Journal Club

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Journal Club

• Amy Rodgers PGY-3 Anesthesia
• October 16, 2006

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Article

• Wrigge H, et al. The effects of different
  ventilatory settings on pulmonary and systemic
  inflammatory responses during major surgery.
  Anesth Analg 2004 98 775-81.

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Outline

• Background
• Question
• Summary of article
• Critical appraisal
• Low tidal volumes in OLV Pros Cons

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Background

• In patients with ALI (acute lung injury), low VT
  of 6mL/kg and mod-high PEEP improved gas
  exchange, ? intra-alveolar and systemic mediator
  levels and improved outcome (compared to VT of
  10-15mL/kg and low to mod PEEP)1
• Major abdominal and thoracic surgery causes a
  systemic inflammatory response
• 1 The Acute Respiratory Distress Syndrome
  Network. Ventilation with lower tidal volumes as
  compared with traditional tidal volumes for acute
  lung injury and the acute respiratory distress
  syndrome. N Engl J Med 2000 342 1301-8.

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Background

• Basic research using small animal models
  demonstrates initiation or perpetuation of local
  and systemic inflammatory responses to
  ventilatory strategies using high VT and/or low
  or zero PEEP
• Mechanical ventilation in healthy patients didnt
  induce a systemic inflammatory response

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Question

• Does the use of high tidal volume ventilation
  cause ALI in patients with healthy lungs?
• Will mechanical ventilation aggravate production
  and/or translocation of cytokines released by an
  inflammatory co-stimulus such as major surgery?

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Summary of Article

• Pulmonary and systemic mediator levels were
  studied in patients undergoing either major
  abdominal or thoracic surgery (used as a clinical
  model of ventilator-associated lung injury)
• The effect of different ventilator settings were
  examined in each group
• Patients were randomly (sealed envelopes)
  assigned to 1 of the 4 groups

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Methods
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Methods

• All pts received midaz, propofol, remifentanil,
  cisatracurium
• Thoracotomy DLT, OLV, FiO2 1.0
• Abdo Single lumen ETT, FiO2 .30
• Standard monitors art line CVP ABG HgB
• RR adjusted to maintain PaCO2 35-45

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Critical Analysis

• Levine, M et al. Users Guide to the Medical
  Literature. JAMA. 1994 271 1615-1619.
• Criteria to guide decisions regarding causation

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Are the results of the study valid?

• Primary
• A) Were there clearly identified comparison
  groups that were similar with respect to
  important determinants of outcome other than the
  one of interest?

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Are the results of my study valid?

• RCT-most reliable evidence for causal
  relationships, minimizes bias and the influence
  of confounding variables
• No statistically significant differences in
  demographic or clinical data among groups
• Four groups
• Abdo surgery vs. Thoracic surgery
• High VT ZEEP vs. Low VT PEEP
• Control group?

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Are the results of my study valid?

• Same anesthetic?
• Single vs. DLT
• FiO2 of 0.3 vs. 1.0 (OLV)
• Fluids?
• Pain mngt ie. epidural?
• Maintenance of anesthesia
• Thoracics ventilation the same during OLV but
  insp pressure limited to 35cm H2O, if exceeded
  limit ventilation changed to pressure control
  with decelerating inspiratory flow to meet
  desired VT

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Are the results of my study valid?

• B) Were the outcomes and exposures measured in
  the same way in the groups being compared?

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Are the results of my study valid?

• Gas flow and airway pressure measured at proximal
  end of tracheal tube with a std monitor for
  ventilatory measurements
• Insp time, vent cycle time, VT , minute vent
  were derived from gas flow curve/signal
• Cytokine and Chemokine Measurements
• Baseline blood samples after induction of
  anesthesia then 1,2, and 3hrs after initiation of
  ventilation, then tracheal aspiration after 3hrs
  only
• Tracheal aspirates 1 lung vs. 2 lungs
• No other clinical outcomes examined

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Are the results of my study valid?

• C) Was follow-up sufficiently long and complete?
• Tested each ventilatory setting for only 3hrs
• Previous studies (experimental and clinical)
  showed this period sufficient time to cause
  ventilation-induced mediator release
• This study showed inflammatory response to
  surgery so likely enough time for
  ventilation-induced cytokine release

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Are the results of the study valid?

• Secondary
• A) Is the temporal sequence of exposure and
  outcome correct?
• Self evident in RCT
• Exposure is allocated before the outcome develops

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Are the results of my study valid?

• B) Is there a dose-response gradient?
• If the frequency of an adverse event increases
  with the dose of an exposure, this is supportive
  evidence of causation
• Plasma inflammatory mediators increased over time
  during thoracic/abdo surgery
• Pulmonary and systemic mediators didnt show a
  significant difference with increased tidal volume

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What are the results?

• How strong is the association between exposure
  and outcome?
• How precise is the estimate of risk?

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What are the results?

• Ventilatory settings do not affect inflammatory
  mediators during abdo/thoracic surgery within
  3hrs
• Abdo/thoracic sx plasma inflammatory mediators
  increased over time (P lt0.001)
• Absolute increase larger in abdo group but
  differences were small (Plt0.05)? minor
  exposure to intestinal bacteria

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Will the results help me in caring for my patient?

• No differences in inflammatory cytokines between
  low vs. high tidal volumes
• Study not powered to evaluate more important
  outcomes
• The question is left unanswered about the effects
  of either method on ALI

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Two-hit model

• Pulmonary inflammation (1st hit) must be present
  for injurious mechanical ventilation (2nd hit) to
  initiate an inflammatory response
• Healthy alveoli overinflate b/c atelectatic
  alveoli produce no counterpressure
• Potentially thoracic/abdo surgery not a big
  enough first hit

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Two-hit hypothesis

• High VT and low PEEP may induce lung inflammation
  to clinically important levels in preinjured or
  infected lungs as previously shown, but not in
  normal lungs even during major surgery
• Normal? Smokers, Lung CA

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Pro Low VT in OLV

• Slinger P. Pro Low tidal volume is indicated
  during one-lung ventilation. Anesth Analg 2006
  108268-70.

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Pro Low VT in OLV

• ALI post pulmonary resection causative factors
• FFP administration
• Mediastinal lymphatic damage
• Inflammation
• Oxygen toxicity
• Excessive IV replacement
• R pneumonectomy higher risk
• Slinger P. Post-pneumonectomy pulmonary edema
  is anesthesia to blame? Curr Opin Anesthesiol
  19991249-54.

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Pro Low VT in OLV

• Early ALI (POD 0-3)
• High intra-op ventilation pressures
• Excessive IV volume replacement
• Pneumonectomy
• Preop ETOH abuse
• Late ALI (POD 3-10)
• Bronchopneumonia
• Aspiration
• Licker M, De Perrot M, Spiliopoulos A, et al.
  Risk factors for acute lung injury after thoracic
  surgery for lung cancer. Anesth Analg 2003 97
  1558-65.

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Pro Low VT in OLV

• ALI Cause multifactorial
• Role of endothelial damage (low-pressure
  pulmonary edema)
• Inflammatory cascade proportional to amt. of lung
  resected
• End-inspiratory lung volume important (ie. COPD ?
  auto-PEEP during OLV ? inspiration starts above
  FRC ? large TV contributing to ALI)
• Caution w/ PEEP in OLV in COPD pts ?
  hyperinflation and increased shunt
• Normal lungs benefit from PEEP in OLV

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Pro Low VT in OLV

• Suggestions
• Lung-protective ventilation (5-6mL/kg)
• PEEP to those w/o auto-PEEP
• Limit plateau and peak insp pressures to lt25 cm
  H2O and lt35cm H2O respectively
• Avoid over hydration to minimize pulmonary
  capillary pressures
• Treat hypercarbia, hypoxemia and pain all can ?
  pulmonary pressures
• Balanced chest drainage system to avoid
  hyperinflation post-op

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Con Low VT in OLV

• Gal TJ. Con Low tidal volumes are indicated
  during one-lung ventilation. Anesth Analg 2006
  108 271-3.

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Con Low VT in OLV

• Small TV
• Atelectasis
• Requires ? RR ? potential for over-distention
  from air trapping/dynamic hyperinflation
• Hyperinflation ? result of airway resistance by
  DLT obstructive lung disease
• Low TV w/ OLV ? decrease mean alveolar pressures
  ? increase PEEP to maintain oxygenation ? volumes
  approach std TV b/c of ? mean airway pressures

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• Questions?
• Have a great fall!