ISICEM 2015 Blog Day 3

adrianAdrian Wong‘s third and final day at the International Symposium on Intensive Care and Emergency Medicine in Brussels summarised for OXICM

Edited by Jamie Strachan

What’s changed in for me in the last 35 years? Reflecting on ICM over the last 35 years

CPR (P Pepe)

The growth of CPR, more non-doctors were being trained. Increased availability of AED Changes and increased importance of chest compression 15:2 à 30:2 à interrupted Other considerations

  • Decreased priority of advanced airway management and drug administration (no atropine, bicarb, etc)
  • Head up or head down position for CPR?

Haemodynamic Monitoring (S Magdar)

1970s – Swan Ganz catheter All the focus was on the left heart (cardiology driven) Future Less and less people know how to use a PA Catheter

  • Move towards less/non-invasive cardiac output monitor
  • Move towards flow directed therapy instead of pressure values

References PACMAN Trial – Summaries of the trials –

Circulatory shock (JL Vincent)

The origins of the word shock – probably the battle field Focus was predominantly on BP The triangle of shock

  • Arterial hypotension
  • Increased blood lactate
  • Altered tissue perfusion – oliguria, impaired skin perfusion, altered mental status

Less invasive monitoring, MORE ECHO ScvO2

  • <70% – more fluids, transfusion, dobutamine
  • >70% – nothing

Nutrition (J Wernerman)

Patients were starving on the ICU Nutritional routines 1980

  • Parenteral nutrition (only)
  • Hyperalimentation
  • Macronutrients in components
  • Use of lipid emulsion
  • High amino acid (protein) intake
  • Gastric tube only for evacuation

Most important development 1980 – 2015

  • High class EN products
  • High class tubings for EN
  • All-in-one formulations for PN
  • Better glucose control
  • Electronic PMSs for adequate balances

NB – 4/5 of these were developed without RCTs and the last was a highly controversial RCT

Renal support (C Ronco)

AW – The development and evolution of renal replacement therapy is truly the stuff of legends Multiple devices were needed for what is now a single machine – pumps, warmer, pressure sensors, filter There is paradigm shift from renal replacement therapy to renal support therapy. Previous absolute indication as now relative.

ARDS management (A Pesenti)

1980 – 2015

  • ARDS is a hypoxaemic disease
  • ARDS is (in part) an iatrogenic disease
  • The rise of the idea of lung protection
  • Mechanical ventilation is dangerous
  • We breath to eliminate CO2
  • If we eliminate CO2 by mechanical ventilation, we will be free to breath as little or as much as we wish

References Lower tidal volume strategy (≈3 ml/kg) combined with extracorporeal CO2removal versus ‘conventional’ protective ventilation (6 ml/kg) in severe ARDS. The prospective randomized Xtravent-study –

The next 35 years

Suspended animation (P Radermacher)

Rationale – to reduce O2 demand Earliest reports date by to 1862 Modern day experiments achieve this by either inducing hypothermia or drugs e.g. NO, H2S Selected references Is pharmacological, H2S-induced ‘suspended animation’ feasible in the ICU? – Deep hypothermic circulatory arrest: real-life suspended animation. –

Inhaled NO to limit ischaemia/reperfusion injury (M Ramsay)

References Ischemia/Reperfusion Injury in Liver Surgery and Transplantation: Pathophysiology – Nitric Oxide in Liver Injury –

Cardiorespiratory monitoring (M Pinsky)

Future CV monitors need to be

  • Continuous
  • Non-invasive
  • Metabolic targets/parameters

These parameters can then be analysed in a combined fashion to predict how patients will respond. These will

  • Define cardiorespiratory state – NOWCASTING
  • Predict onset of cardiorespiratory insufficiency
  • Predict response to therapy – FORECASTING
    • Linking monitoring to management

Healthcare systems linked

  • Telemedicine will be the norm
  • We will not monitor patients, we will monitor the monitors
  • We will still treat the patients not the monitors
  • Healthcare recourse need per unit will decrease drastically by these approaches, as quality of care improves


  • Non-invasive, continuous, metabolic
  • Although one size does not fit all, one knowledge base serves all
  • Linked in real-time to electronic libraries
  • NOWCASTING – illness severity
  • PREDICTING – future instability
  • FORECASTING – response to therapy to reach sufficiency


Implantable Biosensors (TI Tonnessen)

Early warning à early actions Types of biosensors

  • In vitro
  • Non-invasive
    • Not penetrating the skin or mucous membranes
  • Invasive
    • In the blood stream (arterial or venous)
    • In an organ/tissue

Future of biosensors

  • Miniaturisation
    • Insertion without damage to the organ
    • Multiple sensors in the body
  • New material
    • Biofouling
    • Biocompatible
  • Wireless technology
    • Transmission of signals
    • Wireless energy/charging


Monitoring cell happiness (M Singer)

  • No perfect marker (as yet) of early tissue hypoperfusion
  • Some organ beds affected earlier than others
  • All current tools are relatively late, global and non-specific.. but still useful indicators of unwellness
  • Monitoring (adequacy of) tissue oxygenation has to be where it’s at


  • Major component of acute patient management are
    • Rapid restoration of adequate tissue perfusion
    • Prevention of new-onset tissue hypoperfusion
  • Still waiting for the perfect happy cell-o-meter

Monitoring breath (M Schultz)

The development of the electronic ‘nose’ Exhaled breath profiling for diagnosing acute respiratory distress syndrome –

Easy lung imaging (D Chiumello)

The use of various modalities to determine lung recruitment in ARDS

  • Ultrasound
  • Low dose CT
  • PET guided

References Visual anatomical lung CT scan assessment of lung recruitability – Bedside Ultrasound Assessment of Positive End-Expiratory Pressure–induced Lung Recruitment –

Automated respiratory support (L Brochard)

Automated weaning is an example of a Closed-loop system WIND Study group – A NEW CLASSIFICATION FOR PATIENTS WEANING FROM MECHANICAL VENTILATION – Cochrane review –

Brain protection (A Maas) Aim to optimise the design and analysis of clinical trials in TBI, to increase the likelihood of demonstrating benefit of a truly effective new therapy or therapeutic agent

Closed-loop glucose control (R Hovorka)

  • Closed-loop systems are the way forward in glucose control
  • Commercialisation difficult in post NICE-SUGAR Era
  • Outcome studies in glucose control should use closed-loop systems

My propositions for the next SSC guidelines

Mechanical ventilation (T Thompson)

SSC 2012

  • Vt 6
  • Pplat 30
  • Higher PEEP for more severe
  • Recruitment maneuvers
  • Prone for P/F < 100 if experienced
  • Elevation HOB
  • Minimise NIPPV use
  • Weaning protocol
  • No routine use of PAC
  • Conservative fluids
  • No beta agonists

Potential changes

  • Vt 6 as preventative measure
  • Consider proning at P/F 150
  • Centres need to get experience in proning

References Association Between Use of Lung-Protective Ventilation With Lower Tidal Volumes and Clinical Outcomes Among Patients Without Acute Respiratory Distress Syndrome. A Meta-analysis. –

Vasopressor therapy (JL Vincent)

Noradrenaline remains vasopressor of choice Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis – No magic BP Timing of norepinephrine in septic patients: NOT too little too late – Recommendations

  • NA is vasopressor agent of choice (maybe in the future other agents will decrease the need for catecholamines)
  • Optimal blood pressure must be individualised
  • Early vasopressor therapy may be necessary to avoid hypotension
  • Vasopressor therapy should not mask hypovolaemia

Fluid resuscitation (JL Teboul)

Limitations of respiratory variability indices

  • Impossible to predict in SV
  • Impossible to predict in arrhythmias
  • Difficult to interpret if TV too low
  • Difficult to interpret if lung compliance too low
  • Difficult to interpret in case of high frequency ventilation
  • Difficult to interpret under open-chest conditions
  • Difficult to interpret in case of severe RV failure

Passive leg raise – Echo to help assess fluid responsiveness

Steroids (C Sprung)

Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. – Hydrocortisone Therapy for Patients with Septic Shock. CORTICUS – ADRENAL Trial – 2012 recommendations We suggest not using intravenous hydrocortisone as a treatment of adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (see goals for Initial Resuscitation). If this is not achievable, we suggest intravenous hydrocortisone alone at a dose of 200mg per day (grade 2C). This differed from original guidelines which suggested using steroids in patients who had refractory hypotension – phrasing changed. With current body of evidence (and awaiting results of ADRENAL trial), steroids will probably not be recommended in next SCC guidelines.

Adrian Wong is a CUSIC fellow at the John Radcliffe Hospital, Oxford.

ISICEM 2015 Blog Day 2

adrianAdrian Wong is at the International Symposium on Intensive Care and Emergency Medicine in Brussels and summarises his second day here for OXICM

Edited by Jamie Strachan

ICU Organisation

How much intensive care do we need? (G Rubenstein)

Huge variation in ICU bed provision. Not all patients at the same risk of death have the same chance of benefit from the ICU due to individual hospital variation.

In some cases, patients are admitted to ICU because you don’t want to admit them to the ward.


Studies are limited by the fact that its difficult to define what is an ICU bed or even what is an intensivists.


Variation in critical care services across North America and Western Europe –

Evaluation of modernisation of adult critical care services in England: time series and cost effectiveness analysis –

Access to urban acute care services in high- vs. middle-income countries: an analysis of seven cities –

Pros and Cons of separate step-down beds (H Wunsch)

Discharging a patient from ICU to the ward somethings feels like pushing the patient off a cliff.

Potential benefits of step down bed

  • Better outcomes
  • Better flows
  • Cheaper
  • Reduce need for ICU beds


  • More care transitions
  • More expensive
  • Patient distress


  • Profoundly understudied
    • Terminology remains a problem
  • Very mixed results so far
    • Mortality
    • Length of stay
    • Patient experience
  • Challenges of varied configuration
    • Hospitals with separate stepdown units may be fundamentally different in many ways


Hospital mortality of adults admitted to Intensive Care Units in hospitals with and without Intermediate Care Units: a multicentre European cohort study –

Does intermediate care improve patient outcomes or reduce costs? –

Setting up an ICU Echo service (S Huang)

Governance profoundly important

Implementing an Echocardiography Service in the Intensive Care Unit –

Keep quality of sleep (JP Mira)

Few studies and highly heterogeneous

ICU patients have a marked reduction in REM Sleep

Integrated strategy to promote sleep

  • Noise reduction
  • Diurnal lighting practices
  • Use of sleep-promoting pharmacological agent
  • Minimising use of pharmacological agents that inhibit sleep
  • Uninterrupted time for adequate sleep
  • Appropriate physiological support
  • Active promotion of patient orientation
  • Patient-ventilator synchrony
  • Relaxation techniques


Sleep in the Intensive Care Unit –

Feasibility Of Conducting 24-Hour Polysomnography Studies In The Medical Intensive Care Unit:

The effect of earplugs during the night on the onset of delirium and sleep perception: a randomized controlled trial in intensive care patients –

Light in the ICU (M Rosengart)


  • Photoperiodism exists in humans
    • Optimal photoperiod to alter human biology in the context of illness remains to be defined
  • Blue spectrum can alter the biology of critical illness
    • Is there human relevance
  • A light of optimal spectrum, intensity and duration of light can be identified and applied to alter human biology and the course of critical illness


The effect of window rooms on critically ill patients with subarachnoid hemorrhage admitted to intensive care –

Light and the outcome of the critically ill: an observational cohort study –

The optimal ICU design (Halpern)

Showcasing some truly beautiful and functional ICUs. Utrecht ICU looks stunning

Modern rooms – e-glass, booms, environment sensors, webcams, etc

Cost – $1,000,000 per room


  • Optimal ICU design requires extensive planning, simulation and attention to detail
  • The focus of ICU design should be on all aspects of
    • The patient room
    • Family needs both inside and outside the patient room


All patients should walk (J Mancebo)


Functional Disability 5 Years after Acute Respiratory Distress Syndrome –

ICU-Acquired Weakness and Recovery from Critical Illness –

Staffing and work culture (D Angus)

Considerable amount of variation – some easily measured and some less easily measured.

Less easily measured

  • Hierarchy
  • Leadership
  • Followership
  • The ‘it’ factor

BUT caveats

  • I’ll know it when I see it
    • A large part of ICU culture has strong ‘smell’ but remains difficult to define
    • You can tell how good a unit is by the ‘feel’
  • Chicken or egg
    • Optimal patient outcome is likely affected by
      • Number and type of staffing composition
      • Competency of staffing
      • Degree of timework and integration
      • Morale and attitudes
    • Easier said than done
      • From easy to hard
        • Provision and training of staff
        • Coordination and integration of care
        • Sense of teamwork and camaraderie
        • Reversing ‘burn-out’ and ‘getting to great’


  • ICU staging, organisation and culture varies a lot
    • Workforce composition, competency and morale
    • Team interaction, cohesiveness and behaviour
  • These factors appear to affect outcome
    • And many can be positively influenced
  • BUT
    • Some of the largest perceived attributes are hard to capture
    • Bi-directional relationship of cause and effect
    • Some important domains are extremely resistant to change

Keep the ICU doctor happy (M Ramsay)

ICU and ED jobs are stressful

Burnout is a syndrome of emotional exhaustion, de-personalisation, and a sense of low personal accomplishment that leads to decreased effectiveness at work –

Sleep deprivation

  • Deceased efficiency
  • Instability
  • Recent memory deficit
  • Depersonalisation
  • Inappropriate humour

Struggling in silence

  • 300-400 physicians die each yer by suicide
  • Methods: OD, firearms
  • Risk factors: depression, alcohol abuse
  • Higher completion/attempt ratio

High reliability organisation

  • Leadership committed to zero harm
  • Safety culture embedded in organisation
  • Robust process improvement
  • Risk management proactive and not reactive
  • Blame free for small errors but accountability for adhering to safe practice

Emotional Intelligence – out of control emotions make smart people stupid


  • Healthcare is 24 hour operation
  • Understanding how fatigue affects doctor is critical to patient safety, performance and productivity
  • An impaired physician is a waste of a valuable resource
  • An impaired physician is a liability to the organisation and medical staff

Pro/Con debate HFOV



Pro (N MacIntyre)

HFOV makes conceptual sense

HFOV has considerable supportive clinical evidence (but in paeds population)

Recent negative clinical trials problematic

  • Lack of expertise
  • High Paw protocol in the setting of high vasopressor use

Con (N Ferguson)

Not for routine lung protection in moderate ARDS

Carefully selected patients with severe ARDS

  • After consideration of prone, NMB

Assess response to HFOV initiation

  • Significant increase in pressor requirements
  • No significant improvement in oxygenation
Adrian Wong is a CUSIC fellow at the John Radcliffe Hospital, Oxford.

ISICEM 2015 Blog Day 1

adrianAdrian Wong is at the International Symposium on Intensive Care and Emergency Medicine in Brussels and has penned this summary for OXICM

Edited by Jamie Strachan

Opening Plenary Session

Say YES to intensive care (J-L Vincent)

Setting the tone on the 35th anniversary of the ISICEM meeting

In the last 35 years, as a specialty, we are doing less and less e.g. transfusion, fluids, tidal volumes

A cautionary note on the endless pursuit of EBM via RCTs. There are a lot of ‘negative’ RCTs (I personally hate the term ‘negative’ trials. It plays done the huge effort put in by the research team). Patients on the ICU are very heterogenous and hence are we surprised that one size doesn’t fit all?

Perhaps a more positive view point is the fact that although mortality is static, the age of our patient has increased. The burden of ICU care should not be underestimated. Patients may benefit from earlier intervention rather than banging on death’s door before being admitted. Accessibility to ICU care needs to be timely.

Closing note – realise the difference between protocolised care vs intelligent care.

Reducing the global burden of sepsis (S Finfer)

Highlights from the roundtable discussion on understanding the burden of sepsis in the global context.

Areas to be tackled

  • Understanding its epidemiology. Data is scarce from countries in Africa and Asia. Global Burden Of Disease Study –
  • The impact of our changing world on the disease
    • Global warming
    • Ageing population
    • More mobile population/Urbanisation
    • Antibiotic resistance
  • Measures to manage sepsis
    • Prevent ICU-acquired sepsis
    • CVS optimisation
    • Infection control
    • Modulation of sepsis response
  • Morbidity the price of success

With improved data we can also improve awareness among health care workers, the public and politicians (World Sepsis Day 13th Sept)

Sepsis success

  1. Reducing case fatality rates in many countries
  2. World Sepsis Day and increasing awareness
  3. Hand hygiene and prevention initiatives
  4. High quality investigator initiated research
  5. International/global collaboration on many fronts

What did you PROMISE? (K Rowan)

The last in the trilogy of EGDT trial.


Primary outcome

  • No difference in all cause mortality at 90 days in EGDT vs usual care (29.5% vs 29.2%)

Secondary outcome

  • SOFA score at 6 hours and 72 hours
    • higher SOFA scores in EGDT but that is due to intervention
  • Receipt of organ support in critical care
    • More CVS support in EGDT
  • Duration of organ support in critical care
    • No difference
  • Duration of stay
    • No difference
  • All cause mortality
    • No difference at 28 days, hospital discharge and at 1 year

Pooled data (Protocolised Resuscitation in Sepsis individual patient data Meta-analysis) – NO DIFFERENCE IN 90 DAY MORTALITY

In adults, presenting to ED with signs of early septic shock, identified early and receiving IV antibiotics and adequate fluid resuscitation – haemodynamic management according to a strict EGDT protocol does not lead to an improvement in outcome.

Transfusion – does the age of RBC matter? (P Hebert)

Fresh (less than 8 days) RBCs vs standard RBCs in order to improve 90 day mortality and morbidity

Fresh red cells do not appear to be superior to standard issue red cells in critically ill patients

SIRS is dead (R Bellomo)

The original definitions of SIRS/Sepsis are now more than 20 years old

Problems with the definition

  • Terminology does not help us understand the underlying problem
  • SIRS is too sensitive but is not specific
  • SIRS does not reflect the severity of the disease process
  • SIRS may detract from the search for infection

82.2% of ICU patients without infection have ‘SIRS’

Patients can have severe sepsis without SIRS i.e. limited sensitivity and yet they have features of major illness

There is no step-up in risk at having 2 SIRS criteria compared to 3 or 4 – lack construct validity

SEPSIS 3.0 (Singer)

Host response is key

Sepsis is not simply a systemic inflammatory response

Variety of anti-inflammatory and other (mal)adaptive responses occur concurrently

Sepsis should be defined as life-threatening organ dysfunction due to a dysregulated host response to infection

Sepsis = really sick infection

No definition is data driven using SOFA score to characterised organ dysfunction

SOFA superior in ICU but poor on ward and ED.

qSOFA – altered mental status, respiratory rate and systolic BP is superior on ward and ED

Personalised medicine is the future (H Wong)

Precision Medicine Initiative –

ICM deals with syndromes and hence needs personalised care

Current diagnostic tests to define subclasses/endotypes of critical illness are too slow

Future would involve multiplate mRNA testing to allow customise therapy based on biologically-defined endotypes

Should we centralise ICU care?

Advantages and problems (D Angus)

Existing critical care

  • Expensive, poorly distributed and stretched thin
  • Care May be better at larger centres
    • Regionalised trauma systems demonstrate potential
  • But, critical care is more complex than trauma
  • Regionalising critical care
    • Potential benefits
    • Some aspects are not that hard, once incentives aligned


  • Demonstrate projects
  • Regional centres
  • Telemedicine
  • Community/Interhospital outreach
  • Hybrids
  • Areas of future research
    • Reasons for volume outcomes
    • Alternative staffing models

ECMO centres (A Combes)

  • Only experienced centres should run ECMO programmes
    • Both VA and VV ECMO, at least 20 cases per year
  • Create regional networks of hospitals
    • Detect early refractory cardiac/respiratory failure
  • Mobile ECMO retrieval tams in all ECMO centres
    • 24/7

Trauma centres (O Grottke)

Probably the most established regionalised/centralised service

Right patient at the right place at the right time for the right treatment

Benefits have been replicated in studies across the globe

Cardiac arrest centres (J Nolan)

Aim is to maximise myocardial and neurological recovery

PROCAT Registry ( In OHCA patients with no obvious extra-cardiac cause, a significant proportion will have abnormal coronaries found at angiography.

Prognostication post cardiac arrest –


  • Logical progression of existing regionalisation
  • 24/7 access to cardiac cath lab
  • Comprehensive post-resuscitation care
  • Neurological support for prognostication
    • SSEP, NSE, continuous EEG
  • Indirect evidence for better outcomes
  • It’s happening anyway!

Early resuscitation in sepsis

What do you mean by early (J Bakker)

Earlier is better

The effect of goal-directed therapy on mortality in patients with sepsis – earlier is better: a meta-analysis of randomized controlled trials –

Targeting blood pressure (JL Teboul)

Hemodynamic variables related to outcome in septic shock –

Use vasopressors even when hypovolaemia has not been completely resolved

Target higher BP if

  • Normally hypertensive
  • Elevated CVP
  • Increased abdominal pressure


Still a place for transfusion (A Perner)

More pts transfused in EGDT vs usual care groups –

  • PROCESS – 14 vs 8%
  • ARISE – 14 vs 7%
  • Rivers 64 vs 19%

TRISS Study review –

How to prevent renal failure (R Bellomo)

Preventing AKI in sepsis

  • Do not give starch
  • Do not give gelatin
  • Do not give NSAIDs
  • Do not give multiple doses of aminoglycosides
  • Do not give long courses of vancomycin
  • Do not give amphotericin
  • Consider giving chloride-poor or chloride physiologic fluids


  • In septic patients renal protection remains elusive
  • Avoid nephrotoxins
  • Probably best ot maintain a MAP close to basal night-time levels
  • Avoid fluid overload
  • Consider vasopressin
  • Consider global (patient) costs
  • Killing the patient while trying to save the kidney is not a good idea

Improvement sepsis performance in the ED (F Machado)

Describe the challenges of implement a change in practice in the ED with regards to sepsis management

Key – multifaceted approach to get people to do what they agree to do e.g. education, training, incentives, etc.

Improving sepsis performance on the ward (R Dellinger)

Quality improvement project to roll out SSC bundles on the wards in a US hospital

Nurses empowered, electronic notes/warning systems

Pharmacist ensures antibiotics are administered within 15 minutes of being prescribed

The essential haemodynamic variables

Interpretation of heart rate (A Morelli)

Tachycardia can be compensatory or non-compensatory

Compensatory mechanisms are only useful over a short time frame

[Effect of Heart Rate Control With Esmolol on Hemodynamic and Clinical Outcomes in Patients With Septic Shock A Randomized Clinical Trial]

Review –

Arterial pressure (S Magdar)

Step 1 – observe patient. If patient is fully awake, communicating, good colour, urinating, normal BE/lactate, their BP is likely to be adequate. Observe


We are pressure regulated species – arterial pressure is relatively constant under normal conditions

Volume and compliance determine the pressure

CO and SVR determine the central pressure. Central pressure determines the regional flow.

Total energy NOT pressure determines flow – gravitational, elastic and kinetic

CVP (M Cecconi)

FENICE Trial Protocol –

Does the central venous pressure predict fluid responsiveness? An updated meta-analysis and a plea for some common sense. –


  • CVP is an important variable as it is key determinant of venous return
  • Best interpreted when look at
    • Changes CVP
    • Concomitant changes in CO

How to measure pressure accurately (JL Teboul)

Errors in CVP measurement –

Sources of error

  • Inappropriate zero point (anatomical)
  • CVP measured at the foot of c wave
  • CVP and PAOP are measured at end-expiration – will thus depend on SV or IPPV
  • Subtract the estimated PEEP/auto PEEP

How to measure cardiac output accurately? (X Monnet)

Dilution techniques are accurate and should replace PA catheters as the goal standard

Uncalibrated pulse contour analysis

  • SV proportional to amplitude of aortic pressure
  • Relationship is influenced by vascular compliance and resistance. Hence are unreliable in case of changes in vasoactive tone

Volume clamp method e.g. NEXFIN are not very accurate in the ICU setting

CO is not regional blood flow, nor tissue perfusion, but only a part of it

Adrian Wong is a CUSIC fellow at the John Radcliffe Hospital, Oxford.

Critical Care Reviews meeting 2015

A summary of studies discussed at the Critical care reviews meeting held on Friday (23/1/2015) in Northern Ireland – attended by oxicm POCUS fellow Adrian Wong with further notes by Wessex’s Emma Fitzgeraldand wessex / the bottom line’s Duncan Chambler
edited by Jamie strachan

Albumin In Sepsis: Albios Trial

Caironi et al. Albumin Replacement in Patients with Severe Sepsis or Septic Shock (ALBIOS study)- N Engl J Med 2014; 370(15):1412–21.

  • No difference between the groups
  • Target of 30g/L probably is not representative of what we would normally see in these patients
  • Conclusions:
    • Albumin is safe, but we probably don’t need it
    • The haemodynamic benefit is not clinically significant (only a difference of 2-3mmHg)

LInks: paper / pubmed abstract / TBL summary / oxccjc discussion

Raised ICP in paediatric patients with meningitis: RCT ICP v CPP target

Kumar et al. Randomized Controlled Trial Comparing Cerebral Perfusion Pressure-Targeted Therapy Versus Intracranial Pressure-Targeted Therapy for Raised Intracranial Pressure due to Acute CNS Infections in Children. Critical Care Med 2014;42(8):1775-1787

  • Huge improvement in outcome in children with bacterial meningitis when CPP target is used compared with ICP target
  • There seemed to be a benefit related CPPs in the survivors in the ICP group, i.e. the CPP is the thing that matters
  • Conclusions
    • Target a higher MAP
    • ICP monitoring may not be necessary

Links: paper (not open access) / pubmed 

Pick Your Pressure: Optimise trial

Pearse et al. Effect of a Perioperative, Cardiac Output–Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery. A Randomized Clinical Trial and Systematic Review (OPTIMISE) JAMA 2014;311(21):2181-2190

  • Trial failed to enroll emergency patients, large proportion were elective GI patients, mostly ASA2-3
  • Control group received less fluid
  • High use of inotropes both groups
  • High number of epidurals (70%)
  • Very low mortality (3%) ?representative study
  • Difference in outcomes when looking at the interim analysis ?was there a learning curve
  • Didn’t really answer the questions that we wanted it to – as the risk of the patient went up, the benefits of the cardiac monitor algorithm was increased
  • Unclear which monitor should be used
  • BUT it is the largest algorithm trial to date
  • Dopexamine – probably no real benefit over dobutamine
  • Where next? Optimise II…
  • Colloids may have had an effect on the outcomes, but the colloid trials in the peri-op setting may not be as harmful as in the critical care setting

links: paper / pubmed / TBL /JICS podcast

Blood Pressure targets in sepsis

High versus Low Blood-Pressure Target in Patients with Septic Shock (SEPSISPAM study). New Engl J Med 2014; epublished March 18th

  • SCC recommends MAP >65mmHg, in the studies that look at septic shock, most actually use >75mmHg
  • Some evidence that aiming for higher MAP targets may be reno-protective (Badin et al Crit Care 2011)
  • Rationale: which target is best? 65-70mmHg versus 80-85mmHg
  • Difference in frequency of RRT in patients with chronic hypertension
  • Otherwise no differences between the groups BUT the lower target group had higher than intended MAPs, which may compromise the interpretation of the results
  • Hard to know which patients had chronic hypertension – not all had been diagnosed prior to enrollment
  • Higher MAP is safe with no increase in adverse incidence such as mesenteric ischaemia

links: paper / pubmed / TBL / oxccjc

Pulmonary Embolus and Fibrinolysis – Does Size Matter?

Meyer et al. Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism (PEITHO study). N Engl J Med 2014;370:1402-1411

  • RCT – Included RV dysfunction, no CVS instability
  • Use of a composite outcome has been criticized
  • In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke
  • Study details: See The Bottom Line review…

links: paper / pubmed / TBL

Fragility Index – Robustness of RCTs, ie statistically significant but clinically fragile.

Walsh et al. The Statistical Significance of Randomized Controlled Trial Results is Frequently Fragile: a Case for a Fragility Index. Journal of Clinical Epidemiology 2014;67(6):622-628

  • Evidence-Based Medicine – Need to gather information and then need to interpret it.
  • Ioannidis in JAMA 2005 294(2) showed 1/3 clinical studies are later found to be incorrect, smaller or insignificant. Is an open acknowledgement of why studies are inconsistent. Subsequent studies are not being conducted because people are putting too much value on the negative outcome in one study
  • Hypothesis testing versus Estimation
  • P values are NOT an error rate – Estimated error rate of at least 23% (typically closer to 50%) using a p value of 0.05.
  • P<0.05 =some evidence, but is NOT equal to conclusive evidence, i.e. it is “worth another look”
  • This study, looked at the impact of this phenomenon – used PubMed RCTs. Used a fragility index – added an event until p became compromised, i.e. one study needed only 1 more event to compromise the statistical significance in outcome, some needed NO events, which is worrying! Also those lost to follow up exceeded the number of events required, i.e. the fragility index.
  • Good paper – simple idea, it raises the profile of over-interpreting statistical significance. RCTs are often statistically fragile

links: paper / pubmed

Mechanical CPR devices in Resuscitation OHCA

Manual vs. integrated automatic load-distributing band CPR with equal survival after out of hospital cardiac arrest. The randomized CIRC trial. Resuscitation 2014;epublished March 15th

Rubertsson et al. Mechanical Chest Compressions and Simultaneous Defibrillation vs Conventional Cardiopulmonary Resuscitation in Out-of-Hospital Cardiac Arrest. The LINC Randomized Trial. JAMA 2013;311(1):53-61

CRIC Trial and LINC Trial both presented

  • Use of mechanical devices versus standard manual CPR
  • Only included patients with a likely CARDIAC cause for arrest
  • LINC Trial – got DCCV regardless of the initial rhythm
  • CIRC – equivalent survival at hospital discharge regardless of which one
  • LINC – more defibrillations in mechanical group and despite this, there is no difference between the two groups (primary OR secondary outcomes)
  • More adverse incidents with mechanical CPR devices
  •  Conclusion
    • No benefit in outcome in either study
    • Post resus care not standardised
    • Unable to assess manual CPR quality – it may be better than normal standard care (Hawthorn effect)
    • Marked difference in presenting rhythms
    • There are some advantages to the mechanical devices e.g. in the cath lab, mountain rescues etc. or to prevent fatigue, but no evidence to suggest a benefit otherwise

LINC links (!): paper / pubmed

CIRC links: paper / pubmed

Is it Worth Waiting on a ProMISE?

  • 3 studies, but methodology harmonized so that the results could be pooled into a meta-analysis – ProCESS, ARISE, ProMISE trials
  • ProCESS
    • 31 centres in the USA.
    • All academic hospitals? Are they like NHS hospitals?
    • Not all of SCC were adhered to in the protocol
    • Fluid challenge changed mid-trial
    • Sample size was reduced… preserved the ARR, but lost power in the RRR
    • No difference in 60d outcome, but use of long-term facilities is different to UK
    • Not powered on 90d mortality, but similar to UK
    • 51 centres
    • Actual 90d mortality was also lower than the 38% expected and so the results are not as sound as they could have been
  • Both trials do not discount the possibility that there could be a 20% Relative risk Reduction
  • ProMISE
    • Interim analysis – base line mortality assessed and it was not advised that the sample size required changing
  • ICNARC data shows an improvement in mortality from severe sepsis in patients coming from the ED, but higher than that in Australasia
  • Questions around the definition of severe sepsis – in ProCESS and ARISE, mean lactate was 4. Few had BOTH hypotension and a high lactate
  • Fluids: Rivers, ProCESS and ARISE: Less fluids, less ventilation, less blood in these two new studies suggesting better care now with regards to resuscitation
  • ProMISE has good spread of hospitals – better generalizability. Is the only one of the 3 trials that adhered to the pre-specified stats anaylsis plan
  • Interpretation: All are different to Rivers study – earlier recognition of sepsis, timing and design are both different. Resuscitation has changed a lot, but probably because of the Rivers Study
  • The idea of a harmonized study could take off as a model… i.e. a lot of Phase 2 studies that use an intermediary outcomes, but collect what a large RCT would for a primary outcome and then combine them using a meta-analysis. This would have lots of benefits, including having very big sub-groups that could be pooled to get a big sample size
  • Of note – there is no big USA database that could give them accurate mortality estimates… they had to look at some databases and previous studies etc., they chose an increment that was too much. ProMISE could use the data from the ones that came to ICU from ED, but acknowledge that they may have missed some as the ED data was missing – may have missed the ones that improved to not need ICU.

ProCESS Links: paper / pubmed / TBL / oxicm

ProMISE Links: Results due to be released in Brussels this year. Trial info here

ARISE Links: paper (not open access) / pubmed / TBL / JICScast

Sepsis Reconsidered: On behalf of the SCCM/ESICM Taskforce

  • Defining sepsis has been very difficult. SIRS is very sensitive but not specific. This had big implications for tying to establish the incidence and prevalence of sepsis
    • Why is it hard to define? Our definitions aren’t really “definitions”, they are just clinical and epidemiologic surrogates for this underlying pathobiology
    • Need a clinical description that is useful for clinicians and also a “lay” definition for the public
    • The old description of:

Infection -> Sepsis -> Severe sepsis -> Septic shock

  •    … Is not helpful… New idea:

Infection -> Badness -> Sepsis (includes Septic shock)

Badness is hard to define

  • Large database interrogated (university of Pittsburgh) – SIRS and SOFA were not useful at identifying the patients we are interested in
  • A new collection of variables needed to identify risk of developing sepsis / mortality / ICU stay etc.
  • The next stage is to use this discovery set of data from University of Pittsburgh and to validate it using other databases around the world. However, the baseline variables that will predict outcome are still yet to be identified!
  • Organ dysfunction – difficult to define. SOFA is the most popular, it is internationally accepted and is robust in predicting mortality.
  • Septic shock – Large databases have been interrogated to try to get a definition to approximate septic shock
    • Lots of variability in mortality and incidence as a consequence of the inconsistencies in the definitions
    • Reflects more than CVS dysfunction – cellular abnormalities are of prime importance
    • The large databases will be used to try to establish more information
    • Septic shock new definition likely to included– persistent hypotension (?what threshold and ? normalized with support) and/or an elevated lactate
  • The SSC will try to establish new definitions, but think that it is likely to keep evolving


  • Berlin definition of ARDS
  • Concept of VV ECMO
  • History of ECMO – Hill NEJM 1972 286:620-634 – Case report of the first case of VA-ECMO outside of theatre. RCT in the 1970s showed a 10% SURVIVAL in ECMO and the control group!
  • The reports during the H1N1 pandemic changed the view about ECMO. Survival had improved a lot since the 1970s – survival in the 70% range. ICNARC trial highlighted that if you go to an ECMO centre, your mortality is lower…all added to the idea that ECMO is worth looking at more
  • CESAR – first RCT, but heavily criticized as most didn’t actually get ECMO. Also a pragmatic trial – MV was not protocolised. The fragility index was also high – only few more in one group reduced the statistical significance.
  • Case series – ECMO and H1N1 in JAMA vs similar cohort – mortality the same… so, is it really is it the ECMO?!?
  • MA by Munshi: May be a signal, but needs confirmation in a better trial
  • Review of ECCO2R device Terragni P Anaes 2009; 111: 826 
  • Brodie editorial (NEJM 2011 365: 1905-14) highlights the indications and contraindications for ECMO in ARDS in adults
  • Now – Idea of using ECMO in facilitating lung protection.
  • Lots of evidence to suggest that reduced TV (i.e. a dose response curve) leads to better outcomes. ECMO could be the “ultimate” lung protection strategy
  • The SOLVE ARDS Study Program: A physiological study, in progress.. To look at the physiological consequences of ventilation
  • The SUPERNOVA Trial – ESICM Trial ). International pilot about to start – feasibility of “respiratory dialysis”
  • The EOLIA trial – Rescue VV-ECMO for severe it ECMO, rather than the centre
  • Position paper – suggests a minimum standard for anyone to call themselves an ECMO centre. The more cases you do, the better the mortality (data from Ann Arbor)

VITdAL Trial

Amrein et al. Effect of High-Dose Vitamin D3 on Hospital Length of Stay in Critically Ill Patients With Vitamin D Deficiency. The VITdAL-ICU Randomized Clinical Trial. JAMA 2014;312(15):1520-1530

  • Vitamin D is a steroid hormone that regulates about 200 genes and there appears to be a threshold below which skeletal health is impaired (<20ng/ml)
  • Suggestions in the literature that vitamin D deficiency in ICU is common and associated with a higher mortality…Is vitamin D a marker or a contributor?
  • There are a multitude of potential mechanisms of vitamin D e.g. infection / lung/ heart muscle
  • Plasma vitamin D levels are associated with longer duration of mechanical ventilation in patients with sepsis
  • Pilot study showed that the administration of vitamin D increased the serum levels, but not as much as the equivalent dose would have in healthy volunteers.
  • RCT study
    • Primary end-point = hospital LOS. Study cost per patient was 5-10 euros…
    • Almost half of the patients had severe vitamin D deficiency.
    • No difference in the LOS (hospital or ICU). Only corrected vitamin D levels in 52% of the patients (in contrast to the pilot study)
    • There were 4 patients who had fractures in the first six months ?reason for this? Consistent with a study that showed post-menopausal women had a higher incidence of falls and fractures after administration of vitamin D
    • Six month follow up – better functional outcome with vitamin D in the less severely deficient group
  • Guidelines
    • A recommendation of 600IU-800IU for general population, but 200IU in TPN!!
    • Endocrine society say 1500IU-2000IU for at risk patients.

Links: paper not open access / pubmedICN podcast

Statins in ARDS: HARP-2

McAuley et al. Simvastatin in ARDS (HARP 2). New Engl J Med 2014;epublished September 30th

  • Based on the evidence that simvastatin appeared to attenuate inflammatory response in animals, healthy volunteers and was associated with a reduction in systemic inflammation in a phase II study
  • RCT: 80mg simvastatin given in ICU vs placebo (ARDS, 48 hours of mechanical ventilation)
  • No statistically significant difference between the groups (outcomes or physiological variables)
  • There was an improvement in outcome in those patients already established on statins, but not in those who were started de novo
  • Statins are safe… increase in CK and transaminases but no difference in serious adverse events
  • No difference in CRP: ?Anti-inflammatory effect not achieved
  • SAILS study – rosuvastatin vs placebo: no difference between the groups, but a trend the other way, with a non-significant improvement in outcome in the placebo group
  • Where next?
    • Was the dose right? Probably – adverse events happened and so probably couldn’t use a higher dose
    • Prevention may be a more effective strategy
    • May just be an under-powered study – maybe should be powered for mortality

HARP 2 Links: paper not open access / pubmed 

SAILS links: paper / pubmed / oxccjc

TTM Trial

Nielsen et al. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest (TTM study). N Engl J Med 2013;369:2197-2206

  • Overview of TTM trial and background to cooling cardiac arrest patients
  • RCT 33°C versus 36°C
  • All patients had feedback controlled cooling devices (intravascular or surface)
  • Target temperature was achieved in each group
  • No survival difference between the 2 groups, nor any difference in neurological outcome. Trend towards higher complications in the cold arm
  • How can this be so different from previous trials?
    • Fever was not allowed to develop
    • Groups were not comparable
    • High attention to post arrest care
    • Strict rules for prognostication
    • Short time of no-flow and high bystander CPR rate
    • Not as severely ill as in previous trials
  • Support and criticisms both followed the trial
  • Imbalances between groups – if the variables were adjusted for, mortality is even more in favour of the non-cooled arm (still not significant)
  • Higher “ICU” support in the cold group (i.e. inotropes etc.)
  • Criticized for long time to cooling, but was consistent with previous work AND it reflects actual clinical practice
  • Suggestion that hypothermia is more effective when the “no flow” time is longer – In TTM trial – high number of patients had no flow for >8 minutes, but no difference at all between the 2 groups
  • Subgroups – no signal seen in any of the groups, but a tendency towards worse outcome in the hypothermia group in some groups
  • ILCOR and other guidelines are still to come… BUT remember the hazard ratio is 1.1, with adjusted favouring not cooling
  • To come..
    • Is fever dangerous?
    • Does hypothermia work and we are doing it too late?
    • Should we go cooler?
    • Tailored therapy – are sub groups important?
  • Take home message – Target a temperature, could use either one
  • Question about sedation – cooling and sedation and prognostication – TTM used 72 hours after warming. They are collecting this data retrospectively now

Links: paper / pubmed / TBL


  • Harvey et al. Trial of the Route of Early Nutritional Support in Critically Ill Adults (CALORIES Study). N Engl J Med 2014;epublished October 1st 
  • Trial was commissioned
  • Pragmatic and “real life” in nature and used local feeding protocols
  • Balanced groups
  • Only a small proportion were malnourished at enrollment
  • Large number of TPN patients stopped at 119 hours and so look like non-adherence to protocol, probably reflects not wanting to site another line etc.
  • Route and dose were not confounded
  • Slightly higher use of insulin in TPN group, but glucose levels were similar
  • Results
    • Baseline mortality was as predicted (34%).
    • No significant difference between groups.
    • No difference in organ support requirements.
    • No difference in new infectious complications, including CVC infections
    • Episodes of hypoglycaemia and vomiting less in TPN group
    • LOS – no difference
    • Adverse events – no difference (5% each group)
    • No sub-group differences
    • No adherence differences
  • Interpretation / thoughts from the study from Kathy Rowan and why no differences were seen…
    • The management of CVC BSI is much better
    • VAP prevention is better these days
    • Developments in feed technology
    • Caloric targets were not met in either group – ?lack of availability of nutritional products
    • Maybe increasing dose of TPN is associated with increasing infection?

Links: paper not open access/ pubmed / TBL

ECMO – Early Mobilisation

 Importance of early mobilization comes from the functional recovery work undertaken by Margaret Herridge et al.  NEJM 2003

  • ICU acquired weakness is a form of neuromuscular organ failure
  • Risk factors are controversial, but there is a strong signal that corticosteroids are significantly associated (e.g. study in JAMA in early 2000’s: OR 14.9 with >7d of mechanical ventilation)
  • Need to recognize it early and prevent it
  • New ATS guideline – highlighted the importance of it being a clinical diagnosis
  • Bed rest duration is the single most important risk factor in development of ICU acquired weakness Hermanns et al
  • Interventions post hospital had no effect (Cuthbertson et al) – need to act early (e.g. Vasilevskis et al Reducing iatrogenic risks: ICU-acquired delirium and weakness–crossing the quality chasm )
  • Early mobilisation is safe, e.g. Bailey et al Crit Care Med 2007; 35:139-145
  • Review of early mobilization –
  • Early Physical Medicine and rehab QI project (Needham, Fan et al) at Johns Hopkins – Significant reduction in LOS (3 days) with increased mobilization etc. – financially v valuable
  • Best RCT – Schweickert et al Lancet 2009; 1874-1882: Significant improvement and a drop in delirium rates
  • Why aren’t we doing it?
    • Context
    • Barriers
    • Sustainability
      • Need to MEASURE YOUR SUCCESS – to help local change
    • Electrical stimulation of muscles and cycle if need to be sedated etc.

Airway Management

 Too much choice for airway devices and not much evidence for it

  • Poor practice, poor planning, poor performance
  • The psychology: Lots of the evidence is faith-based! People tend to reject the evidence, we think we are better than we are and we always think we can get away with it!!
  • Solution? Need to match the right device to the right patient with the right practitioner
  • There are controllable and uncontrollable factors in difficult airway management
  • A review of NAP4 (very cynical!!!). Need to plan for failure.
  • Airway management in critical care
    • Right preparation
    • Right equipment
    • Right location
    • Right practitioner
    • Right technique
  • References


  • Is it affected by target temperature? Do we need separate guidelines for those who are cooled and those who are not?
  • Purpose is to inform decisions but also to inform relatives and avoid futile care.
  • 50% of resuscitated die, but brain death is rare (5-10%)…withdrawal is based on the assumption of our neuroprognostication
  • But prognostication does not have to mean withdrawal of care
  • Cardiac deaths are uncommon cause of deaths, brain damage is the common cause, but cardiac deaths occur in the early phase
  • 72 hours after normothermia seemed to appropriate (Cronberg, Neurology. 2012)
  • Late awakening with good neurological recovery is still possible – favorable outcome occurred in 8/10 of these (Gold et al Resuscitation 2013)…how can we identify this group?
  • Are we pulling the plug too early?
  • Is there a window of opportunity for withdrawal of care? In the early stages, relatives are prepared for the worst, but get more hope as things improve slightly
  • AAN guidelines 2006 – each part has been shown to be not so secure
  • Low false positive rates: Pupillary reflexes, SSEP, corneal reflexes BUT motor score has a high false positive rate. Same number in both pre and post hypothermia studies
  • Exactly the same after cooling
  • Other modalities? CT/MRI work being done. Biomarkers are coming. EEG (continuous) is useful and will be more common. Standard EEG useful
  • Most important – multi-modal approach
  • New recommendations are underway e.g. ESICM and ERC
  • 3 groups: awake / severe damage / somewhere in the middle
  • Friberg  and Cronberg 2013 have a great approach to this
  • ERC and ESICM guidelines
    • Day 3-5 after rewarming
    • If motor score >1-2 then can wait.
    • Suggestion to wait between tests.
  • Conclusion:
    • The reliability of tools probably not affected by temp
    • Don’t need separate guidelines when Hypothermia used
    • Can’t use 2006 AAN guidelines anymore, but new ones are coming.

Hope you have enjoyed this inaugral collaboration between WICS  and OXCIM 

Many thanks to the Critical Care Reviews team – see you in Belfast next year?

Why do we do that?


Habit that we have got used to when ventilating patients

DOI: This is written as a commentary on what we do with patients who are on ventilators. It is not extensively literature reviewed and is more a reflection on some of the things we do in everyday life on the ICU. I am an enthusiast when it comes to ventilators, am a ventilator trainer for Hamilton Medical and my personality is aligned to processes!

Measurement of oxygenation

There often appears to be a focus on PaO2 on a blood gas.  If we take a patient with a heart rate of 60, then after 1 day there would have been 86400 heart beats or 86400 Sp02 readings (60bpm x 60minutes x 24 hours).  Can we come anywhere near this number of blood gases in a day? In addition we all know Sp02 levels change within a few minute and the oxygen dissociation curve is not fixed in position.  As time progresses we may have a device which gives us a continuous Pa02, but I suspect a long running debate on what the “magic number” might be will then develop.   As ICUs start to continuously measure end tidal C02, the same argument may apply to PaC02, with the caveat of there being a PaC02-ETC02 gap.

Patient’s weight

If the European Union brought out a law that a ventilator would only start to work once the patient’s height and sex had been entered, would lives be saved?  This would allow the patient’s ideal body weight to be calculated and would give the user a better idea of volumes delivered to that patient.  This does not stop the operator entering an erroneous height though!

Absolute vs mls/kg tidal volumes display on the ventilator

Our standard convention is to look at absolute volume on a ventilator. A tidal volume of 500mls is a “nice round number”, which we aim for. However, if your ideal body weight is 50kg then this is not good, but okay if your IBW is greater than 70kg. In addition our tidal volume alarm limits are often 300 to 800mls. Why is it not 4 to 9 mls/kg?

Tidal volumes

There is very good data in ARDS patients who are passive on a ventilator that we should use 6-8mls/kg. What do we do with patients who have COPD, patients with normal lungs or patients who are spontaneously breathing on a ventilator? The spontaneously breathing patient with a high minute volume for whatever reason makes this situation even more difficult. Do you sedate, drive the minute volume down and then control the tidal volume that way? Again we all know that our goal is to get patient’s off a ventilator so this strategy will have its faults.

Lung collapse

A CT scan will often show basal lung collapse or lung US may show something similar. If we go back to our ARDS model of 7mls/kg, if half of lung volume is lost due to collapse, this means our 7mls/kg is across a smaller total lung volume. Do we use an even smaller target tidal volume in this case or try and recruit the lung?

Fixed pressure modes of ventilation

Our targets are tidal volumes of 6-8mls/kg. When a patient is first placed on a ventilator (usually paralysed at this point), setting a fixed pressure to achieve a target tidal volume is usually pretty straight forward. However we all know that the patient’s compliance (lung water, position in bed, sedation, inflammation, passive vs active breathing) and resistance (tube biting, bronchospasm, secretions and end of ETT position) change a lot. The results of these changes to the resistance and compliance will mean an increase or decrease in tidal volume, which will either damage lungs or hypo ventilate the patient. If you know the patient’s ideal weight, have the target tidal volume presented in the mls/kg format and someone watching the ventilator closely all the time, then you can manually fix this issue. In the real world though, I feel we struggle achieving this.

Conclusion and another confession

Outcome for patients being admitted to ICUs for ventilation is improving and it is often difficult to put your finger on the reasons for this. Will the things above make any difference? I am rightly or wrongly a strong believer in ensuring the “basics” are done well. My work place has a ventilator which gives an ideal body weight, displays tidal volume in mls/kg, has a pressure control volume guarantee mode (ASV), has a recruitment tool build it and offers fully automated closed loop ventilation.

Ian Rechner is a consultant in Intensive Care Medicine and Anaesthesia in the Royal Berkshire Hospital, Reading and is the OXICM Regional Advisor for Intensive Care Medicine

When and how should DNACPR decisions be made?

A blog Dr Arup Chakraborty for oxicm

Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) decision-making ended up in the headlines last year when the Court of Appeal judged that Janet Tracey’s human rights had been breached when she had been made DNACPR without her knowledge. It can be an emotive topic and is often portrayed inaccurately in the media (Holby City etc).

Of those in whom CPR is attempted, the success rate (return of spontaneous circulation) is around 18% but in line with medical 
dramas, the general public’s perception is that it is much higher. Success at restarting the heart is almost always followed by a significant period in intensive care and is often associated with significantly reduced mental and physical function.

The Care Quality Commission looks in detail at DNACPR documentation during its inspections. This issue is of importance to clinicians, patients and the general public. I attended a symposium on the subject at the Royal Society of Medicine in October when best practice was discussed by both clinicians and lawyers.

The Tracey case is summarized.

She was a 63-year-old woman who had been in a major road traffic accident on 19th February 2011 and had sustained a cervical spine fracture which led to her being admitted to Addenbrooke’s hospital. She had been recently been diagnosed with inoperable lung cancer and been given a prognosis of 9 months. She deteriorated and was transferred to neuro ICU on 20th February for respiratory failure where she was intubated and ventilated and treated for pneumonia and malignant pleural effusion. She failed two extubations.
On 27th February, the ICU consultant made a first DNACPR order after discussion with an oncologist and Mrs. Tracey’s daughter. Mrs Tracey was still ventilated and not involved in the discussion. She was extubated on 28th February. On 2nd March, the DNACPR was cancelled after Mrs. Tracey’s daughter complained. She was transferred to the ward and reviewed by the Palliative care team. Around this time, Mrs. Tracey told her husband that she was being “badgered” about making a decision about resuscitation. The patient wanted any further discussion to be with her and her husband or one of her children present. On 5th March, a second DNACPR order was made. The patient did not wish to discuss resuscitation and the family was fully involved. All felt palliation was appropriate. Mrs Tracey died on 7th March.

There were two DNACPR decisions. Only the first was the subject of complaint.

At the relevant time the patient had the capacity to make decisions about her treatment and wanted to be involved in decisions. The DNACPR decision does not require clinicians to provide treatment they consider to be inappropriate but underlines the patient’s potential access to a second opinion.

The Resuscitation Council (UK), British Medical Association and Royal College of Nursing were in the process of reviewing and updating their guidance, but delayed publication until after the Tracey judgment. The guidance was previously known as the Joint Statement. The document:

·      emphasises the importance of making anticipatory decisions about CPR as an integral part of good clinical practice: leaving people in the ‘default’ position of receiving CPR should they die, regardless of their views and wishes, denies them of the opportunity to refuse treatment that for many may offer no benefit and that many may not want;
·      once again emphasises that every anticipatory decision about CPR must be based on assessment of the person’s individual circumstances at that time;
·      emphasises the importance of involving people (or their representatives if they are unable to make decisions for themselves) in the decision-making process; this often involves a person making a shared decision with their healthcare professionals, but where CPR has no realistic chance of success it may involve informing people of the decision and explaining the basis for it
·      emphasises that when CPR has no realistic chance of success it is important to make decisions when they are needed, and not to delay a decision because a person is not well enough to have it explained to them or because their family or other representatives are not available; nevertheless a clear plan should be made to explain and discuss the decision with the person and/or their representatives at the earliest practicable opportunity;
·      emphasises that, whenever possible, anticipatory decisions about CPR are best made well in advance, when people are well enough and have enough time to consider them carefully and discuss them fully with anyone that they wish to, including their family and members of their healthcare team;
·      emphasises the increasing recognition that such advance decisions are often best made as part of a broader consideration of the type of care or treatments a person would wish to receive (as well as the type of care or treatments they would not wish to receive) should their health deteriorate so that they are unable to make choices for themselves
·      emphasises the importance of careful documentation and effective communication of anticipatory decisions about CPR.

There is a legal obligation to consult where it is practical and appropriate to do so. If the patient has capacity and he/she has been consulted with, technically there is no further obligation to consult with their relatives.

Where the patient lacks capacity, the principles of the Mental Capacity Act (MCA) should be followed. Specifically those without capacity should have a best interests process initiated (Section 4 of the MCA).

If a patient lacks capacity but their relatives are present for consultation, the process should be straightforward. The process may be more complex when the patient lacks capacity and their relatives are not present. A frail patient with dementia and multiple comorbidities being admitted with sepsis out of hours and without relatives present, is a common occurrence. Pragmatically, it may be a more straightforward process to make an anticipatory DNACPR decision in these cases compared with those lacking capacity due to learning difficulties that are usually younger and less frail.

In an emergency, it is preferable to make an appropriate DNACPR decision in the absence of relatives than to let the patient receive futile CPR. Attempts should have been made to contact the next of kin. In more elective cases, it is preferable to make an appropriate anticipatory DNACPR decision in the absence of relatives but there should be a clear plan in the notes to explain/ discuss/ review decisions.

While an advanced decision can insist on DNACPR, it cannot insist on CPR occurring even if it is deemed futile. Consultees (patient, family, friends, carer, IMCA, Attorney under Lasting Power of Attorney) cannot demand treatment.

While the patient with capacity should be told about the DNACPR decision, they may not want to know or discuss it. Causing distress is not a reason to withhold the above but causing harm (physical or psychological) is. Reasons must be documented.

Consulting means involving or in many cases informing consultee(s) that a DNACPR decision has been made. It is a clinical decision to give CPR and other treatments. It should not be given if clinically inappropriate and not in the patient’s best interests. Where there is disagreement, a second opinion should be sought.

When should CPR decisions me made?

The National Confidential Enquiry into Patient Outcome
and Death (NCEPOD) report, Time to intervene?, suggested that resuscitation decisions should be explicitly recorded routinely on all acute admissions. If CPR discussions became routine and perhaps initiated in clinics, GP practices and nursing homes, the risks
 of attempting unwanted CPR would also be diminished: it is equally important to ensure that patients have the opportunity both to refuse CPR and to question a clinical decision.

Another perception is that the DNACPR decision transforms the doctor from ‘care provider’ to ‘care withholder’. One way of overcoming this is to ensure that CPR decisions are always contextualised within a broader plan of what treatments are to be given, rather than focusing on the one to be withheld. The introduction of Treatment Escalation Plans (TEP) and the Universal Form of Treatment Options (UFTO) in various trusts may facilitate this.

How should DNACPR decisions be made?

This of course is subjective. When I worked at a previous trust, I was involved in drawing up some guidelines along with two geriatricians and an anaesthetic intensivist. I am a medical intensivist.  While the presence of one of these criteria is not in itself an absolute indication for making a DNAR decision, the presence of two or more criteria should prompt one to at least consider an assessment.  The more of these criteria which are present, the less likely the patient is to benefit from CPR.

  •  Advanced malignancy
  • Irreversible organ dysfunction
  • Cardiac e.g. heart failure (on echo)
  • Respiratory e.g. COPD- particularly on home oxygen, severe pulmonary hypertension on echo
  • Liver e.g. cirrhosis
  • Renal e.g. CKD, on dialysis
  • Neurological e.g. dementia (not delirium)
  • Extreme old age
  • Frailty syndrome including cachexia
  • Poor function including exercise tolerance:
  • Inability to carry out activities of daily living (washing, dressing etc): need for carers, NH resident
  • Inability to climb 1 flight stairs or walk several metres; bedbound & hoisted, wheelchair bound, zimmer frame
  • The majority of patients, who are not for intubation or level 3 care, should also not be for CPR (although this should be judged on a case-by-case basis).
  • Those with limited function prior to CPR or ICU admission are likely to have even poorer function in the unlikely event of surviving either.

In summary there is a duty to consult over DNACPR decisions but CPR should not be offered if it is deemed futile. Where there is disagreement, a second opinion should be sought. Making anticipatory decisions about CPR is an integral part of good clinical practice. Clinicians avoiding consideration of CPR is potentially negligent. Earlier discussion of treatments including CPR via TEPs and UFTOs is becoming more widespread.


1 Fritz Z, Cork N, Dodd A et al. DNACPR decisions: challenging and changing practice in the wake of the Tracey judgement. Clinical Medicine 2014 Vol 14, No 6: 571-6

2 Nolan JP, Soar J, Smith GB et al. Incidence and outcome of in- hospital cardiac arrest in the United Kingdom National Cardiac Arrest Audit. Resuscitation 2014;85:987–92.

3 Eccles L. Hospital was wrong to place ‘do-not-resuscitate’ order on terminally ill 63-year-old as court rules doctors have duty to consult with patients first. Available online at article-2660098/Hospital-wrong-place-not-resuscitate-notice- terminally-ill-63-year-old-court-rules-doctors-duty-consult-patients- first.html [Accessed 2 October 2014].

4  British Medical Association, Resuscitation Council (UK) and Royal College of Nursing. Decisions relating to Cardiopulmonary Resuscitation. Available online at DecisionsRelatingToCPR.pdf [Accessed 21 October 2014].

5  National Confidential Enquiry into Patient Outcome and Death. Time to Intervene? A review of patients who underwent cardiopulmonary resus- citation as a result of an in-hospital cardiopulmonary arrest. London: NCEPOD, 2012. Available online at downloads/CAP_fullreport.pdf [Accessed 2 October 2014].

6 Fritz Z, Malyon A, Frankau JM et al. The Universal Form of Treatment Options (UFTO) as an alternative to Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) orders: a mixed methods evaluation of the effects on clinical practice and patient care. PLoS One 2013;8:e70977.

Arup Chakraborty is an consultant in Intensive Care Medicine and Acute Medicine in Milton Keynes Hospital

Salt water mastery


Wet, full, soggy, overloaded, oedematous. Dry, dehydrated, hypovolaemic, a fire hazard. Euvolaemic, replete, just right. The jargon of fluid status is commonly used, and abused on the ICU.

A 70 year old, with a several day prodrome of anorexia, diarrhoea, vomiting (more latterly blood-stained) arrives hypoxic, obtunded, with mottled peripheries, too much lactate and too little BP. We give some oxygen, some antibiotics to cover whichever horrendococcus is suspected, and some fluid. But how much fluid?

Now look at this diagram:

Screen Shot 2014-10-23 at 23.15.28

Is this an oversimplification? Almost certainly but it illustrates a point. With our patient we need to ask: do we want blood volume improved, do we want to rehydrate, or do we want to edge up the Frank-Starling hill?

Resuscitating sepsis

Our super-sick man will be dehydrated, likely hypovolaemic and will almost certainly be fluid responsive.

Recent evidence

ARISE patients received on average 1-3 litres prior to enrolment, 1-3 further litres over the next 6 hours and 1-7 litres over the next 66 hours with a small (and surely clinically insignificant) difference between the groups.

For ProCESS the numbers were very similar. Without the documented output/losses the fluid balance differences can’t be assessed but may turn up in some post-hoc introspection.

So everyone gets a few litres in 6 hours. These studies were both ‘non-positive’ – maybe the end-points for fluid resuscitation in sepsis don’t matter, within traditional doses and timing. Maybe we shouldn’t bolus at all. Maybe we shouldn’t give extra fluid at all. Just get somewhere near euvolaemia, rehydrate and maintain. Paul Marik enjoys showing us the flaws in the formative work on fluid in sepsis, but whether we’re ready to entertain trying out ‘dry resuscitation’ is debatable.

After 6 hours

Beyond the 6 hour package our patient is unlikely to be hypovolaemic. Beyond 6 hours we are very short on evidence-based guidance. Optimizing volume to optimise cardiac output is traditionally the next task. His CVP, PAWP, IVC dimension, LV end-diastolic area, corrected flow time, stroke volume and a number of other measurements all may have some theoretical value, but in actuality are worthless. Predicting fluid responsiveness is not about assessing frank hypovolaemia, for which some of these markers may be of value.

If you want to see how stable a system is, then give it a nudge. Bolus some fluid, or if your keen to avoid an unnecessary bolus then provoke the circulation with a breath (SVV, PPV, VTI variation) or a reversible 2-legs-worth bolus (passive leg raise). An alternative approach, although less applicable to our situation, you could take some fluid away and assess response.

Screen Shot 2014-10-23 at 23.13.17

These dynamic markers predict short term response to fluid. They make no promise about what the cardiac output will be in half an hour, and they make no promise about what the blood pressure will do. They tell you that cardiac output will improve, not that you need it or that it will benefit the patient in the short or long term.

Cut to day 2

Our man by this stage has some sort of ‘LipiccODM rapido™’ device which says his cardiac index is 2.9. TTE shows a capable LV without clear signs of septic cardiomyopathy but mild diastolic impairment. His lactate is 1.0. Noradrenaline is running at 0.2 mcg/kg/min. His urine output might be at or just above the magical 0.5ml/kg/hr but you know he’s taken a bit of a renal hit.

You find yourself mid-way through prescribing a bag of Hartmann’s because you absent-mindedly agreed with a comment “there’s a swing on that A-line, fill him up”.

Why increase his cardiac output. He might be fluid responsive but why does his cardiac output need to be max’d out. It’s at this point you should look ahead to the rest of his stay. Every water molecule and every salt molecule in that bag of fluid you’ve just prescribed needs to be got rid of somehow in the near future. If you enjoy creating a marsh-mallow man and watching him struggle with oedematous lungs, chest wall, abdominal viscera through the rest of their slow wean, then go right ahead.

Admittedly we’re short of a good blood volume monitor but knowing when your markers of fluid responsive are flawed is a good start. A swinging arterial line is normal in a patient breathing patient. And ‘swing’ does not reliably mean a high SVV or PPV.

Screen Shot 2014-10-23 at 23.15.13

Fluid removal

At some point our patient will tolerate fluid removal, or he’ll do it himself once kidney/endocrine/circulatory stars are aligned. No one knows how to manage this phase best but it’s becoming clear that following the theoretical yellow line below will get our man off the unit quicker, potentially in a healthier state, than following the red line.

How and when you achieve this is almost completely evidence free territory. ADQI again have some suggestions regarding targeted fluid removal:

Fluid balance target:

  • Depends on your impression of tolerance (stable dialysis can have litres taken off over a few hours)
  • A common approach is to try 500ml in 12 hours, then increase.

Clinical endpoints:

  • Better oxygenation
  • Less oedema

Safety endpoints:

  • Perfusion safety endpoints – falling BP, SVV > 25% if ventilated, rising noradrenaline requirement, lactate, or ScvO2.
  • Renal endpoints – creatinine or urea rise 10-20%, sodium rise >4 mmol.

Our man needed some help from vitamin F but tolerated over a litre negative balance per day from the third day with a significant decrease in FiO2 after the first 500ml. Extubation was possible on day 4 and renal function was near baseline by day 8 by which time he was back on the medical ward. 


So it’s no longer about being a ‘wet’ or ‘dry’ unit but being wet and dry in all the right places. Fluid is a drug that both saves lives and slows recovery. The finer points of administration and removal are yet to be elucidated but signals are already in the literature regarding the shaping of a patient’s dynamic fluid balance

P.S. Echocardiography is uniquely suited to assessing all these stages fluid assessment using quantitative and qualitative evaluation. But that’s another story.

  1. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006 Jun 15;354(24):2564–75.
  2. Vincent J-L, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006 Feb;34(2):344–53.
  3. Durairaj L, Schmidt GA. Fluid therapy in resuscitated sepsis: less is more. Chest. 2008 Jan;133(1):252–63.
  4. Payen D, de Pont AC, Sakr Y, Spies C, Reinhart K, Vincent JL, et al. A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care. 2008;12(3):R74.
  5. Bouchard J, Soroko SB, Chertow GM, Himmelfarb J, Ikizler TA, Paganini EP, et al. Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int. 2009 Aug;76(4):422–7.
  6. Murphy CV, Schramm GE, Doherty JA, Reichley RM, Gajic O, Afessa B, et al. The importance of fluid management in acute lung injury secondary to septic shock. Chest. 2009 Jul;136(1):102–9.
  7. Bagshaw SM, Gibney RTN, McAlister FA, Bellomo R. The SPARK Study: a phase II randomized blinded controlled trial of the effect of furosemide in critically ill patients with early acute kidney injury. Trials. 2010;11:50.
  8. Boyd JH, Forbes J, Nakada T, Walley KR, Russell JA. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med. 2011 Feb;39(2):259–65.
  9. Grams ME, Estrella MM, Coresh J, Brower RG, Liu KD, National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Fluid balance, diuretic use, and mortality in acute kidney injury. Clin J Am Soc Nephrol. 2011 May;6(5):966–73
  10. Heung M, Wolfgram DF, Kommareddi M, Hu Y, Song PX, Ojo AO. Fluid overload at initiation of renal replacement therapy is associated with lack of renal recovery in patients with acute kidney injury. Nephrol Dial Transplant. 2012 Mar;27(3):956–61.
  11. Teixeira C, Garzotto F, Piccinni P, Brienza N, Iannuzzi M, Gramaticopolo S, et al. Fluid balance and urine volume are independent predictors of mortality in acute kidney injury. Crit Care. 2013;17(1):R14.
  12. Schmidt M, Bailey M, Kelly J, Hodgson C, Cooper DJ, Scheinkestel C, et al. Impact of fluid balance on outcome of adult patients treated with extracorporeal membrane oxygenation. Intensive Care Med. 2014 Sep;40(9):1256–66.