The Prato ICM Conference 2015, Day 2

The Collaborative Clinical Trials in Intensive Care Medicine Conference at the Monash University Prato Centre (#pratoICM15) continues. Read The Prato ICM Conference 2015, Day 1 for highlights and discussion points from the first day of the conference and continue below for an update on Day 2.

Extracorporeal Membrane Oxygenation – Where is this flowing to?

ECMO is continuing to grow in clinical practice, largely as a consequence of advances in technology. The 2009 H1N1 pandemic and the CESAR trial (Peek G, et al. Lancet 2009) propagated the use of this support modality world-wide. The International ECMO Network (ECMONet) is aiming to plan, develop, and implement robust clinical research in this area. This is crucial, as most of the current data supporting the application of ECMO are based on observational cohort studies or cases series. Given that these modalities are expensive, and potentially clinically harmful, this is a significant issue. ECMONet is attempting to develop a global collaboration to improve this evidence base, principally by establishing and supporting high-quality ECMO research centers.

Importantly, there does appear to be a relationship between volume of cases and outcomes in adult ECMO. Centers probably need to perform at least 30 ECMO runs per year to ensure competency. Another major clinical question is how to manage mechanical ventilation in patients receiving VV-ECMO. Typically clinicians provide low tidal volumes (4-6mL/kg), low plateau pressures (~25cmH2O), and avoid diaphragmatic inactivity (by keeping patient’s spontaneously breathing). Higher PEEPs during VV-ECMO appear to be associated with a survival benefit (Crit Care Med. 2015 Mar;43(3):654-64), although as an association only, this may simply reflect the severity of the underlying respiratory process. The role of prone ventilation in patients on VV-ECMO is also uncertain. The LIFEGUARDS project is a large multicenter observational study aiming to describe mechanical ventilation strategies on VV-ECMO, and will hopefully provide robust contemporary data concerning this area of practice.

Registry data from Australia demonstrates that 44% of patients with out-of-hospital VF/VT do not get ROSC. An important question is therefore whether the application of ECMO as a bridge to definitive therapy could be of benefit. Professor Steve Bernard (The Alfred Hospital, Melbourne) has explored this in a small single center study of mechanical CPR, VA-ECMO, induced hypothermia, and early coronary re-vascularisation (CHEER trial) (Resuscitation 86 (2015) 88–94). Three out of nine patients (33%) in the out-of-hospital cardiac arrest group survived (remembering these patients were all in refractory arrest, and therefore without ECMO would have died). Unfortunately to date, these initial positive results have not been replicated in later patients, although work is ongoing. Potential keys to improving outcomes may be in reducing the duration of CPR and the time to successful cannulation. A team based approach, with regular simulation exercises appears to be crucial in establishing this type of program.

TBI – My head hurts.

CENTER-TBI (www.center-tbi.eu) is an initiative to improve outcomes in traumatic brain injury. Major aims are to provide an improved characterization of TBI in Europe, undertake comparative effectiveness research between participating institutions, and develop improved prognostic models. Enrolment has commenced with preliminary data now available. Importantly this project aims to leverage the existing heterogeneity in clinical practice between institutions, as a means of testing interventions on a large clinical scale.

Advances in technology have allowed an improved understanding of the pathophysiological processes in brain injury. Using microdialysis and functional imaging modalities it is becoming increasingly clear that a more personalized approach to TBI care is required. In this respect brain ischaemia occurs via different pathways, including altered cerebral blood flow, microvascular dysfunction and diffusion abnormalities (mediated by nitric oxide), and impaired mitochondrial function. We need to challenge the current paradigms of TBI management, where a step-wise approach is provided in most patients, without tailoring therapy to the physiological abnormality. In addition, although focal changes are often noted on imaging, current clinical interventions are provided in a global manner.

Results from another major trial in TBI patients will be available soon! The EPO-TBI trial has completed recruitment. This study was a stratified, prospective, multi-centre, randomised, double-blind, placebo-controlled, phase III trial in patients with moderate or severe traumatic brain injury to determine whether erythropoietin (EPO) improves neurological function 6 months after injury. This study was conducted in Australia, New Zealand, the Kingdom of Saudi Arabia, France, Finland, Germany, Ireland and Singapore. Interim analysis (after the first 200 patients) demonstrated an incidence of VTE of ~18% (equal to that expected by the study management team). Full data analysis will hopefully be complete by July, with results available in September / October.

Follow @anzicrc and #pratoICM15 hashtag on Twitter to follow events at The Collaborative Clinical Trials in Intensive Care Medicine Conference 2015 in Prato, Italy.

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