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Neonatologist, Perth Children’s Hospital, Australia
MBBS, MD, DNB, DM, FRACP, MSc (Biostatistics)
Probiotics in surgical infants, biostatistics, systematic reviewsA/Prof Shripada Rao
Volume Guided Ventilation: Why is there gap between evidence
and practice?
A/Professor Shripada Rao, MBBS, MD, DNB, DM, FRACP
Neonatologist
Perth Children’s Hospital
University of Western Australia
Topics to cover
1. Basics of different types of ventilation
2. Evidence for Volume Targeted Ventilation in neonates
3. Barriers to implementation
4. How to facilitate implementation
5. Scope for further research
Pressure Controlled Ventilation
• In pressure controlled ventilation, clinician sets the pressure to achieve the desired tidal volume
• Standard modality in neonates
• SIMV, SIPPV, PSV
Pressure Controlled Ventilation
Stiff lung Low tidal volume
After surfactant High Tidal Volume
ETT secretions Decreases TV
Pneumothorax Decreases TV
Excessive crying Widely fluctuating TV
Muscle relaxation Decreases TV
Thorough suctioning Increases TV
For the same set PIP
Pressure controlled ventilation
• Consistent VT delivery is not possible with pressure control
modes
• Variable tidal volumes, lead to Volutrauma
Morley et al. Clin Perinatol. 2012
Experiments in rats
High PIP, High VT strategy
Low (Negative) PIP, High VT
High PIP, Low VT
(Strapped chest and abdomen)
Controls: very low PIP, very low VT
P<0.01
Volutrauma is more harmful than barotrauma
Adapted from Dreyfuss, Am Rev Respir Dis 1988
Horizontal linerepresents the upper 95% CI limit for control values
Pulmonary capillary permeability
Adapted from Dreyfuss, Am Rev Respir Dis 1988And Goldsmith: Assisted Ventilation in neonate
Experiments in rats
High PIP, High VT strategy
Low (Negative) PIP, High VT
High PIP, Low VT
(Strapped chest and abdomen)
Controls: very low PIP, very low VT
Horizontal linerepresents the upper 95% CI limit for control values
Other problems with fluctuating tidal volumes
• Variable tidal volumes can lead to hypercarbia and hypocarbia
Kaiser, Pediatrics, 2007
Hypercarbia and hypocarbia increase the risk of IVH and PVL
Fabres J, Pediatrics 2007Fujimoto, Arch Dis Child 1994;
• Volume Guided Ventilation may be the solution
• In PCV, the control variable is PIP
• Cycling is by time (or flow)
• Volume depends on compliance/resistance
• In traditional volume-controlled ventilation, VT delivery is directly controlled;
• Cycle ends when set VT is delivered• PIP rises passively
Martin Keszler and Colin Morley; In JP Goldsmith, Textbook of assistedventilation in neonates, 2017
Pressure Ventilation vs Traditional Volume Control
Traditional Volume Controlled Ventilation
• Used in Adults and Children
• May not be feasible in neonates
Martin Keszler and Colin Morley; In JP Goldsmith, Textbook of assisted ventilation in neonates, 2017
Traditional Volume Controlled Ventilation is difficult in neonates
• A relatively large portion of the
volume delivered into the circuit is
lost to:
1. The humidifier
2. elastic tubing
3. Leak because of uncuffed
ETTs
VT reaching the lungs is different
from the set VT
Alternative is Volume Targeted Ventilation
• VT -targeted ventilations are modifications of conventional pressure-
controlled ventilation
• They deliver a target VT by microprocessor-directed adjustments of
PIP
• There is automatic adjustment of PIP to deliver a user-set VT
Kezsler 2019, Archives in Childhood-Fetal and Neonatal Ed
Types of Volume Targeted Ventilation
• Volume limit ventilation; Targeted tidal volume (TTV)
• Pressure regulated volume control (PRVC)
• Volume assured pressure support (VAPS)
• Volume Guarantee: Most common type of volume targeted ventilation
Keszler, Early Human Development, 2006
1. The clinician sets the VT
2. The clinician sets the maximum
PIP
3. The flow sensor at the ETT end
measures the exhaled VT
4. And feeds info to the ventilator
5. The ventilator adjusts the PIP up
or down accordingly
Volume Guarantee Ventilation
Adapted from Samir Gupta et al. Pediatrics and Child Health, 2015
Upper limit PIP
• Volume Targeted ventilation can be used along with SIPPV, SIMV or PSV Mode
Hummler H et al. Pediatr Pulmonol 1996;22:305–13.
Triggered vs Untriggered breaths in VG mode
• Because of VG, tidal volume remains relatively constant
• For triggered breaths, the ventilator uses lower PIP
• For Untriggered breaths, it uses higher PIP
Klingenberg C. J Perinatol 2011
Potential advantages of Volume Guarantee Ventilation
• Stable VT delivery; Less Volutrauma
• Auto-weaning of PIP, Less barotrauma
• Stable VT>Stable Minute Volume>Stable PaCO2
• Results in stable cerebral blood perfusion and reduced brain injury
• Weaning occurs in real time, rather than in response to blood gases
• Faster weaning from mechanical ventilation
The ventilators we use for VG
Babylog 8000+ VN 500
Evidence for beneficial effects of Volume Targeted Ventilation in neonates
• Klingenberg C, Wheeler KI, McCallion N, Morley CJ, Davis PG.
Volume‐targeted versus pressure‐limited ventilation in neonates. Cochrane Review 2017
Cochrane Review
• 1065 neonates from 20 RCTs
• Majority: preterm infants <32 weeks or <1500g
• Individual study sample size: 15 to 212 infants
• 17 trials recruited infants in the early neonatal period (<3 days)
• Three trials enrolled preterm infants with mean postnatal age between 33 and 37 days
• RR: 0.73 [0.59, 0.89]
• Total Sample size: 584
Cochrane Review 2017
Death or BPD
• RR: 0.75 [0.53, 1.07]
• N: 771
Mortality before discharge
• RR: 0.68 [0.53, 0.87]• Sample size: 620
Cochrane Review 2017
BPD
RR: 0.53 [0.37, 0.77]Sample size: 712
Severe IVH
RR: 0.45[0.21, 0.98]Sample size: 508
PVL
RR: 0.52 [0.31, 0.87]Sample size: 825
Cochrane Review 2017
Pneumothorax
MD: -1.35 [-1.8, -0.86]N=736
Cochrane Review 2017
Duration of Ventilation
RR: 0.71[0.42, 1.21]
N=246
Cochrane Review 2017
Death (<1000g)
RR: 0.79 [0.62, 1.01]N=224
Cochrane Review 2017
Death or BPD (<1000g)
MD: -0.82 [-4.43, 2.80]
N=198
Cochrane Review 2017
Duration of positive pressure ventilation (<1000g)
RR: 0.63 [0.29, 1.37]
N=247
Cochrane Review 2017
Pneumothorax (<1000g)
Severe IVH (<1000g)
RR 0.53 [0.27, 1.04]N=184
Cochrane Review 2017
Severe IVH or PVL (<1000g)
RR 0.39, 0.99]N=145
Cochrane Review 2017
Severe disability (<1000g)
RR 0.86 [0.47, 1.59]N=209
Cochrane Review 2017
Conclusions by Cochrane Reviewers
• Compared to PLV ventilation, Infants ventilated using VTV modes had reduced rates of
• Death or BPD
• Pneumothoraces
• Hypocarbia
• Severe cranial ultrasound pathologies
• Further studies are needed to identify whether VTV modes improve neurodevelopmental outcomes and to compare and refine VTV strategies
Cochrane Review 2017
Barriers to Implementation
Keszler M, 2013
North American survey-2019
• USA and Canada
• VTV use: 39% in the USA
81% in Canada
Gupta A, Keszler M. Am J Perinatol. 2019
Admin Issues 11%
Equipment not available
26%
Lack of training 13%
Lack of understanding
49%
Miscellaneous 6%
Gupta A, Keszler M. Am J Perinatol. 2019
Reasons for not implementing
Lack of support from senior colleagues!!
Australian and Nordic Survey-2011
• 50 Neonatal Units
• VTV was routinely used in 50% of units
Klingenberg C, Arch Dis Child Fetal Neonatal Ed 2011
Italian Survey
• Volume Targeted ventilation was used in 28% of the NICUs (31/113)
Petrillo F, Italian J Pediatrics, 2019
Too many terminologies and modalities
• Volume Controlled Ventilation; Volume Targeted Ventilation
• Volume Guided Ventilation; Volume limit ventilation
• Volume Guarantee Ventilation; Volume Cycled Ventilation
• Targeted Tidal Volume Ventilation; Pressure regulated Volume control
• Volume assured pressure support ventilation; AND much more!!
How to Introduce VG in the Unit?
• Implement it after much training
• Have a clearly written protocol
• Follow evidence based guidelines for VG
• Don’t try on very sick babies
• Try on stable babies initially
• Have a local champion or ‘super-user
Recommended initial tidal volume and peak inflation pressure settings
Condition Initial VT Initial PIP limit
Preterm RDS 1250–2500 g
4–4.5mL/kg 26 cm H2 O
Preterm RDS 700–1249 g
4.5–5mL/kg 24 cm H2O
Preterm RDS<700g
5.5–6mL/kg 24 cm H2O
Preterm evolving BPD, 3 weeks old
5.5–6.5mL/kg 26 cm H2 O
Severe BPD 7–12 30 cm H2 O
Keszler 2019, Archives in Childhood-Fetal and Neonatal Ed
Recommended initial tidal volume and peak inflation pressure settings
Condition Initial VT Initial PIP limit
Term MAS with classic CXR* 5.5–6 28 cm H2O
Term MAS with white-out CXR
4.5–5 30 cm H2 O
Term CDH 4–4.5 24 cm H2 O
Term or late preterm; Normal lungs
4-4.5 18 cm H2O
Keszler 2019, Archives in Childhood-Fetal and Neonatal Ed
The larger VT/kg requirement in the smallest infants is due to the larger impact of dead space of the flow sensor (0.7 to 1.1mL)
Nassabeh-Montazami. Pediatr Pulmonol 2009
Keszler 2006, Early Human Development
Future RCTs?
• Limitations of evidence: Individual studies had small sample size (20 to 212)
• Largest study (n=212) found no evidence of benefit
• No confirmed evidence of benefit in infants<28w
• Multicentre Mega trial/s, especially <28w
• Long term respiratory and neurodevelopmental outcomes needed
• RCT: Less likely in countries where VTV has been standard of care
• Multicentre RCT in India: Why Not?
Conclusions
• We need to Implement VTV or conduct a mega trial
• Status Quo may not be a great approach
Useful Resources
• Keszler M. Arch Dis Child Fetal Neonatal Ed. 2019 Jan;
• Klingenberg C. A practical guide to neonatal VG ventilation. J Perinatol2011
• Gupta, Samir; Janakiraman, Sundaram. Volume ventilation in neonates. Paediatrics and Child Health, January 2018
• Morley. Volume-limited & volume-targeted ventilation. Clin Perinatol2012
• Textbook of Assisted Ventilation in Neonates: JP Goldsmith
Thank you