Category Archives: Circulation

Appropriate nutrition is integral to patient care (Nestle Health Science sponsored session)

Smart nutrition not more nutrition

(Zudin A. Puthucheary)

Muscle wasting is common in critical illness, significantly greater in the sickest pts 

Intramuscular hypoxia in critical illness

  • unlikely to use glucose as fuel
  • fat can be used but decreased mitochondrial beta-oxidation leads to build up of fat within muscle
  • Increasing CHO / lipid delivery unlikely to be useful in acute critical illness

In ALL pts, ATP levels decreased in 1st week of critical illness, but chronic illness depletes ATP more quickly than in previously well individuals

ASICS trial: considers if ketogenesis can provide alternative substrate for energy

 

Altered protein homeostasis in critical illness: body attempts to increase anabolism but fails.  Can pts exercise to stimulate protein homeostasis? –> low tolerance for exercise during critical illness

 

Smarter use of protein is required

  • with continuous amino acid provision, protein synthesis drops off after 2 hours
  • not all proteins created equally – 10g leucine per 100g whey protein
  • no other amino acid stimulates muscle protein synthesis like leucine, but despite muscle growth, strength is not improved without exercise

 

In practice, cannot separate energy requirement from protein requirement

  • both are necessary
  • the ability of nutritional protein or calories to modulate muscle metabolism is likely to depend on quality and type of nutrition rather than quantity

 

Relevance of outcome measures: only 1% of trials since 2000 measure muscle function as a primary outcome – more trials needed which focus on functional outcome

 

Can nutrition be used to target mitochondrial dysfunction?

(Mervyn Singer)

Mitochondria are important

 

Lactate becomes important fuel source in critical illness – autocannibalism to feed other organs: is muscle wasting adaptive?

Long term Rodent model of critical illness (faecal peritonitis) – rats do not restore diurnal rhythm of metabolism by day 7

 

Strict blood glucose control using insulin- protects hepatocyte mitochondrial structure and function in critically ill pts

 

Fatty acids stimulate production of uncoupling protein –> more heat generated, but mitochondrial membrane potential decreases –> decreased ATP, decreased ROS generation

Oleic acid induces fatty acid oxidation and decreases organ dysfunction and mortality in experimental sepsis (raised IL-6 production in septic mice, but decreased upon addition of oleic acid)

Coenzyme Q10: No difference in clinical outcomes between ubiquinol (reduced Coenzyme Q10) and placebo in pts with severe sepsis / septic shock. No difference in vascular endothelial biomarkers, inflammatory biomarkers, or biomarkers related to mitochondrial injury.

Succinate: in septic rats, succinate increases mitochondrial oxygen consumption –> buildup of succinate during ischaemia causes reperfusion injury through mitochondrial ROS

Supplementing with antioxidants: if the pt is in MOF and damage has already been done, have we missed the boat?

  • Multiple means of modulating mitochondrial function via nutrition with no clear guide on what to do, but one-size-fits-all approach unlikely to benefit anyone

 

Update 2018 ESPEN guidelines

(Mette Berger)

Nutritional Risk Screening tool – quick scoring, screen within first 48 hours of admission

Exact timing of phases of critical illness is less important than the concept of Varying nutritional needs with each phase

  • If oral intake is not possible, early enteral nutrition (EN) is better than delayed EN
  • If EN / oral intake both not possible, implement PN within 3-7 days
  • If pt is very sick, the gut will be affected – don’t give full dose EN in septic shock pts –> risk of severe complications including vomiting, diarrhoea, bowel ischaemia, acute colonic pseudo-obstruction
  • Hypocaloric nutrition (not exceeding 70% energy expenditure) should be administered in early phase of acute illness

 

No strong evidence for high protein delivery – 1.3g protein / kg / day should be given progressively + physical activity may improve the beneficial effects

 

In healthy individuals, consuming breakfast will stop endogenous glucose production

  • this process carries on in sick pts, resulting in a protein loss of ~ 120g / day to generate 1200kcal /day

 

Slow progression in feeding may allow early detection of refeeding syndrome which can be treated

 

Increased protein delivery while decreasing carbohydrate loads

(Juan B. Ochoa)

 

Paradigm: Substitute for what the patient is unable to eat

  • but even 10% hyper caloric overfeeding will worsen outcomes in sick pt

 

No benefit to meeting caloric goals in the first 7 days, and in fact this will have undesirable consequences

 

Belief that 50% of caloric intake should be from carbohydrates is an outdated concept – it is a method of cheap food provision in 19th century prisons

  • regrettably most commercial formulae consist of mostly simple sugar, without complex CHO

 

Ideally use indirect calorimetry to estimate requirements; predictive equations tend to result in overfeeding

 

Protein delivery is affected by choice of feeding formula; hypocaloric high-protein nutrition is safe metabolically and clinically

 

ICM Experimental 1: Mechanisms of Multi-organ Failure

How to protect and resuscitate the mitochondrium: Role of Metformin and Cyclosporin

(Jean-Charles Preiser)

3 post-injury phases: Early Phase attempts to protect cellular integrity at the expense of functionality

  • changes in macro / microcirculation
  • decreased oxygen consumption
  • decreased energy expenditure
  • metabolic shutdown

Hyperlactataemia closely related to severity of sepsis; in established sepsis it is defect of oxygen utilisation, rather than impaired oxygen transport

 

Mitochondria in critical illness– more than just a powerhouse – also key roles in cell signalling (ROS), calcium homeostasis, regulation of apoptosis. Stressed mitochondria release DAMPs, further increasing inflammation and systemic toxicity

 

Metformin directly decreases mitochondrial respiration and increases aerobic glycolysis

Several studies have shown improved outcomes associated with metformin use in ITU patients

Cyclosporin A inhibits opening of mitochondrial permeability transition pore (mPTP), thereby preventing cell death

Rabbit model: cardiac arrest –> resuscitation with either 1. Control or 2. Cyclosporin A or 3. Non-immunosuppressive analogue-Inhibitor of mPTP opening –> organs harvested with functional markers recorded

 

Cyclosporin A (and non-immunosuppressive analogue-Inhibitor of mPTP opening) – protective effect on liver, kidney and heart, but not lung

Clinical:

  1. Cyclosporine before PCI for acute MI (800 pts): randomisation to bolus of Cyclosporine or Placebo –> disappointingly same primary outcome (death any cause / cardiac compromise) in both groups   ??dose ??timing-related
  2. Out-of-hospital cardiac arrest (800pts): randomisation to bolus of cyclosporine vs placebo – No difference in SOFA scores 24 hrs post-admission   ??dose ??timing-related ??inclusion criteria

 

Late and Recovery phases post-injury: Long stayers >5 days – decreased mitochondrial biogenesis, dysregulated lipid oxidation –> weakness, muscle inflammation, impaired anabolic recovery

 

Inhibitors of mitochondrial function may prevent later organ failure if given very early post-injury BUT prolonged mitochondrial dysfunction is not desirable

 

Recommended reading: Feeding mitochondria: Potential role of nutritional components to improve critical illness convalescence

 

The role of the Glucocorticoid (GC) receptor in circulatory shock

(Sabine Vettorazzi)

 

GC production and function is required for efficient response to inflammation – abnormal GC production associated with higher sepsis mortality in animal models and humans

GC binds to Glucocorticoid receptor (GR) –> translocates to nucleus

  • GR monomer –> Represses inflammation
  • GR dimer –> Induces inflammation

 

GR Dimerisation-deficient mouse model (GRdim) created, to clearly discriminate effects of GR monomers from GR dimers (which are completely absent)

Mice subjected to endotoxin-mediated shock: GRdim mice died faster than wild-type mice

  • more severe lactate acidosis
  • higher inotropic requirement for haemodynamic stability
  • impaired lung compliance
  • increased osteopontin levels (with decreased levels of anti-inflammatory IL-10)

 

GR Dimer is important for survival during LPS induced toxic shock, at least during the first 6 hours of shock in GRdim mice (only observed for 6 hours with intensive care support)

 

Why and how the heart fails

(Alain Rudiger)

 

Four shock states –

  • shock –> cardiac dysfunction, MOF
  • combination of shock states commonly occur

 

Cardiac dysfunction during Inflammatory Shock:

  • Elevated BNP and Troponin
  • Arrhythmia
  • Systolic and diastolic dysfunction

 

Is this myocardial injury the reason for cardiac dysfunction?

Little evidence of myocyte necrosis in pts dying of sepsis + impaired contractility is Reversible = functional impairment rather than structural damage

 

Adaptive myocardial depression when myocardium is at risk

  • reprogramming of genes
  • activation of fetal genes (survival program)
  • decreased energy expenditure to keep cells viable

 

Complex process of gene activation / down regulation in multiple cell-types at different times

 

Rat model 6 hours post-onset of faecal peritonitis:  500+ genes up/down regulated

  • –> downstream: signalling cascades e.g. blunted adrenergic cascade / blunted calcium transport
  • –> further downstream: affects electromechanical coupling and decreases myocardial contractility

 

Close interactions between shock, cardiac dysfunction and MOF

The heart fails as a result of multiple factors:

  • Insufficient preload
  • Excessive RV afterload
  • Arrhythmia, dyssynchrony
  • Diastolic dysfunction and impaired contractility

Advanced Critical Care Echocardiography Course- Day 1

Introduction (De Backer)

Consensus statement on training in 2014 https://www.ncbi.nlm.nih.gov/pubmed/24615559  – this is the basis of the ESICM’s European Diploma in advanced critical care EchoCardiography (EDEC) https://www.esicm.org/education/edec-2/

CICM Levels of training https://onlinelibrary.wiley.com/doi/full/10.1002/ajum.12127

So what does advanced CCE measure compared to basic?

-Colour doppler looking at flow patterns and valvular lesions,

-spectral doppler for quantifying valvular abnormalities, measuring cardiac output and measuring intracardiac pressures

-Heart lung interactions

TEE is recommended as essential in EDEC

 

TOE Views (Vieilland- Baron)

http://www.echo-rea.uvsq.fr/echocardiographie-en-reanimation/langue-en/open-educational-resources/the-most-common-echocardiographic-views/03-transesophageal-echocardiography-the-most-common-views-248923.kjsp?RH=1354638851042

Practice online with the Toronto Virtual TEE simulator http://pie.med.utoronto.ca/tee/

LV Systolic function- Vieillard-Baron

-LV Dilation suggests a chronic injury

-LV Systolic dysfunction does not mean cardiogenic pulmonary oedema

-LV systolic function is a combination of contractility and afterload

-RWMA is ischaemia until proven otherwise

LV Systolic Function- Vignon

At the advanced level we are going way beyond “eyeballing” ejection fraction…

 

LV Systolic function- Dessap

Assess in all views:

Visual impression
LV EF (Ideally Simpson’s method of discs)
LV FAC

Don’t forget the importance of afterload!
Good images can be obtained with TTE 90% of the time.

If you are still struggling, strain is becoming more widely available…

LV Diastolic function- McLean

This is an area without much evidence in the critically ill…

ASE recommendations for LV diastolic dysfunction https://asecho.org/wp-content/uploads/2016/03/2016_LVDiastolicFunction.pdf

Applications of diastolic dysfunction guidelines in sepsis https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-017-0342-x

How to measure Diastolic function- Slama

This is really hard!

Problem with these tools is that mitral flow/pulmonary venous flow/Propagation velocity are all rather load dependent
Ea (e’) is probably least of these

EDEC Accreditation structure (De Backer)

Register here https://www.esicm.org/education/edec-2/

Pericardial disease and echo (Paul Mayo)

Twitter thread here https://twitter.com/iceman_ex/status/1177950552526864384

Whatever you do don’t forget that tamponade is a CLINICAL diagnosis!!

Many thanks to all the amazing speakers for sharing their knowledge.

TTM @ #EuAsia19

Optimal depth, timing and duration based on recent clinical trials (K Sunde)

Cardiac arrest is a complex disease

  • several different causes (many untreatable, irreversible, extreme challenging)
  • large heterogeneity
  • challenges the system due to the limited/crucial time-intervals (hypoxia/extreme ischemia)
  • large differences in quality of care within and inbetween systems (both during ALS and in post resuscitation care)
  • very high mortality

Depth and Timing

ILCOR Statement 2003 –

Unconscious adult patients with spontaneous circulation after out-of hospital cardiac arrest should be cooled to 32-34°C for 12-24 hrs when the initial rhythm was VF.

For any other rhythm, or cardiac arrest inhospital, such cooling may also be beneficial.

Outcome, timing and adverse events in therapeutic hypothermia after out-of-hospital cardiac arrest.

  • timing, speed and duration of hypothermia had no impact on outcome!

Confounding aspects regarding early/fast cooling

  • the lack of protection against a drop in core temperature is due to a larger and deeper brain injury! (link)
  • If you are really “dead” you are colder and it is very easy to cool you fast! (link)

Intra-Arrest Transnasal Evaporative Cooling: A Randomized, Prehospital, Multicenter Study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness) link

Duration of TTM

Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest

Prolonged targeted temperature management in patients suffering from out-of-hospital cardiac arrest

Conclusion

  • Cardiac arrest is complex, with large heterogeneity and very high mortality
  • Large differences in quality of care within and inbetween systems
  • Concerning pathophysiology and TTM: depth, speed and duration impacts on the reperfusion injury/brain injury
  • We are concluding based on pragmatic trials not optimizing the intervention tested or considering the ongoing pathophysiology!
  • Outcome assessment: cognitive function/QoL years after the arrest!

Haemodynamic Management During Targeted Temperature Management (Huang CH)

Multiple reasons for haemodynamic instability post-cardiac arrest

Haemodynamic Response Correlated to Outcome – Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest.

Cardiovascular Response & Haemodynamic Changes In Hypothermia Treatment

  • Changes in CV β-adrenoceptor (reduced response)
  • Bradycardia
  • Increase in stroke volume
  • Reduced intravascular volume during hypothermia is by 10– 35%

Lower heart rate is associated with good one-year outcome in postresuscitation patients (link)

Survivors Have Higher Mean Arterial Pressure (link)

Lowest value of DAP over the first 6 h after ICU admission for predicting unfavourable neurological outcome at 3 months (link)

Postresuscitation hemodynamics during therapeutic hypothermia after out-of-hospital cardiac arrest with ventricular fibrillation: A retrospective study

Taiwanese Protocol