Clin Perinatol 34 (2007) 93–105 Volume-Targeted Ventilation of Newborns Jaideep Singh, MD, MRCPCHa, Sunil K. Sinha, MD, PhD, FRCP, FRCPCHb,*, Steven M. Donn, MDc aJames Cook University Hospital, Marton Road, Middlesbrough, TS4 3BW, UK bUniversity of Durham and James Cook University Hospital, Marton Road, Middlesbrough, TS4 3BW, UK cDivision of Neonatal-Perinatal Medicine, C.S. Mott Children’s Hospital, University of Michigan Health System, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0254, USA Traditionally, neonatal ventilation has been accomplished using time- cycled pressure-limited ventilation (TCPLV), wherein the peak inspiratory pressure is selected by the clinician and the ventilator provides each breath without exceeding this set pressure. Because peak pressure was believed to be the primary determinant of lung injury through barotrauma, it was as- sumed that TCPLV would limit lung injury by its ability to control peak pressure. This is an oversimplification. From recent observations it seems that it may actually be the volume of gas delivered to the lungs that is more likely to be the primary determinant of lung damage during mechan- ical ventilation [1]. This finding has given rise to the concept of volutrauma, which is fundamental to understanding the concept of lung volume-pressure hysteresis and the mechanisms of ventilator-induced lung injury (VILI) [2]. It has been shown in animal models that only six manual inflations of 35 to 40 mL/kg given to preterm lambs injures lungs and reduces the response to surfactant therapy [3]. Dreyfuss and colleagues [4] observed significant in- creases in lung edema and transcapillary albumin flux in rats ventilated at high tidal volumes in contrast to rats ventilated with low tidal volumes and high pressures. In another study, high-pressure ventilation with high tidal volumes caused a sevenfold increase in lung lymph flow and protein clearance in sheep, whereas high pressure ventilation with a normal tidal Dr. Singh’s work was supported by a NHS Research & Development Grant. Dr. Donn serves on the Clinical Advisory Board, is a consultant, and is a member of the Speakers Bureau of Viasys Healthcare, Inc. * Corresponding author. E-mail address: [email protected] (S.K. Sinha). 0095-5108/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.clp.2006.12.007 perinatology.theclinics.com 94 SINGH et al volume obtained by chest strapping produced a 35% decrease in lymph flow and protein clearance [5]. Hernandez and colleagues [6] could completely block microvascular damage in ventilated rabbit lungs using tidal volume limitation. Evidence for the importance of volutrauma also comes from the adult acute respiratory distress syndrome network trial [7]. Traditional approaches to mechanical ventilation in adults used tidal volumes of 10 to 15 mL/kg in patients who had acute lung injury and acute respiratory dis- tress syndrome. This trial was conducted to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these pa- tients. The trial found that using lower tidal volumes decreased mortality and increased the number of days without ventilator use. Conversely, ventilation at low lung volumes may also cause lung injury, especially in surfactant-deficient lungs. This injury is believed to be related to the repeated opening and closing of lung units with each mechanical breath (atelectotrauma). This phenomenon may explain the observation that recruitment of lung to increase the functional residual capacity protects against VILI [8,9]. If volutrauma is indeed important in the development of VILI then volume-controlled ventilation (VCV) may have advantages over TCPLV. One of the first ventilators designed and built specifically for use in in- fants was a volume-controlled device. This version was eventually discarded because of technological limitations, including long response times, an ineffective triggering system, inability to deliver the small tidal vol- umes needed by preterm newborns, a highly compliant circuit (which in- creased compressible volume loss), and a lack of continuous flow during spontaneous breathing. Since the introduction of microprocessor-based ven- tilators, however, it is now possible toventilate even the smallest of babies using VCV. This use has been facilitated by the development of sensitive and accurate flow sensors and servo-controlled mechanics allowing accurate measurement and tracking of gas flow to avoid overexpansion (volutrauma) or underexpansion (atelectotrauma) of the lungs and damage attributable to airway flow that is too high or too low (rheotrauma). This development may have advantages particularly in newborns who have respiratory distress syn- drome (RDS) in whom lung compliance (and hence delivery of gas volume to the lungs) may rapidly change in response to the disease process or treat- ment, such as surfactant therapy. VCV differs from volume guarantee (VG), pressure-regulated volume control (PRVC) or volume-assured pressure support (VAPS), which are hybrid forms of ventilation (see related articles in this issue). These are es- sentially pressure-limited modes of ventilation that use dual loop control to maintain tidal volume delivery in the target range. These newer forms of ventilation often lead to confusion and it is crucial that clinicians famil- iarize themselves with the new nomenclature and differences among them, which are often specific to individual devices. VOLUME-TARGETED VENTILATION OF NEWBORNS 95 Principles of time-cycled pressure-limited ventilation and volume-controlled ventilation How does VCV differ from TCPLV? The difference was elegantly de- scribed by Carlo and colleagues [10]. Ventilators can be classified by the var- iables that are controlled (pressure, volume, or flow, which is the integral of volume), and the phase variables, such as those that start (trigger), sustain (or limit), and end (cycle) inspiration. At any one time, a ventilator can be only pressure controlled or volume controlled. Pressure- and volume- controlled breath types have certain specific characteristics, which are re- tained even if changes are made in phase variables by altering the trigger, limit, or cycling mechanism. For example, in TCPLV, a peak inspiratory pressure is set by the operator, and during inspiration gas flow is delivered to achieve that target pressure. The volume of gas delivered to the patient, however, is variable depending on the compliance of the lungs. At lower compliance (such as early in the course of RDS), a given pressure generates lower tidal volume compared with later in the course of the disease when the lungs are more compliant. This phenomenon is illustrated in Fig. 1a. In contrast, the key differentiating feature of VCV is that the primary gas delivery target is tidal volume, which is set by the operator, and the peak inspi- ratory pressure may vary from breath to breath. At lower compliance higher pressures are generated to deliver the set tidal volume. As compliance improves, the pressure needed to achieve the set tidal volume is automatically reduced (auto-weaning of pressure). This relationship is illustrated in Fig. 1b. In adult VCV inspiration is terminated and the machine is cycled into ex- piration when the target tidal volume is delivered. This process gave rise to the term ‘‘volume-cycled ventilation.’’ The use of uncuffed endotracheal tubes in newborns results in some degree of gas leak around the tube, how- ever. True volume cycling thus is a misnomer in neonatal ventilation and the terms volume controlled, volume targeted, or volume limited better describe this modality [11]. Most modern ventilators provide the option of using a leak compensation algorithm to offset this problem. One should also real- ize that there is a discrepancy between the volume of gas leaving the venti- lator and that reaching the proximal airway. Much of this results from compression of gas within the ventilator circuit. This phenomenon is re- ferred to as compressible volume loss. It is greatest when pulmonary com- pliance is lowest. Use of semi-rigid circuits may help to minimize this. It is also affected by humidification. It is therefore critical to measure the de- livered tidal volume as close to the patient as possible (ie, at the patient wye piece). Most current ventilators measure volume delivery during inspiration (VTi) and expiration (VTe). This measurement also enables quantification of gas leak and accurate compensation. Another important feature of VCV differentiating it from TCPLV is the way that gas is delivered during inspiration. In traditional VCV, a square flow waveform is generated (Fig. 2) and peak volume delivery is achieved 96 SINGH et al A Volume Pressure B Volume Pressure Fig. 1. (A) Pressure-volume loops in pressure-limited ventilation. Pressure is plotted on hori- zontal axis and tidal volume delivered on vertical axis. In low compliance lung (broken line loop) the tidal volume delivered is lower than compliant lung (continuous line loop). Pressure delivered by the ventilator is same for the two breaths. (B) Pressure-volume loops in volume- controlled ventilation. Pressure is plotted on horizontal axis and tidal volume delivered on ver- tical axis. Tidal volume delivered is same for the two breaths. In low compliance lung (broken line loop) the pressure needed to deliver the set tidal volume is higher than in compliant lung (continuous line loop). at the end of inspiration [11]. Newer ventilators do allow the option of choosing a decelerating flow waveform. During VCV, inspiratory time is de- termined by the inspiratory flow rate. Because higher flow rates lead to more rapid filling of the lungs, set tidal volumes are achieved faster, which leads to an inverse relationship between flow and inspiratory time in VCV. In con- trast, during TCPLV flow is sinusoidal and the opening pressure is reached quickly (see Fig. 2). After the target pressure has been reached, flow decel- erates rapidly until inspiration is complete. The fixed inspiratory time allows more time for the alveoli to fill giving a theoretical advantage if high open- ing pressures are necessary, such as during the acute stages of RDS.