VANISH Trial – Gordon


International Sepsis Forum Round Table – Mission Accomplished?


An eclectic mix of the worlds most influential sepsis experts discuss what matters to them and you at the opening plenary for the state of the art. Featuring Mervyn Singer, Derek Angus, , ,Claudia Dos Santos, Peter Pickkers &


The New Sepsis Definition – Shankar-Hari


The EUROTHERM trial – Andrews


Mechanisms of ARDS – Summers



Who to admit to ICU – Bassford



The DESIST Trial – Walsh




ECCOR2 / Rest – McNamee





The International Sepsis Forum Round Table: Mission Accomplished in Sepsis? (Plenary)

The International Sepsis Forum Round Table: Mission Accomplished in Sepsis?

Blog by Jack Wong Edited by Adrian Wong



The International Sepsis Forum Round Table: Mission Accomplished in Sepsis?

Chair: Mervyn Singer

From left to right: Derek Angus, Claudia Dos Santos, Peter Pickkers , Ron Daniels, Tim Walsh, Rinaldo Bellomo


Disclaimer: The following summary is the author’s understanding of the round table discussion and it is not verbatim transcription of expert’s statement during the discussion.

In response to the 3 major sepsis trials (ARISE, PROCESS and PROMISE) with negative results (ie. protocolized sepsis management does not change outcome) in contrast to the findings of Rivers et al in the concept of EGDT, Mervyn Singer raise the question about the plausibility of spending millions of dollars in studies for sepsis to the panel.

  • Angus: Albeit the result, trial of protocolized approach as a mean of knowledge dissemination (of sepsis management) is worth probing
  • Dos Santos: Where should we go from here with the findings? Is the problem due to inability to define patient cohort and the future will be scrutinizing our work
  • Pickkers: “Whatever we do in ICU doesn’t work with mortality rates does decrease”
  • Daniels: There is a need to engage non-intensivist, including public and GP etc with the help of protocol and guidelines in sepsis recognition and management. We should stick to using sepsis bundle.
  • Walsh: Doing something is better than doing nothing. Management has changed over time
  • Bellomo: These comment are “rationale” (Reference to previous talk about medicine is all about rational astrology). We might just not understand what we are doing. If study design is appaling then we have to question the credibility of “evidence” (Referring to Rivers) – At the end of the day, we do what we think is right.


Where should we go from here in management of sepsis?

  • Walsh: Proper clinical examination, direct patient assessment is the way to do it.
  • Daniels: Step by step as per bundle
  • Pickkers: Give fluid!
  • Dos Santos: Examine the patient and base it on clinical assessment rather than advance monitor like ECHO etc
  • Angus: More accurate monitoring perhaps (Referring to increasing use of PA catheter in the USA)


Antibiotic resistance problem: Whats your take?

  • Daniels: Give it! in case they don’t get it
  • Pickkers: Watch and give it when indicated.
  • Angus: When it is clear – give it! If it is doubtful then use clinical judgement.
  • Bellomo: If patients is in hospital, give antibiotics! Antibitoics rersistance issue contributed by ICM is minute.
  • Angus: *Reminds Bellomo about risk of CDT diarrhoea*
  • Walsh: Increased awareness nowadays hence more doctors are able to make clinical judgement earlier (regarding when to administer antibiotics)
  • Singer: NCEPOD stated lots of patients with sepsis were not given antibiotics (prompting there is still a gap in appropriate management)

If RCT doesn’t tell us what we do, then what should we do?

  • Angus: Causal inference – we still need to randomized rather than doing things randomly.
  • Dos Santos: Randomization is still the right way to go. What is sepsis as defined by Science? We need to understand process of sepsis more with phenotypes / genetic level / biotyping.
  • Bellomo: Suggests cluster randomization by hospital.
  • Walsh: Careful selection / randomization of patient with better design eg. don’t compare 80 years old with 20 years old.
  • Daniels: All patients are not equal so treat individually.
  • Angus: Commenting re:failure in oncology research when wrong things are measured. With research advancement which might lead to better understand of a disease (eg malignant melanoma) dose not mean it will lead to a better patient outcome (ie mortality)


Could we use more rapid POC test / biomarkers to improve outcome?

  • Walsh: Need more evidence and need more collaboration across the globe.
  • Daniels: It is important to put biomarker result into context.
  • Pickkers: Biomarkers are overrated. Does number means truth?
  • Angus: We have always had biomarkers (Temp, WCC)


De-escalation – When and how to do it?

  • Bellomo: We tend to overload our patients, why are we doing it? We don’t have the answer.
  • Dos Santos: De-escalation is important during recovery phase in high risk patient group but identification of high risk patient is a challenge.
  • Bellomo: Maybe it doesn’t matter at all


New sepsis definition (Sepsis 3.0 to be published in Feb 2016 in SCCM) – Do we need a new definition?

  • Daniels: It is helpful to have more pragmatic guidance to help assessor recognise and treat sepsis.
  • Walsh: We need them to help with trial
  • Pickkers: (Referring to the title of the discussion: Mission Accomplished?) Mission is not at all accomplished. We have no public awareness and we need to put more effort into it.
  • Bellomo: It is a work in progress. A new definition is part of the big process.

Haemoglobin – who needs it?

Blogger Craig Denmade

Transfusion in the ICU

Tim Walsh

Summary/Key messages

  • Blood saves lives!
  • What is the impact of transfusion strategy on mortality?
  • Old vs fresh blood – Walsh et al CCM 2004
  • RCT – trend to better outcomes with restrictive strategy. Safe & may be better.
  • TRICC trial; Hb 70 vs 100, trend to harm with higher Hb
  • (Other evidence to support argument… Presenter slides needed as too many to capture)
  • More blood to augment oxygen delivery associated with harm
  • Transfusion in UGIB (barca/Villanova) liberal group worse outcomes
  • Septic shock population – higher Hb through transfusion does not confer benefit
  • Cardiac surgery population – restrictive strategy signalling harm
  • Areas of uncertainty: cardiovascular disease population, cardioresp co- & acute morbidity
  • Evidence to demonstrate harm with restrictive strategy in IHD/cardiovasc population
  • More ACS in pts with chronic CHD & restrictive strategy (under review)
  • Red cell storage: We don’t need fresh blood in ICU
  • Conclusions: HB trigger 70 appropriate & safe, higher triggers in acute coronary disease, chronic CVD uncertainty – individualise care

References/Further reading

Synthetic blood is the answer

Chris Cooper

Summary/Key messages

  • “Safe” haemoglobin-based blood substitute
  • Creating a haemoglobin genetically to exist outside RBC
  • Lab research – use E.coli to produce Hb, lyse then purify
  • Toxicity of Hb in plasma: binds NO – ‘good’ radicals, redox cycle – ‘bad’ radicals, free haem complement activation
  • Mimic haptoglobin? No.
  • Current direction: Haemoglobin as a true ascorbate peroxidase
  • Making haemoglobin less reactive outside RBC
  • Tyrosine mutations, in-vitro data encouraging
  • Engineered protein exhibits normal oxygen carriage
  • Beginning in-vivo studies

Intravenous iron is the answer

Shaman Jhanji

Summary/Key messages

  • Not discussing PREVENT trial (elective major surgery), focussing on critical care patients
  • Many patients anaemic before arriving in ICU (Vincent JAMA 2002)
  • Anaemia during ICU stay & at discharge Walsh ICM 2005
  • Bleeding, venepuncture, anaemia chronic disease
  • Nutrient deficiencies 10-14% Fe deficient
  • Hepcidin – is iron of any use to our patients?
  • Critical care anaemia due to Fe deficiency or inflammation induced hepcidin increases?
  • Measuring iron def – iron studies not helpful
  • Data suggests iron could be useful in our patients
  • Size of the problem? Lasocki Crit care 2014 (prevalence iron def)
  • Iron and risk infection – free iron risk factor for sepsis
  • Modern iron preparations (lower levels free iron) – data suggests not increased infection
  • Clinical data in ICU patients limited – no increase in haemoglobin but reduction in RBC transfusion (iron dose too low?)
  • IRONMAN trial ongoing – higher dose iron on ICU
  • Anaemia common, our patients likely Fe deficient, iron may reduce transfusion need



  • Transfusion threshold in TBI – individualised care as data lacking
  • Transfusion and duration MV – some subgroup analysis data but uncertainty, hypothesis: improved oxygen carriage > quicker wean, recovery: anaemia and fatigue persists post-ICU
  • Animal kingdom (evolutionary Hb level, normal/physiological Hb): Is the ‘holy grail’ out there?
  • Define chronic cardiovascular disease? Need clear definition in order to assign to treatment groups eg. Liberal vs restrictive

Closing Plenary ICS SoA 2015


Blogger Adrian Wong (@avkwong)


James MacNamee

Summary/Key messages




Tim Walsh

Summary/Key messages

  • Strategies to improve sedation on ICU
  • Unnecessary deep sedation
  • Explore 3 system-wide interventions
    • webbased modular educational resource
    • Feedback of sedation quality at regular intervals
    • introduction of novel technology – RI measure
  • Sedation Quality Assessment Tool to assess the outcome
  • trial protocol
  • Results
    • Typical pt – education and responsiveness technology seem to be best for optimum sedation
    • RI can improve optimum sedation
    • Sedation quality feedback alone was not effect
    • BUT no standardisation of sedation protocol



Who to admit to ICU

Chris Bassford

Summary/Key messages

  • ICU causes harm and doesn’t always work
  • Type 1 error (false positive) – give them a go
  • Type 2 error (false negative) – let them go



Mechanisms of ARDS

Charlotte Summers

Summary/Key messages

  • NOthing seems to work with regards to treating ARDS
  • Why is nothing working?
    • Syndrome not disease
    • Don’t understand biology in humans
  • Known known
    • lots of things can cause ARDS
    • ventilate badly = do badly
  • Known unknowns
    • not everyone gets ARDS
    • one disease or many
    • how do we stop it happening
  • Unknown unknowns
    • Neutrophil biology
    • Pulmonary circulation is special
  • Flow in large pulmonary vessels is pulsatile but not at capillary level


References/Further reading



Peter Andrews

Summary/Key messages

New sepsis definition

Manu Shankar-Hari

Summary/Key messages

  • Sepsis-3 update
  • Why change?
    • SIRS/Sepsis definition messy – different ways to identify a sepsis case
    • New definiton is data-driven
  • Host responses NOT just ‘pro-inflammatory’
  • SIRS negative sepsis is common on the ward
  • Straightforward infection needs to be separated from sepsis
  • New definition is sepsis as bad infection
  • qSOFA – low BP, altered mental state, raised RR (thresholds to be specified in Feb)
  • Septic shock 3.0 – subset of sepsis where underlying circulatory and metabolic shock are likely to lead to increased risk of death
    • post-fluid resuscitation
    • need for vasopressor to support low bp
    • raised lactate



Anthony Gordon

Summary/Key messages



Rehabilitation and Recovery

A session blog from Day 2 of State of the Art, London December 2015. See the full list

Blogger Ben Attwood (@bhca)

The patient experience (video)


Summary/Key messages

  • Video of a patient, ‘Bob’.
  • Honest reflection of experience in critical care. Music was a solace, especially at night when difficult to sleep
  • Warmth of nurses
  • Cried a lot
  • Goals – 3 steps to a chair, walking across a room, first set of stairs. Structure helpful
  • Family and Friends
  • Physio, hydrotherapy, reading (especially Jamie Andrews’, “ Life and Limb”)
  • Feels 60% recovery @2 years. Electric bike real bonus

References/Further reading

Pro-Con: Can we make a difference? (Yes)

Tim Walsh

Definitions of recovery (revival/healing, reclamation)  and rehabilitation (reintegration).

“…quality means care that is personal to each individual” – Darzi

Cancer and stroke patients have clear pathways – what about patient leaving ICU?

Stressful times around discharge from ICU and hospital.

RECOVER RCT – JAMA Int medicine – improving quality during early post ICU therapy

Post intensive Care Syndrome – poor psychological and physical recovery post ICU.

Looks at Re-admission to acute hospital – 23% re-admitted within 3 months as emergency, 50% readmitted within 1 year.

Why might rehabilitation be ineffective?
Patient may not be able to comply.

Acute factors ‘block’ recovery process – muscle lesion
CRP >10mg/L associated with higher risk of poor recovery

Social deprivation and co-morbidities

To finish, defining ‘treatment’ and ‘care’ – patients need individualised therapy through case management, not ‘tick box’ care.

Summary/Key messages

  • Patients suffer excess mortality after ICU
  • More to quality than just therapy
  • Personal support important to patients
  • Education and information vital
  • Patients need individualised therapy through case management, not ‘tick box’ care.

References/Further reading

Pro-Con: Can we make a difference? (No)

Eddy Fan

Eddy says he has no conflicts of interests, although he also says it’s challenging for him to argue against something he believes works!

First – Is it safe/feasible? Bailey et al 2007 Crit Care Med suggests early activity is feasible and safe in respiratory failure patients.

Schweickert, Kress et al Lancet 2009 – Early physical occupational therapy in mechanically ventilated, critically ill patients improves outcome.

Will everyone benefit? There are some clinical phenotypes and molecular mechanisms that may not be modifiable, or have rehab potential.

Can we predict who is at highest risk of developing ICU acquired weakness? Some recent studies suggest Yes.

What is the optimal timing? PRaCTICaL and ReCOVER trials look at this.

Bed rest single risk factor most consistently associated with muscle weakness throughout longitudinal follow-up. Uses ‘Cliff effect’ to illustrate importance of upstream intervention being more useful to than downstream.

AVERT study = RCT for  early mobilisation (within 24 hours of ICU admission)

Burdens of survivorship.

Summary/Key messages

  • Avoid prolonged enforced bed rest/immobility
  • Target lighter levels of sedation (or none!)
  • Prevent development of delirium
  • Avoid potential of neuro/myotrauma
  • Consider early rehabilitation where possible

References/Further reading



When do you start rehab in your ICU?

‘Not early as I’d like”,

  • ‘within 48hrs’ (though this is rarely achieved)
  • ‘PT planned from when the patient is admitted’
  • Try to sit patient up and get to end of bed asap


What sedation approach do you use?

analgesia first.

Perhaps dexmedetatomidine

Could do better!

Improved since targetting RASS.


Pre-existing chronic conditions? Do they not respond or do we need to use different outcome measures?

TW – having thought about this a lot –  probably need different expectations with this cohort. More expertise in chronic disease management required.


Tim Walsh

2012-07-21 12.59.39-1UK

Tim Walsh is Professor of Critical Care at Edinburgh University, Scotland and Honorary Consultant in Critical Care at Edinburgh Royal Infirmary, Edinburgh. He is also current head of Department of Anaesthesia, Critical care, and Pain medicine in the Edinburgh University School of Clinical Sciences He trained in Edinburgh and undertook MD research in the Scottish Liver Transplant Unit, studying oxygen transport during liver transplantation and in acute liver failure. He was appointed consultant in transplantation anaesthesia and intensive care at Edinburgh Royal Infirmary in 1999. Between 1999 and 2011 he was a research active NHS consultant, recognised through an Honorary Chair in Edinburgh University in 2007. In March 2011 he took up the first Chair of Critical Care in Edinburgh University, based in the Centre for Inflammation Research. He leads a multidisciplinary clinical research group with interests including transfusion medicine, sedation in the critically ill, recovery from critical illness and the epidemiology and prevention of ICU acquired infection. He has authored > 100 original research papers, >25 book chapters, and several evidence based guidelines. He founded the Scottish Critical Care Trials Group and was chair from 2000-2013. He is Chair of the National Institute of Healthcare Research Comprehensive Clinical Research Network Specialty Group for Critical Care, which oversees the UK portfolio of Critical Care Research. Other roles include membership of the UK intensive care Critical Care Leadership Forum, and a range of advisory roles relevant to intensive care research.