Reversibility of Lung Collapse and Hypoxemia in Early Acute Respiratory Distress Syndrome

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Reversibility of Lung Collapse and Hypoxemia in
Early Acute Respiratory Distress Syndrome
American Journal of Respiratory and Critical Care
Medicine Vol. 174, 2006. Presented by Dr. Toh
Han Siong Supervised by Dr. ??? 4 December 2006
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Introduction

• Lung collapse is still a concern during the
  critical care of patients with ALI or ARDS.
• Airspace collapse and cyclic recruitment as
  pivotal elements in ventilator-induced lung
  injury
• Insufficient recruitment
• Insufficient PEEP
• When compared with overdistension, similaror
  even greaterimpact on lung injury.

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Detrimental Collapse Hypothesis

• Clinical data confirming this hypothesis are
  lacking.
• Amato et al, 1996 High PEEP Low mortality ?
• Benefits of open-lung approach (OLA)
• Brower et al, 2004 ARDSnet, multicenter
  randomized trial
• 45 cmH2O differential in PEEP negligible
  effect on outcome
• Unbalanced sicker patient selected to high PEEP
  group
• Lung recruitment strategies were not applied
• Benefits associated with OLA lower driving
  pressures used in that protective protocol not
  to high PEEP

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Detrimental Collapse Hypothesis

• Efficacy of conventional recruitment maneuvers
• Success rate is just modest and dependent on
  baseline disease
• Oxygenation/mechanical benefits hardly been
  sustained
• Without significant reduction of alveolar
  collapse
• Without sustained effects
• Negative results were related to suboptimal
  strategy?

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New maximum recruitment strategy

• Clinical efficacy and safety
• Compared with previous OLA
• Assessed the use of
• PaO2 PaCO2 ? 400mmHg
• Indicator of maximum lung recruitment?
• Correlations bet. quantitative CT gas exchange

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• When using 100 oxygen, any degree of hypercapnia
  was associated to a decreased arterial PO2 (1
  1), in proportion to the degree of hypercapnia.

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Methods Patients and Monitoring

• Hospitals ethical committee granted approval
• Written, informed consent from patients
  relatives
• Intubated patients fulfilled criteria of early
  ALI/ARDS
• ABG after 30 min of 10 cmH2O PEEP Vt 68 ml/kg
  ? PaO2/FiO2 lt 300 mmHg
• Receiving stable doses of vasopressors, with MAP
  gt 65 mmHg stable arterial lactate level over
  the preceding 6 h
• Intraarterial blood-gas sensors pulmonary
  artery catheter continuous monitoring of ABG, CO
  venous saturation
• Respiratory-system mechanics, including
  plethysmography

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Methods Experimental Protocol

• All patients were in supine position, sedated,
  and paralyzed, and received 100 oxygen
  throughout the study
• Fluid status was previously optimized according
  to a predefined protocol based on pulse-pressure
  variation.
• Baseline PEEP 510 cmH2O Vt 6 ml/kg for 8 min
• Stepwise maximum-recruitment strategy
• For the first 11 patients, additional protocol
  step (OLA) was interposed before maximum
  recruitment strategy.

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4 min
4 min
2 min
PEEP titration
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Methods OLA

• After baseline MV,
• Recruitment CPAP 40 cmH2O for 40 s
• OLA ventilation for 4 min
• PEEP at lower inflexion point 2cmH2O
• (identified from inspiratory pressurevolume
  curve)
• Driving pressures adjusted to achieve Vt 6 ml/kg

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Methods Maximum-Recruitment Strategies

• PEEP 25cmH2O PCV 15cmH2O driving pressure ?
  peak airway pressure 40 cmH2O ? 4 min
• PEEP 30cmH2O ? peak airway pressure 45cmH2O ? 2
  min
• PEEP 25cmH2O ? 2 min (resting phase ?
  measurement)
• PEEP 35cmH2O ? peak airway pressure 50cmH2O ? 2
  min
• PEEP 25cmH2O ? 2 min
• Until peak airway pressures of 60 cmH2O were
  reached, whenever necessary.

...
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• First step (peak pressure 40cmH2O) was applied to
  all.
• All next steps were conditional on measurements
  collected at the end of previous resting phase
• Protocol was interrupted whenever
• Blood-gas target
• PaO2 PaCO2 ? 400mmHg
• Mixed venous oxygen saturation lt 80
• Mean arterial pressure lt 60 mmHg
• Development of barotrauma (on CT images)

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• If target was not met despite inspiratory
  pressures of 60cmH2O, the maneuver was terminated
  recruitment was considered incomplete.
• 26 patients receive maximum-recruitment strategy
• First 11 patients at the CT scanner
• Remaining 15 patients in the ICU

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Methods PEEP titration

• ?2cmH2O from 25 cmH2O, maintained for 4 min
• Continued until PaO2 PaCO2 lt 380mmHg
• Detecting lowest PEEP (optimum PEEP) maintaining
  sum of blood gases ? 400mmHg
• PEEP titration ? recruitment maneuver (pressure
  used in last step) ? ventilated at optimum PEEP
  level
• Check of maintenance of recruitment efficacy
• First 11 patients CT after 30 min at optimum
  PEEP
• Remaining 15 patients blood gases, hemodynamics,
  and CXR after 6 h at optimum PEEP with Vt 6 ml/kg

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Methods Quantitative CT Image Analysis

• Lung CT during expiratory pause
• Inner contour of each hemithorax was manually
  drawn
• Hyperinflated -1,000 to -850 Hounsfield units
  HU
• Normally aerated -850 to -500 HU
• Poorly aerated -500 to -100 HU
• Nonaerated -100 to 100 HU
• Corresponding volume (mL) and mass (gm)
• We quantified lung collapse in two ways
• (1) nonaerated lung mass/ total lung mass (i.e.,
  percent mass)
• (2) nonaerated lung volume/total lung volume
  (i.e., percent volume)

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Methods Statistical Analysis

• Repeated-measures analysis of variance
• Bonferronis adjustment for multiplicity of tests
  
• Multiple linear regression to assess relationship
  between PaO2 (dependent variable) versus
  CT-derived, respiratory, or hemodynamic variables
  (independent variables)
• Logarithmic transformation of blood gases to
  linearize relationship between PaO2 shunt
  levels.
• Significance was defined as a p level lt 0.05

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Results Characteristics of Patients

• 26 patients (January 1999 April 2003)
• Table 1 Admission and baseline characteristics
• Table 2 Clinical Outcomes
• Approximately 30 other patients with early
  ARDS/ALI were screened but not included because
  of hemodynamic instability or an inability to
  obtain informed consent.

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Results Efficacy of Stepwise Maximum-Recruitment
Strategy

• Improvement in oxygenation
• Decreased in collapse tissue
• Use of airway pressures above 3540 cmH2O was
  crucial.
• To meet the oxygenation criteria, 54 required
  plateau pressures more than 40 cmH2O to achieve
  full recruitment.
• After plateau pressure 60 cmH2O was applied, 2
  of 26 patients did not meet our blood-gas target
  and lung recruitment was considered incomplete.

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Significant improvement in oxygenation (p lt 0.001
to OLA or baseline)
Significant reduction in percent mass of
collapsed tissue (p lt 0.01 to OLA or baseline)
p lt 0.001 p lt 0.005 p lt 0.03
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Bimodal
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Results Maintaining Benefits of Recruitment

• After maximum-recruitment strategy PEEP
  titration,
• 9 patients optimum PEEP 30 min (CT room)
• 15 patients optimum PEEP 6 h (ICU)
• Figure 5
• Oxygenation was maintained or increased during
  the period of recruitment maintenance.

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ICU
CT
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Results Side Effects of Stepwise
Maximum-Recruitment Strategy

• Table 3 Hemodynamic and blood-gas measures
• It was never necessary to interrupt the maneuver
  because stopping criteria were met.
• Figure 6 Fraction of lung volume (CT numbers lt
  -850 HU hyperinflated compartment) during first
  step vs last step
• Nondependent lung regions
• NO any increase in hyperinflated compartment.
• But decrease in hyperinflated comartment.

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Decrease of hyperinflated areas (p 0.06)
Evolution of Nondependent Lung Hyperinflation
More prominent in patients with marked
hyperinflation before (p 0.03)
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Results Correlation between oxygenation and
quantitative CT analysis

• Table 4
• Percent mass of collapsed tissue showed the best
  correlation with changes in PaO2, responsible for
  72 of PaO2 variance in the final multivariate
  analysis (partial correlation, R -0.91 p lt
  0.0001).
• Inclusion of percent mass of poorly aerated
  tissue slightly improved the model, explaining an
  additional 2 of the residual variance (p
  0.008).

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Percent mass rather than percent volume
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• Figure 7
• Percent-volume calculations systematically
  underestimated the percent-mass calculations
• Inverse correlation bet. PaO2 PaCO2 (p lt 0.001)
• Sensitivity/specificity analysis confirmed the
  tight correlation between CT analysis and blood
  gases
• PaO2 PaCO2 lt 400 mm Hg indicated a lung
  condition with more than 5 of collapse
• 85 sensitivity and 82 specificity

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baseline
maximum recruitment
30 min later
OLA
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PaO2 PaCO2 ? 400 at FiO2 100 A reliable index
of complete lung recruitment
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Discussion Major findings

• It was possible to reverse lung collapse and to
  stabilize lung recruitment in the majority
  (24/26) of patients with early ALI/ARDS,
• The proposed maximum-recruitment strategy
  recruited the lung significantly better than OLA
• strong inverse correlation bet. arterial
  oxygenation and amount of collapsed lung mass
  (R -0.91)
• The index PaO2 PaCO2 ? 400 (at 100 oxygen) was
  a reliable indicator of maximum lung recruitment
• (5 of collapsed lung units ROC area 0.943).

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Proper PEEP level

• Success rate and magnitude of lung recruitment in
  this study were unusual, ...
• Antiderecruitment strategy with PEEP levels kept
  at 25 cmH2O during the whole recruiting phase.
• Work as a recruitment keeper
• Decremental PEEP titration detected optimum PEEP,
  resulting in average PEEP of 20 cmH2O.
• Still above average lower inflection point
• Far exceeded PEEP levels used in previous studies

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• Despite Prolonged hypercapnia low tidal volumes
  
• Maintain a stable open lung (collapsed lung mass
  lt 5)
• Confirmed by CT at 30min after recruitment
• Confirmed by maintenance of oxygenation 6 h after
  recruitment (PaO2 PaCO2 ? 400 mm Hg)

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• Estimated distribution of threshold-opening
  pressures
• Reasons for previous negative recruitment studies
  
• Bimodal shape of curve suggests that there are
  two main populations of alveoli in terms of
  opening pressures.

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• Dependent lung frequently require airway opening
  pressures above 3540 cmH2O to recruit.
• not challenged to airway pressure 60 cmH2O
  less than 50 of early ARDS can be recruited.
• Schreiter et al, 2004
• Only previous investigation suggesting similar
  efficacy of recruitment
• Restricted to a population of patients with chest
  trauma
• The protocol was the only one including similarly
  high inspiratory opening pressures (?65 cm H2O).

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OLA vs maximum-recruitment strategy

• OLA suboptimal ?
• Significant collapse on CT ( 28 of parenchymal
  mass)
• PaO2 levels only around 250 mmHg
• Shunt level around 25
• Insufficient opening pressures and time of
  application
• Suboptimal PEEP levels
• Recent ARDSnet trial
• A recruitment protocol could have further
  enhanced their oxygenation results.

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Side Effects

• Barotrauma, Hemodynamic impairment,
  Hyperinflation
• Transient decrease in cardiac index
• No deterioration in mixed-venous saturation
• No decrease in systemic arterial blood pressure
• We did not observe any direct clinical
  consequence
• Definitive conclusion about risk deserves further
  investigation

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• 2 cases of barotrauma occurred after protocol
  completion and probably reflect the usual
  incidence of barotrauma in recent ARDS series
  (?10).
• None of our patients demonstrated increased
  hyperinflation on CT. There was a slight decrease
  of hyperinflation in nondependent lung zones.
• Massive recruitment with an overall increase in
  pleural pressure, consequently decreasing
  transpulmonary pressures at nondependent zones,
  may explain such findings.

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• Precautions minimized potential side effects
• (1) All patients were previously optimized in
  terms of vascular volume vasopressor infusion
• (2) We used pressure-controlled cyclic
  ventilation instead of vital capacity maneuvers
  (sustained pressures) during the high stress
  phases, theoretically minimizing hemodynamic
  impairment.
• (3) The stepwise protocol individualized the
  opening pressures applied, using the minimum
  necessary for that individual.

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Correlation between CT and Blood Gases

• High correlation 72
• Physiology of gas exchange probably became
  simplified, exclusively determined by relative
  proportion of two major compartments
• The aerated one
• The fully collapsed one
• Any impairment in gas exchange should be related
  to the magnitude of pulmonary shunt, rather than
  to ventilation/ perfusion imbalances.

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• Poorly aerated areas (low V/Q areas) was
  responsible for 2 of residual variance in PaO2.
• Partially collapsed zones could no longer disturb
  gas exchange because
• Few regions with very low ventilation/perfusion
  ratios rapidly disappeared, being converted to
  fully collapsed units before our measurement
• Remaining not-so-low ventilation/perfusion areas,
  also receiving poor ventilation through
  intermittently connected airways (but enough to
  keep patent), could no longer disturb arterial
  oxygenation due to the absence of nitrogen.

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Percent Mass of Collapsed Tissue

• Ratio between mass of atelectatic tissue total
  lung mass
• Assumed that lung mass should correspond to
  septal tissue, homogenously filled by
  capillaries, the perfusion per gram of tissue
  was same in open or closed areas.
• Nonrecruited / (Recruited Nonrecruited) gt
• capillaries in collapsed areas / capillaries in
  whole lung
• Capillaries were homogeneously perfused gt
• this proportion should correspond to pulmonary
  shunt

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The percentage of collapsed lung mass explained
72 of PaO2 variance.
PaO2 levels above 320 mmHg (PaO2 PaCO2 ? 400
mmHg), most CT scans presented lt 5 of collapse.
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Limitations

• Proposed maximum-recruitment strategy was only
  applied after intensive fluid resuscitation and
  after excluding patients who were rapidly
  deteriorating.
• The results reported here concern approximately
  half of patients with ARDS screened and some
  selection bias must be considered. However,
  because all exclusions were related to
  nonfulfillment of predefined criteria for
  hemodynamic stability or failure to obtain
  informed consent, the bias, if any, could affect
  results related to hemodynamic tolerance, but
  hardly the reported rate of collapse reversal.

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Clinical Implications

• It is possible to reverse the hypoxemia present
  in the majority of patients with early primary or
  secondary ARDS because its major cause is
  reversible airspace collapse with pulmonary
  shunt.
• Our strategy results in a sustained recruitment
  of more than 95 of airspace on CT analysis, at
  the expense of transient fall in cardiac output,
  but without directly associated barotrauma.
• However, whether this strategy will improve
  outcome or reduce ventilator associated lung
  injury are matters for future studies.

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Thank You for Your Attention