Neonatal high-frequency oscillatory ventilation where are we now

Neonatal high-frequency oscillatory ventilation: where are we now?

Arch Dis Child Fetal Neonatal Ed 2023

Episode Transcript

(00:00):
Review Neonatal high frequency ascillatory ventilation.Where are we now? H David gerl
Tingay one two. This article isavailable for download from the Telegram Neonatologer Channel
abstract. High frequency ascillatory ventilation HFOVis an established mode of respiratory support in

(00:23):
the neonatal intensive care unit. Largeclinical trial data is based on first intention
use in pre term infants with acuterespiratory distress syndrome. Clinical practice has evolved
from this narrow population. HFOV ismost often reserved for term and pre term
infants with severe and often complex respiratoryfailure not responding to conventional modalities of respiratory

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support. Thus, optimal and safeapplication of HFOV requires the clinician to adapt
mean airway pressure, frequency, inspiratoryexpirtree ratio, and tidal volume to individual
patient needs based on pathophysiology, lungvolume state, and infant size. This
narrative review summarizes the status of HFOVin neonatal intensive care units today, the

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lessons that can be learned from thepast, how to apply HFOV in different
neonatal populations and conditions, and highlightspotential new advances. Specifically, we provide
guidance on how to apply an openlung approach to mean airway pressure, selecting
the correct frequency and use of volumetargeted HFOV introduction. It is more than

(01:38):
forty years since the first report ofhigh frequency a sillatory ventilation HFOV use in
humans. Since then, HFOV hasbeen studded extensively in neonates. These trials
generally failed to replicate the lung protectivepotential of HFOV compared with conventional mechanical ventilation
CMV seen in animal studders. Nonetheless, HFOV is now a well established ventilation

(02:06):
mode for severe respiratory failure, bothin preterm and in term infants. Foremost
clinicians, due to highly effective ventilation, HFOV represents a rescue therapy when CMV
is failing. This narrative review summarizesthe status of HFOV delivered via an endotracheal
tube in neonatal intensive care unit NIQUEtoday. The lessons that can be learned

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from the past provides guidance on howto apply HFOV and highlights potential new advances
HFOV. How does it work?HFOV involves the delivery of very small tidal
volumes often less than anatomical dead spaceat very fast rates. During HFOV,

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a continuous distending mean airway pressure PAWis applied to the lung around which a
pressure wave oscillates. Then PAW determineslung volume, alveolar surface area for gas
exchange and pulmonary blood flow, andis the principal factor in oxygenation in an
appropriately recruited lung. Amplitude of thispressure wave p absolute inspiratory time defined by

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its frequency F and inspiratory expytory ie. Ratio of the pressure wave and
the mechanical properties of the intubated respiratorysystem determine the tidal volume VT and minute
ventilation, and thus the rate ofCO two clearance two F VT DCO two.

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When applied optimally for a given setof lung conditions, HFOV provides effective
oxygenation and ventilation while potentially minimizing associatedlung injury. HFOV at frequencies and GT
six h set avoids large pressure andvolume shifts during ventilation, and uses mechanisms

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other than the bulk flow characteristic ofCMV to achieve gas transport. Ten five
mechanisms of gas transport have been describedturbulent mixing, asymmetric velocity profiles also termed
nonlinear means streaming or steady streaming,tailor dispersion, molecular diffusion, and lagrangein
drift. Nonlinear means streaming and lagrangeand drift are often conflated. However,

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they are distinct mechanisms. Nonlinear meansstreaming is a non zero average velocity of
gas flow at a given location.Lagrange and drift is the net motion of
a gas parcel over an inflation cycle, that is, the difference between the
position of the gas parcel at thestart and end of the cycle. Penderlufft
deffect and cardiogenic mixing are additional gastransport mechanisms that could operate during HFOV.

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However, these mechanisms are unlikely tocontribute meaningfully to gas transport between the lung
and oscillator. Our understanding of gastransport during hfo V arises from lung mechanics
models that consider only the flow ratevolume of gas passing across the cross section
of an airway per unit time,rather than the details of the flow field,

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the gas velocity at every point inthe airway Critically, these models cannot
fully incorporate the different gas transport mechanismsoperating in vivo. Recent advances in computational
fluid dynamics allow analysis of h FOVgas transport using more complex lung mechanics models.
These models show that gas transport arisingfrom these mechanisms is a function of

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the ratio of inertial to viscous forces. Inertia is proportional to gas flow and
reduces at each subsequent generation of theairway from the trachea to the alveoli.
This reduced inertia is a consequence ofthe increased total cross sectional area at each
successive airway generation to carry a givenflow rate, thereby reducing the flow rate

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and flow velocity. Viscous forces areinversely proportional to airway vessel diameter. Review
This article is available for download fromthe Telegram Neonatologer channel, and therefore increase
at each subsequent generation of the airway. Hence, different gas transport mechanisms operate

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at different levels of the airway.Turbulence will only occur in the trachea and
primary Bronchi nonlinear mean streaming, tailordispersion and lagrange and drift operate in the
upper and middle generations, while moleculardiffusion is effective in the viscous dominated flows
near the terminal bronchiolis. Consequently,gas exchange and potential for airway and lung

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injury is driven by different mechanisms indifferent parts of the airway. State of
evidence for HFOV in infants nineteen randomizedcontrolled trials compare first intention HFOV with CMV
in preterm infants with early respiratory distresssyndrome RDS. All trials use the composite

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outcome of survival free of broncho pulmonarydysplasia BPD as the primary outcome, but
often with different BPD definitions. Thesetrials are best summarized by the most recent
individual patient data meta analysis. Overall, HFOV did not reduce the incidence of

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mortality, BPD, or other importantcomorbidities compared with CMV, although HFOV use
reduce the need for surgery for patentductors arteriosis. These findings differ slightly from
the most recent systematic review of HFOV, which are identified a small but statistically
significant reduction in the incidence of BPDand the composite outcome of death or BPD,

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an increase in pulmonary air leak comparedwith CMV and online supplemental tables.
One interpretation is hampered by the highheterogen between trials, especially with regard to
outcomes an HFOV strategy. Two earlytrials applied an HFOV paw at or below
the CMV paw. Neither of thesetrials found a benefit of HFOV on mortality

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or BPD and pulmonary air leak.An intraventricular hemorrhage IVH were increased in the
Hiphi trial. HFOV strategies evolved followingthese early trials, specifically appreciating the importance
of optimizing lung recruitment. The useof a high volume strategy HVS during elective

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HFOV for RDS accounts for the reductionin BPD on meta analysis without the reported
risks in earlier trials. Despite awarenessof the importance of an HVS protocol,
compliance was variable. An review thisarticle is available for download from the Telegram.

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Neonatology Channel HVS is broadly defined asat least one of one using an
h fo V poor higher than CMVpoor two Weening fraction of inspired oxygen FIO
two prior to p a W duringHFOV, and or three the use of
any intentional recruitment maneuver. Of these, the use of an alveolar recruitment maneuver

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is the least commonly applied aspect ofHVS. Five out of nineteen studys,
a cumulative meta analysis has demonstrated theimportance of the long protective approach for both
the HFOV and the CMV strategy totrial outcomes. Many of the large trials
of h f o V are nowover ten years old. Ongoing evolution of

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CMV means that for many the CMVstrategies are not considered lung protective to day.
Features missing to varying degrees from priortrials include the use of one synchronization
and promoting spontaneous breathing, two earlyextubation, three a physiological tidal volume approach
specifically using volume targeted modes while allowingfour four permissive hypercapnea, five ventilator settings

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that promote physiologically appropriate, mandatory andspontaneous inflations to provide sufficient co O two
wash out, and six adequate positiveend expiratory pressure PEEP to prevent adialectics.
Only six of the nineteen trials metthese long protective CMV criteria an online supplemental

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table s two. Ten of thenineteen trials use synchronization, seven used volume
targeted ventilation, and eight trials reportedthe use of a minimum peep greater than
or equal to four CMH two O. Other now accepted protective aspects of pre
term management, including antenatal corticosteroids andexogenous seffactant therapy, are variably included in

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the reported trials online supplemental Table sthree. As such, the overall severity
of early lung disease following preterm birthhas lessened since many trials of elective HFOV
for rds were conducted, as hasthe need for intubation rescue. HFOV when
CMV has failed has not been subjectedto rigorous trial evaluation in either pre term

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or term infants. In summary,the available trial data are limited to generalizations
on the safe and effective use ofHFOV. Specifically, systematic review of these
trials impresses the importance of adequate lungrecruitment HVS during management of lung diseases characterized
by adelecticis Thus, optimally recruiting thelung at the bedside requires the clinician to

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understand how HFOV can be individually appliedto each infant. Optimal application of hfov
non respiratory considerations. Unlike CMV,hfo V delivers a constant and high intrathoracic
pressure. Consequently, a transition fromCMV to HFOV may worsen hemodynamic instability and

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necessitate commencement or adjustment of an atropeand or vasopressor support in addition to any
existing cardiovascular dysfunction, as well ascorrection of any biochemical and fluid imbalances.
Pulmonary hypertension and right ventrical dysfunction oftencoexist in infants with severe respiratory failure.

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Inhaled nitric oxide and HFOV are synergisticin pulmonary hypertension related to perencomal lung disease.
The higher byers flow an impact ofbreathing over a fixed higher intrathoracic pressure
during HFOV are poorly tolerated by someinfants, and analgesia, sedation and occasionally
muscle relaxation may be required. Settingthe paw in the recruitable lung. Clinical

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and animal studders consistently demonstrate that correctlysetting the PAW is essential for safe and
effective h fo V, but doingso can be challenging. The optimal PAW
for gas exchange is variable during hf o V and rarely predictable from the
c m V POW. While anHVS is important in conditions characterized by adalectics,

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practical issues such as what p awabove CMV poor to use and how
and when towen FIO two and pa W are not addressed in the met
analysis definition of h vs. Fthree review. The twenty nineteen European Consensus
Guidelines on the Management of RDS recommendan open lung approach on initiation of h

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fo V. Open lung strategies areh vs that provide a method of determining
the optimal p a W and arebased on Lackman's concept of optimizing lung volume.
Collapsed lung regions should be recruited openingthe lung to gas exchange prior to
utilizing lung hysteresis to find the closingpressure and finally applying ongoing ventilation at the

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lowest PAW that maintains recruitment optimal pressurePOPT. This approach aims to target ventilation
on the deflation limb of the quasistaticpressure. Volume relationship of the lung.
Human and animal studders show that applyingHFOV at POPT maximizes oxygenation, lung mechanics,

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ventilation, and uniformity of aeration.Unfortunately, the paw that opens the
adalectatic lung popen, POPT and closingpressure are unknown in each infant. A
POPEN review this article is available fordownload from the Telegram. Neonatology channel ranging

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from eleven to thirty CMH two Ois reported in preterm infants. Consequently,
a step wise approach to p changesis usually applied to determine both popen and
POPT. A core principle of anyopen lung strategy is how lung volume is
defined after a PAW change. Theability of direct measures of volume lung ultrasound

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forced oscillation technique an electrical impedance tomographyto reliably guide PAW changes has not yet
been established. Oxygenation is related tolung volume state during HFOV allowing oxygenation.
Usually the s F ratio SPO twofio two to be a proxy measure of

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volume changes. Improvements in oxygenation withincreasing PAW indicate lung recruitment, while deteriorating
oxygenation indicates at electicis or over distensionfollowing a PAW decrease or increase, respectively.
Provides a suggested approach to applying anopen lung strategy during HFOV in suitable

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infants. See online supplemental figure Sone for volume targeted HFOV algorithm. Most
reports advocate recruitment using two CMH twoO stepwise changes in PAW based on observations
in acute RDS. Less than twominutes is sufficient to stabilize lung volume in
preterm infants with acute RDS, butat least five to ten minutes is required

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in term infants or older preterm infantswith more heterogeneous disease. The longer time
in more mature infants reflects the differentlung pathologies, chest wall mechanics, and
larger volume changes. The time neededfor changes in peripheral oxygenation to be expressed
by bedside monitoring devices also needs tobe considered. To date, no large,

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multi center randomized trials have evaluated HFOVopen lung approach strategies. Initial reports
on the use of open lung approacheswere restricted to observational studies with fixed frequency
p and one to two i Eratio. Following changes in unit practice or
observational physiological studies. All these reportsdemonstrate improved oxygenation and all lung mechanics compared

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with values prior to the open lungstrategy. Importantly, the popt was consistently
two to four cmh two oh abovethe closing pressure. More recently, two
single side interventional trials, including eightyeight and three hundred and sixty four pre
term infants randomly allocated to first intentionCMV or open lung approach HFOV, both

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reported shorter duration of mechanical ventilation andin one study less bpd. Air leak
was not higher in any reports ofopen lung approach HFOV. While caution must
be applied to the benefit and safetyof open lung strategies, these studies demonstrate
that an open lung algorithm can beapplied at the bedside and is well tolerated

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in correctly selected infants. The traditionalview that ventilation and oxygenation are independent during
HFOV is a misnomer. Changes inlung volume during HFOV impact lung compliance VT
and DCO two with optimal CO tworemoval VT and DCO too occurring at popt

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for oxygenation. Conversely, ad electicisand over distension will worsen Ventilation including measures
of VT and DCO two and ortranscutaneous CO two during open lung strategies is
recommended to refine PAW identification and avoidlarge CO two shifts. A potential advantage

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of an open lung approach is thatit can be individualized to the prevailing lung
pathophysiology. Hence, an open lungapproach may be applied to any type of
recruitable lung disease, including RDS,neonatal acute RDS, aspiration syndromes, and
pneumonia. A step wise recruitment approachallows the clinician time to assess clinical response

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and make decisions that are more likelyto avoid prolonged exposures to inappropriately high or
low PAW. A potential limitation ofopen lung approaches is the need to transiantly
and LT five minute expose the infantto deoxygenation or cardio respiratory instability associated with
the respective accompanying over distension and adelecticisto define popen and closing pressure. This

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necessity potentially limits broader uptake of thestep wise recruitment approach and emphasizes the need
for adequate staff training. Nonetheless,these brief periods of hypoxic exposure to achieve
sustained improved oxygenation are arguably likely tobe less harmful than the potential for prolonged
periods of suboptimal lung volumes during ventilationat an inappropriate PA double setting the PAW

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in the non recruitable lung. Notall causes of neonatal respiratory failure are recruitable
online supplemental Table s four for examples, the use of an HVS and specifically
an open lung approach is only indicatedin a recruitable lung with adialectasis. Using
an HVS in conditions or situations ofpulmonary hypoplasia, gas trapping, and cardiac

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failure without primary lung disease is generallycontraindicated. Often these conditions require a PAW
at or less than cmv poor anda focus on avoiding over distension and or
inadvertent volume trauma. A recent prospectiverandomized trial. The victure trial comparing first
intention HFOV and CMV for congen I'LLdiaphragmatic hernia CDH found hfovuse was a SOCIE

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aided with a longer duration of ventilationand higher treatment failure. This finding was
surprising as HFOV is often used inthe management of CDH. The discrepancy likely
reflects the relatively high PAW used inthe intrathoracic pressure on abnormal die fram structure
and Vitter trial. Impact of constanthigh function and the impact on any concombinant

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cardiac dysfunction. Setting the frequency andI E ratio. Although frequency is usually
the least changed setting during HFOV,establishing the correct frequency is critical to ventilation
and lung protection. Unlike CMV,frequency directly impacts delivered VT, and setting

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the frequency requires consideration of lung pathology, infant size, lung mechanics, endotracheal
tube size, and risk of lunginjury. Frequency also influences the transmission of
p potentially impacting the risk of baritrauma. This pressure. Cost of ventilation decreases
as frequency is increased. Resonant frequenciesand GT fifteen hz have been reported in

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preterm infants with RDS and gas exchangemay be maintained at sixteen to twenty herts.
In some preterm infants, however,minimal add a tinal pressure. Damping
is achieved by increasing the frequency beyondthe corner frequency FC of the lung fc
one or two RC, where isresistance and c's compliance in the over damped

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neonatal lung is normally below the resonantfrequency. Unfortunately, practically determining the corner
and resonant frequency is not easily achievedat the bedside. Provides a clinical approach
to applying an initial frequency. TheI E impacts both inspiratory and expiratory VT,
with ratios of one to two inspiratorytime half as long as expiratory time

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at any given frequency, or oneto one inspiratory an expirtory time equal.
Most commonly used at any given frequency, I E of one colon two will
deliver a lower VT and PAW thanan I E of one colon one and
introduces a variable paw drop of twoto four cmh two O between the airway

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opening and the lung, which mayenhance gas transport. Online supplemental Figure S
two. Clinical data on the settingof I E ratio are lacking, but
preclinical and bench studies provide a rationaleto use a ratio of one to two
when gas trapping is present. Reviewdelivering tidal ventilation, modern ventilators incorporate tidal

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volume measurement and display an index ofventilation DCO two. A DCO two of
forty to sixty mL two a kilogramtwo s generally achieves arterial partial pressure of
carbon dioxide PACO two in the mildpermissive hypercapneic range. Higher d two is
required with increased size, decreased spontaneousbreathing frequency, and potentially also with more

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severe lung disease. Changes in DCOtwo are achieved indirectly by changes in tidal
volume by adjusting p and frequency.Importantly, higher tidal volumes are required at
lower frequencies to achieve the same DCOtwo, increasing potential for volume trauma.
Newer oscillators offer an option to moveaway from the traditional pressure control delivery of

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a sillatory ventilation to a pressure limited, volume targeted mode. A key motivation
for using volume targeted ventilation during HFOVis the appreciation that VT changes as the
lung compliance changes A potential consequence ofthis relationship is unwanted fluctuations in PACO two

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and cerebral blood flow. Volume targetingduring HFOV thus offers the possibility of more
protective and stable ventilation and potentially morerapid weaning of P during lung volume recruitment
as lung disease resolves, Using volumetargeting during h fo V requires the clinician
to think differently about how to achievea desired change in DCO two for any

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given target VT. An increase infrequency increases DCO two i opposite to pressure
controlled h fo V, as theventilator will maintain the set VT provided pmax
or ventilator capacity is not limiting VTdelivery. In contrast, reducing frequency increases
the proportion of P delivered to thelung, and thus it remains important to

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target ventilatory frequency close to FC.Exemplar VT and DCO two for infants of
varying weights are provided in due tothe risk of large CO two shifts with
PAW changes. The use of volumetargeted hfo V is appealing during open lung
strategies, although clinical reports are lacking. Similarly, some adjustment is required when

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using volume targeted h FOV for definingpo PT during volume recruitment, the popt
and best lung mechanics being indicated bythe lowest value of displayed p Conclusions.
Large clinical trial data are based onfirst intention use of h FOV in acute
RDS in preterm infants. Clinical practicehas evolved from this narrow population, with

(26:30):
h fo V generally a rescue therapyfor a diverse range of infants and complex
causes of respiratory failure. Evidence forthe ideal h f o V rescue therapy
strategy remains scarce. Thus, optimaland safe application of h FOV requires the
clinician to adapt p AW frequency,i E. Ratio and VT to individual

(26:55):
patient needs based on pathphysiology, lungvolume state, and infant size. This
article is available for download from theTelegram Neonatology channel