Shanholtz – Acute Respiratory Distress Syndrome

Carl Shanholtz, MD, Professor of Medicine in the Division of Pulmonary and Critical Care and Director of the Medical ICU at the University of Maryland presents the multi-departmental critical care curriculum lecture on ARDS.

Lecture Summary by Dr. Jason Nam

Introduction

ARDS is a common disorder of acute injury to lungs. It can occur in children. Lack of standard definition prior to 1994.
Why use P/F ratio in the definition? It is a surrogate measure of shunt. Shunt fraction needs to be done with Swann-Ganz.
Consensus Conference definitions- between American and European

Characteristic	AECC Definition 1994	Berlin Definition 2012
Timing	Acute, without any specification	Maximum within a week after a trigger insult
Imaging	Chest X-ray with bilateral infiltrates	Chest X-ray or CT scan with bilateral infiltrates, not fully explained by effusion, lung collapse or nodules
Non-cardiogenic source of edema	Confirmation of non-elevated left atrial pressure	Respiratory failure not completely explained by excessive volume loading or cardiac failure
Classification	Based on PaO₂/FiO₂	Based on PaO₂/FiO₂ calculated with PEEP >5 cmH₂O
	Acute lung injury:<300	Mild: 201-300
	ARDS:<200	Moderate: 101-200
	–	Severe: <100
Predisposing condition	Not specified	If none identified, then need to rule out cardiogenic edema with additional data

Pathophysiology

Active exudative phase. Leads to the pulmonary edema (non-cardiogenic). Loss of compliance and hypoxemia refractory to supplemental oxygen. Loss of capillary surface area and increase in dead space. We get â€œbaby lungs.â€
When we try to ventilate, we get VILI.

Lung protection strategies

ARMA Trial – mortality was lower, and ventilator-free days higher in the group treated with lower tidal volumes
Improvement in oxygenation doesnâ€™t seem to predict outcome of ARDS. Oxygenation was a bad surrogate for outcome.
Is there a safe plateau pressure? At any quartile. The lower TV patients had an improved mortality.
Is higher PEEP protective? It was thought that moderate-to-severe ARDS patients would benefit from higher alveolar recruitment. Gattinoti, et al, found that moderate-to-severe ARDS patients had more atelectatic and thereby more recruitable lung.
What about driving pressure? driving pressure is directly proportional to mortality regardless of driving pressure and PEEP. No one yet knows how to titrate driving pressures as there is current evidence and interest in closed-lung strategies.
Does lung prevention ventilation strategies prevent ARDS? PReVENT trial. Multicenter RCT in Netherlands. A low tidal volume strategy did not result in a greater number of ventilator-free days than an intermediate tidal volume strategy

Fluid Management and ARDS

Fluid and Catheter Treatment Trial – Fluid conservative vs. fluid liberal. No significant difference in the primary outcome of 60-day mortality. However, the conservative strategy of fluid management improved lung function and shortened the duration of mechanical ventilation without increasing non-pulmonary-organ failures.

Prone positioning

Rationale – Much of the atelectasis in lungs sits behind heart. Prone positioning improves aeration and removes weight of heart off the lungs. More homogenous distribution of pleural pressures and improve V/Q mismatch.
PROSEVA Trial – Early application of prolonged prone-positioning sessions significantly decreased 28-day and 90-day mortality

Neuromuscular blockade

ROSE Trial – Among patients with moderate-to-severe ARDS who were treated with a strategy involving a high PEEP, there was no significant difference in mortality at 90 days between patients who received an early and continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets.
ACURASYS Trial – Enrolled moderate-to-severe ARDS patients. Improvements in 90-day mortality. When compared to ROSE trial, differences could be due to differences in levels of sedation in the trials.

Salvage therapy

H1N1 crisis of 2009 showed increasing use of salvage therapies. Such as inhaled vasodilators. ECMO use for ARDS.
CESAR Trial – ECMO-based management protocol can signiï¬cantly improve survival without severe disability in patients with severe but reversible respiratory failure. Promising trial but major confounders.
EOLIA Trial – Multi-national RCT ECMO vs. protocolized management for severe ARDS. Among patients with very severe ARDS, 60-day mortality was not significantly lower with ECMO than with a strategy of conventional mechanical ventilation that included ECMO as rescue therapy. Stopped early for futility even though there were initial trends for improved survival. There may have been bias in the cross-over leading to survival bias and selection bias.
Needs a confirmatory RCT.
Experimentary therapies – mesenchymal stem cells, vitamin D, antiplatelet therapy, and targeted temperature management.