ISICEM 2016 Day 1

Adrian Wong is at The International Symposium on Intensive Care and Emergency Medicine, which is often affectionately known as “Brussels”.  He has written a mega blog covering the talks he attended today – if you are there he would love you to come up to him, say hello and tell him what you think of his blog! JS

Opening plenary

Personalised Intensive Care Medicine (JL Vincent)

3Ps pyramid – population-based/broad definitions –> personalised. We need to move from population-based to precision medicine.

Failure of large RCTs in ICM can be in part be explained by the sheer heterogeneity of population being studied.

Medicine has always been personalised (Osler)

Genomics – does survival rely solely on the individual’s genetic makeup?

                        e.g. response to vasopressin is different in population

The host response to inflammation is variable


            ARTISAN study which looks at THROMBOMODULIN

Wong et al – Developing a clinically feasible personalized medicine approach to pediatric septic shock.

“SIRS is a hiccup in history”

Report of round table meeting re: recovery after critical illness (Azoulay/Herridge)

3rd round table meeting – 2002 and 2009

2002 – Angus: Surviving Intensive Care

2009 – Griffiths and Hall: Exploring ICU-acquired weakness

Broached the idea of extending rehabilitation outside ICU but also focussed on the long-term effects on patients beyond ICU

Opportunities to improve care

  • Critical care is a disease continuum
  • Patient and family centred and engagement
  • Sound biological plausibility
  • Pts are heterogeneous
  • Role of rehabilitation in changing outcome

Long term cognitive impairment after critical illness (BRAIN-ICU study)

Depressive symptoms in patients and spouses are common

The Impact of High Versus Low Sedation Dosing Strategy on Cognitive Dysfunction in Survivors of Intensive Care Units: A Systematic Review and Meta-Analysis.

Early intensive care sedation predicts long-term mortality in ventilated critically ill patients.

The longer MV, the greater the weakness

NICE guidelines on rehabilitation after critical illness (2009)

Patient-centred outcomes/spiritual care – independent life, cognitive function, ability to work, absence of chronic pain, etc

            These may not be the same as what the doctor is aiming for

Intensive care may need to integrate with palliative care

  • Relieve distress
  • Support person
  • Manage uncertainties
  • Elicit values
  • Help caregivers

10 recommendations:

  • Look outside the ICU and embrace continuum including pre-ICU trajectory/recovery/adaptation
  • Patient and family engagement and personalised care
  • Heterogeneity risk stratification
  • Open the ICU doors
  • Addressing pain
  • Understand role, timing, indication and duration of rehabilitation
  • Comprehensive understand of neuroendocrine derangements
  • Role of long germ follow up
  • Adoption of proven strategies from other clinical settings
  • Development a comprehensive education agenda for all stakeholders

ICU-acquired infections (van der Poll)

Incidence, Risk Factors, and Attributable Mortality of Secondary Infections in the Intensive Care Unit After Admission for Sepsis

Host-response to sepsis: balance of pro- and anti-inflammatory response

Strategies = anti-inflammatory agents and immune stimulatory agents

Primary end-point – ICU-acquired infection (>48hrs after admission)

Patients who developed secondary infection where sicker (SOFA, APACHE2)

13.1% of patients admitted to ICU with sepsis will develop an ICU-AI (with attributable mortality of 10.9% by day 60)

15.1% of patients admitted to ICU with non-sepsis diagnosis will develop ICU-AI

Age isn’t a risk factor (with attributable mortality of 21.1% by day 60)

LOS with ICU-AI is significantly increased


DahLIA trial: Dexmedetomidine to lessen ICU agitation (Reade)

Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated Delirium

We don’t know how to treat delirium

Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study.

Mechanism of dexmedetomodine – sedative a2-agonist (substantially less hypotentive than clonidine)

Inclusion – pts who remain intubated only because of their degree of agitation require such a high dose of sedative medication

Intervention dex 0.5ug/kg/hr (0-1.5) or placebo

Primary end-point: ventilator-free hours after extubation

74 patients randomised (96 target)

Fewer pts in dex group required additional sedative drugs

Dex group had significantly more ventilator-free hours: 144.8 vs 127.5

Nurses thought patient was ready for extubation quicker

Time to extubation faster

Dex patients had less time CAM-ICU positive

Adding dex to standard care is likely to be a cost-effective intervention


Early vs late parenteral nutrition in critically ill children (PEPaNIC) Van der Berghe

Early versus Late Parenteral Nutrition in Critically Ill Children

Critically ill patients unable to be fed by mouth

Cochrane collaborative (2009) Nutritional support in critically ill children

Nutritional practice in PICUs varies

  • 70% start EN within 24-48hrs
  • 50% start PN within 24-48hrs
  • Adult trials question the benefit of early PN

This trial looked at early PN to supplement EN compared to EN alone

PN initiated within 24hrs after PICU admission

Both groups had early EN

End point – new infections and duration of PICU stay

1440 randomised

No difference in mortality (hint that early PN might be harmful)

Early PN associated with more infection

Duration of ICU stay increased by PN

Early PN increased MV days

Withholding PN for 1 week superior to early PN


Hypoxaemia following major surgery – NIVAS study (Jabir)

Effect of Noninvasive Ventilation on Tracheal Reintubation Among Patients With Hypoxemic Respiratory Failure Following Abdominal Surgery

Development and validation of a score or prediction of postop respiratory complications Brueckmann et al

A Trial of Intraoperative Low-Tidal-Volume Ventilation in Abdominal Surgery


Treatment of Acute Hypoxemic Nonhypercapnic Respiratory Insufficiency With Continuous Positive Airway Pressure Delivered by a Face Mask

This trial – primary outcome number of re-intubation within 7 days. Inclusion resp failure within 7 days of surgical procedure

300 pts randomised

NO HIGH-FLOW NASAL CANNULA. Only traditional NIV mask used

Re-intubation 46 (control) vs 33% (NIV)

NIV group had less lung infections within 30 days

NIV increased ventilator-free days


Post-extubation high-flow nasal cannula vs conventional oxygen therapy in low-risk pts

Effect of Postextubation High-Flow Nasal Cannula vs Conventional Oxygen Therapy on Reintubation in Low-Risk Patients

Would HFNO prevent reintubation in low risk pts within 72 hours

Low risk – <65, APACHE2<12, BMI<30, adequate secretion management, absence of heart failure, <1 co-morbidity, absence of airway patency problems

10347 screened; 527 randomised. Majority excluded as deemed high risk for intubation

HFNO had lower reintubation rate (4.9% vs 12.2%) – also less laryngeal oedema and stridor


Individualised management of ARDS (L Brochard)

Max Harry Weil Memorial Lecture

ARDS initially described in Lancet 1967


4499 pts with hypoxemic respiratory failure

3022 with ARDS

We don’t ventilate them very well – too much TV, PEEP variable etc.


ARDS – is not a single entity.

Comparisons of Berlin definition for ARDS with autopsy (Thille AW et al AJRCCM 2013)

Subphenotypes of ARDS (Calfee CS et al Lancet Resp Med 2014)

2 phenotypes identified – Phenotype 1 has better survival characteristics

Higher vs lower PEEP in ALI/ARDS Systematic Review (JAMA 2010)

PEEP induced lung volumes to predict alveolar recruitability (Dellamonica ICM)

Oxygenation response to PEEP predicts mortality in ARDS (Goligher EC et al)


ARDS management

The concept of the baby lung. Small lung does not mean stiff lung

Stress (pressure) and Strain (deformation)

Strain – increase in lung vol/FRC

Lung stress and strain during mechanical ventilation: any safe threshold?


Compliance = tidal volume/driving pressure

Driving Pressure and Survival in the Acute Respiratory Distress Syndrome




Reducing VILI is still the most important possibility to improve survival post ARDS. Individualised ventilation should be based on

  • Recognising ARDS
  • Assessing severity
  • Individually titrating Vt (strain) and PEEP



SOSD Phases of fluid resuscitation

Circulatory Shock – JLV and De Backer

Four phases of intravenous fluid therapy: a conceptual model

Salvage (Shapiro)

  • Fluid management in sepsis has changed considerably despite it being a time critical diagnosis
  • Obtain a minimal acceptable BP

Perform lifesaving measures


During salvage, LIBERAL FLUID RESUSCITATION – 30mls/kg??


The Bottom Line – Fluid review section


  • Approximately 4-5l
  • Antibiotics
  • Ensure critical interventions
  1. Qns which fluid – anything you can swim in
  2. Qns diastolic dysfunction – becoming more important. BUT not in the salvage phase
  3. Qns what are your markers for success – multiple e.g. BP, HR, biochemistry. When you have a BP you can leave the bedside for a minute


Optimisation (De Backer)

  • Provide adequate oxygen availability
  • Optimise CO, SvO2, lactate

Why give fluids? Expect an increase in tissue perfusion

Delayed fluid is associated with greater activation of inflammation CCM 2012 40 2841

Improvement in microcirculation associated with improved organ function

Fluids and CO (Muller Anaesthesiology 2011) – not all improve CO

Why restrict fluids? Oedema deleterious – lung oedema and tissue oedema

A positive fluid balance is associated with a worse outcome in patients with acute renal failure

Sepsis in European intensive care units: results of the SOAP study.

The Adult Respiratory Distress Syndrome Cognitive Outcomes Study Long-Term Neuropsychological Function in Survivors of Acute Lung Injury

Fluid challenges in intensive care: the FENICE study A global inception cohort study

What DBD would do (pic)


Qns what markers? Lactate. Arterial Veno CO2 gradient



Stabilisation (Slama)

  • Provide organ support
  • Minimise complications

Aim for zero or negative balance during this phase

FINNAKI study –

A positive fluid balance is an independent prognostic factor in patients with sepsis

Chloride – Association between intravenous chloride load during resuscitation and in-hospital mortality among patients with SIRS.

Meta-analysis of chloride – Meta-analysis of high- versus low-chloride content in perioperative and critical care fluid resuscitation.

RRT and diuretics to transition to de-escalation phase


De-escalation (Marshall)

  • Wean for vasoactive drugs
  • Achieve a negative fluid balance

Prefers the term de-resuscitation

How? Spontaneous, diuretics, RRT

Strategies – fluid restrict, initial resuscitation then restrict, active de-resuscitation

Who? >72 hrs in ICU and net fluid balance > 6l




Early resuscitation in sepsis

Arterial BP targets (JL Teboul)

Why do we use vasopressor?

When to initiate?

  • Early. May not have completely be fluid resuscitate yet.
  • Look at diastolic BP

Which MAP target in septic shock?




Lots of oxygen (P Rademacher)

Altered oxygen extraction in illness and sepsis

Understanding the benefits and harms of oxygen therapy

Hyperoxia in experimental sepsis CCM 2009 37 2465

  • In animals studies, hyperoxia is anti-inflammatory and improves hemodynamics/metabolism
  • And does not cause ALI

Eur J Emerg Med 2014 31 233 Stojmeijer et al.

Hyper2S – hyperoxia and hypertonic saline (2*2 trial)

BUT trials stopped early due to worse outcome in both intervention groups


  • Hyperoxia group had better PaO2 (obviously)
  • Hyperoxia group had better SOFA by D7
  • BUT adverse events noted. Hyperoxia had more weakness, atelectasis
  • Higher mortality in hyperoxia group at D28 and D90

Hyperoxia CANNOT be recommended in pts with septic shock


Should EGDT be abandoned (De Backer)

Varpula et al ICM 2005 31 1066

Rationale for EGDT – prevent development of tissue hypoperfusion achieving targets for  MAP, SvO2 and CVP

Rivers – more fluids, RBC, Dobutamine and vasodilatory agents, sedation and mechanical ventilation. BUT criticism – single centre, potential confounders, few pts made the difference….

PROCESS, ARISE, PROMISE all didn’t show a difference

EGDT: do we have a definitive answer – De Backer and JLV 


Difference with Rivers

High ScVO2 can mean anything!


How useful are changes in lactate levels? (Fries)

EGDT what do we do now? Levy

Serum lactate as predictor of mortality in patients with infections (ICM 2007)

Serial blood lactate levels can predict the development of MOF following septic shcok (Bakker 1996 Am J Surg) – time with high lactate probably more important than the initial lactate

Lactate clearance

EMShockNet investigators – lactate clearance vs non-lactate clearance groups

Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial.

Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy: A Randomized Clinical Trial

German Lactate in Severe Sepsis trial




How to interpret veno-arterial pCO2 (JLT)

Simplified Fick equation

High PCO2 difference is due to blood stagnation caused by low cardiac output state

6mmHg is the magic number


EtCO2 as a cardiac output monitor (Monnet)

Revision of physiology of etCO2

3 determinants of etCO2

  • Alveolar ventilation
  • Pulmonary blood flow
  • CO2 production

Provided production of CO2 is constant, etCO2 can be used to reflect CO

End-tidal CO2 pressure determinants during hemorrhagic shock –

Relationship between etCO2 and CO is not linear

Partial pressure of end-tidal carbon dioxide successful predicts cardiopulmonary resuscitation in the field: a prospective observational study –

etCO2 can be used with fluid balances



Haemodynamic monitoring

Why (Perel)

Haemodynamic instability in sepsis –

Haemodynamic status of a critically ill patients is very complex

Clinical review: Update on hemodynamic monitoring – a consensus of 16 –

Getting the Full Diagnostic Picture in Intensive Care Medicine: A Plea for “Physiological Examination”

No evidence that any form of monitor improves outcome on the ICU

Perioperative cardiovascular monitoring of high-risk patients: a consensus of 12


How (Biais)

  • PAC
  • Transpulmonary thermodilution
  • Pulse pressure analysis
  • Arterial line – calibrated vs non-calibrated
  • Oesophageal Doppler
  • Bio-reactance/bio-impedence


  • Many device available
  • Perfect device doesn’t exists
  • Know limitations
  • Will not improve outcome by itself


Who (Monnet)

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

A systematic review and meta-analysis on the use of preemptive hemodynamic intervention to improve postoperative outcomes in moderate and high-risk surgical patients

Choice of monitor in theatre depends on whether vascular resistance is going to be stable


Also see Robs trial summary:

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