Mechanical ventilation has been utilized to treat neonatal respiratory failure for nearly a half century. The earliest applications began as modifications of adult ventilators, treating babies of modest size and prematurity by today’s standards.22 Most devices were time-cycled, pressure-limited ventilators. Landmark advances in respiratory care occurred in the 1970s. Antenatal corticosteroids were shown to enhance fetal lung maturity, and transcutaneous oxygen monitoring taught much about the vulnerability of the preterm infant. The 1980s brought pulse oximetry and high-frequency ventilation, which greatly expanded the therapeutic armamentarium. The surfactant replacement era began in the 1990s and was accompanied contemporaneously by patient-triggered ventilation, real-time pulmonary graphics, and a host of pharmacologic agents. Finally, in the new millennium, the microprocessor was incorporated into neonatal ventilators to greatly expand capabilities, monitoring, safety, and efficacy. This technological revolution has extended survival to infants born extremely prematurely as well as those with severe pulmonary disease that was heretofore lethal. Continuous positive airway pressure is a form of continuous distending pressure (CDP), which is defined as the maintenance of increased transpulmonary pressure during the expiratory phase of respiration. When positive pressure is applied to the airways of spontaneously breathing infants, it is called continuous positive airway pressure (CPAP), whereas distending pressure applied to a mechanically ventilated infant is called positive end expiratory pressure (PEEP). Thus, both CPAP and PEEP are types of CDP (although not technically a form of ventilation) that provide low-pressure distension of the lungs and prevent the collapse of alveoli at the end of expiration. Continuous distending pressure helps to maintain functional residual capacity (FRC) and thus facilitates gas exchange throughout the respiratory cycle. In addition, CPAP supports the breathing of premature infants in a number of other ways, including abolition of upper airway occlusion and decreasing upper airway resistance, enhancement of diaphragmatic tone and activity, improvement in lung compliance and decrease in lower airway resistance, increase in tidal volume delivery by improving pulmonary compliance, conservation of surfactant at the alveolar surface, and reduction in alveolar edema.56 CPAP may be administered invasively through an indwelling endotracheal tube, or it may be provided noninvasively using a variety of different nasal interfaces. This is referred to as nasal CPAP (NCPAP). Long nasopharyngeal tubes are still used in some centers, but have the disadvantage of high resistance and therefore a large reduction in delivered pressure. They are also difficult to suction. Single nasal prongs are usually cut from endotracheal tubes and passed 1 to 2 cm into one nostril with about 3 cm residing externally. Although resistance is usually less than with nasopharyngeal tubes, it is still high with this device, and there is a loss of pressure from the other nostril. Nasal masks are now used in the belief that they reduce trauma to the nostrils. However, it is often difficult to produce a good seal without undue pressure, which may still cause injury in the region between the nasal septum and the philtrum. Short binasal prongs are available in several designs; all have two short tubes that provide the least resistance of any other nasal interface. Current meta-analysis shows that short binasal prongs are more effective at maintaining extubation and preventing reintubation than single nasal prongs.23 The gas mixture delivered by CPAP is derived from either continuous or variable flow (Box 73-1). Continuous-flow CPAP consists of gas flow generated at a source and directed against the resistance of the expiratory limb of the circuit. Ventilator-derived CPAP and bubble or underwater CPAP are examples of continuous-flow devices, whereas infant flow drivers (flow-driven CPAP) and Benveniste valve CPAP are examples of variable-flow devices. Underwater bubble continuous positive airway pressure (BCPAP) is a continuous-flow system used since the early 1970s. In this method, the blended gas is heated and humidified and then delivered to the infant through a secured low-resistance nasal prong cannula. The distal end of the expiratory tubing is immersed under water and the CPAP pressure generated is equal to the depth of immersion of the CPAP probe. It has also been proposed that chest vibrations produced by the bubbling may contribute to gas exchange. BCPAP is an effective and inexpensive option to provide respiratory support to premature babies. In a recent randomized, controlled trial, BCPAP was found to be at least as effective as flow-driven CPAP in postextubation management of babies with respiratory distress syndrome.42 The clinical use of NCPAP in the neonate falls into one of several groups: (1) early use in resuscitation, (2) management of RDS, (3) postextubation care, (4) treatment of apnea, and (5) management of mild upper airway obstruction (Box 73-2). An early randomized trial of CPAP for resuscitation of newborns was conducted by Finer et al. in 2004. About 50% of infants required intubation for resuscitation, which was not affected by the use of CPAP/PEEP. The need for intubation was mostly dependent upon the gestational age, with 100% of infants at 23 weeks and only 18% of infants at 27 weeks requiring intubation. By 7 days of age, 80% of infants had required intubation.35 Aly et al. demonstrated a failure rate of about 50% in infants less than 26 weeks’ gestation treated initially with CPAP.2 With respect to the management of RDS, most of the available data arose from observational studies and suggest that CPAP may obviate the need for surfactant and may avoid intubation in some babies. It is important to note that most of the data are from the era preceding both surfactant and the widespread use of antenatal steroids. Initially there were a number of controlled trials that were either small in number or used different protocols, making it difficult to derive meaningful conclusions. A large international multicenter randomized trial suggested that NCPAP may be an acceptable alternative to endotracheal intubation in the delivery room but that a number of issues remained unresolved.57 Three times as many babies receiving CPAP developed pneumothorax compared with those who were intubated. Longer-term outcome data of the studied infants are not yet available. An alternative strategy of intubation, surfactant administration, and rapid extubation to NCPAP, referred to as the ENSURE technique, has been explored but did not prove to have any advantage.82 Despite this, it is gaining popularity. Another large, multicenter randomized trial was conducted by the Neonatal Research Network. Using a factorial design, infants between 24 and 28 weeks’ gestation were randomized to either CPAP or intubation and surfactant treatment, as well as high and low pulse oximetry targets. The primary outcome was death or bronchopulmonary dysplasia (using a physiologic definition). There were no differences between groups.80 A follow-up study, conducted at 18 to 22 months’ corrected age also failed to show significant differences in the composite outcome of death or neurodevelopmental impairment.85 CPAP is an established method of providing respiratory support following extubation from mechanical ventilation. Multiple studies confirm that postextubation CPAP enhances the success rate of extubation and decreases the need for reintubation.19,19a Despite its widespread use, a number of problems still persist.34 Nasal prongs rarely fit tightly into the nostrils, thus resulting in gas leak and inability to maintain a baseline pressure. The set CPAP level is rarely maintained in the pharynx. The best way to reduce nose leak is to ensure that the prongs are of sufficient size to snugly fit the nostrils without making them blanch. A chin strap can be used to reduce leaks around the mouth, but it is not simple to use in practice. Nasal trauma is also a common problem with NCPAP. It is mostly caused by incorrect positioning of the prongs. To prevent injury, the nasal device must not be pushed up against the columella. Selection of appropriate-size prongs, constant nursing vigilance, and attention to correct positioning are necessary to prevent nasal injury during NCPAP. An observational series found significant nasal complications in 13.2% of infants with 7 or more days of nasal CPAP. Injuries included columellar necrosis, seen in 5.5%, ulceration in 6 nasal cavities (3.3%), granulation in 3 nasal cavities (1.6%), and vestibular stenosis in 4 nasal cavities (2.2%). Intranasal complications were seen as early as 8 to 9 days after nasal CPAP.45 Flow of gas in excess of 2 L/min through a small nasal cannula provides some degree of CPAP. Because it is easy to use, utilization of this technique has increased in many units. However, a major problem is that the CPAP level is usually not measurable in clinical practice and has been shown to be highly variable depending on the leak at the nose and/or mouth.19 Nasal leaks are indeed problematic, because the nasal cannula fits loosely in the nostrils. The reintubation rate in babies receiving high-flow nasal cannula CPAP is significantly higher compared with NCPAP. A recently introduced device, which provides CPAP by using heated and humidified gas at very high flow rates (e.g., 7 L/min) had some degree of popularity until problems with infection and air leak were found. The device also delivers a substantial amount of water to the lungs. A recently published meta-analysis included four randomized, controlled trials and did not confirm any advantage of HFNC in terms of safety and efficacy over other forms of noninvasive respiratory support in preterm babies.89 The mechanism of action of NIPPV remains unclear. It is not known whether mechanical inflations during NIPPV are transmitted to the lungs; clinical studies show contradictory results. Other trials also found no differences in tidal volume or minute volume when comparing NCPAP with SNIPPV. Similarly, there are conflicting reports on work of breathing, pulmonary mechanics, and thoracoabdominal synchrony during comparisons of NCPAP with SNIPPV.21 The availability of synchronized NIPPV has decreased because the sole device capable of providing it has been withdrawn from the market. Several studies have compared nonsynchronized NIPPV with NCPAP for treatment of apnea in premature infants, but showed no advantage of NIPPV over NCPAP. Trials have also compared SNIPPV with NCPAP following extubation and found a significant reduction in extubation failure using SNIPPV. Studies have also assessed NIPPV as a primary strategy to treat RDS while avoiding intubation. These studies reported improved carbon dioxide removal, reduced apnea, and shorter duration of ventilation in the NIPPV group. Nonetheless, these are small studies and used sufficiently different protocols to prevent generalizable conclusions. A large randomized, controlled trial consisting of more than 1000 babies of less than 30 weeks’ gestation and birth weight less than 1000g did not show any advantage of NIPPV over CPAP either as a means of early respiratory support to treat RDS or to facilitate extubation.55 This is now further supported by yet another large mulicenter study.51a Indications for assisted ventilation may be thought of as absolute and relative (Box 73-3). Absolute indications include entities encountered in the delivery room, such as the failure to establish spontaneous breathing despite bag and mask ventilation, persistent bradycardia despite positive-pressure ventilation by mask, or the presence of major anomalies such as diaphragmatic hernia or severe hydrops fetalis, where there is a high likelihood of immediate respiratory failure. In the neonatal intensive care unit, sudden respiratory or cardiac collapse with apnea and bradycardia unresponsive to mask ventilation and massive pulmonary hemorrhage are two examples of absolute indications.40 The two major factors that are responsible for oxygenating the blood are the fraction of inspired oxygen and the pressure to which the lung is exposed (Box 73-4). The role of inspired oxygen can be understood from the alveolar gas equation (see Chapter 71). Oxygenation is also proportional to mean airway pressure (mean Paw), which is the average pressure applied to the lungs during the respiratory cycle and is represented by the area under the curve for the pressure waveform. Inflation of the lung exposes more of the pulmonary surface area to alveolar gas. Thus, those factors that increase mean airway pressure will, up to a certain point, improve oxygenation (Figure 73-1).14 The most direct impact comes from positive end expiratory pressure (PEEP) because it is applied throughout the respiratory cycle. PEEP is the baseline pressure, the lowest level to which airway pressure falls. It is used to take advantage of Laplace’s law, by maintaining some degree of alveolar inflation during expiration, thus reducing the pressure necessary to further inflate the alveolus during inspiration. There is a 1 : 1 relationship between PEEP and mean Paw; for every 1-cm H2O increase in PEEP, there is a 1-cm H2O increase in mean Paw. Excessive PEEP is potentially harmful. It may overdistend the alveoli, increasing the risk of air leaks; it may impede venous return and cardiac output; and it may decrease the amplitude, leading to carbon dioxide retention (see Complications of CPAP).12 Peak inspiratory pressure (PIP) will also increase the mean Paw, but this will be proportional to the inspiratory time (TI) or duration of positive pressure. PIP is the driving pressure and also establishes the upper limit of the amplitude. Excessive PIP poses many of the same risks as excessive PEEP, including hyperinflation (over-distension) of the lung, leading to excessive stretch of the alveolar units (baro- or volutrauma); high intrathoracic pressure with decreased venous return and cardiac output; and air leaks. Additionally, if PIP and/or PEEP is/are inadequate, there may be alveolar atelectasis and resultant damage to the lung from cyclic opening and closing of lung units, a process referred to as atelectrauma.17 Finally, circuit gas flow will also impact mean Paw. If the TI is held constant, more volume (and hence higher pressure) will be delivered as flow is increased. If the flow is set too high, turbulence, incomplete emptying of the lung, inadvertent PEEP, and hyperinflation may occur.60 If the flow is set too low, air hunger and asynchrony will result. The injurious effects of improper airway flow have been referred to as rheotrauma.26 Ventilation refers to carbon dioxide removal. Its two primary determinants are tidal volume and frequency (Box 73-5).12 Tidal volume is determined by the amplitude of the mechanical breath, or the difference between the peak (PIP) and baseline (PEEP) pressures. During conventional ventilation carbon dioxide removal is the product of tidal volume and frequency. Clinically, this is usually expressed as the minute volume, or mL/kg/min, of exhaled gas. It is also important to consider the contribution of spontaneous breathing to minute ventilation (which is not always measured), and that pulmonary blood flow is also a key element in carbon dioxide removal, as well as oxygenation. During high-frequency ventilation, carbon dioxide removal is the product of frequency and the square of the tidal volume.9 Thus, small changes in amplitude may have a profound effect on arterial carbon dioxide tension (see later). Control of ventilation during patient-triggered ventilation requires an understanding of the physiology of gas exchange. Most newborns will have intact chemoreceptors and will seek to maintain normocapnia. This is accomplished by adjustments in minute ventilation. Thus, if the clinician sets the amplitude too low, the baby will compensate by increasing the spontaneous (and hence, triggered) breathing rate. Conversely, if the amplitude is set too high, the infant’s hypercapnic drive will be abolished and the baby will “ride” the ventilator rate.27a Carbon dioxide tension is affected by minute ventilation, which in turn is the product of tidal volume and frequency during conventional mechanical (tidal) ventilation (CMV). Of these two parameters, adjustment in tidal volume (by adjusting the amplitude) has a more predictable effect on minute ventilation.12 If expiratory time is set at one time constant, approximately 63% of the change in pressure or volume will occur; if it is lengthened to three time constants, changeover will increase to 95%, and at a five time constant-length, it will approach 99%. Thus, setting the expiratory time at less than 3 to 5 times the length of the time constant will increase the risk of gas trapping and potentially inadvertent PEEP and alveolar rupture.13 Among conventional mechanical ventilators, it is advisable to use a simple hierarchical classification to describe devices according to the variables they utilize (Figure 73-2). These variables fall into two categories, those that control the type of ventilation (called ventilatory modalities) and those that determine the breath type (called ventilatory modes).11,15,36 At any one time, the ventilator can control only a single variable—time, pressure, or volume. However, the same ventilatory device can operate using different control variables at different times. Ventilatory modalities can target either pressure or volume as the primary variable. Because volume is the integral of flow, volume- and flow-controlled ventilation are actually the same. When pressure is controlled, volume will fluctuate according to the compliance of the lungs, and conversely, when volume is controlled, pressure will fluctuate as a function of compliance.11,29 The mechanical breaths delivered by the ventilator have four phases, and more than one variable can be used to design the type of breath to suit the underlying lung mechanics and/or pathophysiology. The first of these is the variable that initiates or triggers inspiration (trigger). The second is the variable that is used to limit the inspiratory gas flow (limit). The third is the variable that changes inspiration to expiration and vice versa (cycle). The final is the variable that maintains the baseline pressure during expiration (PEEP).12 A number of variables can be used to trigger a breath. In the past, most neonatal ventilators used time to start inspiration. The clinician programmed either a set inspiratory time or ventilator rate and inspiratory : expiratory ratio, and the exhalation valve would open and close according to the lapse of time. More recently, other triggering variables have been introduced, allowing for the synchronization of the onset of mechanical breaths to spontaneous breathing. The clinician can set a threshold flow or pressure, above which the ventilator initiates a mechanical breath. These variables are used as a surrogate for spontaneous effort and include pressure or flow, with time as a backup. Most present ventilators use flow-triggering devices because this requires less effort to trigger and is thus associated with less work of breathing.28 The cycling mechanism is the variable used to end inspiration. Most neonatal ventilators, including high-frequency ventilators, are time cycled, but changes in airway flow may also be used to end the inspiratory phase.27,67 Termination of inspiration occurs when decelerating inspiratory flow has reached a preset percentage of peak inspiratory flow. At this point, the exhalation valve opens and expiration begins. Flow cycling more accurately mimics the physiologic breathing pattern and allows for the mechanical breath to be fully synchronized to the spontaneous breath during both inspiration and expiration. Changes in transthoracic electrical impedance that occur during spontaneous respiration can also be used to generate a trigger signal.87 Thus, triggering during both active inspiration and active expiration can achieve total synchronous breathing between the baby and the ventilator. A recent addition to neonatal ventilation has been Neurally Adjusted Ventilatory Assist. This modality uses the electrical activity of the diaphragm to trigger, cycle, and control the level of support.10 Although there is a paucity of clinical data, the method appears promising but will require further investigation. Using different phase variables, which are interchangeable, a variety of ventilatory modes can be generated that are applicable to both pressure- and volume-controlled modalities. The commonly used ventilatory modes are intermittent mandatory ventilation (IMV), synchronized intermittent mandatory ventilation (SIMV), assist/control (A/C) ventilation, and pressure support ventilation (PSV).43 Figure 73-3 is a graphic comparison of IMV and SIMV demonstrating the effects of asynchronous ventilation. In the A/C mode, the ventilator delivers a mechanical breath each time the patient’s inspiratory effort exceeds the preset threshold criterion. When the patient triggers the ventilator to deliver a mechanical breath, the breath is said to be assisted. This mode also provides the safety of a guaranteed minimal mechanical breath rate (the control rate, set by the operator) in case no patient effort occurs or is detected. A/C breaths can be time cycled or flow cycled. During A/C ventilation, as long as the baby breathes above the control rate, lowering the control rate will have no effect on the total respiratory rate, and thus the reduction of pressure should be the primary weaning strategy (see later).67,75 Pressure support ventilation was developed to help intubated patients overcome the imposed work of breathing created by the narrow lumen (high resistance) endotracheal tube, circuit dead space, and demand valve (if one is being used). It is, however, a spontaneous breath mode. Spontaneous breaths that exceed the trigger threshold result in the delivery of additional inspiratory pressure to a limit set by the clinician. These breaths are flow cycled, but for safety purposes they may be time limited. Most commonly, PSV is used in conjunction with SIMV to support spontaneous breathing between SIMV breaths with something more substantial than PEEP (Figure 73-4). If the pressure limit of the PSV breath is adjusted to provide a full tidal volume breath, it is referred to as PSmax. If the pressure applied is just enough to overcome the imposed work of breathing, it is referred to as PSmin. PSV is a relatively new neonatal mode, but it is gaining wide acceptance.61,62 It appears that it is most commonly used as a weaning strategy with low rate SIMV.65 Pressure-targeted modalities are characterized by limiting the amount of pressure that can be delivered during inspiration. The clinician sets the maximum pressure, and the ventilator will not exceed this level. The volume of gas delivered to the baby will vary according to lung compliance and the degree of synchronization between the baby and the ventilator. If compliance is low, less volume will be delivered than if compliance is high.71,73,74 In IMV, tidal volume will fluctuate depending on whether the baby is breathing with the ventilator or against it. There are three main pressure-targeted modalities: pressure-limited ventilation (PLV), pressure control ventilation (PCV), and pressure support ventilation (PSV), which is also a mode. All three are pressure-limited. Some devices allow both PLV and PCV to be time or flow cycled. Traditional PSV is flow-cycled but time limited. Inspiratory flow during PLV is continuous and is set by the clinician. During both PCV and PSV, inspiratory flow is variable and is related to lung mechanics and patient effort. It accelerates rapidly early in inspiration then decelerates quickly, producing a characteristic waveform.24 Some devices allow modulation of the accelerating portion by offering an adjustable rise time. This enables “fine tuning” of flow to avoid pressure overshoot or flow starvation and helps to achieve optimal hysteresis of the pressure-volume loop. Both PLV and PCV are used as mandatory modes (IMV, SIMV, or A/C). PSV is a spontaneous mode; that is, it is applied to spontaneous breaths the baby takes between mandatory mechanical breaths to support spontaneous breathing and overcome the imposed work of breathing created by the narrow lumen endotracheal tube, circuit dead space, and demand valve (if one is used). Because it is patient-triggered and flow-cycled, it is completely synchronized to the baby’s own breathing, thus the baby controls the rate and the inspiratory time. The clinician sets the pressure level to augment spontaneous breathing. PSV can be used in conjunction with SIMV, or in patients with reliable respiratory drive, it may be used as a primary modality.25 There is an evolving body of evidence that PSV is both safe and efficacious.11,15,36,41,47,64 Still to be determined is the best way to apply PSV as a weaning tool. Table 73-1 compares the characteristics of pressure-targeted modalities. TABLE 73-1 Characteristics of Pressure-Targeted Modalities Broadly speaking, volume-targeted ventilation can be provided in several ways. Volume-controlled ventilation (VCV) targets a set tidal volume, which is delivered irrespective of lung compliance or the pressure required to deliver it (pressure may be limited for safety reasons). Hybrid ventilators are essentially pressure-targeted but aim to deliver the tidal volume within a set range using computer-controlled feedback mechanisms. Finally, standard pressure-targeted ventilation can function in a quasi–volume-targeted capacity if strict and vigilant attention is paid to volume delivery.20 The principal feature of VCV is that it delivers the set tidal volume irrespective of the underlying lung compliance by automatically adjusting the peak inspiratory pressure (Figure 73-5). Another important feature of VCV that differentiates it from PLV is the way that gas is delivered during the inspiratory phase.74,81 In traditional VCV, a square flow waveform is generated and peak volume and pressure delivery are achieved at the end of inspiration (Figure 73-6). These may be thought of as “back end” loaded breaths. In comparison, in PLV the gas flow pattern accelerates rapidly, then decelerates, resulting in the achievement of peak pressure and volume delivery early in inspiration. This produces a “front end” loaded breath. Because these are very different, certain disease states might be more amenable to one form than the other.
Assisted Ventilation and Its Complications
Continuous Positive Airway Pressure and Noninvasive Ventilation
Nasal Continuous Positive Airway Pressure
Methods of Generating Continuous Positive Airway Pressure
Bubble CPAP.
Clinical Indications for CPAP in Newborns
Practical Problems of NCPAP
Complications of CPAP
High-Flow Nasal Cannula
Noninvasive Nasal Ventilation
Clinical Indications for NIPPV
Indications for Assisted Ventilation
General Principles of Assisted Ventilation
Oxygenation
Ventilation
Time Constant
Classification of Mechanical Ventilators
Control Variables (Ventilatory Modalities)
Phase Variables (Ventilatory Modes)
Modes of Ventilation
Assist/Control Ventilation
Pressure Support Ventilation
Pressure-Targeted Modalities
Pressure-Limited
Pressure Control
Pressure Support
Parameter
Limit variable
Pressure
Pressure
Pressure
Inspiratory flow
Fixed
Variable
Variable
Cycle mechanism
Time or flow*
Time or flow*
Flow (time limited)
Volume-Targeted Modalities
Volume-Controlled Ventilation.
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