Authors
- Patthum, Arisara
- Peters, Micah
- Lockwood, Craig
Abstract
Review question/objective: The objective of this systematic review is to systemically identify, appraise and synthesize the best available evidence regarding the safety and effectiveness of invasive mechanical ventilation (IMV), in optimizing patient-ventilator interaction by using the Neurally Adjusted Ventilatory Assist (NAVA) compared with conventional IMV modalities in critically ill pediatric and adult patients in intensive care units (ICUs).
Does NAVA have a better capability in reducing patient-ventilator asynchrony compared to the conventional IMV among critically ill pediatric and adult patients on ventilator support in an intensive care environment?
Is NAVA safer than the conventional IMV to be used in critically ill pediatric and adult patients in an intensive care environment?
Background: Invasive mechanical ventilation is a common intervention in ICUs. It is used to sustain respiratory function in acute respiratory failure when a patient's ventilatory capabilities are unable to adequately meet the metabolic demands of the body.1-3 The goals of mechanical ventilation are to reduce excessive respiratory effort, ensure adequate oxygenation,4 avoid ventilator induced lung injury, and optimize patient-ventilator synchrony.5,6,7 Patient-ventilator asynchrony (PVA) occurs frequently in ICUs. Numerous investigators have reported a number of asynchrony incidences. It ranges from 10-88% of breathing observations during assisted mechanical ventilation.8,9,10-15 Patient-ventilator asynchrony may occur as a result of inadequate or excessive sedation16 and suboptimal ventilator settings,17-21 and it is associated with adverse clinical consequences including hypoxia, cardiovascular compromise, anxiety and fear,22 patient discomfort,9,18,23-25 sleep fragmentation,26,27 prolonged mechanical ventilation,9 and possible diaphragmatic injury.28-30 It is also associated with a longer duration of mechanical ventilation, longer ICU stay, and increased morbidity11 and mortality.7 Therefore, identifying the best modality of IMV to optimize patient-ventilator interaction is a necessary empirical goal in minimizing adverse outcomes and providing optimal care to ventilated critically ill patients.
Internationally, epidemiology of IMV in adult ICUs from an analysis of the Simplified Acute Physiological Score III (SAPS III) Project database demonstrates that 53% of intensive care patients are mechanically ventilated.31 In addition, IMV is required in 17%-64% of children in pediatric intensive care units (PICUs).32-34 The rates of IMV have increased more than 10% over a seven-year period,35 contributing to a substantial increase (approximately 44%) in the annual critical care cost and accounting for 13% of total hospital costs.36 Additionally, intensive care costs for mechanically ventilated patients is more than US$2000 per day.37
Mechanical ventilation can be used to support a patient's ventilatory system by delivering breaths, which can be either controlled or assisted.4,38,39 It can be set to control airway pressure, flow, volume and respiratory timing or a combination of them and to synchronize with the patient's neural breathing efforts (neural trigger) and inspiratory effort.4,40 In synchronizing with the patient's inspiratory effort It works also either by the reversal of the expiratory flow (flow sensor) or by a drop in the pressure (pressure sensor). These mechanisms are known as a pneumatic trigger.41
Patient-ventilator asynchrony can be defined as a mismatch between the patient and ventilator inspiratory and expiratory times.30,42,43 It is also referred to as the difficulty of harmonizing the respiratory cycle generated by the complex respiratory control system with the mechanical cycle of the ventilator,44 and the uncoupling of the mechanical delivered breath (ventilator) and the neural respiratory effort (patient). Patient-ventilator asynchrony can be detected by measurement of electrical activity of respiratory muscles (diaphragm or transverse abdominus) or esophageal pressure43,45 or ventilator graphic waveforms.9,19 Patient-ventilator asynchrony is associated with the conventional assist modes, which are influenced by multi-factors related to both ventilator and patient.46,22,47 Patient-related factors of asynchrony include respiratory mechanics, minute ventilation, respiratory muscle capacity, and respiratory drive. Ventilator factors include the method of respiratory triggering, i.e. pneumatic trigger and neural trigger. Furthermore, the interface of the ventilator circuitry and humidification system can contribute to PVA.18,48
Triggering asynchrony is found to be only one type of problem associated with suboptimal patient-ventilator interaction.19 Asynchrony events are more frequent with pneumatic triggered compared to neural triggered IMV.49,50,51-53 Several clinical studies and a meta-analysis comparing conventional controlled modes to patient triggered ventilation modes in neonates demonstrate a shorter duration of ventilation in the latter modes.54-58 Unsuccessful weaning in prolonged weaning patients is associated with a high incidence of ineffective triggering.10 Muscle fiber injury and diaphragm injury and atrophy are caused by excessive assistance and prolonged support from mechanical ventilation.59-61 Conventional ventilation can induce loss of inspiratory muscle force, as much as 75%.62,63 An asynchrony index at least 10% contributes to a longer duration of mechanical ventilation as well as a higher rate of tracheostomy in medical patients.9 However, it is not associated with prolonged IMV in trauma patients.13 Ventilator asynchronized patients tend to receive excessive levels of ventilator support,9 and sedation.11 Additionally, adjusting the pressure support level64 and the sedation level can alter PVA.12 Furthermore, there has been a report that 42% of all increases of sedation account for PVA.65 Conversely, greater sedation is associated with increased risk of ineffective effort.12 Therefore, reduced duration of mechanical ventilation, promoted spontaneous breathing,66-71 and reduced sedation are factors that contribute to positive outcomes in mechanical ventilated patients72-77 that may be caused by optimizing patient-ventilator interaction.
An ideal approach in optimizing patient-ventilator interaction would be to connect the patient respiratory centers to the ventilator, as similarly and naturally as the brain stem is connected to the respiratory muscles via the phrenic nerves.4 The technique of transforming neural drive into ventilatory support output is by measuring of the neural excitation of the diaphragm, which is a diaphragmatic electrical activity (EAdi). The diaphragmatic electrical activity signal is then used to control NAVA. The diaphragmatic electrical activity is generated by the neural respiratory output signal from the brain stem, and is modulated by input from multiple respiratory reflexes feedback to the respiratory centers.40
Recently, advances in computer technology have made it possible to obtain reliably diaphragmatic electrical activity, free of artifacts and noise and in real time.78-80 A new modality of neurally trigger ventilator was introduced to a clinical practice to improve patient-ventilator synchrony.39 A neurally trigger mechanical ventilation is called Neurally Adjusted Ventilatory Assist(NAVA),40 the latest development of mechanical ventilation that became available to clinicians in a clinical setting. Neurally Adjusted Ventilatory Assist may be considered to be an assist mode where the level of ventilatory assist is proportional to diaphragm muscle electrical activity. The timing and intensity of the EAdi signal both determine the timing and intensity of the ventilatory assist, resulting in a high level of synchrony.41 The diaphragmatic electrical activity signal reliably monitors and controls the ventilatory assist.81
Neurally Adjusted Ventilatory Assist uses EAdi to trigger and cycle off the ventilatory assist and to control the inspiratory ventilation.82 The diaphragmatic electrical activity is obtained from the crural portion of the diaphragm via a nasogastric feeding tube with an array of eight bipolar electrodes mounted at its distal end. The signals are amplified, band-pass filtered and digitized.4,83 With NAVA, the ventilators apply pressure to the airway opening throughout inspiration in proportion to the EAdi signal times. A preset gain constant is referred to as the NAVA level. Therefore, during inspiration, peak airway pressure (Paw) is instantaneously coupled to EAdi. The support delivery is under the patient's control. This corresponds to patient demands, irrespective of variations in muscle length or contractility.84
Several studies have evaluated the impact of increasing pressure support (PSV) levels versus NAVA levels, using similar methods of setting the ventilator. All studies show that NAVA averts the risk of over assistance when the assist level increased gradually. In addition, NAVA does not depend on measurement of airway pressure or flow, and is synchronous with inspiratory (neural) efforts, which is independent of the presence of leaks or intrinsic positive end expiratory pressure (iPEEP), therefore, brings about improved patient-ventilator synchrony.14,85-90 In contrast, there has been a report that a very high level of NAVA results in unstable periodic breathing patterns with delivery of high tidal volume, followed by periods of apnea and signs of discomfort.91
Based on original physiological concepts, NAVA adds a new modality to patient-ventilator interaction during spontaneous breathing by using EAdi. There is compelling evidence that NAVA improves patient-ventilator interactions and increases respiratory variability in comparison with conventional pneumatic triggering ventilators, which have a number of limitations in correcting the inappropriate timing and delivering of pressure. Many investigators have conducted numerous clinical trials to evaluate the safety and efficacy of NAVA since it was first introduced into clinical practice. There is clear evidence that NAVA is safe and effective in optimizing patient-ventilator synchrony compared to the conventional mechanical ventilation modalities.14,52,85,86,89,92,93 Several clinical trials (ongoing studies) have been registered to evaluate a newly advanced neural trigger ventilation modality.94 However, to date there is no systematic review available to inform and guide clinicians in the clinical setting regarding safety and effectiveness of NAVA. Therefore, a systematic review to analyze and synthesize the best available scientific evidence is proposed to measure outcomes across included studies regarding the safety and effectiveness of NAVA as a solution to inefficient patient-ventilator interactions.
Article Content
Inclusion criteria
Types of participants
This review will consider critically ill adult and pediatric patients across all demographic groups, with or without existing comorbidities and with any causes precipitating respiratory failure requiring IMV via endotracheal intubation and tracheostomized intubation in intensive care units.
Types of intervention
This review will consider studies that evaluate the safety and effectiveness of NAVA.
Types of comparators
This review will consider the studies that used standard conventional IMV as comparators for the intervention.
The current standard IMV includes ventilators (modes) that use the automated closed-loop feedback mode, the pneumatic triggering modality, shape-signal triggering and high frequency oscillatory ventilation (HFOV). For the purpose of this review the automated closed-loop feedback modes refer to the Smartcare/PMTM, Adaptive Support Ventilation (ASV), Automode, Proportional Assist Ventilation (PAV+), Mandatory Minute Ventilation (MMV), Proportional Pressure Support (PPS), Intellivent-ASV(R) and Mandatory Rate Ventilation (MRV); and the pneumatic triggering modality is defined as a mechanical ventilator that uses flow, volume or pressure to measure patient inspiratory effort.
Types of outcomes
This review will consider studies that include the following outcome measures:
Primary outcomes:
1. Incidence of PVA: can be detected by measurement of electrical activity of respiratory muscles (diaphragm or transverse abdominus) or esophageal pressure,43,45 or ventilator graphic waveforms,9,19 and as defined and measured in the included studies.
2. Length of IMV: defined as time in hour from being intubated to the time of being extubated and ability to maintain spontaneous breathing without any mechanical ventilation support, including non-IMV support, for more than 48 hours.95 If reintubation is required within 48 hours, the duration of IMV is counted until successful extubation. The length of IMV is also as defined by included studies.
3. Sedation requirements (dose required), type of sedation strategies used (infusion or injection) and sedative agents used (i.e. Benzodiazepine VS non-Benzodiazepine): as defined in the included studies.
4. Breathing effort: can be detected by measuring of esophageal pressure, diaphragmatic electromyogram, ultrasonography the motion of diaphragm96 or as defined in the included studies.
Secondary outcomes:
1. Patient ventilatory parameters including inspired oxygen fraction, tidal volume, airway pressure and flow and inspiratory rate.
2. Arterial blood gas (ABG) values, oxygenation, oxygen saturation, capnography (EtCO2) and transcutaneous CO2.
3. Intensive care unit length of stay defined as time from intubation to time of being discharged from ICU.
4. Mortality from all causes and from invasive mechanical ventilation related and as stated in the included studies.
5. Adverse outcomes from using either NAVA or standard mechanical ventilation:
* Extubation failure defined as the need for reintubation for any reason within 48 hours,95 and as stated in the included studies.
* Ventilator Associated Pneumonia (VAP); VAP diagnosis criteria are as defined by the Centers for Disease Control and Prevention (CDC) or as stated in the included studies.97
* Ventilator Associated Condition) (VAC); definition criteria are as defined by the VAP Surveillance Definition Working Group98 or as stated in the included studies.
* Incidence of volutrauma, biotrauma and atelecttrauma as stated in the included studies.
Types of studies
This review will look at any experimental study design, including randomized controlled trials, non-randomized controlled trials and quasi-experimental studies. Additionally, in the absence of experimental studies, the observational study designs including; prospective and retrospective cohort studies and case control studies, will also be included.
Search strategy
The search strategy aims to find published studies. A three-step search strategy will be utilized in this review. Firstly, an initial limited search of MEDLINE and CINAHL will be undertaken followed by an analysis of the text words contained in the title and abstract and of the index terms used to describe the article. Secondly, search using all identified keywords and index terms will then be undertaken across all included databases. Finally, the bibliographies of retrieved trials, in progress trials and review papers will be searched for potential relevant trials. Studies published only in English will be considered for inclusion in this review. In addition, the first authors of relevant included studies will be contacted to obtain further information if required.
Electronic databases to be searched (from 2007 when the first human trials were conducted)99 include:
MEDLINE (2007 to present)
CINAHL (2007 to present)
EMBASE (2007 to present)
Cochrane Central Register of Control Trials (2007 to present)
Scopus (2007 to present) and
Web of Science (2007 to present)
The initial key words will include: "Neurally Adjusted Ventilatory Assist", "NAVA", "pressure support ventilation", "volume controlled ventilation", "pressure controlled ventilation", "artificial respiration", "invasive mechanical ventilation", "asynchrony", "dyssynchrony", "patient-ventilator interaction", patient-ventilator asynchrony" All search terms will be combined using Boolean operator OR and AND.
Assessment of methodological quality
Selected studies for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review. Standardized critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I) will be used. Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer.
Data collection
Data will be extracted from study papers included in the review using the standardized data extraction tool from JBI-MAStARI (Appendix II). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives.
Data synthesis
Data from papers, where possible, will be pooled in statistical meta-analysis using the JBI-MAStARI software. All results will be subjected to double data entry to minimize the risk of error during the data entry. Where appropriate, Relative Risks and/or Odds Ratios and their associated 95% confidence interval will be calculated for analysis of categorical data. For continuous data collected using the same scale, the weighted mean differences (WMD) and standard deviation will be calculated. For data collected using different scales, the standardized mean differences (SMD) will be calculated. Statistical heterogeneity will be assessed using standard Chi square test and if found will be investigated prior to any further analysis. Where appropriate, a meta-analysis will be conducted using JBI MAStARI. Where statistical pooling is not possible, the findings will be presented in narrative form.
Where possible (i.e. suitable studies are identified that meet the inclusion criteria) subgroup analyses will be performed; these will include:
1. Type of patients, i.e. surgical, medical, trauma, neonate, pediatric, versus adult patients
Conflicts of interest
None of the authors have conflicts of interest.
Acknowledgements
As this systematic review forms partial submission for the degree award of Masters of Clinical Science with the Joanna Briggs Institute, at the University of Adelaide, a secondary reviewer (Ms Rincy Jimmy) will be involved in the critical appraisal.
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Appendix I: Appraisal instruments
Appendix II: MAStARI data extraction instrument[Context Link]
Keywords: patient-ventilator interaction; patient-ventilator asynchrony; Neurally Adjusted Ventilatory Assist; invasive mechanical ventilation