Feed, or wait and eat, in pancreatitis

pancreas nutition pythonAnother addition to this year’s flurry of nutrition work.

Tradition has us bypassing the stomach and duodenum for nutrition in pancreatitis – intuitively sensible. To challenge this the Dutch PYTHON trial group has recently published its findings.

Multicentredly, they randomized 200-ish patients with acute ‘high-risk’ pancreatitis (defined as mGlasgow of >/= 3, CRP >150, APACHE >/=8) to start naso-jejunal feeding (25Kcal/Kg/dy if on ICU) within 24 hours or to wait up to 3 days and then encourage (the ‘on-demand’ group). Powered to detect 5% difference in major infection (pancreas or other) OR death within 6 months. The protocol was pretty well-adhered-to.

There was no difference in primary outcome (~30%), major infection rate (~25%), death rate (~10%), necrosis (~60%), mechanical ventilation (~12%). 5-10% got parenteral nutrition. 

 

  • Importantly only a fifth needed ICU care. So of those predicted to get severe pancreatitis presumably many didn’t.
  • Target calorie delivery was rarely achieved until day 3 or 4 in the early fed group and 6 or 7 in the other.
  • Interestingly, more than 2 thirds of of the ‘on-demand’ group didn’t need tube feeding.

 

So early NJ feeding doesn’t appear superior to delaying addressing nutrition until day 4 and starting oral intake.

How useful is this result? Accurately predicting severe pancreatitis is clearly problematic and for studies like this mean that the sample ends up being very heterogeneous. Regarding study design, mixing timing and route may have limited the applicability of these results, and many are inherently suspicious of composite outcome measures. 

We need a way to better predict severe pancreatitis. And then perhaps a 2×2 look at timing and route?

Shock taskforce – define, diagnose, monitor, treat it right.

My notes on this modern primer on shock by 11 well-known shock experts (shoxperts?). Interesting mix of evidence-base and expert opinion/enthusiasm. Definitely some echophiles amongst them.

Definition

Life-threatening, generalized, acute circulatory failure associated with inadequate oxygen utilization by cells (dysoxia leading to hyperlactataemia).


Pathophysiology

  • Insufficient circulating volume,
  • Pump failure (muscle problem or rhythm problem),
  • Obstruction (PE, pleural/pericardial effusion),
  • Distributive shock (vasodilatation – sepsis, anaphylaxis, spinal injury),

or a combination of the above.

 


 

Diagnosis

Clinical, haemodynamic and biochemical.

3 Clinical ‘windows’
  1. Peripheral – cold, clammy, discoloured skin
  2. Renal – <0.5ml/Kg/hr
  3. Neurological – obtundation, delirium

Hence – Serial assessment HR, BP, temperature, skin features, urine output and mental state

Hypotension and shock

Hypotension (SBP<90, MAP<65, drop of 40)

  • NOT a prerequisite for diagnosing shock.

Lactate

  • >1.5 mmol/l is associated with increased mortality, >2 usually. More predictive than almost any other marker (particularly inflammatory markers). But prognostic value does depend on the type of shock.
  • Elevation not simply due to abnormal oxidative phosphorylation.
  • Potentially protective and therefore a marker of severity rather than a ‘toxin’ needing to be removed.
  • Early reduction with therapy is a good sign.
  • Seems useful in guiding therapy, ie targeting lactate clearance (20%/2hr for first 8hr) – Jones and Jansen say so.

ScvO2

  • Low values (potentially inadequate O2 delivery) and high values (inadequate O2 use) are prognostically bad. But normal value can be misleading.
  • Elevated venoarterial CO2 difference ((ScvCO2-PaCO2) >6mmHg or 0.8KPa) may be a better marker of insufficient blood flow.

Therefore:

Serial lactate measurement is crucial.

If CVC in place then measure ScvO2 and venoarterial difference.

 


 

How/when to monitor cardiac function

Use cardiac monitors to 1) Identify shock 2) Select therapy 3) Evaluate response

Often a mixture of types of shock. Early echo quickly helps in decisions re fluid ‘v’ inotrope ‘v’ pressor ‘v’ definitive intervention.

 

Blood pressure target

Use an arterial line and CVC if not improving with initial treatment.

Individualize the target.

  • MAP >65 is default, but:
  • ‘higher’ if known hypertensive or if more seems to help.
  • ‘lower’ in uncontrolled bleeding

No new comment about targets in brain injury – ?stays at 90 mmHg.

Improving perfusion
  • Fluid early, as described below.
  • Inotropic agent (no specific recommendation) if BOTH inadequate cardiac output AND impaired cardiac function.
  • Do not use inotropes for impaired cardiac function with sufficient cardiac output.
  • Do not supranormalize oxygen delivery.
Evaluating response
  • Fluid responsiveness markers
  • End tidal CO2 changes (in ‘steady state’ ventilation)
  • Resolution of preload dependancy markers (where they were marked)
  • Arterial pressure, change in pulse pressure (not PPV), CVP, PAOP are all flawed.
  • Cellular dysoxia markers – theoretically nice but take longer to change.

Therefore:

Measure cardiac output if clinically not responding well to initial therapy.

Sequential assessment is key.

 


 

Preload and Fluid Responsiveness

Knowledge of preload is not knowledge of preload responsiveness.

Dynamic variables for fluid management are best:

  • Stroke volume variation
  • Pulse pressure variation
  • IVC variation
  • Passive leg raising

All have confounders (tidal volume, abdominal pressure, dysrhythmia, cardiac and pulmonaru state, open chests etc.) and SVV,

PPV and IVC variation are only valid in the absence of spontaneous breathing.

Therefore:

Echo may be best way to determine type of shock. If you don’t use it you may miss-manage 25% of septic patients.

Assess volume ideally using dynamic markers.

Static preload markers should not be used alone (CVP, PAOP, change in pulse pressure (not PPV)). However, immediate fluid is recommended if very low value of static markers.

Do not target LV filling pressure.

When deciding to give fluid use a measured fluid challenge and assess response, don’t just pile it in.

FLUID RESPONSIVENESS DOES NOT MEAN THEY NEED FLUID. Assess lung water where possible (TPTD or ultrasound).

 


Methods of monitoring

Echo

Echo can characterize the circulatory disturbance, aid therapy selection and assess response.

In addition to obvious structural abnormalities it is used to assess:

  • Direct stroke volume measurement using Doppler (velocity-time integral across an outflow tract)
  • Ejection fraction reflects the balance of contractility and afterload, so needs to be interpreted in the context of type of shock, and inotrope/pressor use.
  • Filling pressures can be estimated using pulsed Doppler and tissue Doppler. Combining these allows a ‘load-independant’ assessment (the E wave of LV inflow adjusted by the E’ wave of the MV annulus longitudinal movement). E/E’ >15 suggests high LV filling pressure, <8 suggests low. In practice it’s rarely outside this range.
  • RV size can be assessed with 2D echo, (ideally) using end-diastolic area values. RV:LV >0.6 suggests moderate RV dilatation, in turn suggesting acute cor pulmonale when accompanied byabnormal septal motion.
PA catheter
Provides a lot of numbers (RAP, PA pressure, PAOP, ScvO2, PvO2, O2 extraction etc.)
Accurate cardiac output monitor.
Use beyond specific indications is contentious (lack of benefit, possible harm, expense).
Transpulmonary thermo/lithium dilution
Less invasive. Also lots of numbers (global end-diastolic volume, extra-vascular lung water, cardiac function index).
Intermittent calibration with continuous waveform analysis in between.
Uncalibrated pulse contour analysis
Either via an arterial line or finger pleth. Complicated maths to estimate artery characteristics. Precision, accuracy and reliability is being questioned.
Oesophageal Doppler
Velocity time waveform of the descending aorta. Normogram for arterial cross-sectional area. Derived variables. Reliability issues largely relate to positioning.
Bioreactance
Phase shift of high frequency current put across the thorax. Yet to prove itself.
Tissue microcirculation monitoring
Tissue CO2
Near-infrared spectroscopy occlusion test
Muscle O2 saturation changes with occlusion (DeOx and ReOx).
Microvideoscopic techniques, looking at capillary density, perfusion and flow heterogenity in eg tongue epithelium.
All currently research tools only.

 

Therefore:

Sequential echo is useful if not vital.

Do not use PAC routinely.

PAC or TPTD in severe shock.

Other uncalibrated and minimally invasive devices are yet to be validated.

 

 

 

Know your phases and master fluid management

ADQIThe ADQI renal authority turns its attention to fluid strategy in ADQI III’s BJA article.

 

 

 

 

 

Choose the right fluid balance target for the stage of critical illness:

  1. Rescue – first few minutes; generous fluid boluses to treat shock. Obviously, not all patients require this phase.
  2. Optimization – few hours; assessment of tissue perfusion, use of fluid responsiveness markers, working towards stability
  3. Stabilization – next few days; cover losses but otherwise minimize fluids and keep balance neutral-ish.
  4. De-escalation – mobilize fluid; allow or encourage it out; negative balance.

Different measurements and vital signs are valid (or used) at different stages. The utility of ScvO2, cardiac output monitoring, echo and fluid responsiveness markers for assessing volume status are largely confined to the ‘optimization’ period.

Lack of attention in the optimization and stabilization stage is common. Fluid in drugs and electrolyte replacement adds up and often passes relatively unchecked.

In addition a current article in Crit Care involved 492  patients in a prospective registry-collected observational study. Multivariate LR was used to assess whether fluid balance and hypotension (on RRT) was related to death or prolonged renal support. Positive fluid balance, or hypotension, in the first seven days of renal support was associated with greater mortality, but not long term renal support.

It’s difficult to draw any firm conclusions from this observational study. Although many variables were adjusted for, some can never be. Immortal time bias is a particular potential problem in this instance. However it as least adds more weight to ADQI’s assertions.

Immortal bias

 

More on ‘shaping’ fluid balance on the OXICM site.

 

 

 

Towards global consensus on end of life care principles in the ICU

End of life care 2The  WELPICUS study group have used an interesting approach (using the Likert scale to assess a number of statements) to try to gain international consensus (from more than 30 countries) on what matters in end of life care in the ICU.

 

 

 

Autonomy and decision making

There was considerable support for respecting advanced directives (AD), but not necessarily for doctors to encourage patients to write them. There is little current use AND low medical adherence. Patients with capacity may change their mind. Don’t break the law to follow an AD! So, know the law.

Decision making and capacity key elements reaffirmed.

  • Possession of necessary values,
  • ability to communicate and understand,
  • ability to reason.

Strong support for 3-tier model:

  1. Autonomous decision making where possible;
  2. Acknowledge previously communicated views when capacity is lost;
  3. Elsewhere, act in best interests.

Capacity is felt to be conditional – ICU collects complex cases and complex decisions for which a basic level capacity may be insufficient. (America/Europe historical disparity on this is lessening). Patients known preferences trump relatives preferences.

Gain consent for invasive procedures when possible.

Use shared decision making

Large international variation in involvement of surrogates in decisions about EOL. Europe very keen on shared decision making.

Life-sustaining treatments

Consensus gained on withdrawal of treatment when chances of surviving are very low or patient’s wishes against it are known. Includes CPR!

Not yet complete consensus on details of withdrawal/withhold/palliative issues due to legal issues in various countries. Again, know the law!

Decisions regarding end of life care should be made in by the multi-disciplinary ICU/home team AND in discussion with patient/family.

The intent must never be to shorten life, even if this is allowed by law.

Brain death

Near consensus on discontinuation of all therapy after BD. If the family does not accept brain death then most countries allow discontinuation anyway, but if their wishes are honoured then the patient is NOT required to remain on the ICU.

Palliative care

Physical, social, spiritual and emotional needs attended to – in order to facilitate as much autonomy as possible.

end of life consensus

Inadvisable actions

Non-beneficial treatments and investigations should be avoided. Difficulty with what ‘beneficial means’.

Documentation

Document decisions and their rationale.

Education

Everyone needs educating and teaching should be culture/law/religion specific.

Clinical ethics committees

These committees can be useful for advice where opinions differ.

Uncontested statements

Keep families included, informed and happy

Maximise life-saving but bear in mind long-term QOL

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The global mind-set on end of life principles appears to be converging but some interesting differences remain.

Emphasis on shared-decision making is evident.

——————————————————-

Personally, I find the comments about ‘very low chance of surviving’ unhelpful. On the whole we can make death on the ICU humane and largely dignified. But, in many cases we don’t have reliable markers of long-term outcome for individuals. We know that it almost always ends badly but to aim for the improbably tiny ‘bulls-eye’ of a good outcome you risk hitting the far larger surrounding zone of drawn-out death or unacceptable quality of life.

Consequently I often find, in discussions with patients and families regarding withdrawing, withholding or limiting treatment that the following elements need to be explained:

  • Death is most probable whatever we do.
  • There may be a tiny chance of survival, but…
  • what is much more likely, if we continue aggressive treatment, is that death will be protracted and potentially unpleasant or the quality of long-term health will be (unacceptably?) low.

Any advice on handling these discussions?

Be wiser, do less to be better.

Choose wiselyOver the last couple of years, 4 US critical care societies put together a literature-scouring taskforce as part of the Choosing Wisely campaign. After a lengthy process they came up with 5 cost-effective, tradition-questioning recommendations:

 

 

 

 

 

1. Do not order diagnostic tests at regular intervals (such as every day), but rather in response to specific clinical questions;

Avoid anaemia (and so transfusions). Avoid ultimately inconsequential incidental findings demand further work-up.

 

2. Do not transfuse red blood cells in hemodynamically stable, non-bleeding ICU patients with an Hb concentration greater than 7 g/dl;

A threshold of 7 mg/dl results in better survival, fewer complications, and reduced costs. And preserves a precious resource. But unelucidated subgroups may exist.

 

3. Do not use parenteral nutrition in adequately nourished critically ill patients within the first 7 days of an ICU stay;

If not malnourished prior to admission, early PN (even in those not tolerating EN) is possibly harmful and costs more.

 

4. Do not deeply sedate mechanically ventilated patients without a specific indication and without daily attempts to lighten sedation;

Protocol-based approaches can safely limit unnecessary deep sedation – eg lightest effective dose; analgesic before sedative; daily sedation holds.

 

5. Do not continue life support for patients at high risk for death or severely impaired functional recovery without offering patients and their families the alternative of care focused entirely on comfort

Routinely engage high-risk patients and their next of kin or advocate in discussions about limiting the level of aggression of treatment. Promotes patient’s/family’s values, improves the quality of death, and reduces family distress. Initiating palliative care pathways/team may be beneficial even where death is not necessarily expected.

__________________________

Whether or not these would be your top five the ambition is laudable and these 5 recommendations, originally published in January, have generally withstood criticism over the last 9 months, and ‘savings’ are being made.

 

EN or PN for getting the calories in?

Everyone knows early enteral nutrition’s a good thing, don’t they?Calories outcomes

A large (2400) pragmatic (real-life!), randomised, unblinded trial in non-elective admissions to 33 UK ICUs, CALORIES looked at the difference in early feeding enterally ‘v’ parenterally, powered for a 20% difference (RRR, or 6% ARR) in mortality at 30 days. Feeding was started within 36 hours of admission, aiming to achieve 25 kcal/kg/day by 72hr, and continued for 5 days. A different focus to EPaNIC and Doig 2013 in that the patients were able to receive either EN or PN.

Most patients in each group didn’t achieve their target, and caloric intake was about the same in each. The parenteral group had less hypoglycaemia (4 ‘v’ 6%), smaller gastric residuals (~100 v ~1000ml) and less vomiting.

But 90 day mortality was no different (around 33%), nor was the length of stay or rate of infective complications, liver dysfunction, GI ischaemia, abdominal distension, aspiration or electrolyte disturbance.

About 7% of the parenteral group (ie to enteral) and 1.5% in the other direction – of uncertain significance.

PN might be expected to be more likely to deliver target calories but in the real world there are logistical barriers to this. Based on this study route doesn’t matter, so long as the patient group is similar to yours (15% post-op, APACHE 20, mean age 65, mortality 30% etc)!

Early ‘v’ late PN’s not beneficial but early EN and PN have the same outcomes? Depends on how you feel about EpANIC‘s shortcomings perhaps. Better feed formulation and less CRBSI may have changed the risk/benefit balance.

Is this a myth busted? Cost, technical aspects and patient specific factors will continue to inform our choice, but maybe we can we be freer with our early PN. And will the guideline compilers act on this?

Acute heart failure – NICE guideline

NICE AHFThe new NICE guideline for acute heart failure in adults is out. Leaves quite a lot of room for interpretation; few hard and fast recommendations. Sizeable section on further research.

 

 

 

 

In a nutshell:

Have a heart failure team

  • Cardiology ward and outreach

Diagnosis

  • Rule out heart failure if BNP <100 or NT-proBNP <300.
  • Echo those with elevated BNP.

Therapy

No routine opiates and don’t use PA catheters.

1. Stop the beta blocker if shocked, bradycardic on in 3rd degree block

2. Diuresis:

  • start or augment
  • consider ultrafiltration if diuretic resistant.

3. Nitrates:

  • not routinely
  • give for concomitant myocardial ischaemia, severe hypertension or regurgitant aortic or mitral valve disease. NOT nitroprusside.

4. Inotropes

  • not routinely
  • use if the cause is reversible – not clear what this means.

5. NIV:

  • straight away for cardiogenic pulmonary oedema with  dyspnoea AND acidosis.
  • consider if respiratory failure not settling, or patient is tiring.

6. Specialist centre involvement

  • Discuss early if reversible severe acute heart failure or potential heart transplant recipient.
  • Get their valve sorted if that’s the problem!

Once stable

  1. Beta blocker – watch rate
  2. ACE – watch renal function
  3. Aldosterone antagonist

Research recommended

1. Fluid removal

  • Dopamine
  • Thiazides
  • Ultrfiltration

2. Balloon pumps

 

 

Comment:

St.Emlyns blog and their recommended reading

 

Refining, not consigning, EGDT?

ARISE protocolPROCESS has been backed up by ARISE in goal-directed therapy for sepsis. PROMISE is awaited (finished recruiting in July).

A large (1600), international, randomised, un-blinded, intention-to-treat trial with sensible exclusion criteria, conducted 2008-2014 of excellent quality. ARISE showed no benefit in using a protocolised 6 hour package for septic shock which involved continuous ScvO2 and CVP targetting

 

 

 

Their protocol included:

1. Supplemental oxygen if saturations <93 (No PaO2 limit)

2. Targets – using pressor (or dilator), red cells, dobutamine, mechanical ventilation to acheive:

  • CVP >8 (or 12 in ventilated)
  • MAP  target range of 65 to 90 mmHg.
  • Continuous ScvO2 >70%

The control group had conventional local management (usually guideline-driven) and weren’t aloud to peak at ScvO2. Both groups received around 2 litres over the 6 hours. Enrolment meant antibiotics had already been given (mean time around 70 mins for both groups).

This surely doesn’t damn EGDT but suggests that the ‘goals’ are now more (or less) clearly:

  • Definitely
    • early antimicrobials – within the first hour?
  • Probably
    • fluid repletion – at least some, but likely to vary with pathology?
    • blood pressure control – 65 as a minimum, but maybe previous BP has an impact?
    • cardiac output improvement when necessary, but not supra-normalising, and not using dopamine?
    • hope to see some lactate reduction!

None of this detracts form sepsis being a ‘thing’ to take seriously and jump on (like MI & CVA). The surviving sepsis campaign quickly issued an update suggesting that ScvO2 and CVP may not be necessary targets. They also point out that whatever the weaknesses of individual elements of the SSC guidelines, if you adhere to them you can expect to do better than institutions that don’t, as demonstrated by their metrics published earlier in the month. Some have commented that a hospital that adheres to a guideline is more likely to be a hospital that has systems for recognition of critical illness, is introspective with its processes, educates internally, collects data and audits well – a better hospital.

It might be argued that perhaps there wasn’t comprehensive equipoise prior to these studies. EGDT has largely been embraced by a specialty short of breakthroughs. Perhaps a worldwide Hawthorne effect plays some part in these ‘non-positive’ studies.

Maybe more of our pre-conceptions about managing sepsis will be stripped away. Maybe in a few years we’ll be practising glycocalyx-protective bolus-less resuscitation, with permissive hypotension and permissive hypoxia. But we will still stay alert for the diagnosis, start the clock and give antimicrobials early. And for now, Rivers EGDT remains as good as any other!

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