, requires special equipment and training, and continuous assessment of patient-ventilator dyssynchrony using ultrasound is not feasible in clinical practice.
Overall, noninvasive techniques based on end-expiratory and end-inspiratory occlusions (Pocc, P0.1 and plateau pressure during assisted ventilation), are well-validated techniques for accurate estimation of respiratory drive and inspiratory effort. Despite not always being continuous (although it is sometimes possible for P0.1), they can very easily be performed at frequent intervals; no extra equipment or training is required. Importantly, they do not provide information regarding patient-ventilator synchrony, and therefore, it is recommended to complement these with careful examination of available airway pressure and flow tracings for the diagnosis of patient-ventilator dyssynchrony.
Based on physiological and epidemiological evidence, monitoring respiratory drive and inspiratory effort might be useful to prevent potentially injurious ventilation from intubation to liberation as described in [Table 2]. At early stages, in patients with significant lung injury, it can help avoiding excessive sedation. Allowing for some inspiratory effort very early during mechanical ventilation, especially if lung injury is not too severe, might be beneficial in targeting an intermediate range of effort.[3] Specific targets for the different parameters have been suggested in a recent review,[9] however, these need validation and might vary in different patient populations. In addition, what is the right timing to control drive and effort remains to be elucidated.
In any case, integration of simple, noninvasive techniques to detect potentially injurious drive and effort such as P0.1 and Pocc into clinical practice is highly recommended in combination with careful examination of airway pressure and flow signals.
Financial support and sponsorship
Dr. Irene Telias reports a salary support grant from the Canadian Institutes for Health Research in the form of a Post-Doctoral Fellowship Award.
Conflicts of interest
Dr. Irene Telias reports personal fees from Medtronic, Getinge and MbMED SA, Argentina outside of the submitted work. Dr. Laurent Brochard reports research grants from Covidien Medtronic, equipment support from Philips, equipment support from Sentec, equipment support from Air Liquide, grants and equipment support from Fisher Paykel, grants from General Electric, outside the submitted work.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]
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