Novos Modos de Ventilação Mecanica

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    Med Intensiva. 2014;38(4):249---260

    www.elsevier.es/medintensiva

    UPDATE IN INTENSIVE CARE MEDICINE: MECHANICAL VENTILATION

    New modes of assisted mechanical ventilation

    F. Suarez-Sipmann, in representation of the Acute Respiratory Failure Working Groupofthe SEMICYUC

    Department of Intensive Care Medicine, Uppsala UniversityHospital, Hedenstierna Laboratory, Department of Surgical Sciences,

    University ofUppsala, Uppsala, Sweden

    KEYWORDSPatient---ventilationsynchrony;Assisted mechanicalventilation;Work of breathing

    Abstract Recent major advances in mechanical ventilation have resulted in new exciting

    modes of assisted ventilation. Compared to traditional ventilation modes such as assisted-

    controlled ventilation or pressure support ventilation, these new modes offer a number of

    physiological advantages derived from the improved patient control over the ventilator. By

    implementing advanced closed-loop control systems and using information on lung mechan-

    ics, respiratorymuscle function and respiratory drive, these modes are specifically designed to

    improve patient---ventilator synchrony and reduce the work of breathing. Depending on their

    specific operational characteristics, these modes can assist spontaneous breathing efforts syn-

    chronically in time and magnitude, adapt to changing patient demands, implement automated

    weaning protocols, and introduce a more physiological variability in the breathing pattern. Clin-

    icians have now the possibility to individualize and optimize ventilatory assistance during the

    complex transition from fully controlled to spontaneous assisted ventilation. The growing evi-

    dence ofthe physiological and clinical benefits ofthese new modes is favoring their progressive

    introduction into clinical practice. Future clinical trials should improve our understanding of

    these modes and help determine whether the claimed benefits result in better outcomes.

    2013 Elsevier Espaa, S.L. and SEMICYUC. All rights reserved.

    PALABRAS CLAVESincronapaciente---ventilador;Ventilacin mecnicaasistida;Trabajo respiratorio

    Nuevos modos de ventilacin asistida

    Resumen Los mayores avances en ventilacin mecnica de los ltimos anos se han producido

    en el desarrollo de nuevos modos de ventilacin asistida. En comparacin con los modos tradi-

    cionales como la ventilacin controlada-asistida o la presin de soporte, ofrecen una serie de

    ventajas fisiolgicas as como un mayor control sobre el ventilador por parte del paciente.

    Basados en la utilizacin de algoritmos de control de asa cerrada que incorporan informa-

    cin de la mecnica, la actividad de la musculatura respiratoria y del estmulo respiratorio,estos modos estn disenados especficamente para mejorar la sincrona paciente-ventilador

    y reducir el trabajo respiratorio. Dependiendo de las caractersticas de funcionamiento

    Please cite this article as: Suarez-Sipmann F, por el Grupo de Trabajo de Insuficiencia Respiratoria Aguda de la SEMICYUC. Nuevos modosde ventilacin asistida. Med Intensiva. 2014;38:249---260. Corresponding author.E-mail address: [email protected]

    2173-5727/$ see front matter 2013 Elsevier Espaa, S.L. and SEMICYUC. All rights reserved.

    umento descargado de http://www.medintensiva.org el 26/02/2015. Copia para uso personal, se prohbe la transmisin de este documento por cualquier medio o formato.

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    250 F. Suarez-Sipmann

    especficas de cada modo, estos pueden ayudar en los esfuerzos respiratorios espontneos del

    paciente de forma sincronizada en tiempo y magnitud, adaptarse a sus demandas, realizar

    protocolos automatizados de reduccin del soporte y devolver al patrn respiratorio una vari-

    abilidadmsfisiolgica. El clnico tiene ahora a su disposicinmodos que permiten individualizar

    y optimizar la asistencia ventilatoria mecnica en la compleja transicin de la ventilacin con-

    trolada a la ventilacin espontnea-asistida. La creciente evidencia de las ventajas fisiolgicas

    y clnicas de estos nuevos modos as como las nuevas posibilidades de monitorizacin que ofre-

    cen, estn llevando a su paulatina introduccin en la prctica diaria. Futuros estudios permitirn

    aumentar nuestro conocimiento acerca de estos modos y debern determinar si sus beneficiosse traducen en mejores resultados clnicos.

    2013 Elsevier Espaa, S.L. y SEMICYUC. Todos los derechos reservados.

    Introduction

    Mechanical ventilation (MV) is a life support measure that isused when the respiratory system ofthe patient is unable tomeet the metabolic demands ofthe body. The indications ofMV range from disease processes that affect gas exchange

    to simple switching off of the respiratory control systemduring anesthesia. Mechanical ventilation is usually startedwith a controlled ventilation phase during which the clini-cian takes full control ofthe ventilatory process, ensuring aminimum level ofgas exchange and adequate muscle rest.Once the underlying disease condition has been corrected,a transition phase is started in which the patient gradu-ally begins to participate in the ventilatory process. In thisphase, which is referred to as assisted ventilation, the aimis to provide ventilatory support synchronized in time andmagnitude with the inspiratory effort of the patient as thelevel ofmechanical ventilation is gradually reduced.

    The greatest advances in MV correspond to the devel-opment of new assisted ventilation modes. Impulsed byimportant technical innovations, these newmodes offer the-oretical advantages with respect to the traditional assistedventilation modes such as assisted-controlled ventilation orpressure support ventilation. However, their slow introduc-tion to clinical practice and the fact that their superiorityin terms ofclinical outcomes has not yet been firmly estab-lished have caused the traditional modes to remain themostwidely used techniques.1

    The present review describes new assisted ventilationmodes that have been grouped as follows: (1) modes thatadapt to the instantaneous inspiratory effort of the patient,such as proportional assist ventilation (PAV) and neurallyadjusted ventilatory assist (NAVA); (2) automated modes

    that can be adapted to the patient demands, such as adap-tive support ventilation (ASV) and the NeoGanesh systemmarketed as SmartCareTM; and (3) modes that introduce bio-logical variability in theventilatory pattern, such as variablepressure support ventilation (V-PSV) or noisy ventilation.

    The challenges ofassisted ventilation

    Assisted ventilation has the difficult task of harmonizingthe operation of two complex systems, i.e., patient andventilator---each with its own control center and ventilatorypump (Fig. 1). The respiratory control system (RCS) iscomposed of an automatic system and a voluntary system.

    The former integrates information from neurological andchemical peripheral afferents at brainstem level, whilethe voluntary or behavioral system in turn is located insupramedullary and cortical structures. In healthy indi-viduals, the respiratory stimulus has three main origins:(1) chemical, mediated by changes in PaO2, PCO2 and pH;

    (2) metabolic, mediated by less well known mechanisms;and (3) a conscious origin that disappears during sleepphases.2 In effect, during sleep, the respiratory patternis almost exclusively conditioned by chemical stimuli,which for example explains the apneas seen in responseto minor changes in PCO2 in sedated patients.

    3 During thewaking state, the voluntary control system is activatedand influences the respiratory patterns in a variable andoften unpredictable manner. As a result, patients subjectedto assisted ventilation can develop complex respiratorypatterns that affect interaction with the ventilator, therebycomplicating mechanical assist.

    In order to activate the muscle pump, the automaticcontrol system transmits the respiratory impulses along the

    efferents (motor neurons). The voluntary system not onlyinteracts directly with the automatic system, but also hasefferents that can directly activate the muscle pump with-out passing through the automatic control filter2 (Fig. 1).The difficulty of harmonizing the respiratory cycle gener-ated by this complex RCS with the mechanical cycle of theventilator is reflected by the fact that both are in manifestasynchrony in approximately 25% of all patients.4 An ele-ment that contributes to this situation is the fact that thetraditional ventilation modes are rigid---delivering prefixedvolumes or pressures without taking into account the fre-quent changes in patient demands or the changes betweenthe sleeping and waking states. Moreover, in the case of

    assisted-controlled ventilation, the clinician assigns a fixedinspiratory time that rarely coincides with the physiolog-ically variable time set by the respiratory control center(neural time).

    Assist modes adapted to the instantaneousinspiratory effort ofthe patient

    These modes are represented by PAV and NAVA, and haveopened a new range of possibilities for assisted ventilation.Based on solid physiological principles, these techniquesoffer a series of theoretical advantages that make themparticularly attractive for improving patient---ventilator

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    New modes of assisted mechanical ventilation 251

    Muscle

    pump

    Respiratorycontrol system

    Voluntary

    control system

    Automatic

    control system

    Efferents

    Afferents

    Pressure(cmH

    2O)

    Flow

    (l/sec)

    Chemoreceptors

    Stretch receptorsMuscle receptors

    Patient Ventilator

    Chemoreceptors

    Ventilatory

    pump

    Ventilator control system

    (microprocessors)

    Figure 1 Principles ofpatient---ventilator interaction. Assisted ventilation has the difficult task ofharmonizing the operation of

    two complex systems, i.e., patient and ventilator---each with its own control center and ventilatory pump. The respiratory control

    system (RCS) is complex, and is composed ofan automatic system and a voluntary system. The afferents transmit the stimuli from

    the sensors (central and peripheral chemoreceptors, stretch receptors andmuscle receptors) to the control system, regulating theneural respiratory impulse. The automatic control system emits the efferents (motor neurons) that activate and regulate the muscle

    pump. The voluntary system in turn can modulate the activity ofthe automatic system or directly activate the muscle pump.

    synchrony. This is because in these modes the RCS ofthe patient takes control of the respirator and is freeto determine its own respiratory pattern. Consequently,none of the entities such as volume, pressure and flow arepre-established; rather the ventilator simply assists thepattern chosen by the patient. In both of the mentionedmodes the ventilator functions as an additional muscle,proportionally assisting the instantaneous efforts of the

    patient over the entire inspiratory phase. In addition, and incontrast to the other modes, ventilatory assist ceases at thesame time as patient effort. This affords improved harmonybetween the mechanical and neural ventilatory times.

    Upon taking control of the RCS, the ventilatory patternrecovers the characteristic variability of the natural res-piratory pattern. Furthermore, under conditions in whichthe RCS is functionally intact, the afferents from thechemical and neural sensors modulate the intensity andcharacteristics of the respiratory impulse. This implies thatboth PAV and NAVA theoretically pose a lesser risk ofunder-or over-assistance, which often constitutes a cause ofasynchrony with the traditional modes.5 Both assist modes

    require sufficient patient alertness and functional integrityofthe RCS, which is affected by sedation.

    Proportional assist ventilation

    Proportional assist ventilation (PAV) was introduced in theearly nineties,6 and represents a synchronized assist ven-

    tilation mode in which the ventilator provides pressureassistance proportional to the instantaneous effort of thepatient.

    Principles ofproportional assist ventilation

    In the PAV system the ventilator detects the inspiratoryeffort of the patient by precisely measuring the flow andvolume leaving the ventilator toward the patient. Bothparameters are conditioned by the inspiratory decreasein alveolar pressure which the patient generates throughmuscle contraction. The flow and volume are amplified byrespective adjustable gain controls, and the sum of both

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    252 F. Suarez-Sipmann

    Pmus

    P elastic

    P resistive

    Paw

    Flow Volume

    Motor

    Piston

    AV

    AF

    1

    2

    3

    Flow

    (l/sec)

    Pressure(cmH2

    O) 4

    Palv

    Figure 2 Schematic representation ofthe PAV system. The PAV mode affords assistance proportional to effort through the contin-

    uous measurement ofthe flow and volume (1) leaving the ventilator toward the patient, conditioned to the muscle pressure (Pmus)

    generated by the patient and which leads to a decrease in alveolar pressure (Palv). The flow and volume are amplified (AF and AV) by

    adjustable gain controls (2), and the sum ofboth signals conforms the input control signal (3) that generates the pressure response

    of the ventilator motor. The latter drives the piston, causing the ventilator to respond with rapid flow delivery to the patient in

    proportion to his or her Palv, overcoming the elastic and resistive pressure. The pressure-time and flow-time curves resulting from

    the mechanical cycle (4) show that the pressurization pattern is gradual, reaching the maximum value at the end of inspiration,

    and exhibiting proportionality at all times. Note that expiratory cycling coincides with the drop in inspiratory pressure, i.e., the

    cessation ofinspiratory effort (second broken line), and the more physiological sinusoidal morphology of flow of the inspiratory

    phase.

    constitutes the control signal that generates the pressureresponse of the ventilator. The latter reacts with the rapiddelivery of flow in response to this control signal (Fig. 2).

    The proportionality of the assistance is determined bythe motion equation of the respiratory system. Accordingto this equation, the total pressure that must be appliedto insufflate the lung must overcome the resistive pressure(flow resistance) and the elastic retraction pressure (vol-umeelastance) ofthe respiratory system:

    Ptotal = flow resistance+ volume elastance

    During assisted ventilation, the total pressure is the sumof the pressure generated by muscle contraction of thepatient (Pmus) and the pressure generated by the ventilator(Pvent).

    Ptotal = Pmus + Pvent

    The levels of flow and volume assistance are adjustedindependently by the user. This requires an estimation ofthe passive mechanical characteristics, resistance and elas-tance, at the start of adjustment and on an intermittentbasis. Once these are known, the pressure assist afforded

    by the ventilator is determined by the sum ofthe flow andvolume assistance:

    Pvent = (%Flow assistance) Resistance

    + (% Volume assistance) Elastance

    Because of the changing nature of respiratory mechan-ics, the system requires frequent measurement ofelastanceand resistance. There is consequently a risk of excessiveor insufficient assistance in cases of estimation error or a

    lack ofconcordance between the estimated and the actualvalues. In the event of over-estimation, compensation isexcessive, and the expiratory cycle may be delayed, pro-longing assistance beyond the cessation of inspiratory efforton the part of the patient---this being known as the run-away phenomenon.7,8

    A simplified and improved form has recently beenintroduced, called proportional assist ventilation with load-adjustable gain factors, or PAV+. This mode offers twoessential improvements: (1) the noninvasive and semi-continuous measurement ofrespiratorymechanics, allowingautomatic closed-loop adjustment of the assist level. Thismeasurement is made by introducing brief pauses (300ms)

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    New modes of assisted mechanical ventilation 253

    at the end of inspiration every 8---15 respirations to esti-mate resistance9 and elastance10; and (2) the automaticadjustment of a single level offlow and volume assistancethat becomes a constant fraction ofthe measured values ofresistance and elastance.

    Functioning ofproportional assist ventilation withload-adjustable gain factors (PAV+)

    During ventilation in PAV+ mode, we simply need to adjustthe percentage by which the ventilator must assist patienteffort. Accordingly, an assist level of 70% means that theventilator will contribute 70% to the total pressure reached,leaving the remaining 30% to the patient. The proportional-ity is simplified as follows:

    Proportionality=%assistance

    100 %assistance

    For an assist level of 70%, the proportionality is 3; inother words, the system multiplies instantaneous pressure

    assistance by a factor of 3.After activating the inspiratory trigger through pressure

    or flow, the inspiratory pressure progresses with the estab-lished proportionality, following a profile identical to that ofPmus. The result is gradual pressurization, reaching themaxi-mum pressure only at the end ofinspiration. In the momentin which the effort of the patient begins to decrease, thedelivery offlow also decreases---expiratory cycling thereforegenerally coinciding with the cessation of patient effort.

    PAV and PAV+: clinical characteristics

    Many clinical studies have compared the physiological

    advantages of PAV versusconventional assistmodes. Marantzet al.7 characterized the physiological response to PAVamong patients dependent upon mechanical ventilation.They found that during PAV, in the absence of limitationsimposed by respiratory mechanics, the RCS of the patientdetermines the tidal volume (Vt) and the frequency inresponse to variable assist levels. The patients tend to lowerVt and to increase the frequency in order to maintain thechosen minute volume. This results in a reduction of theinspiratory pressures.

    With respect to pressure support ventilation (RSV),PAV has shown similar muscle discharge11---14 and betterhypercapnia compensation.15 In response to an increasein elastic loading of 30%, Kondili et al.16 recorded

    greater efficiency in compensation (lesser increase of thework of breathing) with PAV+ than with PSV. Xirouchakiet al. compared the effectiveness of PSV versus PAV+in maintaining critical patients dependent upon mechan-ical ventilation in assisted ventilation. They found PAV+to significantly increase the probability of remaining withspontaneous ventilation, in addition to considerably redu-cing patient---ventilator asynchrony.17 Thanks precisely toa decrease in patient---ventilator asynchrony, Bosma et al.showed PAV to afford superior sleep quality, with fewer dis-ruptions, in comparison with PSV.18

    The PAV system depends on pneumatic triggering, andtherefore has the same limitations for inspiratory cycling

    in patients with dynamic hyperinsufflation and intrinsicpositive-end expiratory pressure (PEEP) as the traditionalmodes. Although expiratory cycling, based on flow, accom-panies the cessation of inspiratory effort, expiratoryasynchronies have been described particularly with highassist levels.19

    The PAV mode can also be used in noninvasive ventilation(NIV). Compared with PSV, mainly in patients with chronic

    obstructive pulmonary disease (COPD), PAV usually affordshigher levels of tolerance, a better physiological response,and fewer complications.20---22 However, PAV has not beenassociated with a decrease in the need for intubation incomparison with PSV. This could be related to the fact thatleakage---the main cause of disadaptation and asynchronyduring NIV23---equally affects triggering in PAV and in PSV.

    Proportional assist ventilation and monitoring

    With the PAV+ system we have semicontinuous monitoringof the elastance and resistance of the respiratory system.In addition to providing valuable evolutive information, it

    allows us to immediately assess the response to changesin the respiratory parameters or to quickly detect possiblecomplications. The system is also able to estimate and mon-itor Pmus, which is the only unknown factor of the motionequation. Knowing Pmus, we in turn can calculate the workofbreathing, helping to select an adequate assist level witha view to avoiding excessive muscle work or rest.24

    Neurally adjusted ventilatory assist

    Neurally adjusted ventilatory assist (NAVA) is a new assistedventilation mode synchronized and proportional to theeffort of the patient that has become available only inthe last few years.25 As control signal for both assist andfor inspiratory and expiratory cycling of the ventilator, thismode uses the electrical activity of the diaphragm (EAdi).The latter is recorded via transesophageal electromyogra-phy using a modified nasogastric tube, also known as anEAdi catheter, which is similar in size and function to aconventional nasogastric tube but equipped with severalmicroelectrodes at the distal tip for recording EAdi. Correctpositioning of the catheter is carried out using the trans-esophageal electrocardiographic signal recorded throughthe same electrodes as a guide. The operator can check cor-rect positioning (at the esophageal hiatus) on the ventilatorscreen, based on a simple algorithm.26

    The electrical activity ofthe diaphragm

    The utilization of EAdi for control of the ventilator has aseries of theoretical advantages. In effect, EAdi is a signalthat directly (i.e., without calculations or estimates) mea-sures the efferents from the RCS, integrating the sum oftime and space ofthe neural respiratory impulse that resultsin diaphragmatic activation.27 The amplitude of the signaldepends on the degree of recruitment and on the inten-sity and frequency of triggering of the motor units, andconsequently reflects the intensity with which the patientwishes to breathe.27,28 From its origin, the signal takes lessthan 20ms in triggering the mechanical response of the

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    254 F. Suarez-Sipmann

    EAdi(V)

    TI neural

    EAdi peak

    0

    2

    4

    6

    8

    10

    12

    EAdi expiratory

    Expiratory cycling

    70% of max EAdi

    Inspiratory cycling(EAdi exp + 0.5 to 2 V)

    TE neural

    60

    40

    20

    0

    20

    40

    60

    Flow

    (l/min)

    Edi(V)

    0

    2

    4

    6

    8

    10

    12

    14

    B

    0

    5

    10

    15

    20

    25

    Pressure(cmH2

    O)

    Time

    A

    TI mechanical TE mechanical

    Figure 3 EAdi signal and characteristic respiratory curves during ventilation in NAVA. (A) EAdi signal. The start of inspiration isgiven by the increase in EAdi activity (first broken line) from the expiratory activity, which under normal conditions is 0. At the

    point where EAdi reaches a threshold value (first dotted line), the ventilator starts assist until EAdi drops to 70% ofthe maximum

    value (second dotted line). The neural inspiratory time comprises the period between the two solid lines, and ends when EAdi

    reaches its maximum value. The mechanical ventilatory time comprises the period between the two broken lines (inspiratory and

    expiratory cycling). Note that although minimal, there is a phase lag in the time between the neural and mechanical times due to

    the imposed cycling criteria. (B) The curves corresponding to pressure, flow and EAdi ofa cycle show the perfect inspiratory (first

    broken line) and expiratory cycling synchrony produced immediately after the start of the neural time of the patient, in relation

    to the cessation of inspiratory effort. In the same way as in PAV, pressurization is gradual, and in NAVA follows or parallels the

    morphology ofthe inspiratory phase of EAdi. The NAVA level is 1, and we can see that the end-inspiratory pressure reached is

    22cmH2O, which corresponds to EAdi (=12)NAVA level (=1) + PEEP level (=10).

    Adapted from Suarez-Sipmann et al.30.

    diaphragm29---this beingabout three to four times faster thanthe pneumatic trigger response time ofmodern ventilators.It is therefore the signal closest to the origin ofthe respira-tory stimulus that current technology is able to offer.

    Functioning ofthe NAVA system

    During NAVA, inspiratory cycling is determined by the detec-tion ofthe elevation of EAdi over the expiratory level, with asensitivity threshold determined by the operator. Expiratory

    cycling occurs when EAdi decreases to 70% of the maxi-mum inspiratory value (Fig. 3). This allows adjustment ofthe duration of the mechanical inspiratory and expiratorytimes to the neural inspiratory and expiratory times of thepatient determined by the RCS, in a way which no other ven-tilatory mode is able to do.30 In addition, the NAVA systemeliminates the limitations ofpneumatic triggering, since itisnot affected by leakages or the presence ofdynamic hyper-insufflation. This defines NAVA as the ventilatorymode whichtheoretically offers the greatest level ofpatient---ventilatorsynchrony.

    In the same way as during PAV, the inspiratory assist isat all times proportional to the effort of the patient and

    is determined by a proportionality constant adjusted bythe operator, called the NAVA level, which amplifies theinstantaneous progression of EAdi during the inspiratoryphase. The pressure in the airway (Paw) over the level ofPEEP, in each moment during inspiration, is expressed asfollows:

    Paw = EAdi (V) level NAVA+ PEEP

    Different methods have been proposed for adjusting the

    NAVA level, which theoretically should be that affording anadequate level of muscle discharge. Brander et al. havedescribed a method based on the response of Vt and Pawto ascending NAVA levels.31 Starting from low levels, theauthors described a double response comprising a gradualincrease to a certain NAVA level beyond which Vt and Pawreach a plateau. The optimum NAVA level would be thatcoinciding with transition from an ascending phase to theplateau phase of the Vt and Paw values. Roze et al. in turnhave proposed adjustment to a NAVA level that reaches 60%ofthemaximumEAdi obtained after a standardized test withminimum assist (pressure support ventilation with 7 cmH2Oand PEEP 0) with a duration of1 h.32

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    New modes of assisted mechanical ventilation 255

    Paw

    peak

    (cmH

    O)

    2

    RR

    flow

    (bpm)

    EAdipeak

    (V)

    CVEAdipeak

    TV/Kg(ml/Kg)

    CVTV

    NAVA level

    0.55

    10

    15

    20

    25

    30 40

    2241

    20

    18

    16

    14

    12

    10

    8

    6

    4

    2

    0

    12

    10

    8

    6

    4

    2

    0.6

    0.5

    0.4

    0.3

    0.2

    0.1

    0.0

    0.7

    0.6

    0.5

    0.4

    0.3

    0.2

    0.1

    2.551.50. 844321 1612

    35

    30

    25

    20

    15

    105.25.15.05.25.1 8443244 161284 1612321

    0.5 1.5 2.5 4321 0.5 1.5 2.5 4321 8442.510.5 16124 8 16124 8 1612 321.5

    PS

    PSNAVA level PSNAVA levelPSNAVA level

    SPlevelAVANSPlevelAVAN

    Figure 4 Effect ofdifferent NAVA levels and pressure support. Note that in NAVA, and in contrast to pressure support ventilation

    (PSV), greater assist levels do not increase the tidal volume or decrease the respiratory frequency, and the pressure in the airway

    reaches a plateau with higher assist levels---corresponding to a decrease in EAdi. The increase in assist is accompanied by increased

    variability in tidal volume in NAVA, while it decreases in PSV. PS: pressure support ventilation; EAdi: electrical activity of the

    diaphragm; CV EAdi peak: coefficient ofvariation ofthe electrical activity ofthe diaphragm; CV TV: coefficient ofvariation ofthe

    tidal volume; Paw: pressure in the airway; RR: respiratory frequency; TV/kg: tidal volume per kg ideal weight. *p< 0.05 versus the

    lowest assist level for the same ventilatory mode. **p< 0.05 versus the highest assist level for the same ventilatory mode.

    Adapted from Patroniti et al.38.

    NAVA: clinical characteristics

    Several clinical studies have evaluated and comparedthe physiological response to NAVA. These studieshave consistently recorded significant improvement inpatient---ventilator synchrony, a lesser over-assistancetendency, and greater variability ofthe respiratory patternin comparison with PSV in different groups ofpatients.33---40

    Ineffective effort, i.e., inspiratory effort ofthe patient thatis not accompanied by mechanical assist, virtually disap-pears with NAVA.34 Likewise, in contrast to PSV, incrementsin assist level have been shown to exert less effect uponthe inspiratory and expiratory cycling times,35 ensuringbetter synchrony over a broad assist range. Patroniti et al.38

    have published a detailed description of the ventilatory

    pattern during NAVA. In patients with respiratory failure,the authors compared the response to increasing NAVAlevels with increasing PSV levels (Fig. 4). With NAVA, thepatients maintained similar Vt and respiratory frequencyvalues, even with high assist levels, despite an increase inPaw, which corresponded to a decrease in EAdi. In contrast,during PSV, both Vt and pressure increased (up to >100%with the maximum level), while the frequency and EAdidecreased.

    In the same way as during PAV, studies with NAVA haveshown that patients tend to select a protective tidal volume(6ml/kg) with moderate assist levels and a generally higherrespiratory frequency.

    The NAVA mode has been shown to facilitate assisted ven-tilation also in patients with seriously impaired respiratoryfunction. In this respect, the NAVAmode reduced asynchronyin patients subjected to extracorporeal oxygenation supportand with severely impaired lung distensibility37 versus PSV,and achieved better auto-regulation ofPCO2during weaningfrom extracorporeal oxygenation41---in both cases maintain-ing protective ventilatory parameters with low Vt values.

    Because of its operating characteristics, NAVA may beparticularly interesting in the context ofNIV, since it is notaffected by leakages. In this regard, Piquilloud et al.42 andBertrand et al.43 reported a significant reduction of asyn-chronies with NAVA versus PSV during NIV both in patientswith exacerbated COPD and in hypoxemic patients.

    NAVA and monitoring

    The EAdi signal offers new and interesting possibilities inrespiratory monitoring. By affording a direct and continuousmeasure of the central respiratory stimulus of the patient,the signal allows us to evaluate the response to changes inassist level, detect apneas, evaluate sedation effects, andalso assess the neural respiratory stimulus. EAdi is the besttool available for monitoring patient---ventilator synchrony,since it offers direct information on the neural inspiratoryand expiratory times and their relation to the mechanicaltimes. It allows us to determine the neural frequency (the

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    256 F. Suarez-Sipmann

    real frequency ofthe patient), thereby enhancing the valueof this variable in determining the degree ofpatient stressor wellbeing. A number of indices derived from the EAdisignal have recently been described. Neuroventilatory effi-ciency, measured as Vt/EAdi, indicates the capacity of thediaphragm to generate volume, standardizedwith respect tothe neuronal stimulus. In one same parameter it integratesinformation on the respiratory stimulus, diaphragmatic

    function, and respiratory loading, and has been shown tobe a good predictor ofweaning.44,45 Neuromechanical effi-ciency, measured as Paw/EAdi during an occlusion in whichthe patient inhales against a closed valve, provides an esti-mate ofthe capacity ofthe diaphragm to generate force inrelation to the neural inspiratory effort. Based on neurome-chanical efficiency, Bellani et al. have derived a method toestimate Pmus from EAdi, thereby producing more objectiveinformation for determining the best NAVA level.46

    Automated modes adaptable to patientdemands

    These modes encompass closed-loop control modes thatincorporate algorithms and control rules which transferphysiological and clinical reasoning principles to auto-mated assist protocols. According to different physiologicaland clinical objectives, these modes automatically adjustthe pressure or minute-volume levels administered to thepatient, adapting to the needs of the latter over time.Adaptive support ventilation (ASV) performs cycle-to-cycleadjustments of tidal volume (through changes in pressure)and respiratory frequency, adapting them to changes inrespiratory mechanics. NeoGanesh or SmartCareTM in turnperforms adjustments, in cycles ofseveral minutes, in deliv-ered pressure support ventilation, adapting the levels to the

    changing conditions of the patient. The aim is to simulateclinical reasoning in order to avoid under- or over-assistanceand to achieve a decrease of the automated support.

    Adaptive support ventilation

    Adaptive support ventilation (ASV), described in the earlynineties, is based on the physiological principle describedby Otis and Mead47,48 which establishes that for a given levelofalveolar ventilation there is an optimum respiratory fre-quency that results in less work ofbreathing---a kind oflawof minimum effort. According to this principle, in orderto reach one same alveolar ventilation level at very low

    frequencies, we require a greater Vt, increasing the workto overcome the elastic load of the respiratory system. Incontrast, at high frequencies, the work of breathing mustincrease to overcome the resistive load, with a pattern cha-racterized by rapid shallow breathing. Between these twoextremes lies the optimum combination of frequency andvolume for achieving the desired alveolar ventilation.

    Functioning ofASV

    Unlike the other examined modes, ASV in fact is a mixedmode that can function as a controlled or assisted modeaccording to the contribution of the patient.

    Figure 5 schematically represents the principles of thefunctioning and control system of ASV. The operator estab-lishes a target percentageminute-volume based on the bodyweight ofthe patient.

    Vmin =%Vmin ideal weight

    1000 in adult patients

    Under normal conditions, % Vmin is 100%, with the possi-bility of choosing between 25 and 300%, depending on theconditions ofthe patient.

    It should be remembered here that minute-volume is thesum of the alveolar ventilation volume (the effectivevolume) and the dead space volume. Accordingly, ASV incor-porates the estimation of dead space in its algorithm, andwhich the system assumes to be 2.2ml/kg. The ASV sys-tem then adjusts the level of pressure and respiratoryfrequency cycle-to-cycle, following its algorithm to main-tain the ventilatory pattern according to the establishedtarget minute-volume, in consistency with the mechanicalcharacteristics of the respiratory system and the spon-taneous respiratory frequency of the patient. Inspiratorycycling uses the conventional pneumatic trigger by pressureor flow, while expiratory cycling is by flow as in the case ofPSV.

    ASV: clinical characteristics

    Due to its mixed nature, ASV has been studied both ascontrolled mode and as assist mode. Most clinical studieshave focused on examining ASV under passive ventilation

    (controlled) conditions, comparing it with other modes,and specifically evaluating whether ASV yields protectiveparameters (low Vt and Paw) in an automated and efficientway.

    As assist mode (which is what interests us in this review),ASV has been studied mainly as a mode designed to facili-tate weaning. It has been shown to be a safe and effectivetechnique that simplifies the weaning process in the post-operative period of heart surgery49---51 and in patients withCOPD,52 and is moreover associated with a lesser consump-tion ofresources. In comparative studies, ASV has not beenfound to shorten the mechanical ventilation times in heartsurgery,50,51 though shortened times have been recorded inCOPD patients, where Kirakli et al. observed a shortening of

    the weaning time ofover 24 h compared with PSV.53The best comparative clinical study to date on the effect

    ofASV upon patient---ventilator synchrony was published byTassaux et al. In comparison with synchronized intermittentventilation (SIMV-PSV), these authors found ASV to improvesynchrony, reducing the muscle load for a similar deliveredminute-volume.54

    The ASV mode has recently received improvements, withaddition to the algorithm of closed-loop control for end-expiratory CO2 (etCO2)

    55 and oxygen saturation. The resultis an evolved ASV system called IntelliVentTM, which allowsus to implement a protective ventilatory strategy in boththe control phase and in assistance to weaning.56

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    New modes of assisted mechanical ventilation 257

    PinspFR

    PinspFR

    PinspFR

    PinspFR

    Tidalvolume

    Respiratoryfrequency

    FRTarget

    VTTarget

    I:E

    Pinsp

    Values entered by the clinician

    Body weight

    Target % min vol

    Pmax, PEEP, FiO2

    IsoVM

    curve

    Mechanics of the respiratory systemCompliance, resistance, PEEPi

    Flow/volume curve

    Expiratory time constant

    Calculation of

    respiratory frequency

    Figure 5 Functioning ofASV. Before starting, the clinician enters the data referred to patient weight, percentage minute-volume

    (estimated a priori according to the patient and disease condition), FiO2, PEEP and the maximum inspiratory pressure limit (Pmax).

    Analysis ofthe flow-volume curve determines the expiratory time constant, and minimum squares fitting is used to calculate the

    respiratorymechanics and the presence ofintrinsic PEEP. The closed-loop control algorithm ofthe ASV system adjusts the inspiratory

    pressure according to the iterative equation derived from Otis and Mead. The combinations oftarget minute-volume and frequency

    are continuously adjusted to reach and keep the patient on the minute-isovolumetric curve (IsoVM).

    Adapted from Tassaux et al.54.

    Automated adjustment ofpressure support:NeoGanesh-SmartCareTM

    NeoGanesh and its commercial version SmartCareTM consti-tute an automated, knowledge-based weaning technique.The control algorithm incorporates rules for action basedon clinical reasoning, in an attempt to reproduce the PSVadjustments which the clinician would decide in the samecontext.

    Functioning ofSmartCareTM

    The control algorithm of the system uses the values ofVt, respiratory frequency and etCO2. These values areaveraged every two minutes (every 5min in the case ofchanges in pressure level) and provide the algorithm witha ventilatory diagnosis. The system responds as follows:(1) it reduces the level ofPSV in the case ofdiagnosed over-assist (e.g., the combination of high Vt with low frequencyand etCO2); (2) it increases assist in the event of insuffi-cient assistance (increasing frequency together with otheradditional criteria); and (3) it introduces no changes in thecase of normal ventilation. The aim is to move the patienttoward a zone ofrespiratory wellbeing in order to start the

    weaning process. This zone ofwellbeing is derived from thepatient characteristics (body weight, type ofillness, size ofthe endotracheal tube, type ofhumidifier). The values areentered by the clinician in the ventilator, and determine thelimits ofVt, frequency and etCO2, and the PSV adjustmentsrequired. The automated weaning protocol involves auto-matedadaptationofthe PSV level followed by an automatedPSV reduction phase, and finally an automated spontaneousbreathing test.

    SmartCareTM: clinical characteristics

    SmartCareTM is able to facilitate the weaning process,reducing resource consumption and shortening the timeon mechanical ventilation. Clinical studies have reportedsomewhat discordant findings in relation to such benefits,depending on whether the control group included57 or didnot include58 weaning protocols and sufficient resources(patient/nurse ratio).59 In themost recentmulticenter studyinvolving 92 patients with over 24 h ofmechanical ventila-tion, automatedweaning shorted the duration ofmechanicalventilation by one day, and also lessened the need fortracheostomy compared with a protocolized conventionalweaning group.60

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    258 F. Suarez-Sipmann

    Variable pressure support ventilation (noisyventilation)

    Variability is an intrinsic characteristic not only of the res-piratory system but also of any complex biological system,and the loss of such variability is generally associated withfunctional impairment.61 There is a growing evidence of thebeneficial effect ofvariability, understood as cycle-to-cycle

    changes in Paw and Vt and/or respiratory frequency, uponthe respiratory system.62 All the new assist modes describedthus far introduce respiratory variability, the latter beingdetermined to one degree or other by the patient. Variablepressure support ventilation (V-PSV) introduces random vari-ability in the levels ofpressure support ventilation, resultingin a ventilatory pattern that is variable but independent ofthe demands ofthe patient and his or her inspiratory effort.

    Functioning ofvariable ventilation

    V-PSV (noisy ventilation) is based on the recurrent applica-

    tion ofa set of600 pressure values generated on a randombasis. These values follow a normaldistribution,with a meanand standard deviation adjusted to achieve the desired levelof variability (measured by the coefficient of variation; ingeneral 10.3, to afford a variability of30%).63 The meanpressure value is adjusted to obtain a Vt of6ml/kg, and thepressure limits are determined by the adjusted upper pres-sure limit and the expiratory pressure level (PEEP or CPAP).The clinician can adjust the level of variability between 0and 100%, and the systemmaintains a stablemean pressure.

    Experimental studies have consistently shown benefi-cial physiological effects, such as improved gas exchangeand respiratory mechanics. A relevant aspect is the possi-ble benefits in terms of lung protection.64 The mechanisms

    underlying the improvement in respiratory mechanics arenot fully clear, but an alveolar recruitment effect has beenpostulated, together with possible stimulation of the pro-duction and release ofsurfactant.65

    Although an attractive mode, the lack of clinical datameans that many questions still need to be answered beforethe true clinical usefulness of the technique can be estab-lished. As an example, what pattern or level of variabilitywould have been most appropriate for a given situation? Inthis respect, Spieth et al.63 used an experimental surfactantdepletion model to show that the best choice for improv-ing respiratory mechanics and gas exchange corresponds toa coefficient of variation of 30%, which interestingly coin-cides with the normal respiratory variability values duringspontaneous ventilation.63 In patients we will have to deter-mine whether this level of variability is also optimum, andwhether extrinsic variability offers advantages with respectto the intrinsic variability ofthe patient (such as that intro-duced in PAV or NAVA), as well as explore the effects uponpatient---ventilator synchrony.

    Conclusions

    These are very interesting times for mechanical ventila-tion. The constant technological advances have allowed thedevelopment of new assisted ventilation modes with the

    capacity to adapt to the changing patient needs. The newmodes allow the patient a total control of the ventilatoryprocess, causing the ventilator to act as an accessorymusclein synchronywith patient inspiratory effort. Newmodes thatincorporate increasingly complex closed-loop or knowledge-based control systems are paving the way toward gradualautomatization of the mechanical ventilation process. Itcan be expected that such modes and automatization will

    gradually find their way into routine clinical practice. Theresults of future studies will help us to better define theiradvantages, indications and benefits in assisting patientssubjected to mechanical ventilation.

    Conflicts of interest

    The author serves as a consultant to Maquet Critical Care.

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