Neonatal ventilators: how do they differ?

(2009) 29, S73 S78 r 2009 Nature Publishing Group All rights reserved. 0743-8346/09 $32 www.nature.com/jp REVIEW Neonatal ventilators: how do they differ? Department of Pediatrics, Division of Neonatal-Perinatal Medicine, CS Mott Children s Hospital, University of Michigan Health System, Ann Arbor, MI, USA Remarkable technological advances over the past two decades have brought dramatic changes to the neonatal intensive care unit. Microprocessor-based mechanical ventilation has replaced time-cycled, pressure-limited, intermittent mandatory ventilation with almost limitless options for the management of respiratory failure in the prematurely born infant. Unfortunately, much of the infusion of technology occurred before the establishment of a convincing evidence base. This review focuses on the basic principles of mechanical ventilation, nomenclature and the characteristics of both conventional and high-frequency devices. (2009) 29, S73 S78; doi:10.1038/jp.2009.23 Keywords: prematurity; respiratory failure; mechanical ventilation; neonatal ventilators (HFOV) were widely used in the United States. 2 The decade of the 1990s saw the incorporation of the microprocessor into the neonatal ventilator and this greatly expanded the scope of neonatal ventilation, which became a symphony under the direction of a clinical conductor. The clinician is now able to control target modality, the mode of ventilation, tidal volume delivery, minute ventilation, the cycling mechanism, assist sensitivity and even the rise time on some devices. 3 Sophisticated, lightweight transducers with minimal deadspace now provide real-time breath-to-breath displays of pulmonary waveforms and loops, providing the clinician with valuable information regarding the patient ventilator interaction and allowing for adjustments in strategy as the patient or the disease changes. 4 Successful management may depend on an understanding of how these facets of ventilator management differ and how to best use them in an individual patient. It was the best of times. It was the worst of times. Charles Dickens A Tale of Two Cities (1859) Introduction Neonatal respiratory failure has been treated with mechanical ventilation since the early 1960s. 1 Early attempts used adult ventilators that were modified for neonatal use. The first widespread neonatal devices consisted of continuous flow, timecycled, pressure-limited devices to provide intermittent mandatory ventilation (IMV). For nearly a quarter of a century, this was the preferred method of treating newborns. Options were limited, as clinicians could control only the fraction of inspired oxygen, peak inspiratory pressure, positive end-expiratory pressure (PEEP), inspiratory time, rate and circuit flow. Patient ventilator asynchrony was a common problem, and spontaneous breathing between mechanical breaths was supported only by PEEP. In the 1980s, high-frequency ventilation was introduced as an alternative form of mechanical ventilation, and both high-frequency jet ventilation (HFJV) and high-frequency oscillatory ventilation Correspondence: Dr, Department of Pediatrics, Division of Neonatal-Perinatal Medicine, F5790 CS Mott Children s Hospital, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0254, USA. E-mail: smdonnmd@med.umich.edu Classification of neonatal ventilators Neonatal ventilators can be classified as either devices that deliver tidal ventilation, usually referred to as conventional mechanical ventilators, or devices that deliver smaller gas volumes at rapid rates, referred to as high-frequency ventilators (Table 1). Conventional (tidal) ventilation Conventional mechanical ventilators may be described by the target or limit modality (pressure or volume) and the manner in which this is achieved (such as pressure-limited or pressure-control, or volume-limited ventilation), and by the cycling mechanism, or mode. This is the manner in which the ventilator initiates and terminates the inspiratory phase of the respiratory cycle, such as by time or changes in airway flow or pressure. 5 There are four modes of ventilation, IMV, synchronized intermittent mandatory ventilation (SIMV), assist/control ventilation (A/C) and pressure support ventilation (PSV), a mode applied only to spontaneous breaths. 6 The latter three are patient-triggered modes, in which inspiration is initiated by the ventilator in response to a signal, which is representative of a spontaneous breath, such as a change in airway flow or pressure. Most current-generation neonatal ventilators are microprocessor based. They offer multiple modes and modalities and sophisticated interfaces, which enable real-time displays of graphic or

S74 Comparison of neonatal ventilator modalities alphanumeric data. This enables the clinician to customize ventilation to the individual needs and pathophysiology of the individual patient. This marks a radical departure from the early days of neonatal ventilation, when babies were essentially managed in a singular manner, largely on the basis of technological limitations. Table 1 Classification of neonatal ventilators Conventional (tidal ventilation) Modes Intermittent mandatory ventilation (IMV) Synchronized intermittent mandatory ventilation (SIMV) Assist/control ventilation (A/C) Pressure support ventilation (PSV) Modalities Pressure targeted Pressure limited Pressure control Volume targeted Hybrid High-frequency ventilation High-frequency jet ventilation (HFJV) High-frequency oscillatory ventilation (HFOV) Hybrids Modes of ventilation The mode of ventilation describes how mechanical breaths are delivered to the patient (Figure 1). IMV describes a mode in which all mechanical breaths are delivered to the patient at regular intervals chosen by the clinician. Breaths are delivered irrespective of patient effort and can thus result in significant asynchrony, wherein the baby may be trying to exhale against positive inspiratory pressure, leading to inefficient ventilation. 7 Asynchrony may result in significant disturbances, including pneumothorax and irregular cerebral blood flow velocity, and it has been associated with intraventricular hemorrhage. 8 In addition, spontaneous breaths are supported only by PEEP and may thus contribute to an increased work of breathing. SIMV uses timing windows to deliver a mandatory mechanical breath, which is synchronized to the onset of a spontaneous breath occurring within the timing window. If the patient fails to breathe, a breath is provided when the window closes. Expiratory asynchrony can still occur, and spontaneous breaths are also unsupported. A/C is a mode in which all spontaneous breaths that exceed the trigger sensitivity result in the delivery of a mechanical breath (assist) synchronous to the patient s inspiratory effort. If the patient fails to breathe or cannot trigger the ventilator, a control breath will be provided at the desired interval. However, the timing mechanism resets after each mechanically delivered breath, and Figure 1 Comparison of IMV, SIMV and A/C.

Comparison of neonatal ventilator modalities S75 hence the control breaths are not truly mandatory as they are in IMV or SIMV. PSV is a means to apply an inspiratory pressure burst to spontaneous breaths. It is usually used in conjunction with SIMV, but may be used alone in patients with reliable respiratory drive. PSV is a triggered mode, initiated and terminated by the patient [true PSV is flow-cycled (see below) and time-limited]. PSV can be adjusted to provide full support (pressure sufficient to deliver a full tidal volume breath) or partial support. 9 Modalities of ventilation The modality refers to the target or limit variable of the mechanical breath. Generally, there are only two modalities of neonatal conventional mechanical ventilation, pressure or volume. In pressure-targeted ventilation, pressure is limited, while volume is variable and is dependent on lung mechanics. In volume-targeted ventilation, volume is limited, while pressure is variable; as compliance improves, pressure is automatically weaned to provide the targeted volume (Figure 2). A mechanical breath may be classified according to three features: trigger, limit and cycle. The trigger refers to the mechanism used to initiate the breath, which may be time, or a change in airway pressure or flow. The limit refers to the targeted variable. Finally, the cycling mechanism is what causes the breath to end, or to cycle from inspiration to expiration. Time cycling is the oldest mechanism. Here, inspiration ends after a pre-set inspiratory time has elapsed, and the exhalation valve opens. The inspiratory time for each mechanical breath will be controlled by the ventilator and will be identical. Flow cycling describes a mechanism whereby inspiration ends when the decelerating inspiratory flow has decayed to a small (that is, 5%) percentage of the peak inspiratory flow. 10 The ventilator reads this as a signal that the patient is about to terminate his own breath, and cycles directly into expiration without reaching a zero-flow state. This enables the patient to control the inspiratory time (and rate) and allows for both inspiratory and expiratory synchrony. It also safeguards against gas trapping and inversion of the inspiratory:expiratory ratio during PTV, where time cycling can result in expiratory times that get progressively shorter the faster the patient breathes. Pressure-targeted modalities Most clinicians are familiar with time-cycled, pressure-limited ventilation, in which mechanical breaths are initiated and terminated by time, and which are limited by a pre-set inspiratory pressure limit that cannot be exceeded. The inspiratory flow is constant and the delivered tidal volume is related to pulmonary compliance. It will also be affected by the degree of asynchrony between the patient and the ventilator. Newer ventilators allow the choice of flow cycling to minimize asynchrony. Time-cycled, pressure-limited ventilation can be delivered using IMV, SIMV or A/C. Pressure control ventilation describes a pressure-targeted modality in which there is variable inspiratory flow, which is proportional to patient effort. Pressure control ventilation produces a rapidly accelerating inspiratory flow waveform, which peaks and then rapidly decelerates. It results in rapid pressurization of the ventilator circuit and delivery of flow (and hence volume) early in inspiration. 11 In other words, the mechanical breath is front end loaded and peak pressure and volume delivery occur early in inspiration. Some devices also have an adjustable inspiratory rise time, which allows a qualitative modification in the slope of the inspiratory pressure waveform. Pressure control ventilation is usually time-cycled, although some ventilators enable it to be flow-cycled. Pressure control ventilation breaths can be applied with IMV, SIMV or A/C. PSV is also pressure-targeted. It is pressure-limited, flow-cycled and has a variable inspiratory flow. It is applied only to spontaneous breaths, either during SIMV or used alone in patients with reliable respiratory drive. Rise time may also be adjusted on some devices. Table 2 summarizes the features of the three pressure-targeted modalities. Volume-targeted modalities Volume-targeted modalities target or limit the delivered gas volume. However, because cuffed endotracheal tubes are not used in neonatal patients, true volume cycling cannot be accomplished. There is always some degree of leak around the endotracheal tube, Table 2 Features of pressure-targeted modalities Figure 2 Comparison of pressure- and volume-targeted modalities. Note that with pressure targeting, the delivered tidal volume depends on compliance; at low compliance, less tidal volume is delivered at the same pressure. With volume targeting, volume delivery is constant; if compliance is low, the ventilator will increase the pressure, and conversely, if compliance improves, pressure will be auto-weaned. Pressure limited Pressure control Pressure support Limit variable Pressure Pressure Pressure Flow Continuous Variable inspiratory Variable inspiratory Cycle mechanisms a Time or flow Time or flow Flow, with time limit a Cycle mechanisms vary according to the device.

Comparison of neonatal ventilator modalities S76 and additionally, a certain amount of the delivered tidal volume will be compressed within the ventilator circuit (especially if compliance is poor). This is referred to as compressible volume loss. 12 Volume-targeted modalities have differing algorithms on various ventilators. Some use a breath-averaging technique or make adjustments on the basis of the previous breath, whereas others control the amount of volume delivered to the circuit. A key element for all systems is the ability to measure the volume of gas that actually reaches the patient by measuring it not at the machine but at the patient wye. 13 Volume-targeted breaths classically produce a square flow waveform, in which inspiratory flow is held constant until inspiration ends. This results in a steady ramping of pressure and volume, such that peak volume delivery and pressure occur at the end of inspiration. Thus, volume target breaths are back end loaded and may have inherent advantages in some clinical situations. Clinical evidence IMV vs PTV Numerous small studies have compared IMV with both SIMV and A/C using mostly physiological (for example, gas exchange, pressure, rapidity of weaning, etc.) or short-term (for example, oxygen dependency at 36 weeks postmenstrual age) outcome measures. 7,14 22 The balance of these studies used first- or secondgeneration devices, and yet virtually all have shown the superiority of PTV, with the exception of the Baumer trial. However, this trial, the largest to date, was an open trial that used a multiplicity of devices and had variable levels of experience among collaborating centers. Because of its large size, it has skewed the meta-analytic conclusion from showing a positive effect to one of no difference. Pressure targeted vs volume targeted Several clinical trials have compared pressure- and volumetargeted ventilation for treating preterm babies with respiratory distress syndrome (RDS). 23 25 All are relatively small and addressed primarily physiological (mainly pneumothorax and duration of ventilation) and short-term outcomes. A recent meta-analysis of these trials indicates that there is a statistically significant reduction in pneumothorax and in the duration of ventilation, as well as a very strong trend toward decreased chronic lung disease (CLD) in babies treated with volume-targeted ventilation. The trial of Singh et al. 25 also looked at longer-term follow-up and showed a medical correlate at 24 months corrected age, with increased hospitalizations, wheezing and cough in infants treated with pressure-targeted ventilation compared with their volume-targeted counterparts. 26 Pressure support ventilation Trials examining the use of PSV in newborns have also been limited to physiological effects and short-term outcome measures, but the results are encouraging and suggest the need for future trials. 6 The studies of Reyes et al. 27 and Gupta et al. 28 show the benefits of PSV in improving spontaneous tidal volumes and minute ventilation. Further work needs to be carried out to address the optimal balance between mechanical and spontaneous support. High-frequency ventilation High-frequency ventilation differs from CMV in providing smaller tidal volumes, often less than the anatomical deadspace, at a much more rapid rate. The major devices used in the United States include HFJV and HFOV. 29 HFJV delivers tidal volumes of 1 to 3 ml kg 1 at rates between 240 and 660 breaths per minute. These are injected directly into the airway or through a special triple lumen endotracheal tube. Exhalation during HFJV is passive, similar to that during CMV. It is used in tandem with CMV, which provides PEEP and may be used to give sigh breaths or low-rate CMV. In clinical practice, management with HFJV is similar to that with CMV. Oxygenation is proportional to mean airway pressure and ventilation is proportional to amplitude (the difference between peak inspiratory pressure and PEEP). Jet pulsations are created by a flow interrupter placed close to the patient wye. This produces a high-velocity laminar flow, which has the ability to bypass airway disruptions, making it suitable to treat significant thoracic air leaks. HFOV differs from HFJV in several ways. First, the delivered tidal volumes are smaller (1 to 2 ml kg 1 ) and are delivered at a faster rate, usually 8 to 15 Hz. Second, the most commonly used device operates by applying a piston to a diaphragm, pushing gas into the lung during inspiration, and actively drawing gas from the airway during expiration. With HFOV, the lung is inflated to a static volume, then oscillated around the mean airway pressure. In this manner, oxygenation and ventilation are uncoupled. Changes in oxygenation are facilitated by adjusting the mean airway pressure, and changes in ventilation are made by altering the amplitude. These can generally be carried out independently of each other. Although the mean airway pressure measured at the proximal airway tends to be higher with HFOV than with CMV, the actual pressure seen at the alveoli is actually lower because of the very short inspiratory time and the damping effect of the airways. Clinical evidence HFJV has been shown to be a more effective means of treating pulmonary interstitial emphysema than rapid-rate CMV, with shorter time to resolution and decreased mortality in the sub-group of smallest infants. 30 Keszler et al. 31 also showed a decreased incidence of CLD and the need for home oxygen in infants enrolled in an RDS treatment trial. Friedlich et al. 32 showed a significant

Comparison of neonatal ventilator modalities S77 reduction in the mean airway pressure in a group of infants with hypoxemic respiratory failure unresponsive to either CMV or HFOV. HFOV is a popular rescue technique but has also been applied as a primary treatment strategy in babies with RDS. Study results have been conflicting. Other than in the Provo trial, 33 mortality does not seem to have been affected. Some studies suggest a modest reduction in CLD in survivors, but with no reduction in short-term neurological outcomes. Two high-frequency rescue trials, one with HFOV and one with HFJV, failed to show a reduction in the need for extracorporeal membrane oxygenation therapy in eligible infants, 33,34 although HFOV seems to be a better rescue strategy than IMV. 35 Concern over an increased incidence in intracranial hemorrhage has been expressed. Two recent studies, published in the same journal and using similar methodologies, found differing results. 36 Courtney et al. 37 compared HFOV with SIMV in infants of 600 to 1200 g birthweight and found a small reduction in the incidence of CLD. However, it is plausible that this difference might be more attributable to the use of SIMV in the control group, and that if A/C had been used, it might have even disappeared. Johnson et al. 38 reported the results of the UKOS study, a comparison of HFOV with time-cycled, pressure-limited ventilation in infants of 23 to 28 weeks gestation, and found no reduction in CLD. The Cochrane review shows no difference in mortality, but there are some trends favoring HFOV, including decreased CLD (oxygen need at 28 to 30 days) in survivors, decreased death or CLD (oxygen need at 28 to 30 days) and decreased CLD (oxygen at 36 to 37 weeks PMA). However, there are trends toward an increase in severe intraventricular hemorrhage and periventricular leukomalacia, and an increased incidence of air leaks. When a high-volume strategy was used in the study design, pulmonary outcomes were more favorable. 39 On balance, HFOV is not recommended as a primary strategy for RDS. 29,39 On the horizon As technological advances continue to occur at rapid rates, new techniques are being explored to improve the outcomes of preterm infants with RDS. Closed loop control of oxygen is under investigation to determine whether more tightly controlled oxygen saturation in ventilated babies can reduce complications. 40 Various forms of adaptive ventilation are also in the preliminary stages of development and investigation, including proportional assist ventilation, 41 mandatory minute ventilation, 42 volume-assured pressure support 43 and adaptive support ventilation. 44 Conclusion Tremendous technological advances have revolutionized the mechanical ventilation of newborns. However, this has been a double-edged sword. Ventilation has never been safer, but it has also never been this complicated. Clinicians need to approach ventilator management in the same manner as that in which they approach pharmaceuticals. They ought to learn the prototype first, master concepts and principles, learn indications and limitations, and then expand the use. In addition, they should pay attention to evidence and allow it to augment experience. 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