12 Current Respiratory Medicine Reviews, 2012, 8, 12-17 of the Neonate: Principles and Strategies Steven M. Donn*

Department of Pediatrics, Division of Neonatal-Perinatal Medicine, C.S. Mott Children’s Hospital, University of Michigan Health System, Ann Arbor, MI 48109-5254, USA

Abstract: The advent of microprocessor-based technology has revolutionalized the treatment of respiratory failure in the newborn. Clinicians are now able to customize ventilatory strategies to the specific pathophysiology of the patient. Sophisticated monitoring provides breath-to-breath feedback on patient-ventilator interactions. This paper will focus upon the basic principles of mechanical ventilation, and will review various strategies that may be employed to manage the wide range of respiratory disorders encountered by preterm and term newborn infants, including respiratory distress syndrome, meconium aspiration syndrome, persistent pulmonary hypertension of the newborn, and bronchopulmonary dysplasia. Keywords: Newborn, prematurity, respiratory failure, mechanical ventilation.

INTRODUCTION This era has also been marked by significant pharmacological advances in treating newborns with Newborns with respiratory failure have been treated with respiratory failure, including antenatal corticosteroids to mechanical ventilation since the early 1960s. The first induce fetal lung maturation, exogenous surfactant to treat attempts at assisted ventilation were performed with adult respiratory distress syndrome (RDS), cyclo-oxygenase ventilators, modified to fit small babies, which achieved inhibitors to close a patent ductus arteriosus (PDA), and token success but were very problematic in meeting the inhaled nitric oxide (iNO) to reduce pulmonary vascular unique needs of these relatively small patients [1]. The resistance in persistent pulmonary hypertension of the development of continuous flow techniques, whereby the newborn (PPHN). baby had a fresh gas source from which to breathe between mechanical breaths, was a major advance and became the mainstay of treatment for more than a quarter of a century. BASIC PRINCIPLES OF MECHANICAL VENTILATION Virtually all infants, irrespective of their underlying lung Indications disease, were ventilated with time-cycled pressure-limited (TCPL) ventilators using the intermittent mandatory Mechanical ventilation is used to provide all or part of ventilation (IMV) mode. the work of when a newborn is unable to achieve adequate pulmonary gas exchange, exhibiting either As more and more preterm babies survived, the hypoxemia, hypercapnia, or both. Mechanical ventilation challenges and limitations of the first generation neonatal may also be necessary in situations where lung function is mechanical ventilators became more apparent, as did the normal, but respiratory drive is inadequate. This can occur if recognition that not all babies – nor their pulmonary the baby is pharmacologically depressed (for example, after problems – were alike. Technological enhancements brought maternal narcotics or magnesium sulfate therapy), has high-frequency ventilation (HFV) to the neonatal intensive neuromuscular disease, or exhibits central nervous system care unit (NICU) in the 1980s as an alternative to depression for any reason, such as intracranial hemorrhage, conventional mechanical ventilation (CMV). The use of hypoxic-ischemic encephalopathy, or central apnea. pulse oximetry to assess oxygenation non-invasively became Extrapulmonary conditions, such as airway or cranio-facial widespread practice. anomalies, may also require mechanical respiratory support. The 1990s saw the incorporation of the microprocessor into the ventilator, along with the development of Oxygenation lightweight, low deadspace transducers rendering the ability to more accurately measure airway flow and pressure, create The major determinants of oxygenation are the fraction volume measurements, and provide instantaneous feedback of inspired oxygen (FiO2) and the mean airway pressure [4]. with both data and real-time pulmonary graphics [2]. This Increases in the fraction of inspired oxygen may be used to also led to the development of patient-triggered ventilation overcome alveolar hypoxia, reduce pulmonary vasoconstrict- (PTV) [3] and, to a large extent, led to the evolution of ion, and improve ventilation-perfusion mismatch. Care must patient- and disease-specific strategies. be taken with its use in very preterm babies, as it has been associated with the subsequent development of retinopathy of prematurity [5].

*Address correspondence to this author at the F5790 C.S. Mott Children’s Mean airway pressure refers to the average pressure Hospital, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-5254, USA; applied to the lung during the respiratory cycle. It may be Tel: +1 734 763-4109; Fax: +1 734 763-7728; graphically depicted as the area under the curve for a single E-mail: [email protected] ventilator cycle. It is used to recruit lung volume and to

1875-63 87/12 $58.00+.00 © 2012 Bentham Science Publishers Mechanical Ventilation of the Neonate Current Respiratory Medicine Reviews, 2012, Vol. 8, No. 1 13 increase the surface area of the lung exposed to gas long. A newer version appears to have overcome this exchange. Optimally, the lung should be ventilated at problem. functional residual capacity. Ventilating above this point End-tidal carbon dioxide (capnometry) is another may expose the lung to excessive pressure () and technique that is available, but it has not been utilized very volume (volutrauma), and ventilating below this point may much, probably because its use increases ventilator subject the lung to , where lung units are deadspace and there is little clinical information regarding its injured by the repetitive opening an closing of this still utility in the newborn [11]. delicate (and developing) tissue [6]. One of the most important advances in monitoring was Several factors contribute to mean airway pressure. the advent of real-time pulmonary graphics [2]. Breath-to- Positive end-expiratory pressure (PEEP) has the greatest breath displays of waveforms (pressure, flow, and volume), effect, as every 1 cm H O increase in PEEP results in a 1 cm 2 and displays of pulmonary mechanics (flow-volume, H O increase in mean airway pressure. Peak inspiratory 2 pressure-volume, and other loops) provide the clinician with pressure (PIP) also contributes to mean pressure, and the a wealth of information regarding the status of the baby and longer the inspiratory time (T ), the greater the effect. i the interaction between the baby and the ventilator. Several Ventilator rate may have a small effect on mean airway conditions may be seen graphically before they are clinically pressure, as there is more area under the curve for a given apparent, such as gas trapping and hyperinflation. Digital time at a faster rate, if all other conditions are kept constant. displays of V , and minute ventilation may decrease the Rise time, a feature on some ventilators that offer variable T frequency of blood gas analyses, and trends in parameters inspiratory flow, may also be used to qualitatively adjust such as compliance and resistance provide objective inspiratory flow to avoid pressure overshoot or air hunger, assessments of treatments such as surfactant or conditions which may cause rheotrauma. bronchodilators.

Ventilation Conventional Mechanical Ventilation Ventilation refers to the removal of carbon dioxide. Conventional mechanical ventilation refers to a form of During conventional ventilation, the amount of carbon assisted ventilation in which the delivered gas volumes dioxide removed is proportional to the tidal volume (V ), T approach physiologic tidal volumes, and the patterns of which in turn is determined by the difference between PIP breathing attempt to mimic physiologic breathing. It may and PEEP (often referred to as amplitude), and frequency also be referred to as tidal ventilation. There are several (rate) [7]. Thus, to increase ventilation, amplitude or tidal different ways in which this is accomplished in clinical volume can be increased by raising the PIP, lowering the practice. Conventional ventilators are commonly designated PEEP, or doing both, or by increasing the rate. by their modalities, such as pressure-targeted or volume- During HFV, carbon dioxide removal is proportional to targeted, which are really a reflection of how gas flow is the rate and the square of the VT [8]. This is why even small delivered to the patient. changes in amplitude can have a profound effect on arterial carbon dioxide tension, much more so than altering the rate. Continuous Flow Ventilation Continuous flow ventilation is utilized in traditional Monitoring of the Ventilated Newborn TCPL ventilation. Bias gas flow through the ventilator Although mechanical ventilation is a life-saving tool, it is circuit is set by the clinician. When the exhalation valve not without hazards and potential complications and closes, this flow is diverted to the patient and the lungs are demands constant clinical vigilance. Newborns receiving inflated. The rate of inspiratory flow and the tidal volume mechanical ventilation should be monitored closely for the delivered to the patient, are determined by lung mechanics. development of situations which could lead to lung or Cycling is accomplished by setting a fixed inspiratory time, systemic injury. Fortunately, present day ventilators are although many newer ventilators allow the clinician to use equipped with numerous alarms which alert clinicians when flow cycling (described below). Peak pressure is also set by various parameters can not be met or are exceeded. the clinician. Setting the proper circuit flow is important. If too low, the peak pressure may not be reached; if set too Virtually all NICUs now monitor oxygenation high, hyperinflation, turbulence (and inefficient gas continuously with pulse oximetry [9]. This device displays exchange), and inadvertent PEEP may result. the percent saturation of hemoglobin and is relatively accurate. However, clinicians must realize that the linearity between arterial oxygen tension and saturation disappears as Variable Flow Ventilation saturation approaches 98%. Use of dual site pulse oximetry Variable flow ventilation produces a rapidly accelerating has been used to detect right-to-left shunting in babies with inspiratory flow waveform, which subsequently decelerates PPHN and can be used as an adjunct to manage systemic fairly quickly. It results in rapid pressurization of the blood pressure in this condition. ventilator circuit and delivery of peak pressure and peak Transcutaneous monitoring of both oxygen and carbon volume delivery early in inspiration. It may thus be dioxide is possible [10]. Electrodes are affixed to the skin, considered to be a “front end loaded” breath [12]. This gas heated, and used to approximate the arterial tensions of these flow pattern is utilized in both pressure control ventilation gases. Earlier versions required substantial heating to 43 or (PCV) and pressure support ventilation (PSV) [13]. Both of 44 degrees Centigrade and produced burns if left in situ too these modalities are pressure limited and delivered tidal 14 Current Respiratory Medicine Reviews, 2012, Vol. 8, No. 1 Steven M. Donn volume will be proportional to lung compliance. PCV was will cycle 2 sec after the prior breath if no patient effort is originally time cycled, but several ventilators now offer flow detected). cycling. PSV is flow cycled and time limited. Theoretical Clinicians must be aware that as long as the baby is advantages of variable flow include treatment of homo- breathing above the control rate, further reduction in the geneous lung disease characterized by the need for a high control rate will have no impact on gas exchange. Thus, the opening pressure (such as RDS), as well as situations primary weaning strategy should be the reduction in peak characterized by high resistance, where a higher flow rate pressure during pressure targeted ventilation (TCPL or may be beneficial in overcoming this. PCV).

Constant Flow Ventilation Pressure support ventilation was introduced into neonatal intensive care in the early 1990s. It is a spontaneous mode of Constant flow ventilation is utilized in volume targeted ventilation, in which an inspiratory pressure assist can be ventilation [12]. Gas flow accelerates to a pre-selected limit applied to fully or partially support spontaneous breaths. and is then held constant until a targeted volume of gas is PSV is flow cycled and pressure and time limited. It is delivered, and then decelerates. This type of flow delivery generally used in combination with SIMV, but it may be a results in achieving peak pressure and peak volume delivery stand alone mode if the baby has reliable respiratory drive late in the inspiratory phase, and thus it is a “back end [13]. It is most often utilized during the weaning phase of loaded” breath. It produces a square flow waveform. This mechanical ventilation, where it mimics A/C; the SIMV should be advantageous when lung disease is heterogeneous breaths are used as “control” breaths, and the PSV breaths to avoid over-ventilation of compliant areas and under- are the “assist” breaths. PSV will decrease the patient work ventilation of atelectatic areas. It should also offer of breathing and facilitates weaning by unloading the advantages in disease states characterized by rapidly respiratory musculature during spontaneous breathing [16]. changing compliance, as the pressure will be automatically adjusted to provide the desired tidal volume. Recent Cycling Mechanisms advances in some ventilators allow clinicians to select a decelerating waveform, but the advantages of such are yet to Cycling refers to the way in which inspiration is be determined. transitioned to expiration, and the way in which expiration is transitioned to inspiration. Mechanisms of cycling include Modes of Ventilation time, flow, and volume. However, because cuffed endotracheal tubes are not used in the newborn, there is Modes of ventilation refer to the way that breaths are always some degree of leak around the endotracheal tube delivered to the patient. In intermittent mandatory ventilation precluding volume as a reliable cycling mechanism in (IMV), the clinician sets a rate at which the ventilator is to neonatal intensive care. cycle, and mechanical breaths are delivered to the baby at Time cycling is the oldest and widest practice method. regular intervals, irrespective of the baby’s own spontaneous Inspiration ends after a preset time elapses. Time cycling breathing, which is supported only by PEEP. This often may be the primary mechanism, but it is also used as a back- results in asynchronous breathing, where the baby may be exhaling against positive pressure. Asynchrony has been up mechanism to flow cycling. Time cycling gives the clinician the ability to determine how long a breath will last. shown to result in inefficient gas exchange, widely variable Consideration needs to be given to the respiratory time tidal volume delivery, air leaks, increased work of breathing constant, the product of resistance and compliance, which [13], and irregularity of arterial blood pressure and cerebral determines how much time is necessary for the equilibration blood flow velocity [14]. The latter has a strong association of pressure (and volume) in the lung. Expiratory time needs with intraventricular hemorrhage in preterm babies [14]. to be 4-5 times the length of the time constant to avoid gas Synchronized intermittent ventilation (SIMV) is a form trapping. of patient triggered ventilation (PTV). It is similar to IMV Flow cycling can be used to terminate inspiration based except that when it is time to cycle a mechanical breath, the on the natural decay of the inspiratory flow waveform. Here, ventilator will look for the initiation of a spontaneous breath the clinician can choose a point on the decelerating limb and then synchronize the mechanical breath to the spontaneous breath. If the baby fails to breath or fails to where the breath should be terminated. This is usually 5-15% of the peak inspiratory flow rate. The ventilator recognizes trigger the breath, the mechanical breath will still be this point, which is just before the baby is terminating his delivered. Again, spontaneous breaths between mechanical own breath, and inspiration ends, cycling directly into breaths are supported only by PEEP. expiration. In other words, the baby does not achieve a zero Assist/control ventilation (A/C) can be used to achieve flow state just prior to expiration. There are two major full synchrony between mechanical and spontaneous breaths advantages to using flow cycling. First, it achieves complete [15]. Each time that the baby starts to breathe and exceeds synchrony between the ventilator and the baby. The baby the assist sensitivity or trigger level, a mechanical breath will initiates the breath and terminates the breath, thus be provided. Thus, the baby controls the ventilatory rate. establishing both the ventilator rate and the inspiratory time. Assist sensitivity is usually based on an inspiratory flow Secondly, it is a safeguard against gas trapping during PTV. change, and enables even the tiniest babies to avail If time cycling is utilized during PTV and the baby becomes themselves of this method. If the patient fails to trigger the tachypneic, the faster the baby breathes, the shorter the ventilator, breaths are provided at intervals defined by the expiratory time becomes because the inspiratory time is control rate (e.g., if the control rate is 30/min, the ventilator fixed. At rapid rates, the baby could inverse the Mechanical Ventilation of the Neonate Current Respiratory Medicine Reviews, 2012, Vol. 8, No. 1 15 inspiratory:expiratory ratio with resultant gas trapping and that was available was TCPL ventilation and IMV, clinicians inadvertent PEEP. With flow cycling, because inspiration tended to treat virtually all of the disorders similarly. Better always ends at a percentage of peak inspiratory flow, the understanding of cardiopulmonary pathophysiology and ratio will be maintained, and the inspiratory time will get enhanced ventilatory diagnostic and therapeutic techniques has shorter. When flow cycling is working successfully, the greatly (and fortuitously) altered the approach to one which is actual inspiratory time will be shorter than the set inspiratory both disease- and patient-specific. time, which becomes a limit variable. Respiratory Distress Syndrome High-Frequency Ventilation RDS is the most common respiratory illness among infants High-frequency ventilation (HFV) differs from CMV in two born prematurely. It results from both anatomical and major ways. First, the delivered gas volumes are less than the biochemical abnormalities of the underdeveloped lung. Affected anatomical deadspace, generally 1-3 mL/kg. Thus, it is non-tidal infants display underdeveloped alveoli, small and poorly ventilation. Second, these devices operate at very rapid rates. supported airways, and protein and fluid leak into the air spaces. There are two preeminent forms of HFV, high-frequency jet They lack pulmonary surfactant, leading to impaired gas exchange and progressive atelectasis, resulting in increased ventilation (HFJV) and high-frequency oscillatory ventilation work of breathing. The chest wall is usually more compliant (HFOV), as well as some hybrids. than the lungs, adding to difficulty in breathing. The From a practical standpoint, most of the principles of biochemical abnormality is surfactant deficiency. Exogenous mechanical ventilation for CMV also apply to HFV. Oxyge- surfactant is provided to help establish an air-liquid interface, nation is proportional to mean airway pressure. Ventilation maintaining the alveolar surface free of liquid to facilitate gas differs slightly, however, in being the product of frequency exchange, and to reduce the collapsing forces that can lead to (rate) and the square of the delivered gas volume. Even small progressive atelectasis [20]. changes in the determinant of the delivered volume (PIP and RDS is a low lung volume disease. Goals of mechanical PEEP) can have profound effects on carbon dioxide elimination ventilation should be aimed at establishing normal functional and must thus be monitored aggressively [17]. residual capacity and ventilating the lung at a point where compliance is best. PEEP is used to maintain a degree of High-Frequency Jet Ventilation alveolar distension at end-expiration, to take advantage of the HFJV is accomplished by the delivery of high velocity Laplace relationship, lower surface tension, and decrease the pulsations directly into the airway or proximal endotracheal work of breathing. PIP is used to provide driving pressure to tube. Rates vary from 240-660 breaths per minute. HFJV is expand the lungs, and to establish the amplitude and hence, VT used in tandem with a conventional ventilator, which delivery. provides PEEP and can be used to deliver occasional Different approaches have been espoused. CMV strategies mechanical breaths, or sighs. HFJV relies on passive have utilized both pressure-targeted and volume-targeted exhalation (the elastic recoil of the lungs) to drive expired ventilation [21, 22]. As additional evidence has accumulated, it gas from the airway. It has proven to be very effective in appears that volume-targeted ventilation may reduce the treating air leaks, such as pulmonary interstitial emphysema duration of mechanical ventilation and the incidence of air [18] and recurrent pneumothorax, and in the management of leaks, with a strong trend to reducing BPD [23]. A recent study major airway disruptions, such as tracheo-esophageal fistula also showed improved pulmonary outcomes at one year and broncho-pleural fistula [19]. corrected age [24]. PTV, although offering many short term benefits, has not been shown to decrease BPD [25], nor has High-Frequency Oscillatory Ventilation permissive hypercapnia [26, 27]. HFOV is provided by a stand alone device. It functions at In a similar vein, HFOV has been utilized as a primary a faster rate than HFJV, generally in the 8-15 Hz range. It strategy. The evidence, on balance, is that although some short utilizes active exhalation, where expired gas is actively term physiologic advantages have been demonstrated, long term removed from the airway during exhalation. A unique outcomes are no better than with CMV. Two very similar feature of HFOV is the uncoupling of oxygenation, studies, one using HFOV vs SIMV [28], and one using HFOV controlled by adjustments in the mean airway pressure, and vs TCPL ventilation [29], with about 25% of the CMV infants ventilation, controlled by adjustments in the amplitude. receiving PTV, had disparate results. One study using HFJV as Unlike CMV (or HFJV), these adjustments can be made a primary strategy showed a slight reduction in the need for independent of one another without adversely affecting the supplemental oxygen at discharge [30]. other. HFOV has been used as a primary strategy for all An important question that still needs to be addressed is types of respiratory disorders in the newborn, but it is more what are the clinically relevant outcome measures of neonatal frequently utilized as a rescue tool for intractable respiratory ventilation studies [31]? It appears that BPD may now be more failure unresponsive to CMV [17]. a function of extreme prematurity than a complication of mechanical ventilation [32]. DISEASES AND STRATEGIES The newborn infant may be affected by numerous Meconium Aspiration Syndrome respiratory disorders with very different pathophysiologic Meconium aspiration syndrome (MAS) continues to be a features. In the early era of mechanical ventilation, when all significant problem despite the myriad of advances in 16 Current Respiratory Medicine Reviews, 2012, Vol. 8, No. 1 Steven M. Donn perinatal care. It is characterized by the aspiration of the standard treatment, even in babies with MAS or other meconium-stained amniotic fluid, respiratory distress, and a parenchymal lung disease. There is little doubt that many typical radiographic appearance of fluffy infiltrates and infants suffered significant complications from hypocapnia, hyperexpansion. The disorder results from both direct and hyperoxia, and extreme alkalosis. indirect effects of meconium on the lung. Meconium may CMV strategies need to be carefully planned to avoid obstruct small airways, increasing the risk of gas trapping complications, especially those that might contribute to elevated and air leak. It may incite inflammation, leading to impaired pulmonary vascular resistance, including hyperinflation and gas exchange. It can inactivate surfactant. It may contribute high intrathoracic pressure, and the avoidance of extremes of to increased pulmonary vascular resistance and secondary oxygen and carbon dioxide tensions. Similar cautions need to be PPHN (see below) [33]. applied to HFV, as well. In contrast to RDS, MAS is a high lung volume disease. The advent of iNO has changed the approach to PPHN. This The goals of mechanical ventilation are to accomplish selective pulmonary vasodilator relaxes the pulmonary vascular adequate pulmonary gas exchange without increasing the endothelium, resulting in decreased pulmonary vascular risks of hyperinflation, gas trapping, air leak, and PPHN. resistance, breaking the vicious circle of PPHN. For iNO to Multiple approaches to managing severe respiratory work, however, the lung must be adequately inflated. It appears failure from MAS have been attempted. CMV strategies that the combined use of HFOV and iNO works better than should address the pathophysiology. PEEP can be used to either therapy alone [38]. stent open the smaller airways. Use of short inspiratory times ECMO may be considered in term or late preterm infants and slower rates may avoid gas trapping. Theoretically, with intractable failure. Its success rate depends on the constant flow ventilation should be of benefit when disease underlying disease. is patchy, but a definitive study has not yet been accomplished. Bronchopulmonary Dysplasia Clinicians have utilized HFV to treat MAS. Combining exogenous surfactant and HFJV improves oxygenation [34]. Bronchopulmonary dysplasia (BPD), also referred to as HFOV has also been used, especially in conjunction with chronic lung disease (CLD), is the most common respiratory inhaled nitric oxide (iNO), used to dilate the pulmonary sequel of prematurity. Initially, BPD was thought to represent vasculature and decrease right-to-left shunting [35]. the traumatic effects of pressure and oxygen therapy. However, recent evidence suggests a multifactorial etiology, with the Infants who continue to exhibit intractable respiratory common denominator being a reduction in the number of failure may be candidates to undergo extracorporeal alveoli [32]. Various definitions have been used in the medical membrane oxygenation therapy (ECMO), which has a 94% literature, including the need for supplemental oxygen at 36 survival rate in babies with an estimated mortality of >80%. weeks’ postmenstrual age. Using this, the incidence among very Unfortunately, ECMO is an expensive and highly low birth weight (<1500 g) infants is 30-40%. technological treatment, and it is not universally available. Infants with BPD are likely to be <1500 g at birth and many received only modest ventilatory and oxygen support. Their Persistent Pulmonary Hypertension of the Newborn chest radiographs show a diffuse, hazy pattern with fine, lacy PPHN is characterized by a group of disorders in which the infiltrates. Histopathologically, they show decreased alveolari- normal fall in pulmonary vascular resistance that is supposed to zation, minimal small airways disease, and less inflammation happen at birth does not occur. Elevated pulmonary vascular and fibrosis than was seen in an earlier era. resistance leads to diminished pulmonary blood flow and the The foremost goal of mechanical ventilation is to avoid shunting of de-oxygenated blood across the fetal channels- the further lung injury. Re-adjusting one’s expectations of gas foramen ovale and/or the ductus arteriosus. The pathophysio- exchange is necessary to achieve this. Rapid rate (>60 logy may be thought of as a vicious circle, where hypoxemia breaths/min) CMV did not show any benefits over slower rate leads to acidosis, acidosis exacerbates pulmonary vascular ventilation [39]. Using modest levels of PEEP (6 cm H O) was constriction, which reduces pulmonary blood flow. This 2 associated in improved oxygenation without a concomitant decreases oxygen uptake and carbon dioxide removal, further increase in carbon dioxide tensions [40], perhaps by helping to contributing to tissue hypoxia and more acidosis. In addition, stent the airways. Short term success has been demonstrated acidosis and decreased pulmonary blood flow may damage the anecdotally for PTV [41], PSV [42], and HFOV [41], and the pulmonary epithelium and inhibit production of surfactant from use of iNO [43, 44], but no long term outcome measures have Type II cells. PPHN may be an idiopathic primary disorder, or it been adequately evaluated. Careful attention must be paid to may be secondary to a host of disorders, including RDS, MAS, adjunctive treatments, including the nutritional approach and sepsis/pneumonia, congenital diaphragmatic hernia, pulmonary evaluation of cardiac function. hypoplasia, and even transient tachypnea of the newborn. Ventilatory management of PPHN depends on a large extent SUMMARY to what the underlying pathophysiology is. This is nicely illustrated by the history of the disorder. It was first described by Neonatal intensive care, especially mechanical Gersony et al. in 1969 in newborns with severe hypoxemia and ventilation, has changed dramatically in the past 30 years. clear lung fields [36]. In the late 1970s, when Peckham and Fox No longer are all infants treated the same, no matter what the showed that hyperventilation could radically improve cause of their respiratory failure. Mechanical ventilation is oxygenation below some critical value of paCO2 [37], it became now a multi-faceted treatment, offering numerous options to attack complex pathophysiology. Mechanical Ventilation of the Neonate Current Respiratory Medicine Reviews, 2012, Vol. 8, No. 1 17

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Received: November 15, 2010 Revised: December 9, 2010 Accepted: January 2, 2011