Neonatal Ventilators: How Do They Differ?

SM Donn Department of Pediatrics, Division of Neonatal-Perinatal Medicine, CS Mott Children’s Hospital, University of Michigan Health System, Ann Arbor, MI, USA

(HFOV) were widely used in the United States.2 The decade of the Remarkable technological advances over the past two decades have brought 1990s saw the incorporation of the microprocessor into the dramatic changes to the neonatal intensive care unit. Microprocessor-based neonatal ventilator and this greatly expanded the scope of neonatal mechanical ventilation has replaced time-cycled, pressure-limited, ventilation, which became a ‘symphony’ under the direction of a intermittent mandatory ventilation with almost limitless options for the clinical ‘conductor.’ The clinician is now able to control target management of respiratory failure in the prematurely born infant. modality, the mode of ventilation, tidal volume delivery, minute Unfortunately, much of the infusion of technology occurred before the ventilation, the cycling mechanism, assist sensitivity and even the establishment of a convincing evidence base. This review focuses on the rise time on some devices.3 Sophisticated, lightweight transducers basic principles of mechanical ventilation, nomenclature and the with minimal deadspace now provide real-time breath-to-breath characteristics of both conventional and high-frequency devices. displays of pulmonary waveforms and loops, providing the clinician Journal of Perinatology (2009) 29, S73–S78; doi:10.1038/jp.2009.23 with valuable information regarding the patient–ventilator Keywords: prematurity; respiratory failure; mechanical ventilation; interaction and allowing for adjustments in strategy as the patient 4 neonatal ventilators or the disease changes. 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.’ Classification of neonatal ventilators Charles Dickens A Tale of Two Cities (1859) 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 Introduction rates, referred to as high-frequency ventilators (Table 1). Neonatal respiratory failure has been treated with mechanical ventilation since the early 1960s.1 Early attempts used adult Conventional (tidal) ventilation ventilators that were modified for neonatal use. The first Conventional mechanical ventilators may be described by the target widespread neonatal devices consisted of continuous flow, time- or limit modality (pressure or volume) and the manner in which cycled, pressure-limited devices to provide intermittent mandatory this is achieved (such as pressure-limited or pressure-control, or ventilation (IMV). For nearly a quarter of a century, this was the volume-limited ventilation), and by the cycling mechanism, or preferred method of treating newborns. Options were limited, as mode. This is the manner in which the ventilator initiates and clinicians could control only the fraction of inspired oxygen, peak terminates the inspiratory phase of the respiratory cycle, such as by 5 inspiratory pressure, positive end-expiratory pressure (PEEP), time or changes in airway flow or pressure. There are four modes inspiratory time, rate and circuit flow. Patient–ventilator of ventilation, IMV, synchronized intermittent mandatory asynchrony was a common problem, and spontaneous breathing ventilation (SIMV), assist/control ventilation (A/C) and pressure between mechanical breaths was supported only by PEEP. In the support ventilation (PSV), a mode applied only to spontaneous 6 1980s, high-frequency ventilation was introduced as an alternative breaths. The latter three are patient-triggered modes, in which form of mechanical ventilation, and both high-frequency jet inspiration is initiated by the ventilator in response to a signal, ventilation (HFJV) and high-frequency oscillatory ventilation which is representative of a spontaneous breath, such as a change in airway flow or pressure. Correspondence: Dr SM Donn, Department of Pediatrics, Division of Neonatal-Perinatal Most current-generation neonatal ventilators are microprocessor Medicine, F5790 CS Mott Children’s Hospital, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0254, USA. based. They offer multiple modes and modalities and sophisticated E-mail: [email protected] interfaces, which enable real-time displays of graphic or Comparison of neonatal ventilator modalities SM Donn S74 alphanumeric data. This enables the clinician to customize Modes of ventilation ventilation to the individual needs and pathophysiology of the The mode of ventilation describes how mechanical breaths are individual patient. This marks a radical departure from the early delivered to the patient (Figure 1). IMV describes a mode in which days of neonatal ventilation, when babies were essentially managed all mechanical breaths are delivered to the patient at regular in a singular manner, largely on the basis of technological intervals chosen by the clinician. Breaths are delivered irrespective limitations. of patient effort and can thus result in significant asynchrony, wherein the baby may be trying to exhale against positive 7 Table 1 Classification of neonatal ventilators inspiratory pressure, leading to inefficient ventilation. Asynchrony may result in significant disturbances, including pneumothorax Conventional (tidal ventilation) and irregular cerebral blood flow velocity, and it has been Modes associated with intraventricular hemorrhage.8 In addition, Intermittent mandatory ventilation (IMV) spontaneous breaths are supported only by PEEP and may thus Synchronized intermittent mandatory ventilation (SIMV) contribute to an increased work of breathing. Assist/control ventilation (A/C) Pressure support ventilation (PSV) SIMV uses timing windows to deliver a mandatory mechanical Modalities breath, which is synchronized to the onset of a spontaneous Pressure targeted breath occurring within the timing window. If the patient fails to Pressure limited breathe, a breath is provided when the window closes. Expiratory Pressure control asynchrony can still occur, and spontaneous breaths are also Volume targeted unsupported. Hybrid A/C is a mode in which all spontaneous breaths that exceed the trigger sensitivity result in the delivery of a mechanical breath High-frequency ventilation (assist) synchronous to the patient’s inspiratory effort. If the patient High-frequency jet ventilation (HFJV) fails to breathe or cannot trigger the ventilator, a control breath High-frequency oscillatory ventilation (HFOV) will be provided at the desired interval. However, the timing Hybrids mechanism resets after each mechanically delivered breath, and

Figure 1 Comparison of IMV, SIMV and A/C.

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

Pressure limited Pressure control Pressure support Figure 2 Comparison of pressure- and volume-targeted modalities. Note that with pressure targeting, the delivered tidal volume depends on compliance; at low Limit variable Pressure Pressure Pressure compliance, less tidal volume is delivered at the same pressure. With volume Flow Continuous Variable inspiratory Variable inspiratory targeting, volume delivery is constant; if compliance is low, the ventilator will a Cycle mechanisms Time or ﬂow Time or ﬂow Flow, with time limit increase the pressure, and conversely, if compliance improves, pressure will be auto-weaned. aCycle mechanisms vary according to the device.

Journal of Perinatology Comparison of neonatal ventilator modalities SM Donn S76 and additionally, a certain amount of the delivered tidal volume but the results are encouraging and suggest the need for future will be compressed within the ventilator circuit (especially if trials.6 The studies of Reyes et al.27 and Gupta et al.28 show the compliance is poor). This is referred to as compressible volume benefits of PSV in improving spontaneous tidal volumes and loss.12 Volume-targeted modalities have differing algorithms on minute ventilation. Further work needs to be carried out to various ventilators. Some use a breath-averaging technique or address the optimal balance between mechanical and spontaneous make adjustments on the basis of the previous breath, whereas support. 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 High-frequency ventilation machine but at the patient wye.13 High-frequency ventilation differs from CMV in providing smaller Volume-targeted breaths classically produce a square flow tidal volumes, often less than the anatomical deadspace, at a much waveform, in which inspiratory flow is held constant until inspiration more rapid rate. The major devices used in the United States ends. This results in a steady ramping of pressure and volume, such include HFJV and HFOV.29 that peak volume delivery and pressure occur at the end of inspiration. HFJV delivers tidal volumes of 1 to 3 ml kgÀ1 at rates between Thus, volume target breaths are ‘back end loaded’ and may have 240 and 660 breaths per minute. These are injected directly into inherent advantages in some clinical situations. 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 Clinical evidence to give sigh breaths or low-rate CMV. In clinical practice, IMV vs PTV management with HFJV is similar to that with CMV. Oxygenation is Numerous small studies have compared IMV with both SIMV and proportional to mean airway pressure and ventilation is A/C using mostly physiological (for example, gas exchange, proportional to amplitude (the difference between peak inspiratory pressure, rapidity of weaning, etc.) or short-term (for example, pressure and PEEP). Jet pulsations are created by a flow interrupter oxygen dependency at 36 weeks’ postmenstrual age) outcome placed close to the patient wye. This produces a high-velocity 7,14–22 measures. The balance of these studies used first- or second- laminar flow, which has the ability to bypass airway disruptions, generation devices, and yet virtually all have shown the superiority making it suitable to treat significant thoracic air leaks. of PTV, with the exception of the Baumer trial. However, this trial, HFOV differs from HFJV in several ways. First, the delivered tidal the largest to date, was an open trial that used a multiplicity of volumes are smaller (1 to 2 ml kgÀ1) and are delivered at a faster devices and had variable levels of experience among collaborating rate, usually 8 to 15 Hz. Second, the most commonly used device centers. Because of its large size, it has skewed the meta-analytic operates by applying a piston to a diaphragm, pushing gas into the conclusion from showing a positive effect to one of no difference. lung during inspiration, and actively drawing gas from the airway during expiration. With HFOV, the lung is inflated to a static Pressure targeted vs volume targeted volume, then oscillated around the mean airway pressure. In this Several clinical trials have compared pressure- and volume- manner, oxygenation and ventilation are uncoupled. Changes in targeted ventilation for treating preterm babies with respiratory 23–25 oxygenation are facilitated by adjusting the mean airway pressure, distress syndrome (RDS). All are relatively small and and changes in ventilation are made by altering the amplitude. addressed primarily physiological (mainly pneumothorax and These can generally be carried out independently of each other. duration of ventilation) and short-term outcomes. A recent Although the mean airway pressure measured at the proximal meta-analysis of these trials indicates that there is a statistically airway tends to be higher with HFOV than with CMV, the actual significant reduction in pneumothorax and in the duration of pressure seen at the alveoli is actually lower because of the very ventilation, as well as a very strong trend toward decreased chronic short inspiratory time and the damping effect of the airways. 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 Clinical evidence infants treated with pressure-targeted ventilation compared with HFJV has been shown to be a more effective means of treating their volume-targeted counterparts.26 pulmonary interstitial emphysema than rapid-rate CMV, with shorter time to resolution and decreased mortality in the sub-group Pressure support ventilation of smallest infants.30 Keszler et al.31 also showed a decreased Trials examining the use of PSV in newborns have also been incidence of CLD and the need for home oxygen in infants enrolled limited to physiological effects and short-term outcome measures, in an RDS treatment trial. Friedlich et al.32 showed a significant

Journal of Perinatology Comparison of neonatal ventilator modalities SM Donn S77 reduction in the mean airway pressure in a group of infants with ventilator management in the same manner as that in which they hypoxemic respiratory failure unresponsive to either CMV or HFOV. approach pharmaceuticals. They ought to learn the prototype first, HFOV is a popular rescue technique but has also been applied as master concepts and principles, learn indications and limitations, a primary treatment strategy in babies with RDS. Study results have and then expand the use. In addition, they should pay attention to been conflicting. Other than in the Provo trial,33 mortality does not evidence and allow it to augment experience. 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 Disclosure HFOV and one with HFJV, failed to show a reduction in the need for SM Donn is a paid consultant for Cardinal Health and has grant extracorporeal membrane oxygenation therapy in eligible support from Dey, LP. This paper was based on a talk presented at infants,33,34 although HFOV seems to be a better rescue strategy the Evidence vs Experience in Neonatal Practices Fifth Annual CME than IMV.35 Concern over an increased incidence in intracranial Conference, which was supported by an unrestricted educational hemorrhage has been expressed. Two recent studies, published in grant from Dey, LP. 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 References incidence of CLD. However, it is plausible that this difference might 1 Delivoria-Papadopoulos M, Levison H, Swyer P. 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