SMCC 3100 A

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SMCC 3100 ABclinical background
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VENTILATOR PATTERN INFLUENCES NEUTROPHIL INFLUX
AND ACTIVATION IN ATELECTASIS-PRONE RABBIT LUNG

• Rabbits, /- lavage, CMVnor, CMVlav, HFOV
• Both the degree of neutrophil activation and lung
  injury can be minimized by preventing cyclic
  alveolar/airway expansion and collapse in the
  surfactant-deficient lung by use of appropriate
  ventilator patterns.

Sugiura et al. J. Appl. Physiol. 1994 77 1355 -
1365
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Ventilator Induced Lung Injury

• Control animal histology

Sugiura M, JAP 1994 771355
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Ventilator Induced Lung Injury

• CMV animal histology

Sugiura M, JAP 1994 771355
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Ventilator Induced Lung Injury

• HFOV animal histology

Sugiura M, JAP 1994 771355
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Ventilator Induced Lung Injury

• HFOV Stimulates Significantly Less Neutrophil
  Activity Than CMV
• Neutrophil Activity Has a Role in the Genesis of
  ARDS, Releasing Active Oxygen Species,
  Proteinases and Arachidonic Acid Metabolites.
• Sugiura M, JAP 1994 771355

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Matsuoka CMV granulocytes n ö
time function ø J Appl Physiol 1994, 76,
539-544 Imai CMV infl. Mediators ö AmJ
Respir Crit Care Med 1994, 1150,
1550-1554 Takata CMV lung compliance
neutrophils ö morph.changes AmJ
Respir Crit Care Med 1997, 156, 272-279
Mediator release

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c. Clinical trials

• 1. NICU
• 2. PICU
• 3. ICU

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HFOV Prospective Randomized Controlled Trials

• 1. HIFO Study Group. Randomized study of
  high-frequency oscillatory ventilation in infants
  with severe respiratory distress syndrome. J
  Pediatr 1993 122(4)609-19
• 2. Clark RH, Gerstmann DR, Null DM, deLemos
  RA. Prospective randomized comparison of
  high-frequency oscillatory and conventional
  ventilation in respiratory distress syndrome.
  Pediatrics 1992 89(1)5-12
• 3. Gerstmann DR, Minton SD, Stoddard RA,
  Meredith KS, Bertrand JM. Results of the Provo
  multicenter surfactant high frequency oscillatory
  ventilatory ventilation controlled trial.
  Pediatr Res 1995 37333A (abstract)
• 4. Ramanathan R, Ruiz I, Tantivit P, Cayabyab
  R, deLemos R. High frequency oscillatory
  ventilation compared to conventional mechanical
  ventilation in preterm infants with respiratory
  distress syndrome. Pediatr Res 1995 37347A
  (abstract)
• 5. Clark RH, Yoder BA, Sell MS. Prospective,
  randomized comparison of high-frequency
  oscillation and conventional ventilation in
  candidates for extracorporeal membrane
  oxygenation. J Pediatr (1994 Mar) 124(3)447-54
• Arnold, JH, et al. Prospective, randomized
  comparison of high-frequency oscillatory
  ventilation and conventional mechanical
  ventilation in pediatric respiratory failure.
  Crit Care Med 1994 221530-1539.
• 7 Plavka R. et al. Prospective randomized
  comparison of conventional mechanical ventilation
  and very early high frequency oscillation in
  extremely premature newborns with respiratory
  distress syndrome. Intensive Care Med 1999 25
  68-75.
• 8 Rimensberger PC, First intention high
  frequency oscillation with very early lung volume
  optimization in very low birth weight infants
  with respiratory distress syndrome, Pediatrics
  Vol. 105 No. 6 June 2000

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HFOV Prospective RCTsOutcomes Summary

• The Randomized Controlled Trials of the 3100A
  have Demonstrated that the 3100A
• Reduces the severity of CLD in RDS infants
• Decreases the cost of hospitalization for RDS
• Decreases the need for ECMO in eligible
  candidates
• Decreases air leak in severe RDS
• Improves survival without CLD in pediatric ARDS

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Picu 1 Arnold

• 5 tertiary care PICUs
• patient eligibility
• weight lt 35 kg
• Diagnosis of
• acute diffuse lung injury
• airleak syndrome

Arnold JH et al. Crit Care Med 1994 22 1530 - 39
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Patient outcome

• CV HFOV
• ventilator days 22 20
• new ALS 6 4
• cross-over () 66 38
• survivors () 59 66
• O2 at 30 days () 59 21

p 0.039
Arnold JH et al. Crit Care Med 1994 22 1530 - 39
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Pediatric Randomized Controlled Trial

• At 30 days there were significant differences in
  outcome measures that reflected a benefit for the
  use of HFOV

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Pediatric Randomized Controlled Trial

• Six month follow-up demonstrated a continued
  difference in outcome measures that reflected
  significant benefits for the use of HFOV for
  Pediatric ARDS

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Pediatric Randomized Controlled Trial
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Outcome

• HFOV with aggresive volume recruitment strategy
  results in
  significant improvement in oxygenation
• Despite higher Paw
• lower frequency of barotrauma
• lower incidence of suppl. O2 at 30 days
• improved outcome c/w CV

Arnold JH et al. Crit Care Med 1994 22 1530 - 39
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HFOV, predictors of survival

• OI at 24 hrs lt 42
• Decreasing OI

MAP/CDP x FiO2 x 100 PaO2
OI
Arnold JH et al. Crit Care Med 1994 22 1530 - 39
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HFOV,from PICU to ICU
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ICU, the 3100B Pilot Study
17 adult patients with severe ARDS failing
aggressive CMV (including inverse ratio
ventilation), satisfying ECMO criteria
Fort P,et al.HFOV for adult RDS,a Pilot Study.
Crit Care Med 199725937-947
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Outcome

• HFOV with aggressive volume recruitment strategy
  results in
  significant improvement in oxygenation
• Despite higher Paw
• lower frequency of barotrauma
• lower incidence of suppl. O2 at 30 days
• improved outcome c/w CV
• Predictors of survival
• post-treatment OI at 72 hrs
• Increasing OI

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Multicenter Oscillatory ARDS Randomized
Controlled Trial
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Multicenter Oscillatory ARDS Randomized
Controlled Trial

• Comparison of the 3100B Adult HFOV and a Pressure
  Control Ventilation approach in severe ARDS in 10
  University based centers
• Open lung strategies in both arms
• Limited pressures and permissive hypercapnia in
  both arms
• Entry with a P/F ratio lt200 on PEEP gt 10 cmH2O

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MOAT2 - Exclusion Criteria

• Weight lt 35 kg
• Severe asthma or COPD
• Intractable shock
• Severe airleak (gt 3)
• FiO2 gt 80 for gt 48 hours
• Age lt 16 years
• Non-pulmonary terminal diagnosis

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Patient Demographics - Baseline
HFOV CV N 75 73 Age
48 (17) 51 (18) Kg 78 (25) 81 (26) Apache
II 22 (6) 22 (9) Sepsis 47 47 Pneumonia 19
16 Trauma 21 18 ? immun 12 14 Airl
eak 16 19 NS
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Physiological Parameters - Baseline
HFOV CV N 75 73 PIP 39
(7) 38(8) PEEP 13 (3) 14 (3) mPAW 22
(5) 24 (7) TV (ml/kg) 8.2 (3) 7.8 (3) FiO2
71 (19) 72 (19) PaO2 mmHg 76 (20) 73
(18) PaCO2 mmHg 44 (12) 45 (12) P/F 114
(37) 111 (42) OI 24 (15) 27 (19) MAP mmHg
80 (14) 76 (12) CO lpm 7 (2) 7
(3) NS
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Ventilator Strategies - Goals

• Normalize lung volume
• Minimize peak ventilator pressures
• Physiological targets included
• Oxygen Saturation gt 88
• Delay weaning mPaw until FiO2 lt 50
• pH gt 7.15
• PaCO2 in the range of 40 70 mmHg

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HFOV - Oxygenation Strategy

• Open lung strategy
• Initial mPaw 5, increase in 2-3 cmH2O
  increments Q 20 - 30 mins if FiO2 gt 60 until max
  45 cmH2O
• IT 33
• Goal FiO2 lt 60 with SpO2 gt 88

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HFOV - Ventilation Strategy

• ? P chest wall vibration - increase 10 cm H2O
  increments if rising PaCO2 to max ?P of
  approximately 90 100 cmH2O
• Hz 5 (could decrease to 3 Hz)
• ET cuff leak if rising PaCO2
• Goal pH gt 7.15 and PaCO2 40 - 70 mmHg

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CV - PCV Strategy

• Pressure Control Mode
• TV 6 10 ml/kg (actual body weight)
• PEEP 10 (increment to 18 cm H2O)
• IE 12 to 21 (no Inverse Ratio with PEEPlt 18)
• Goals SpO2 gt 88, PaCO2 40 - 70 mmHg, pH gt 7.15
• Wean PSV when PEEP 5 and FiO2 40

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Strategy Compliance
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Mean PAW - first 72 hours
plt0.001
HFOV
CV
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Clinical Indicators During Treatment
HFOV CMV
time plt 0.01, vent plt 0.001
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Outcomes
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Retrospective Analysis - Outcome Stratified by
Median PIP ? 38 cm H20
HFOV CV N 38 42 PIP 33
(5) 32 (4) PEEP 13 (3) 13 (3) TV
(ml/kg) 8.5 (.3) 7.9 (.2) PaO2/FiO2 115
(39) 120 (37) OI 22 (17) 21 (14) APACHE
II 21 (6) 20 (7) Sepsis 45 45 Mortality
30 d 26 52 Mortality 6 mo 39 62
Plt0.018 Plt0.045
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Survival - PIP ? 38 cm H20 (post-hoc)
30d p0.019 90d p0.026
HFOV
CV
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Overall Survival
30d p0.057 90d p0.078
HFOV
CV
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Outcomes
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MOAT2 - Secondary Outcomes
HFOV CV N 75 73 ? BP 0 3 Airleak 9
12 O2 Failure 5 8 OIgt42 at gt48h pH lt
7.15 5 8 Mucus Plug 5 4 NS
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Post-Hoc Analysis Predictors of Outcome

• Oxygenation Index Response
• Entry Indicators of Compliance (Peak Inspiratory
  Pressure)

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Predictors of Outcome

• OI at 16 hours was the only significant
  predictor of mortality in a stepwise logistic
  regression analysis.
• Risk of death increases 2 for every OI increase
  of 1 at 16 hours
• e.g., Patients with OI of 25 have a 55 risk of
  death, for those with an OI of 15 its only 35

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Conclusions

• HFOV associated with relative reduction in 1 mo
  mortality of 29 (P0.098) and 6 mo mortality 20
  (P0.143)
• No significant difference HFOV vs CV in airleak,
  hypotension, oxygenation failure, ventilation
  failure or mucus plug
• Data supports effectiveness and safety of HFOV
  for ARDS

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HFO as Lung Protective Ventilation Strategy in
ARDS
Department of Anaesthesiology Johannes Gutenberg
University Mainz, Germany
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N42 Jan. 1998 April 2001 Primary Study
Endpoint Improvement of oxygenation HFOV
adverse events Secondary Study Endpoint 30 day
mortality
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Patient selection Patients with oxygenation
disorder meeting following criteria Failure of
conventional ventilation No heartfailure No
severe obstructive lung disease Body weight 35 kg
or more Exlusion Pregnancy Death expected
within 24 hrs
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Failure CMV PaO2/FiO2 ratio lt 200 mmHg No
improvement over 2hrs with optimized
PCV (Improvement increase PaO2/FiO2 ratio at
least 50 PCV Max PEEP 15 cmH2O Max
Insp. Airway Press. 35 cmH2O Rate IE
Ratio set to avoid intrinsic PEEP PaCO2
rise permitted to art. PH of 7.20
Recuitment Maneuvers allowed and performed
routinely
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Recuitment Maneuvers Respirator switched to
CPAP Mode CPAP 40 cmH2O for 30 seconds After
maneuver PEEP increased to 3-5 cmH2O above
initial If improvement repeated up to Max PEEP
of 15 cmH2O
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If at 2hrs after optimized conventional PCV no
improvement in oxygenation, patient was
allocated to HFOV
Initial Settings HFOV FiO2 of 1.0 CDP 5 cmH2O
above last MAP of conventional ventilation Insp.
of 33 Freq. 5 Hz Bias Flow 30 ltr/min Oscill
amplitude depending of body weight (later
titrated to target PaCO2
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CDP Management

• Lung volume recruitment by stepwise increase CDP
  up to 40 cmH2O
• CDP increased as long as PaO2 increased
• If PaO2 decreased after raising CDP, trend in
  PaO2 was analyzed
• Pos. trend in PaO2 considered as slow recruitment
• Decrease of PaO2 without pos. trend signalized no
  further recruitment
• (overdistension of ventilated
  compartments of the lung)
• Consequently CDP was reduced
• After achieving max. recruitment lowest possible
  CDP sought in order to
• keep the lung open.
• (CDP reduced to the point of lung collapse, seen
  as PaO2 decrease and
• then adjusted 2 3 cmH2O above this
  point

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Amplitude Management

• Targeted PaCO2 between 35 and 80 cmH2O
• Art. pH more than 7.20
• Art Bicarb. more than 19 mmol/L
• Adjusted by increasing (hypercapnia) / decreasing
  oscillation amplitude
• 
  (hypocapnia)
• Consisting hypercapnia despite oscillation
  amplitude of more than 90,
• oscillation frequency was reduced in steps of
  0.5, to a lower limit of 3 Hz

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Hypotension defined as MAP less than 60 mmHg for
2 hrs. After changing to HFOV or related to
increase of CDP
HFOV was stopped if hypotension remained
unresponsive to optimization of filling
pressures, vasoactive and/or inotropic support
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• Weaning HFOV
• Immediately after steady state, weaning started.
• First by weaning FiO2
• Second by stepwise reduction of CDP
• Patients with improved and stable oxygenation
  requiring FiO2 lt 0.6
• and a CDP lt 25 cmH2O were weaned to
  conventional ventilator
• PCV settings according to CDP level on HFOV

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Changing Medical Practice

• Changing Medical Practice is the Most Difficult
  Task
• 6 ml/kg tidal volume ventilation for ARDS
• Rubenfeld GD, et al ATS 2001
• Reasons of Non-Compliance
• Reluctance to give up control to a protocol
• Patient comfort
• Acidosis
• Oxygenation
• Therefore
• Most patients with ARDS are not managed with LPV
• HFOV has the potential to remove most barriers to
  use of LPV