The optimal treatment for respiratory distress syndrome (RDS) in extremely low birth weight newborn infants now consists of surfactant therapy, ventilator support and aggressive nutritional support.1,2 Introduction of surfactant therapy has significantly reduced both the mortality and morbidity in premature infants. However, despite all the preventive efforts the prematurity rate has increased in the United States. As a result of this trend the majority of the infants requiring mechanical ventilation in the current neonatal intensive care units are less than 1000 g. This has created new challenges in managing these infants respiratory distress to reduce mortality, morbidity and improve neurological outcome. Advances in optimal resuscitation, maintenance of thermal environment, early surfactant therapy, gentle ventilation, aggressive nutritional support, early treatment of patent ductus arteriosus, control of infection etc. have been adopted to reduce mortality and morbidity. However, despite all these advancements in neonatal care the incidence of bronchopulmonary dysplasia (BPD) has not decreased.3,4
BPD develops in extremely premature infants who undergo mechanical ventilation early in life. Although the development of BPD is dependent on many factors, it has been shown that the decision to intubate and start mechanical ventilation is associated with a higher incidence of BPD.5 Studies have shown that pressure damage (barotrauma), high tidal volume (volutrauma) and generation of inflammation (biotrauma) and exposure to high oxygen concentration are among the main etiologies in the development of BPD. Recent studies have further shown that volutrauma may be more important than barotraumas in the genesis of BPD.6–8 Therefore, one of the strategies to prevent BPD has focused on preventing this ventilator associated lung injury (VALI) with less invasive gentle ventilation.9
Over the last two decades the neonatal mechanical ventilation has undergone significant changes mainly driven by the development of the microprocessor technology. Several new ventilators are now available with various modes for assisted ventilation. None of these modes have been proven to be superior in published comparison trials. The modes of ventilator support currently available for premature babies are as follows: 1. Nasal continuous positive airway pressure (N-CPAP), 2. Conventional mechanical ventilation (CMV), 3. High frequency ventilation consisting of high frequency oscillatory ventilation and jet ventilation (HFV), 4. Nasal intermittent positive pressure ventilation (NIPPV), and 5. High flow nasal cannula. Each one of these ventilator supports has advantages and disadvantages and there are extensive reviews published on these modes.1,10–12 None of these modes has been shown to reduce the incidence of BPD. Therefore CMV still remains the main primary mode of ventilator support for premature babies. This two part review will first focus on the newer modes that are available in CMV and discuss the evidence in favor of volume support rather than pressure support from published studies. In the second part of the manuscript the usefulness of bedside pulmonary graphics in CMV will be discussed.
CONVENTIONAL MECHANICAL VENTILATION
CMV mainly consisted of time cycled pressure limited (TCPL) ventilators for a long time. In this mode a preset pressure is delivered to the lungs at a preset time over positive end expiratory pressure (PEEP). The tidal volume (TV) therefore varies from breath to breath and is the dependent variable. In the traditional volume controlled ventilation a preset tidal volume is delivered at a preset time. The pressure here then becomes the dependent variable. In either one of these modes the spontaneous breaths are not synchronized with the baby's breaths. Therefore, significant asynchrony may develop in these modes when the baby is exhaling while the ventilator is giving a preset inspiratory breath. Over the last decade synchronization of the ventilator breaths with the baby's breaths has become possible using various technologies and methods. Among these synchronization methods flow triggering at the airway opening (at the endotracheal tube) appears to be by far the most optima.13 The various terminologies that are used in these ventilators are described below: Synchronized intermittent mandatory ventilation (SIMV): Here the ventilator provides a certain number of mandatory breaths that are synchronized with the baby's breaths. Assist control (AC): Here every spontaneous breath is supported by a ventilator breath. A minimum back up rate is set in case there is apnea. Pressure support ventilation (PS): Here the ventilator supports each breath just like AC, but terminates each breath when inspiratory flow declines to a preset threshold usually 10%-20% of peak flow. Pressure regulated volume control ventilation (PRVC): This is a pressure limited time cycled mode that adjusts the inspiratory pressure to a set targeted tidal volume (TV) based on the pressure achieved to reach the TV of four test breaths. Subsequent adjustments are made based on the previous breath (Servo-I, Maquet. Inc., Bridgewater, NJ, USA). Volume assured pressure support (VAPS): This is a hybrid mode designed to assure that the targeted TV is reached. Each breath starts with a pressure limited breath, but if the TV is not reached the devise converts to a flow cycled mode by prolonging the inspiratory time (Bird VIP, Viasys Medical Systems, Conhohocken, PA, USA). Volume guarantee ventilation (VG): Here a set TV and a set pressure limit are chosen up to which the ventilator opening pressure may be adjusted (Draeger Babylog 8000 plus, Draeger Medical Inc., Telford, PA, USA). Volume limited ventilation (VL): Here when the targeted TV is reached the devise terminates inspiration thus avoiding excess TV delivery (Bear Cub 750 PSV, Viasys Medical Systems). Targeted tidal volume (TTV): Here the devise increases the rise time of the pressure wave form to improve the TV limit to the desired target (SLE-500, Specialized Laboratory Equipment Ltd., South Croydon, UK).
In addition to these, there are newer novel methods of ventilation in development as follows: proportional assist ventilation (PAV): here the ventilator develops inspiratory pressure in proportion to patient effort giving positive feed back. This concept assumes a mature respiratory system which is not the case with premature babies.13 Neurally adjusted ventilator assist (NAVA): Here the ventilator uses the patient's own respiratory drive from a bipolar electrode mounted on a nasogastric tube positioned in the esophagus at the level of the diaphragm. The ventilator adjusts the level of support based on the inspiratory effort.13
Despite all these available modes the unique nature of the newborn lung mechanics with a very compliant chest wall surrounding a very stiff lung, use of uncuffed endotracheal tubes contributing to air leaks and the very small tidal volume that needs precise measurement and delivery into the lung has made conventional ventilation still a challenging problem in the daily management of these babies.13 In addition, the sudden changes in compliance that occurs after surfactant replacement requires close monitoring needing immediate adjustments in ventilator support. Therefore it is very essential to become familiar with the available modes and how to effectively use them in the NICU depending on the ventilator that is in use.
CURRENT TRENDS IN CONVENTIONAL VENTILATOR MANAGEMENT
There is no consensus regarding the superiority of one ventilator mode over the others. Each ventilator mode has certain unique features which are not available in others making comparison difficult. There are no large randomized controlled studies looking at the long term outcome with these newer ventilator modes. However, one concept that is emerging in the ventilator management of neonates is volume ventilation as it is now well established that volutrauma not pressure that contributes to the development of BPD.14–17 Studies published comparing volume vs. pressure ventilation have only looked at short term outcome with fewer numbers of patients lacking the power to predict long term benefits. In addition, the various study designs have also made the comparisons difficult. Currently synchronized ventilation is the accepted normal mode of ventilation in the majority of the NICUs in the USA irrespective of the ventilator mode that is chosen. Addition of SIMV and AC will depend on the operator preference. Likewise, the preference of pressure or volume ventilation is dependent on the operator and how effective the ventilator is able to deliver the preferred TV. Although several studies have been published comparing volume ventilation to pressure ventilation a recent meta-analysis of Cochrane review included only four studies that met their criteria for comparison.18 The ventilators used in these four studies were all different. A total of 178 infants were included in this pooled analysis. The results of the analysis showed no difference in mortality between the groups which was the primary outcome of the analysis. However, no study reported the combined outcome of death or supplemental oxygen requirement (BPD). In addition, the volume targeted group showed a significant reduction in duration of ventilation (weighted mean difference -2.9 (-4.28, -1.57)), incidence of pneumothorax (RR 0.23 (0.07, 0.76)) and the incidence of severe intracranial hemorrhage (RR 0.32 (0.11, 0.90)) when compared to the pressure targeted group. There was no difference in the incidence of BPD defined as requirement for oxygen at 36 weeks corrected age.19–22 The conclusion of the analysis affirmed a sound theoretical basis for the use of volume targeted ventilation. The review did not identify any adverse events with volume ventilation when compared to TCPL ventilation. Finally, the analysis failed to show any long term benefit in the outcome of death or neurodevelopmental impairment.
Among the studies that looked at PRVC vs. TCPL ventilation, Piotrowski et al19 compared PRVC with intermittent mandatory ventilation in 60 infants <2500 g birth weight. There was no difference in the duration of ventilation or BPD. A subgroup analysis showed a reduction in duration of ventilation in the PRVC group in infants <1000 g. D'Angio et al23 compared PRVC to SIMV in 213 infants with birth weight of 500 g -1249 g. There was no difference in the incidence of BPD or duration of ventilation.
Among the studies that looked at volume controlled ventilation, Sinha et al21 studied 50 infants weighing 1200 g or more and randomized them to either VC or TCPL ventilation. The VC group reached success criteria (time to achieve AaDO2 <100 mmHg, mean airway pressure <8 cmH2O) faster and a shorter mean duration of ventilation. There was a trend towards a reduced incidence of intraventricular hemorrhage and BPD in the VC group. Singh et al24 in 109 infants between 600 g and 1500 g randomized in similar fashion between VC and TCPL and showed no difference in the time to reach success criteria or total duration of ventilation. A sub group analysis showed faster weaning in the VC group in babies weighing <1000 g.
Among the studies that looked at volume guarantee ventilation, Cheema et al25 studied volume guided ventilation compared to SIMV in a group of 40 infants (GA 27.9 weeks, BW 1064 g) using a randomized, crossover trials using the volume guarantee mode (VG). They showed that VG is feasible in neonates and can achieve equivalent gas exchange with significantly lower peak airway pressures. Keszler and Abubakar22,26,27 have published several studies showing breath to breath TV variability was significantly reduced in VG mode compared with AC mode, VG mode reduced hypocarbia and excessively large TV when AC was compared with AC plus VG and a higher variability of TV and increased work of breathing noted with AC plus VG when compared with SIMV plus VG. Lista et al28 showed decreased inflammatory cytokines in infants with RDS when PS plus VG was compared with PS alone (target TV 5 ml/kg). They speculated that VG may reduce ventilator associated lung injury reducing volutrauma. Several other similar studies have been published all favoring the beneficial effect of volume ventilation.29 But it is not known whether the short term benefits seen translate to long term effects in reducing mortality, BPD and improved neuro developmental outcome. There is definitely increasing evidence that volume ventilation is better than pressure ventilation in neonates. Some of the newer ventilators even have algorithms built in to compensate for potential excessive or lower TV delivery and thus deliver the targeted TV (volume guarantee). The tidal volume needed to maintain adequate ventilation appears to be 5 ml/kg on day 1 advancing to 6 ml/kg by the end of the third week.13
PULMONARY GRAPHICS MONITORING IN NEWBORN MECHANICAL VENTILATION
In the seventies, mechanical ventilation of the neonate primarily consisted of devises using continuous flow, pressure limited and time cycled modes, without patient synchronization. The neonatal ventilators provided very basic information such as positive end expiratory pressures (PEEP), peak inspiratory pressures (PIP), ventilator rates, inspiratory time and oxygen concentration. The clinician was left to adjust ventilator modes by clinical observation, chest excursions, chest × ray findings and blood gas measurements.30 Adjusting ventilator parameters were based on best clinical judgment as no physiological measurement was possible in real time. Later, the introduction of pulse oximetry enabled clinicians to dynamically titrate oxygen requirement in real time without the need for frequent blood gas measurements. In the late eighties, pulmonary function measurement was available at the bedside. The main component of this portable equipment was called a pneumotachograph. This was a bulky devise requiring cleaning between patients and also required the babies to be taken off the ventilator to insert the devise. There was thus the potential for the endotracheal tube to be dislodged and ventilation lost during the set up. In addition, it also added dead space to the circuit which increased the work of breathing. The values obtained from this devise were tidal volume, compliance and resistance. While these measurements were useful it only gave a “snap shot” of events at the time of measurement and was not helpful in ventilator management with constant changes in clinical status.31
The various newer models of ventilation such as PRVC, PS, VG etc. have been described previously. All these are now possible due to the introduction of proximal airway sensors that are positioned between the endotracheal tube and the ventilator circuit. These devises are extremely light, stay in line and add very minimal dead space. They are disposable and therefore very easy to use. These sensors are either thermal or differential in type. The sensor detects either flow or pressure and converts it into a useful analog value. The flow is processed by the software in the machine and a continuous display of tidal volume measurements both during inspiration and expiration, pulmonary compliance, resistance and work of breathing is displayed. In addition, these sensors also detect patient's breaths or “triggers” and distinguish them from ventilator breaths and patient breaths. This helps pressure support ventilation for spontaneous breaths. In association with these developments, they also display real time pulmonary graphics on the ventilator screen.32,33 The variables measured are now available as a continuous display rather than “snap shots” enabling the operator to monitor pulmonary function in “real time” at the bed side. A brief description of the common wave forms and examples are described below.
Pulmonary graphics display
This continuous display consists of graphs and numerical values of the various parameters measured, such as mean airway pressure (MAP), peak inspiratory pressure (PIP), positive end expiratory pressure (PEEP), inspiratory and expiratory tidal volumes (TV), compliance and work of breathing (WOB). Clinicians can use these values displayed in real time and optimize the ventilatory assistance close to normal respiratory physiology. These measurements can be significantly variable because of constantly changing dynamics in babies. However, it does help the clinician to assess the trend and make changes in the ventilator support as needed for a given clinical situation. Assessment of real time pulmonary graphics is now the accepted standard of care in most neonatal intensive care units in the USA.34
Basic wave forms
The three basic pulmonary wave forms displayed are pressure, volume and flow. The typical pressure wave form has upward (inspiration) and downward (expiration) scalars. The peak of the upward scalars represents the PIP and the area under this curve represents the MAP. The inspiratory time (IT), flow and frequency can be determined from this tracing (Figure 1). Oxygenation is a function of MAP. MAP can be increased by increasing the PEEP, PIP, IT, flow and/or frequency (Figure 2). Ventilation is a function of tidal volume and frequency. In this scalar machine triggered breaths will have no negative deflection at the start. The patient triggered breaths will have negative deflection at the start if the breaths are being pressure triggered. The greater the patient's effort to trigger the breaths the greater will be the negative deflection. There will be no deflections seen with flow triggering. If PEEP is added the baseline will be above zero.
The volume wave form is similar in appearance to the pressure wave form except that the peak volume is reached earlier in pressure ventilation as opposed to the end of inspiration in volume ventilation (Figure 3). In contrast in volume targeted ventilation the peak volume delivery occurs at the end of inspiration (shark's fin appearance).
The flow wave form has two components. There is a positive deflection and a negative deflection above the base line. Deflection above the baseline represents flow into the lungs (inspiration) and deflection below the baseline represents flow away from the lungs (expiration). The highest point of the curve above and below the baseline represents peak inspiratory and peak expiratory flow. These wave forms help distinguish between pressure targeted and volume targeted breaths, inadvertent PEEP and resistance. The pressure and volume targeted breaths look different on display. The volume targeted breaths are more “square” and the pressure targeted breaths are more “sinusoidal” in shape. There is no evidence to support one flow pattern is superior compared to the other. However, squire wave might distribute gas more evenly in the lungs as the initial burst of flow at the beginning of inspiration would pop open the alveoli and allow for better gas exchange. If the expiratory flow does not return to baseline before the next breath starts there will be auto PEEP or inadvertent PEEP. If inadvertent PEEP is detected this could be corrected by decreasing the frequency, inspiratory time to give more time for expiration and sometimes by adjusting the PEEP levels (Figure 4).
The pressure volume (PV) loop is the relationship between pressure and the generated volume. This loop begins at PEEP. The inflation curve ends at PIP and the lungs start to empty. The inflation curve (upward) and the deflation curve (downward) of the loop are different and describe the mechanical properties of the lung (hysteresis). Spontaneous breaths go clockwise and the positive pressure breaths go counter clockwise. The line connecting the beginning of inflation to the end of inflation represents the dynamic compliance of the lung. The compliance is mathematically determined as the change in volume divided by the change in pressure and displayed both as a loop and numerical value on the screen. The distortion of the PV loop may indicate disturbances in the lung mechanics. The PV loop helps to optimize inflation and adequate tidal volume delivery avoiding over inflation. Inadequate hysteresis may also be indicative of inadequate flow. The pressure volume loop may be used to determine the change in compliance after surfactant therapy as the loop will become more vertical with better inflation with improving compliance. PV loop will also help to optimize inflation if the loop has a “beaked” appearance. In such situations either the pressure or the volume will need adjustment to correct the over inflation of the lung. PV loop could also be used to optimize PEEP (Figures 5 and 6). The loop will not meet at the bottom with air trapping or leaks.
The flow-volume loop describes the changes in these parameters over the inspiratory and expiratory phase of respiration. The flow is plotted on the Y axis and the volume on the X axis. Inspiration is above the horizontal line and the expiration is below. In some ventilators this is reversed. The shape of the inspiratory flow will match what is set on the ventilator. The shape of the expiratory flow represents passive exhalation. This curve should be generally smooth and circular in appearance (Figure 7). When there is resistance to flow either during inspiration or expiration the characteristics of the loop changes and helps both in diagnosis and treatment. The expiratory flow is long and more drawn out in patients with less recoil. The flow “scoops” with increase in resistance. Increase in resistance is seen in conditions like meconium aspiration syndrome, respiratory distress syndrome and bronchopulmonary dysplasia (BPD). In addition, the flow-volume loop may help to optimize PEEP, and to detect air leaks and turbulent flow. During pressure support ventilation, flow-volume loops help detect supported breaths. The loop becomes very jagged with water or secretion build up in the circuit. They also help in detecting endotracheal tube leaks when the ventilator starts auto-cycling, misinterpreting the leak as spontaneous breaths. If there is abnormal flow volume loops detected the cause should be identified and interventions undertaken as needed. For example if leak is detected all the connections need to be checked for leaks and the flow sensor is working appropriately. If there are still leaks either pressure or tidal volume needs to be decreased. If there is water in the circuit this should be drained.
Bed side pulmonary graphics help distinguish mechanical breaths from patient triggered breaths. From the scalar tracings it is easy to distinguish SIMV, IMV and AC breaths (Figure 8).
The configuration of these wave forms as a continuous display will help fine tune ventilator management to prevent complications. In addition, the waveforms will also readily distinguish when the baby starts “auto cycling” the ventilator. This is a situation where the leak around the endotracheal tube is perceived as a breath and the machine starts delivering rapid breaths more than the set breaths.
Current ventilators available differ in the way the graphics are displayed. The options available now are unlimited starting from basic displays to changing the configuration of the flow patterns as the disease progresses. Every clinician should become familiar with the available modes and interpreting the displayed graphics of the machine they are using and take the necessary corrective actions as needed. Most ventilators also have the capability to store captured information for later down load and analysis of data.
Pulmonary graphics help the clinician with real time data that will compliment bedside examination, blood gas determination, chest X-ray and the state of the disease process. Careful monitoring of pulmonary graphics will help to monitor changes after surfactant administration, bronchodilator and diuretics treatments, air leaks, changes in airway resistance, air trapping and inadvertent PEEP. Closely monitoring these changes will help clinicians to optimize ventilatory support.
It is still unclear which modality is superior in preventing morbidities associated with mechanical ventilation despite the availability of several modalities of ventilation and real time pulmonary graphics. Likewise, there is no real consensus as to how to optimize ventilation based on real time pulmonary graphics among clinicians. Each machine is different in the way the data are displayed and the computer algorhythm used to calculate data making comparison very difficult among them. Because of this, there are no large randomized studies or evidence supporting that ventilator management based on pulmonary graphics reduce alveolar over distension, barotrauma or chronic lung disease.6 However, there is evidence to support some superiority of volume ventilation over pressure ventilation in preterm infants.18,24,29 Bedside pulmonary graphics should be used as an additional tool complementing clinical examination, blood gas measurements, oximetry trends and chest X-ray evaluation in the management of ventilator supported neonates.
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Keywords:© 2010 Chinese Medical Association
pulmonary graphics; mechanical ventilation; newborn