Respiratory Trials·org

Topic

ARDS

Low tidal volumes, PEEP strategy, proning, paralysis, and steroids.

Everything in ARDS is tested on top of lung-protective ventilation. Ventilating at 6 mL/kg predicted body weight rather than 12 reduced mortality from 39.8% to 31.0% (ARMA) — an absolute reduction no subsequent drug has come near.

Prone positioning is the other intervention that clearly saves lives, halving 28-day mortality in severe ARDS (PROSEVA). Earlier proning trials were negative; this one selected severe disease, proned early, and proned for at least 16 hours at a time. Those three choices are the intervention.

More PEEP and more oxygen are not better. Recruitment manoeuvres with PEEP titrated to best compliance increased mortality (ART), and targeting a PaO2 of 55 to 70 mmHg was stopped early for safety with excess mesenteric ischaemia (LOCO2). Improving oxygenation is not the same as improving outcome.

Neuromuscular blockade improved adjusted 90-day survival when compared against deep sedation (ACURASYS) and did nothing when compared against lighter sedation (ROSE). Read together, the pair suggest what helped may have been avoiding deep sedation rather than the paralysis.

Extracorporeal support has never had a clean positive trial. Referral to an ECMO centre improved survival without disability, but a quarter of those referred never received ECMO and the control arm had no mandated lung-protective strategy (CESAR). Immediate ECMO did not significantly beat conventional ventilation with ECMO held in reserve — but 28% of controls crossed over and 57% of those died (EOLIA), so the trial tests timing rather than the therapy.

Corticosteroids reduced ventilator days and mortality in established moderate-to-severe disease (DEXA-ARDS), in an unblinded trial stopped early for slow recruitment.

PEEP strategy

Trial Year Therapy Effect Finding
ART 2017 Recruitment manoeuvres with titrated PEEP Aggressive recruitment with titrated PEEP increased mortality
ExPress 2008 Increased recruitment PEEP strategy Recruitment-oriented PEEP did not reduce mortality but shortened ventilation and organ failure
LOVS 2008 Open lung ventilation strategy An open-lung strategy with recruitment and high PEEP did not improve mortality
ALVEOLI 2004 Higher PEEP Higher PEEP added nothing once tidal volume and plateau pressure were already limited

Corticosteroids in ARDS

Trial Year Therapy Effect Finding
DEXA-ARDS 2020 Dexamethasone Dexamethasone reduced ventilator days and mortality in established moderate-to-severe ARDS
LaSRS 2006 Methylprednisolone Steroids for persistent ARDS improved physiology, did not improve survival, and harmed late starters

Extracorporeal support

Trial Year Therapy Effect Finding
EOLIA 2018 Veno-venous ECMO Immediate ECMO did not significantly beat conventional ventilation with ECMO held in reserve
CESAR 2009 Referral to an ECMO centre Referral to an ECMO centre improved 6-month survival without disability in severe respiratory failure

Neuromuscular blockade

Trial Year Therapy Effect Finding
ROSE 2019 Cisatracurium Routine early paralysis added nothing when the comparator was lighter sedation
ACURASYS 2010 Cisatracurium Early cisatracurium improved adjusted 90-day survival in severe ARDS

Oxygenation targets

Trial Year Therapy Effect Finding
LOCO2 2020 Conservative oxygen targets Targeting a low PaO2 in ARDS did not help and raised safety concerns

Prone positioning

Trial Year Therapy Effect Finding
PROSEVA 2013 Prone positioning Prone positioning halved mortality in severe ARDS

Tidal volume and ventilator strategy

Trial Year Therapy Effect Finding
ARMA 2000 Low tidal volume ventilation Ventilating at 6 mL/kg instead of 12 cut ARDS mortality from 40% to 31%

What ventilator variable matters

Trial Year Therapy Effect Finding
Driving pressure pooled analysis 2015 Driving pressure Driving pressure predicted survival better than tidal volume or PEEP, even within protective settings

Key references

Guidelines, standards and reviews for this topic.