1. Low Tidal Volume Ventilation Brad Winters, Ph.D., M.D. Armstrong Institute for Patient Safety and Quality

2. Purpose of Low Tidal Volume Strategies Lung Protection – “Volutrauma” – Barotrauma – Ameliorate activation of chemical inflammatory mediators – Prevent development of ARDS – Improve oxygenation – Improve outcomes (ARDS mortality is as high as 60%)

3. Traditional Ventilation Large tidal volume (Vt) ventilation; > 10cc/kg Became common after Bendexin published in 1963 a study showing the development of atelectasis in patients on lower tidal volumes Since atelectasis is viewed as undesirable (shunt, hypoxia) this large tidal volume approach became the norm. However, this approach has been shown to increase morbidity and mortality in critically ill patients, esp. those with ARDS

4. The Problem with Large Vt In acute lung injury there is a breakdown in lung architecture This leads to stiff lungs with areas of over- inflation and under-inflation Large Vt results in over-distension of some areas This leads to inflammatory responses that damage the lung

5. The Problem with Large Vt This can also lead to barotrauma (rupture of alveoli, pneumothorax etc.) Additionally, some airspaces collapse but then re-open cyclically causing “volutrauma” due to shear stresses from the “popping open and closed” Much of the problem is related to the pressure effects of the large volumes

6. Low Vt: the new way Based on animal studies and some small clinical studies, the “ARDSNET” Trial compared outcomes using traditional tidal volumes (>10 cc/kg) to lower volumes (4- 6cc/kg) finding significant benefit. Several more studies and a meta-analysis led to the conclusion that large Vt and the high pressures it generates were harmful.

7. Low Vt: the new way Based on this body of literature: – For ARDS, It is recommended that patients should be ventilated with Vt of 6-8 cc/kg And that plateau pressures should be measured, documented and targeted to be no more then 30 cm H20.

8. Role of PEEP Use of Positive end-expiratory pressures (PEEP) of ≥ 5 cm H20 is recommended along with the low Vt PEEP helps to prevent alveolar collapse at these low Vt, preventing atelectasis and “volutrauma” How much PEEP is required is unclear, there are several published Vt:PEEP protocols (ARDSNET) What is clear is that zero PEEP (“ZEEP”) is to be avoided.

9. Who should get Low Tidal Volume? The evidence strongly shows that anybody who meets criteria for Acute Respiratory Distress Syndrome (ARDS) or Acute Lung Injury (ALI) should receive this therapy. Criteria – Lung injury of acute onset (not a chronic process) – Bilateral CXR opacities not explained by cardiac causes (CHF) – Resp failure not explained by heart failure or volume overload – PAO2/FIO2 ratio < 200 (ALI) or 150 (ARDS) OR Alternatively, – mild ARDS: ratio is 201 - 300 mmHg (≤ 39.9 kPa) – moderate ARDS: 101 - 200 mmHg (≤ 26.6 kPa) – severe ARDS: ≤ 100 mmHg (≤ 13.3 kPa)

10. Other Options for ARDS? For ARDS, there are other popular strategies instead of Low Vt Airway Pressure Release Ventilation (APRV) or Bi- Level Ventilation Certain centers prefer these modes for ARDS and they have potential advantages For right now, the jury is out in terms of direct comparisons of the two strategies (limited data) The consensus is clear that until there is more data, Low Vt strategy should be used in patients with ARDS/ALI

11. What about non-ARDS patients on mechanical ventilation? There is emerging evidence that pre-emptive Low Vt strategy is good for a wider range of mechanically ventilated patients. The basis for this “pre-emptive” approach is that the initial injury may be subtle and not obvious and data suggests the diagnosis is often delayed Once ARDS/ALI criteria are met – the “cat is out of the bag” – only a few hours of mechanical ventilation with large Vt may start the cascade

12. Pre-emptive Low Vt The deleterious effects of conventional large Vt ventilation just amplifies the injury: – “multi-hit theory of ARDS” In this way some progression to ARDS is “iatrogenic” Most patients admitted to an ICU will have at least one risk factor for this

13. Acute Lung Injury Risk Factors Sepsis, Severe Sepsis, Septic Shock (from non- lung source) Pneumonia (with or without sepsis) Aspiration and Toxic Inhalation Severe Burns Trauma Pancreatitis Cardio-pulmonary Bypass Massive Transfusions (Transfusion Associated ALI)

14. Pre-emptive Low Vt Several studies have shown that employing a low Vt, high PEEP strategy vs. a large Vt, low PEEP strategy – Reduces inflammatory biomarkers – Improves Oxygenation – Improves Clinical Outcomes Those who seem to benefit most are critically ill patients and patients intra-operatively undergoing high risk procedure (CABG, TAA etc) Large RCTs are ongoing

15. Pre-emptive Low Vt One recent multi-center RCT (Futier et al. NEJM, Vol. 369 Aug. 2013 pp 428-37) of intra-op patients who were intermediate to high risk for pulmonary complications undergoing major abdominal surgery found that a Low Vt lung protective statistically reduced pulmonary complications, need for intubation or non- invasive ventilation (BiPAP) and length of stay.

16. Pre-emptive Low Vt The clinical evidence is quickly mounting that most if not all patients on mechanical ventilation, whether in the ICU or the operating room, would benefit from a Low Vt strategy.

17. Low Vt in practice Identification of patients who meet criteria: ARDS, ALI, at risk for ARDS – Need a strategy for this – Stakeholders (Resp therapy, Nursing etc) – Consistent practice: Make sure every patient is assessed every day, Daily Goals? If your approach will be to employ Pre-emptive Low Vt, how do you make sure it gets applied immediately after intubation? Create a process to implement: order sets – RT initiated – Physician initiated – Part of mechanical ventilation orders for at risk patients

18. Low Vt in practice Early on establish controlled ventilation so Vt can be controlled Unclear when to allow assisted ventilation as patient improves though early return (as soon as possible) to spontaneous ventilation is considered desirable – Problem with assisted ventilation is that Vt is harder to control – Clinician judgment is necessary

19. Setting the Vt For ARDS/ALI – 6-8 cc/kg predicted body weight (PBW) For pre-emptive Low Vt – Absolutely use <10 cc/kg PBW – 6-8 cc/kg is is likely best (NEJM article used this) PBW uses height and a standardized calculation commonly used in the ICU for medication dosing – Your pharmacists can share this if you are not already using it – Do not use actual body weight as this will over estimate the Vt especially for patients with BMI>25 – Of note over the years that these trials have been done the incidence of BMI>30 has gone from 10% (1980s) to 40% now.

20. Setting the PEEP Low Vt does cause atelectasis (Bendixen was right in that regard) PEEP counteracts this tendency 8-12 cm H2O is recommended by many especially if ARDS is diagnosed but anywhere between 5-15 is probably fine. – Many studies of pre-emptive Low Vt use 5-8 cm H2O. Don’t use ZEEP – Associated with hypoxia, VAP and increase mortality

21. Setting FIO2 Usually start at 100% Need to reduce ASAP with target below 60% – This reduces denitrification atelectasis – Reduce oxygen toxicity In ARDs patients it is recommended to target Oxygen Sat= 88-92% Do the same if using a pre-emptive Low Vt approach though if oxygenation is good, may start at 60%. One possible exception is the use of hyperoxia in abdominal surgery to reduce SSI. Will need to reconcile this for these patients.

22. Respiratory Rate Using Low Vt requires increased respiratory rates to prevent hypercarbia (elevated carbon dioxide) Maintain minute ventilation as best possible – Minute ventilation = Vt x Resp Rate/min Often start at about 20 bpm but may need to increase to 30 or more. This may be difficult especially if the patient had a high minute ventilation before going on the ventilator Downsides with these high rates include – Breath-stacking and high auto-PEEP – This can drop BP by dropping preload and decreasing cardiac performance

23. Respiratory Rate If Resp Rate is kept below 30 these problems are less likely to occur However, minute ventilation may then be too low to control CO2 Therefore, CO2 is usually allowed to rise moderately (into the 50’s mmHg) causing a respiratory acidosis This is referred to as Permissive Hypercapnia Usually tolerated well unless there is also a severe metabolic acidosis Dialysis may be necessary under some circumstance to control pH

24. Plateau Pressure Need to keep <30 cm H2O To achieve this, Vt may need to be dropped further Bronchodilators, sedation or rarely paralysis may be necessary. Sedation and paralysis should be used very sparingly, especially paralytics The Respiratroy Therapist may also be able to adjust the inspiratory waveform or gas flow or other vent parameters to meet this target

25. Translation into Practice Closing the Quality Gap It is estimated that less then half of ARDS patient get low Vt applied in their care A much smaller fraction of “at-risk” patients likely receive this therapy Focusing on adaptive change, that is how we do our work, is essential to closing this gap

26. Discussion