Grand Rounds November 2009

Sarah M. McMullen,
R5 CCM
Tuesday November 3, 2009

This presentation has been adapted to enhance online viewing

 to review the benefits of allowing preserved
spontaneous breathing in acute respiratory
failure, emphasizing ALI/ARDS

 to review partial ventilatory support modalities
used in acute respiratory failure

 to present the results of a systematic review

 Acute inflammatory lung injury
› resulting from direct or indirect pulmonary insult
 American-European Consensus Conference
(1994) definitions:
› ALI
 Acute pulmonary failure with PaO2/FiO2 <300mmHg
 Bilateral infiltrates on chest film
 PCWP <18 mmHg, or no clinical evidence of elevated LAP
› ARDS
 as above, with PaO2/FiO2 <200mmHg, regardless of
PEEP

 EARLY
› Exudative: infiltration, activation of inflammatory
cells  endothelial injury, capillary disruption,
pulmonary oedema
› Proliferative: fibroblastic infiltration and
remodelling
 LATE
› Fibrotic: consolidation, fibrosis  stiff lungs

 Alveolar collapse
› Superimposed pressure on the lung
› Cephalad shift of diaphragm
 Diffuse lung consolidation, multifocal patchy
involvement and lobar or segmental disease
 Primarily in DEPENDANT lung regions
› Ventilation and perfusion are no longer matched
› Severe arterial hypoxaemia

 Open Lung Approach: PEEP, low tidal
volume, static peak pressures, permissive
hypercapnia

 Adjuncts: prone position, inverse ratio, iNO,
tracheal insufflation, HFO, liquid ventilation,
ECMO, pharmacologics

 Haemodynamics
 Monitoring
 Gastrointestinal
 Renal
 CNS
 Weakness
 Immune system
 Sleep

 Barotrauma
 Heterogeneous ventilation
 Physiologic dead space and shunt
 Diaphragm and respiratory muscles disuse,
atrophy
 Mucociliary dysmotility
 Ventilator-associated pneumonia (VAP)
 Ventilator-associated lung injury (VALI)

VILI/VALI
The Lancet 2003

VENTILATOR ASSOCIATED LUNG INJURY:
COMPONENTS
VOLUTRAUMA
overdistension (High EIV)
ATELECTRAUMA
damage
shear injury
BIOTRAUMA
inflammatory mediator-related
BAROTRAUMA
injury
high pressure damage
OXYGEN TOXICITY

 Early institution of modes allowing
spontaneous breathing (SB) helps mitigate
complications associated with controlled
mechanical ventilation (MV)

 Physiologic and haemodynamic benefits are
associated with preserved SB

 Improved VA/Q matching, gas exchange
› By allowing contraction of the diaphragm
› Improved ventilation of dependant areas 
better V/Q matching, less atalectasis and shunt
 Improved cardiac indices: CO, CI, and less
use of vasopressors/inotropes
 No increase to oxygen cost of breathing
 Less analgo-sedative drugs

 Pressure Support
 SIMV
 APRV – airway pressure release ventilation
 PAV – proportional assist ventilation
 NAVA – neurally adjusted ventilatory assist

 Gold standard of partial ventilatory support
 Can be used in early ARF and during weaning
 The patient’s inspiratory effort triggers the ventilator, which
delivers a flow up to a preset pressure limit depending on
the desired minute volume
› Note: the pressure delivered is independent of the amount of
patient effort
 Flow cycles off when a percentage of peak inspiratory flow
is reached.
 Tidal volumes vary as in spontaneous breathing

 Developed as a method of partial ventilatory support
to facilitate weaning

 A demand valve was placed so the spontaneous
breath could occur without having to breathe through
the various valves and apparatus of the ventilator.

 The patient could breathe spontaneously while also
receiving mandatory breaths.

 As the patient’s respiratory function improved, the
number of mandatory breaths was decreased

 Continuous positive airway pressure with an
intermittent release phase
 Phigh for a prolonged time (Thigh): adequate
lung volume, alveolar recruitment
 Time-cycled release phase to Plow for a short
time (Tlow): CO2 removal (ventilation)
 Unrestricted spontaneous breathing allowed
at any time

 Mode of ventilation during which the pressure
delivered by the ventilator was positively related
to the inspired flow and volume
› i.e., pressure in proportion to patient effort

 Preset PROPORTION between applied pressure
and inspiratory muscle effort
› Proportionality constants in the equation of motion
dictate how much the applied pressure will increase
for a given increase in inspiratory muscle effort

 NAVA uses the electrical activity of the diaphragm
(EAdi) to control the ventilator
 Eadi represents the central respiratory drive and reflects
the length and intensity of the patient's neural effort.
 Mechanical inspiratory assist starts when the respiratory
center initiates the breath and is therefore independent
of any pneumatic component.
 During inspiration, the pressure delivered is proportional
to the EAdi and the inspiratory pressure assist ceases
when the neural activation of the diaphragm starts to
decline after reaching the inspiratory maximum value.

 Respiratory failure requiring mechanical ventilation remains
one of the most common reasons for admission to an
Intensive Care Unit (ICU).

 Mechanical ventilation aims to restore gas exchange and to
unload the work of breathing.

 The adverse effects associated with controlled ventilation
are being increasingly recognized, including haemodynamic
compromise, the need for deep sedation and/or muscle
paralysis and VALI.

 Hypothesis
› In contrast to controlled ventilation, partial
ventilatory support modes allow the
preservation of spontaneous breathing efforts
by the intubated patient, and contractions of
the diaphragm, which may mitigate the
adverse effects of controlled mechanical
ventilation.

 Objectives: To investigate:
› which modes of ventilation allow preserved
spontaneous breathing during mechanical ventilation,
and which of these modes have been investigated?
› what are the beneficial effects of preserved
spontaneous breathing during mechanical ventilation
in acute lung injury, and what are the effects on
outcomes?
› what evidence exists (and of what level is it) that the
use of partial ventilatory support in acute lung injury
improves outcomes?

 search strategy keywords:
› common known modalities of assisted breathing
› ALI/ARDS
 MEDLINE, Cochrane, and EmBase electronic databases
searched for articles in English, French and German.
 Reference lists from comprehensive reviews,
observational studies and identified clinical trials were
hand-searched.
 EXCLUDED: Studies pertaining to weaning, chronic ventilation,
non-invasive, ECMO.

Modified Oxford Centre for Evidence-
Based Medicine Levels of Evidence
System
1a Multicentre RCT/Meta-Analysis/SR
1b Good individual RCT
of RCTs
2a SR of cohort studies or missing
2b Prospective cohort/lower quality
criteria for SR in RCTs
3a SR of
RCT case control studies or missing
criteria for SR in cohort studies
3b Retrospective cohort/case control
4a Case
study series/low quality 3b study
4b Clinical/observational study
5 Experimental animal study
6a Comprehensive review of the
literature without documented
6b Expert opinion/case report/
methodology
technical note

 Airway pressure release, pressure support,
proportional assist, and synchronized
intermittent mandatory ventilatory modes
were most commonly investigated.

 Only nine studies involving 664 patients
reported predefined outcomes: 2 RCTs
(Grade 1b), 6 Grade 2b studies, 1 3b study

 28 animal and 41 observational clinical studies
consistently demonstrated findings of improved
haemodynamics and gas exchange, without
increased oxygen cost of breathing.

 Six grade 2b studies demonstrated the same
positive physiologic effects;

 No study compared two different partial ventilatory
modes, and none were powered to assess
mortality.

 30 Trauma patients at risk of ARDS; APRV vs PCV
 Mortality: not reported
 ICU LOS: 23+/-2d vs 30+/-2d (p<0.05) APRV vs PCV
 VFDs: 15 +/-2d vs 21 +/-2d, APRV vs PCV (p<0.05)

 APRV associated with increased CRS, PaO2, CI, DO2
(p<0.05); decreased QVA/QT, O2 extraction (p<0.05)

 pts with PCV needed higher doses of sufentanil,
midazolam, norepinephrine, dobutamine (all p<0.05).

 APRV vs SIMV+PS in 58 adult pts with early ARDS
 Mortality: 17% APRV vs 18% SIMV (p=0.91)
› BUT: underpowered, stopped early for futility

 ICU-Free days: 11.9+/-1.7 vs 10.7+/-1.4 (APRV vs SIMV)
 VFDs: 13.4+/-1.7 vs 12.2+/-1.5 for APRV vs SIMV-PS
 Inspiratory pressure 25.9+/-0.6 vs 28.6+/-0.7 cmH20 for APRV vs
SIMV-PS (p=0.007)
 improved organ function: SOFA-score decreased by 2.8 +/-0.8 vs
1.7+/-0.2 (APRV vs SIMV)
 LIS decreased 0.8+/-0.1 vs 0.6+/-0.2 (APRV vs SIMV)

 While unorthodox to include an expansive
range of study designs and publication types
within a systematic review, the scope was
kept broad due to lack of volume of high
quality studies, and there was no intention to
undertake any statistical analysis.

 Despite benefits of preserved spontaneous
breathing consistently shown in clinical and
experimental data,
› the anticipated effects on outcomes in acute
respiratory failure and ALI/ARDS are not
supported by high levels of evidence
› but it is unknown whether this disparity mirrors
clinical practice.

 Survey of Intensivists’ practices for
ventilatory management in ALI/ARDS

 Pilot study, RCT…?

Grand Rounds November 2009

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