All posts by Adrian Wong

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

Lessons from Clinical Challenges in Neuro-Critical Care

Traumatic Brain Injury

Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research

Trajectories of early secondary insults correlate to outcomes of traumatic brain injury: results from a large, single centre, observational study

Clinical applications of intracranial pressure monitoring in traumatic brain injury : report of the Milan consensus conference.

 

Intracranial Haemorrhage

Definition: non-traumatic bleeding into the brain parenchyma

2nd most common type of stroke (10-30%)

5.3 million cases worldwide, 3 million deaths (2010 Global Report on Diseases)

Less than 40% of patients regain functional independence

Most important risk factors:

  • hypertension
  • anticoagulation

The critical care management of spontaneous intracranial hemorrhage: a contemporary review

Blood pressure management: BPsys < 140 -160 mmHg

  • Higher systolic pressures may lead to hematoma expansion and increased edema.
  • Prospective trials: INTERACT II, ATACH II

Correction of coagulopathy, if possible… or not?

  • Vitamin-K-antagonists (Phenprocoumon, Marcumar): Yes. Use PCC (prothrombin complex concentrate)
    •  INR-goal: < 1.3
  • DOACs: if specific antidote available and within 2-3 half lifes of substance, probably yes.
  • Heparin: use protamine.
  • Aspirin / Clopidogrel: may depend on hemorrhage size

Summary: intracranial hemorrhage

  • Data: meanwhile useful prospective works available
  • Difficult to estimate who will decompensate
  • Prognosis difficult to estimate, likely to be worse after large ICH.
    No application of score systems for single patients
  • Superficial, cortical hemorrhage: open surgery
  • Large Basal ganglia hemorrhage (> 30 ml): minimally invasive surgery
  • Intraventriular hemorrhage: EVD + Lysis (+ lumbale Drainage)
  • Decompressive surgery: trial ongoing.
  • Massive hemorrhage (> 100 ml): conservative approach
  • ICP monitoring standard in ventilated patients, optionally pbtO2, EEG, eCox, …

Subarachnoid hemorrhage

Transcranial Doppler ultrasound goal-directed therapy for the early management of severe traumatic brain injury.

Calcium antagonists for aneurysmal subarachnoid haemorrhage – Cochrane Review

Transcranial Doppler versus angiography in patients with vasospasm due to a ruptured cerebral aneurysm: A systematic review.

Hyponatraemia: Practical Management

  • Monitor volemia and Natremia after SAH
  • Fluid restriction is not recommended
  • Isotonic saline (0.9%) for drug dilution and fluids (1-3L)
  • We rarely use 3% saline (1 ml/Kg of 3% NaCl increases the PNa by 1mmol/L)
  • Consider hydrocortisone in case of vasopressor use
  • Vaptans are not useful
  • Consider urea (0.5 -1g/Kg/Day) for HypoNa + euvolemia

Summary

  • Late risk: vasospasm
  • Monitoring: depends on severity and risk of vasospasm
  • At least: TCD and ICP, PbtO2 and CMD in tissue at risk
  • HypoNa is frequent: no fluid restriction! NaCl, Steroids, Urea

Acute Management of Status Epilepticus

International League Against Epilepsy (ILAE) task force on classification

SE = Status Epilepticus

◦ condition resulting

  • from the failure of the mechanisms responsible for seizure termination
  • from the initiation of mechanisms which lead to abnormally prolonged seizures

◦Long-term consequences

  • neuronal death, neuronal injury, alteration of neuronal networks, depending on the type and duration of seizures

RSE = Refractory Status Epilepticus

  • SE that persists despite adequate administration of benzodiazepines and at least one antiepileptic drug

SRSE = Super Refractory Status Epilepticus

  • SE that continues or recurs ≥24h after onset of anaesthetic therapy, including recurrence on the reduction or withdrawal of anaesthesia.

Convulsive status epilepticus (CSE)

  • SE with convulsions / seizures / myoclonus

Non-Convulsive Status Epilepticus (NCSE)

  • SE without clinical signs à EEG diagnosis

ESICM Webinar – FOCUS on #POCUS

*This webinar was kindly sponsored by GE*

We would love to hear from you and any feedback/questions would be welcomed. OR if you want to find out more about #POCUS fellowships……

The presentation….

https://www.icloud.com/keynote/0TjTY6dm-GTqkL_YCFewLu4kA#ESICM_webinar

Reference list

What is #POCUS

Lichtenstein D, van Hooland S, Elbers P et al. Ten good reasons to practice ultrasound in critical care. 

Lichtenstein D and Mezière G (2008) Relevance of lung ultrasound in the diagnosis of acute respiratory failure. The BLUE-protocol. 

Perera P, Mailhot T, Riley D et al. The RUSH exam: Rapid ultrasound in shock in the evaluation of the critically ill. 

Lichtenstein D.A. Lung Ultrasound as the First Step of Management of a Cardiac Arrest: The SESAME-Protocol. In: Lung Ultrasound in the Critically Ill. Springer, 2016 Cham

Training in #POCUS

Malbrain MLNG, De Tavernier B, Haverals S et al. Executive summary on the use of ultrasound in the critically ill: consensus report from the 3rd Course on Acute Care Ultrasound (CACU). 

Mayo P, Beaulieu Y, Doelken P et al. American College of Chest Physicians/La Société de Réanimation de Langue Française statement on competence in critical care ultrasonography. 

Expert Round Table on Ultrasound in ICU. International expert statement on training standards for critical care ultrasonography. 

Wong A, Galarza L and Duska F. Critical Care Ultrasound: A systematic review of international training competencies and program. 

Galarza L, Wong A and Malbrain M. The state of critical care ultrasound training in Europe: A survey of trainers and a comparison of available accreditation programmes. 

Future of #POCUS

Robba C, Goffi A, Geeraerts T et al. Brain ultrasonography: methodology, basic and advanced principles and clinical application. A narrative review. 

Aitkinson P, Beckett N, French N et al. Does point-of-care ultrasound use impact resuscitation length, rates of intervention and clinical outcomes during cardiac arrest? A study from the Sonography in Hypotension and Cardiac Arrest in the Emergency Department (SHoC-ED) Investigators. 

Feng M, McSparron JI, Kien Dt et al. Transthoraccic echocardiography and mortality in sepsis: analysis of MIMIC-III database.

If you are REALLY interested in pushing the limits of ultrasonography in critical care … https://thinkingcriticalcare.com/

Recommended textbooks