ARDS Ventilation Anwar Murad Amiri Hospital

Introduction ● ARDS is a devastating clinical syndrome that affects both medical and surgical patients. ● The majority of these patients develop profound hypoxia requiring intubation and mechanical ventilation. ● Mortality ranges from 25-60%. ● Even though mechanical ventilation is the mainstay of supportive therapy, it can actually exacerbate the lung injury. ● We need to remember: o Mechanical Ventilation is NOT the treatment in these patients. o We should not actively HARM the patient via ventilator induced lung injury (VILI).

The Ventilator is a Weapon ● Too much pressure? o Leads to alveolar distension (volutrauma) o Release of cytokines (biotrauma) o Edema formation o Alveolar Hemorrhage o High tidal volumes have been shown to lead to lung injury rather than high airway pressures ● Not enough pressure? o Leads to cyclical collapsing and inflation of alveolar that leads to shear injury (atelectrauma) ● Therefore we need to be careful how we ventilate these patients

The K.I.S.S Principle My Axiom

● ARMA Trial o NEJM 2000 o Multicenter RCT o 861 patients with ALI/ARDS randomized to “traditional” ventilation (12ml/kg) vs low tidal volume (6-8ml/kg) o The low tidal volume group has significantly lower mortality rate and duration of mechanical ventilation compared to the control group. o Controversial findings  Did the control group truly represent standard of care? o 2 meta-analyses and several RCTs show a strong benefit and is well tolerated. Low Tidal Volume Ventilation

May be beneficial in patients without ARDS

ARDSNET.ORG

● Permissive hypercapnia o Low tidal volumes WILL lead to respiratory acidosis o But is this necessarily harmful?  Cerebral edema  Significant pulmonary hypertension  RV failure  Hemodynamically instability/Arrythmias o General consensus says that pCO2 is not an issue but rather the acidemia itself  Can tolerate a pH as low as 7.20  Bicarbonate infusions have been suggested to buffer the acidemia

● Rapid delivery of low tidal volumes (3-15 breaths/second) to minimize VILI. ● Initial studies suggested early application was beneficial in ARDS High Frequency Oscillation Ventilation

● 548 patients from 39 centers o Clinical features of ARDS with P/F<200 randomized to HFOV vs conventional mechanical ventilation.  Lung protective strategy o HFOV group required more sedation, paralytics, and vasoactive drugs o Study terminated early when interim analysis suggested marked harm from the intervention (Target thresholds had not been reached)

● 795 patients at 13 centers with clinical features of ARDS and P/F<200 o Randomized to HFOV vs conventional mechanical ventilation ●No statistical significance between the two groups in respect to 30 day mortality (approx 41%) ○ Interestingly, mortality rate in both groups similar to intervention arm of OSCILLATE Trial ●HFOV arm required more sedatives and neuromuscular agents.

● What does it mean? o Adherence to a conventional lung protective strategy should probably remain as the first line intervention in ARDS. o HFOV should not be considered a first line treatment for these patients BUT it is still an option for ARDS refractory to our normal measures.  Use it as rescue therapy High Frequency Oscillation Ventilation

● First described in 1970s ● Shown to improve oxygenation in ARDS patients o Homogenous distribution of alveolar inflation o Redistribution of lung perfusion o Postural drainage of respiratory secretions ● Even though it showed improvement, several studies did not show a decrease in mortality ● Meta-analyses since then showed marked improvement in patients with severe ARDS Prone Positioning

● PROSEVA Trial o 474 patients in 27 ICUs  Each had at least 5 years experience in prone positioning  Patients with severe ARDS (P/F <150) randomized to standard care or proning (within 1 hour of randomization, 16 hours per day, everyday up to 28 days or longer if physician prescribes)  Both groups were managed via a lung protective strategy.

● First real markedly positive study when all previous studies showed no benefit ● Implemented in ICUs with established experience ● Complications do exist, but UNCOMMON if proper precautions taken Too Good to be True?

The evidence is growing….And remember, our practice has changed since those initial studies

If you are careful, It can be done with no adverse events.

● Emphasis is placed on applying high PEEP in order to maximize alveolar recruitment and minimize atelectrauma. ● This can be combined with low tidal volume ventilation in order to avoid marked alveolar distension (Open Lung Ventilation) ● Three multicenter RCTs explored this approach for ALI/ARDS ● A meta-analysis/systematic review was published in 2010 Open Lung Ventilation/High PEEP

Most recent systematic review of 7 studies was published in 2013 in the Cochrane Library and is likely more representative of our current practice of ARDS management

● Improved oxygenation with no statistically significant change in mortality with high PEEP o Both ALI and ARDS ● Trend towards benefit with high PEEP ● Marked heterogeneity in these studies ● The studies that showed the possible benefit also included a LTVV strategy

● Open lung ventilation is likely only helpful if LTVV is prioritized ● No clear evidence supporting its use o How much to apply? o How to titrate? o How well is it tolerated? o Why does improved oxygenation not translate to reduced mortality? ● Higher PEEP can be considered in moderate to severe ARDS if combined with LTVV So?

● Extra Corporeal Membrane Oxygenation o Existed for decades o Gained popularity for hypoxic respiratory failure during the H1N1 pandemic o Small case series/uncontrolled trials reported good outcomes o With the onset of refined and smaller ECMO devices, it has become an attractive option for intensivists for severe ARDS. ECMO

● CESAR Trial (Lancet 2009) o Only multicenter RCT studying its role o 180 patients randomized to conventional therapy (at designated units) vs referral to specialized centers to be considered for ECMO. o Death/disability at 6 months occurred in 37% of ECMO group compared to 53% of conventional group o Several methodology issues!!  76% patients randomized to ECMO actually got it (rest got lung protective MV)  Lung protective strategy suggested but not mandated in conventional group  ECMO group got more steroids and neuromuscular blockers ECMO

● Certainly an option but likely only as rescue therapy ● Should be limited to specialist centers ● No evidence based guidelines for its implementation o ELSO guidelines are the most comprehensive but don’t necessarily represent consensus or standard of care ● Complications o Bleeding (less of an issue with the newer cannulas) from anticoagulation o Thrombosis o Ischemia ● Expensive! ● Need more evidence before we should consider it an integral part of ARDS managment! So?

● Recruitment Maneuvers o Application of CPAP for a brief time (35-40cm H2O for 40 seconds) o Not clear if change in outcomes o Should probably be considered as rescue therapy at this time ● Esophageal Pressure Monitoring o Analogue of pleural pressure in order to determine transpulmonary gradient (true marker of alveolar distension) o One RCT (NEJM Nov 2013) of 61 patients showed improved oxygenation and compliance compared to conventional ventilation o More evidence needed to see if this influences outcomes ● Inhaled Nitric Oxide o Meta analysis of 9 trials (n=1142 patients) showed no reduction in mortality in ARDS regardless of severity (Crit Care Med, Feb 2013) Other options

1.Low Tidal Volume Ventilation 2.Prone positioning (if feasible) 3.Low Tidal Volume Ventilation 4.Optimize PEEP 5.Consider rescue therapies (ECMO/HFOV/iNO) 6.Low Tidal Volume Ventilation! What should I be doing?

Thank You Questions?