Wessex ICS Blog

Nutrition

Nutrition

Nutrition - regional ICM teaching - March 2014

Venue: University Hospital Southampton

Summary: Dr Phil McGlone


Trevor Smith Cons Gastro UHS.

  • Gastric residual volume less than 200mls not evidenced based
  • Only one study suggests that less than 500m is safe
  • All PN vs EN trails are of high versus low volume feeding.
  • The meta analysis from the early 2000’s are based on old, outdated trials and probably have little if any relevance to care in the ITU today.

Practical aspects of prescribing nutrition Mark Tomlin Cons Pharmacist

Malnutrition Universal Screening Tool (MUST)
1 - Score for low BMI (20, 18.5-20, <18.5)
2 - Score for recent weight loss (5%, 5-10%, >10%)
3 - Score for poor nutrition for last 5 days, or likely to be poor for over 5 days.

1+2+3 Score > 2 Identifies high risk patients
40% of hospital patients are malnourished and this is linked to slow recovery and poor wound healing. ICU patients may loose 10% of their muscle mass each week.
Is it evolutionary that we don’t eat when acutely unwell?

MUST score quantifies detection of malnourished patients for dietetic support (>2 implies refer)
Patients who are not eating oral foods normally get referred to dieticians
If still not eating orally, consider enteral tube feeding (NG, NJ, PEG).
Document length of enteral tube at nostril
Note position check. pH <5 aspirates (H2A,PPI) and X-ray
Use of a size 8fr will aid aspiration. Use a fine bore tube unless continuously high gastric aspirates and patient is at risk of aspiration
30 degree elevation to avoid reflux and aide diaphragm movement

Macronutrients - Normal

  • 25-35kcal/kg/day total energy ave. 70kg = 1750-2450
  • 1kcal per kg/hr (actual body weight)
  • 6.2G protein = 1G Nitrogen
  • (0.13-0.24G nitrogen) per Kg/dayave. 70kg = 9.1-16.8G N/day
  • 30-35ml/kg/day fluid ave 70kg = 2.1-2.5L/day =>85-100ml/hr
  • Fibre as appropriate

Macronutrients – Acutely unwell

  • Energy total – 1500-2000 kcal/day, ideally 1:1 CHO to fat ratio
  • Protein – 7-12 G N/day
  • Fluid – 1-2.5L/ day, 40-100ml/hr
  • However always first bag over 48hrs
  • Not on same day of operation due to SIRS
  • What can a sick or under-perfused liver utilise, before jaundice or ALP rise

Nutritional needs

  • Bariatric patients still need feeding. Stress of ITU is not the time to diet. ABW for 1kcal/Kg/hr? (Obese IBW +25%)
  • Increase rate of enteral feed in increments of 30ml/hr if gastric residuals remain <250ml at 4hrly aspirates
  • Continuous feeding or physiological breaks?
  • Achieving targets
  • laxatives
  • Phenytoin, doxy, cipro. Other IV/oral conversions
  • TPN vs PN/EN do you believe in a trickle?

  • Start at 30ml/hr standard feed
  • Aspirate after 4 hours, if less than 200ml replace and increase by 30ml/hr until full rate (70-90ml/hr).
  • If more than 200ml aspirate replace 200ml, discard remainder and decrease rate by 30ml/hr to minimum 10ml/hr
  • At 10ml/hr, continue for 24 hours then add metoclopramide
  • If still not absorbing after 48 hours, reduce opioid if possible to Morphine < 5mg/hr or Fentanyl < 2ml/hr
  • add Erythromycin 500mg BD IV/NG
  • After 48 hours (OR day 5) consider TPN

Parenteral
  • Last resort, not an emergency
  • Unstable mixtures, incompatible with other drugs, dedicated line
  • Risk of line insertion
  • Audit of line placement and X-ray check
  • Plan for more than 5 days, or persevere with Enteral
  • EN 10ml/hr to avoid gut atrophy and translocation
  • Phased introduction of PN over 48 hours
  • Phased re-introduction of enteral
  • Reliable EN for 24 hours before stop PN

Refeeding
  • Poor nutrition previous week –obvious and oesophagectomy, post op. actual calories
  • Previous nutrition status (BMI<18.5kg/m2)
  • Recent wt loss > 10% in 6 months
  • Alcoholics, drug abuse, IDDM, laxatives, antacids, diuretics, cytotoxics
  • Start with 10kcal/kg/day (70kg=700kcal)
  • Slow increases
  • Thiamine 200-300 (Pabrinex 250) per day

Vitamins & Minerals

Vitamin B compound Strong (2TDS RFS)
Vitamin C 500-1000mg/day (Pabrinex 500)
Selenium ACE 1 daily
Solvazinc 1 TDS
Sanatogen A-Z 1 daily
Folic Acid 5-10mg
Vitamin B12 – Hydroxocobalamin 1mg IM/IV

Don’t fiddle with the food to manage the fluid

Dedicated Line
Central preferred – but PICC, or peripheral
Virgin line
Maintenance - High flow
Minimal interruption – discuss
Not usually haemofiltration Lines
Expected other drugs, compatibility reshuffle
New Line – last option due to risks of insertion
Monitoring central lines

Parenteral nutrition is not a preferred option, it is undertaken when enteral is not possible.
Many of the problems of PN are due to gut atrophy, i.e. a lack of EN. Thus wherever possible give 10ml/hr EN to maintain gut integrity. PN for feeding the patient, EN for feeding the gut thus TPN is no longer appropriate
PN increases the infection risk but not mortality
PN is a planned event when EN has failed for 5 days. It is an inherently unstable mixture, takes 3 hours to make and costs about £100/day

Indirect Calirometry, Glutamine, & Selenium - Richard Lowe ST4 ICM

TEE - total energy expenditure
BEE – Basal energy expenditure
REE – Resting energy expenditure
DIT – Diet induced thermogenesis
AEE – Activity energy expenditure
TEE = (BEE + DIT + AEE)

RQ – respiratory quotient
CO2 produced (VCO2) / O2 used (VO2)
Normal range 0.7 – 1.2
Dependent on fuel source
Carbohydrate - 1
Protein - 0.8
Fat - 0.7
Production of chemical energy proportional to gas exchange
Weir equation used to calculate energy expenditure
Energy expenditure = (3.9VO2 – 1.1VCO2) – 2.17(urinary N2)
Abbreviated weir equation used
REE = (3.94 x VO2) + (1.1 x VCO2)

BEE may be significantly altered in critical illness
Obligatory feeding – PN
PN often results in overfeeding
Hyperglycaemia
Inflamation
Liver function abnormalities
CO2 retention
EN often associated with feeding intolerance
Underfeeding
BMR increased up to 40% in critical illness

Burns and trauma patients known to be heavily catabolic

Indirect calirometry (metabolic cart)
Substitute for calirometry (cumbersome / expensive)
Measures inspired & expired gas flows / volumes and concentrations (CO2 /O2)
Non invasive and accurate

TICACOS
Intensive Care Medicine Feb 2011
Israeli study
Single centered
130 patients
Randomized but unblinded
Mechanically ventilated for at least 3 days
Patients over 18
Mechanically ventilated
Expected to be ventilated > 3 days
Enteral nutrition with an energy target determined by INDIRECT CALIROMETRY
25 kcal/kg/day of enteral nutrition
PN used to supplement EN when needed
Primary outcome – 30 day survival
Secondary outcome
Length of mechanical ventilation
New pressure sores
Unplanned surgery / surgical complications
Renal impairment
Liver impairment
Infectious complications
Assigned within 48 hours
REE calculated by IC
Deltatrac 2 monitor used
Dietician led
Fed enterally as per protocol
PN used to make up shortfall
25 kcal/kg/day
Weight from patient / relative
Nursing led
IC measurements taken also
PN to make up shortfall from EN
Study group received more calories than measured to need
Control received less calories than calculated to need
Mean calorie intake significantly higher in study group
Study group patients had higher mean energy and protein intake
Significantly more in study group had PN in days 1 – 3
Trend towards lower mortality in study group with “intention to treat” p = 0.058
Significantly lower mortality for study group when “per protocol”
Hospital (28.5% v 48.2% p = 0.023)
60 day (57.9 +/- 9.9% v 48.1 +/- 7.6% p = 0.023
Similar ICU mortality
Increased length of ICU stay
Increased ventilation days
More total infections
Trend towards higher VAP

Dietician led care
Relatively small numbers
Could it be related to type of feeding
PN
More protein
Was it just that they were fed more
Calculated energy requirements looked quite good

Immunonutrition
Feed (EN or PN) enriched with pharmaconutrients to
IMPROVE IMMUNE RESPONSE
MODULATE INFLAMATORY RESPONSE
Critical illness response
Oxidative stress and SIRS – free radicals, inflamatory cascade
Mitochondrial damage – contributing to MODS
Vitamins and trace elements taken into organs for protein and immune cell production
Relative deficiency of antioxidants

Glutamine

Non essential amino acid
Participates in many metabolic processes
Becomes “essential”
Increased utilisation in critical illness
Plasma levels decrease
Low glutamine shown to have worse outcomes in some studies
Oudemans-Van Straaten 2001 Int Care Med (n = 25)
Favourable outcomes in burns patients – reduced bacteraemia, mortalilty and LOS
Garrel 2003 Crit Care Med

Canadian clinical practice guidelines suggest enteral glutamine should be considered in trauma and burns patients
When Parenteral nutrition prescribed to critical care patients glutamine supplementation “should be considered”
AVOID in patients with SHOCK and MOF - REDOXS

NEJM – April 2013
1223 patients – ventilated with 2+ organ failure
40 ICU’s: US, Canada and Europe
4 way randomisation
Placebo
Glutamine
Antioxidants
Both
Glutamine give IV and oral
Dipeptiven 0.35 g/kg / day IV
42.5 g alanyl-glutamine / glycine-glutamine dipeptides enteral
IV selenium 500mcg
Selenium 300mcg enterally
Zinc - 20mg
Beta Carotene - 10mg
Vitamin E - 500mg
Vitamin C -1500mg
Trend towards increased mortality at 28 days in patients receiving glutamine
32.4% v 27.2% (p = 0.05)
No significant difference attributed to antioxidants
30.8% v 28.8% (p = 0.48)
In hospital mortality
6 month mortality
Median time to discharge alive
ALL SIGNIFICANTLY HIGHER WITH GLUTAMINE
No significant effect on secondary outcomes with antioxidants
Big study population
Relevant to our practice
Causes
High dose of glutamine
Mixed administration
Early administration
Low glutamine levels not consistently found in their patients
Funding – Fresenius / Biosyn
P = 0.044
Many patients excluded
Not all prescribed supplements given
Cocktail of antioxidants

Canadian clinical practice guidelines (2013) - Arginine
4 level 1 studies, 22 level 2 studies
No clear evidence of benefit (Mortality / infection)
3 studies showing possible harm (Bower / Ross / Bertolini)
Increased costs
NOT RECOMMENDED FOR CRITICAL CARE PATIENTS

Selenium
Important precursor to glutathione peroxidase
Important plasma antioxidant
RDA 40 – 80 mcg/day
Selenium levels inversely proportional to APACHE 2
Forceville 2007
Angstwerm 1999 – replacing selenium increases glutathione

Any benefit
Number of studies
Cocktail of antioxidants – never alone
SIGNET study probably best study
502 ICU / HDU patients with GI failure needing PN
No clear evidence of benefit
Significant reduction in infections in selenium group who received PN for > 5 days

Recent Trials in nutrition Phil Mcglone ST5 ICM/Anesthetics
What does the recent literature tell us about how much and when to start nutrition in critical care?
EDEN
EpANIC
EPN
CALORIES
EDEN

Initial trophic versus Full enteral feeding 6 days
Hypothesis
Trophic feeding – increase VFD

Methods
Multi-centre
2008-2011
Patients
<48hrs of ALI onset
<72hrs MV
Randomization
6hrs to extubation, death or 6 days
Full Feed
Protocol 25ml/hr to target 25-30Kcal/kg/day
90% achieved this
Trophic
Protocol 10mls/hr (20kcal/hr)
Primary outcomes
VFDs to 28 days
Secondary end points
GI intolerance
60 day mortality
New infections
Daily % of goal feeding
Organ failure free days
Results
1000 patients
Primary endpoint
No significance difference
14.9 VFDs vs 15
Secondary endpoints
None
Except GI intolerance
Regurg .4 vs .7 %
Vomiting 1.7 vs 2.2%
Elevated GRVs 2.2% vs 4.9% (>400mls
Conclusion
Modest differences in calorie provision for well-nourished patients during the first week of ALI/ARDS does not appear to affect patient outcome in the ICU.
Reduced-calorie feedings may reduce perceived GI intolerance and decrease administration of prokinetic and anti-diarrheal medications.
What doesn’t it tell us
BMI 30, these patients were well nurished
AGE 50 these pts were young
Severe malnutrition were excluded
½ extubated within 6/7 so quite early!
GI difference no clinical ramifications in the study….

EPaNIC
Background
Enteral nutrition fewer complications
Miss Targets however
? Combining Parenteral and Enteral
Risks overfeeding
Liver dysfunction, infection and death
Background
controversy regarding PN
underfeeding with EN alone for up to 7-10 days (American guidelines)
21
supplemental PN (European) within 24-48 hours in patients who are expected to be intolerant to EN within 72 hours of admission.
Canadians conclude there are insufficient therefore maximize the benefits of EN (small bowel feeding tubes and motility agents) are used prior to starting PN.
Proponents of the use of early supplemental PN have focused on data demonstrating that the cumulative energy deficit or caloric debt is associated with adverse clinical outcomes in critically ill patients.
24
Opponents cite the literature demonstrating increased adverse events in patients who receive PN during their ICU stay.

Data from existing randomized trials are inconclusive
Question
PN to prevent caloric deficit
Supplement EN early in disease
Lead to reduced complications
Vs
Withholding PN for 1/52
Methods
PRCT
MC 7 ICU’s
2007-2010
2328 patients delayed PN until day 8
2312 patients received PN within 48hrs
Inclusion Criteria:
Admission to a participating ICU, a nutritional risk screening (NRS) score of 3 or more (on a scale of 1 to 7, with a score ≥3 indicating that the patient was nutritionally at risk) and did not meet any of the exclusion criteria.  
The primary end points
ICU days (for survivors and nonsurvivors)
time to discharge from the ICU.
secondary endpoints
new infections, infection site, duration of antibiotic therapy, inflammation (C-reactive protein), time to vent wean, need for tracheostomy, acute kidney injury, need for and duration of pharmacologic or mechanical hemodynamic support, liver dysfunction, duration of the hospital stay and time to discharge from the hospital, functional status according to the distance walked in 6 minutes and the proportion of patients who were independent in all activities of daily living, and the total incremental health care costs from randomization to hospital discharge!!!!!

The early PN group
D
20 at 45 mL/hr on the day of admission
day 2 the difference between calculated goals and the amount of EN was provided as PN. 
When EN provided at least 80% of nutrition needs PN was held.  
The late PN group
D
5 to meet whatever hydration was not provided by EN
only received PN if enteral feedings were not providing at least 80% of calculated needs by day 8. 
Calorie
corrected ideal body weight
with 24 kcals/kg for females > 60 years
30 kcals/kg for females <  60 years
30 kcals/kg for males > 60 years
36 kcals/kg for males < 60 years.
The primary outcome
median stay in the ICU was 1 day shorter in the late-initiation group than in the early-initiation group. 
There was a statistically significant increase in the likelihood of earlier discharge alive from the ICU (hazard ratio, 1.06; 95% confidence interval [CI], 1.00 to 1.13; P=0.04). 
There were no significant differences in ICU, hospital or 90-day mortality between the groups.
The median duration of hospitalization was 2 days shorter in the late-initiation group
There were significantly fewer patients that developed new infections in the late-initiation initiation group,
Duration of mechanical ventilation and the course of renal-replacement therapy were significantly shorter in the late-initiation group.
Authors conclusions
“Early initiation of PN to supplement insufficient EN during the first week after ICU admission in severely ill patients at risk for malnutrition appears to be inferior to the strategy of withholding PN until day 8 while providing vitamins, trace elements, and minerals. Late parenteral PN was associated with fewer infections, enhanced recovery, and lower health care costs.”
How Do These Results Apply?
Can these result be generalized to all Critical care
early PN group received a large parenteral glucose load (1200 kcal) over the first 48 hours
Van den Berghe study.10 This concept of tight glucose control has subsequently been shown to be ineffective and potentially harmful.
How Do These Results Apply?
ninety percent surgery patients (mostly cardiac),
(58.5%) appeared to be admitted electively.
70% of subjects averaging only a 3-4 day length of stay.
Only moderately severely ill, with an 8% ICU mortality (and 11% hospital mortality).
Almost 75% of study patients had a normal or slightly high BMI between 20 and 30.
Most practitioners would not consider there to be a role for early PN in low mortality risk patients with short ICU stays and a normal BMI
Finally, it is hard to attribute the adverse events seen in this study to early PN, when the majority of study patients received very little exposure to early PN.
(58%) of the patients in the early PN group were exposed only to 1 to 2 days of PN.
Only 25 % late PN patients ever received PN.
It is plausible that the increase in adverse events seen in this study in the early PN group were due to the delivery of a large glucose load in the first 48 hours in the ICU. This may be related to increased insulin resistance in the early phase of acute illness.
While early PN in low risk patients is clearly harmful,
it is not clear whether supplemental PN added to insufficient EN early in the course of high risk patients would also be harmful

EPN

EPaNIC results targeted wide spectrum of patients
Systematic reviews show benefits PN when EN Contraindicated
mortality and infection however these were based on Small Trials
Uncertainty surrounding infection implications

This is reflected in the guidelines Reflected in guidelines within 24-48hrs (European) vs 7-10days (US)

EPN trial

Plan
MCT
RCT, single blinded
Assess effects of PN within 24hrs of ICU admission
With short term relative contraindications to enteral nutrition.
Inclusion
Within 24hrs admission
Expected to stay remain on ITU calendar day after enrolment
Considered to be ineligible for EN as decided by attending
Were not expected to get EN day of or after enrolment
Central access
Exclusions
Moribund
Not expected to survive 24hours
Palliative care
Allergy
Known long term contraindication to EN
Weight <35kg
Height < 140cm
Malnutrition as primary reason for admission
Intervention
Received PN on day 1 and reached goal calories by day 3
Reevaluated day 3 for EN
Control
Standard care
Primary outcome
60 day mortality
Secondary outcomes
Quality of life and physical function measures
Tertiary end points
Infections
Organ failure
Day RRT
Fat loss, muscle loss etc
Results
No difference in 60 day mortality
Statistically difference in quality outcome measures but not enough to meet the pre established definition that would be clinically meaningful
No difference infection rate
1.07 days fewer ventilation early PN
0.43 fewer coagulation failure days early PN
Less Fat and muscle wasting early PN

Conclusions
Early PN reduced mechanical ventilation days
Did not shorten hospital stay of ICU stay
No harm in early PN
Subjective opinion that patient could not have EN
Bias as investigators knew which group ? Earlier extubation
standard group
25% PN <48hrs in >1/3 standard care got PN
? Too similar to detect difference in infection rate
?? Measures of Fat and Muscle loss, skin fold and upper arm measures shown to be poor
I would have liked to have seen europe vs US debate answered.
Allowing larger tx differences
More likely to see outcome differences
Indeed subgroup analysis of 40% standard grp whom remained unfed maybe useful
EN – GI intolerance
PN – Infectious problems ? Reducing
Formulations and central access improvements

Calories
The primary objectives:
To estimate the effect of early (defined as within 36 hrs of the time/date of original admission to the ICU) PN compared with early EN on mortality at 30 days.
To estimate the incremental cost effectiveness of early PN compared with early EN at one year
Secondary objectives: to compare the following:
Duration of specific & overall organ support in the ICU between PN & EN
Infectious & non-infectious complications in the ICU between PN & EN
Duration of ICU & acute hospital length of stay between PN & EN
Mortality at discharge from the ICU & from hospital between PN & EN
Mortality at 90 days & at one year between PN & EN
Nutritional & health-related quality of life at 90 days & at one year between EN & PN
Resource use & costs at 90 days & at one year between PN & EN
Estimated lifetime incremental cost-effectiveness between PN & EN

Inclusion criteria:
Patients who either on, or soon after admission within 36 hours that are:
Adult (18 years or over)
An unplanned admission (including planned admissions becoming unplanned e.g. unexpected postoperative complications)
Expected to receive artificial nutrition for two or more days in the ICU
Not planned to be discharged within three days from the ICU

Results to follow !!!
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