Positive End-Expiratory Pressure Setting in Adults With Acute Lung Injury and Acute Respiratory Distress Syndrome

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Positive End-Expiratory Pressure Setting in
Adults With Acute Lung Injury and Acute
Respiratory Distress Syndrome
JAMA 2008299(6)645-655
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A Randomized Controlled Trial

• Presented by R2 ???
• Supervised by V.S. ???

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Background

• PEEP in ARDS/ALI Level 1 evidence
• Improves oxygenation and reduce
• intrapulmonary shunting
• PEEP-induced alveolar recruitment
• Volume-pressure relationship
• Ventilator-induced lung injury
• combination of small tidal volume and
• high PEEP

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Objective

• Compare the effect on outcome of a
• strategy for setting PEEP
• increasing alveolar recruitment while
• limiting hyperinflation
• (high PEEP with low tidal volumes and
• maximum P plateau)
• minimizing alveolar distension in patients
• with ALI
• (moderate PEEP with low tidal volumes)

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Primary end point of study

• Mortality within the first 28 days

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Patients (Inclusion criteria)

• Endotracheal mechanical ventilation for
• hypoxic respiratory failure
• PF ratio lt 300
• recent bilateral pulmonary infiltrates
  consistent
• with edema
• no left atrial hypertension (PCWP lt 18 mmHg)
• no more than 48 hours before enrollment

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Patients (Exclusion criteria)

• Age lt 18 years old
• known pregnancy
• participation in another trial within 30 days
• IICP
• sickle cell disease
• severe chronic respiratory disease requiring
• long term oxygen therapy or home mechanical
• ventilation
• actual body weight gt 1kg/cm of height

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Patients (Exclusion criteria)

• severe burns
• severe chronic liver disease
• bone marrow transplant
• chemotherapy-induced neutropenia
• expected duration of mechanical ventilation
• shorter than 48 hours
• decision to withhold life-sustaining treatment

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Design

• Multicenter randomized controlled trial
• September 2002 to December 2005
• 37 intensive care units in France
• 767 adults
• Mean SD age, 59.9 15.4 years

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Ventilation Strategies
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Weaning Protocol

• Basically from day 4 onward
• Daily PEEP weaning trial
• if PaO2FiO2 gt150 mmHg and FiO2 lt0.6
• Setting - FiO2 0.5 and PEEP 5mmHg
• ABG 20-30 minutes later
• Maintain if SpO2 lt 88 and if PaO2FiO2 lt 200
  mmHg
• Change to assist-control or pressure support
  ventilation
• to keep tidal volume lt 10ml/kg and plateau
  pressure or
• inspiratory pressure lt 30cmH2O and PEEP of 5
  cmH2O

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Different values

• Weaning trigger value (PaO2FiO2 gt150 mmHg )
• Abort value PaO2FiO2 lt 200 mmHg
• Reasons
• 1. avoid inducing an unwanted disadvantage in
  the
• low PEEP
• 2. it was possible that oxygenation could
  improve
• when removing higher levels of PEEP
  because the
• original PEEP setting was not titrated
  based on
• oxygenation

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Criteria for Spontaneous Breathing test

• Successful PEEP weaning test
• Presence of the following
• - no infusion of vasopressors agents or
  sedatives
• - adequate responses to simple commands
• - cough during suctioning
• Consisted of breathing spontaneously up to 2
  hours on a T-piece or pressure-support
  ventilation with an inspiratory pressure of 7cmH2O

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Outcomes Measures

• Primary evaluation criterion
• - the proportion of patients who died within
  28 days
• after randomization
• Secondary criteria
• - 60-day mortality
• - hospital mortality censored on day 60
• - numbers of ventilator-free days
• - organ failure-free days from day 1 to day
  28
• - the proportion of patients who experienced
  
• pneumothorax
• - requiring chest tube drainage between day 1
  and day 28

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Data Collection

• Collected at the time of randomization
• - severity of underlying medical conditions
• - severity of acute illnesses
• - ventilatory settings
• - arterial blood gases
• - history or cause of lung injury
• Monitor daily for 28 days (ventilatory settings,
• arterial blood gases, cointerventions and
  organ
• failures)
• Followed up until day 60 after randomization or
  death

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Definition

• Septic shock international consensus conference
  crtiteria
• Organ failure ODIN score
• The number of ventilator-free days to day 28 -
  the number of days of unassisted breathing to day
  28 after randomization, assuming a patient
  survives and remain free of invasive or
  noninvasive assisted breathing for a least 2
  consecutive calendar days
• The number or organ failure-free days the
  number of days alive and free of organ failure as
  defined in the ODIN score

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Critical care medicine 2003- International
consensus conference criteria
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Statistical Analysis

• Sample size calculation
• Sequential, symmetric trial analysis using
  triangular test
• Interim analysis (18)
• Analysis interim-to-treat basis
• Statistical software PEST, version 4
• P lt.05, clinically significant

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Results

• Study populations
• Respiratory variables
• Adverse events
• Prespecified evaluation criteria
• Adjunctive treatments

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Results
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RR 1.12
RR 1.10
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Total extubation rate NO difference in 2 groups
(23.1 vs 21.1, p.61)
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Comment

• Increased recruitment strategy while limiting
  overdistension is benefit
• - ?MV dependent days with organ failure
• - improved oxygenation and compliance
• - without significant barotrauma
• But not reduce 28-day or 60-day mortalities
• And increased fluid requirements (around 400ml)

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Ventilatory strategy

• PEEP titration based on plateau pressure v.s.
  oxygenation
• NOT incorporate recruitment maneuvers due to
• controversial efficacy and safety.
• Applicability at the bedside
• PEEP weaning procedure

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Increased recruitment strategy

• PEEP weaning procedure
• Slow weaning from high PEEP
• PEEP level (6.7 cmH2O)
• Not reduced mortality
• Increased in fluid requirements reflected poor
  tolerance in some patients
• Beneficial in those with a high potential of
  alveolar recruitment (lung injury severity)
• Adverse effects

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Limitations

• unblinded nature of study
• adjunctive therapies (rescue therapy such as
• inhaled nitric oxide and prone ventilation)
• less non-pulmonary cause of ARDS

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Conclusion

• Lung recruitment strategy with
• HIGH PEEP and
• P plateau at 28 to 30 cmH2O
• NOT reduced mortality
• But improved morbidity!