Journal club on NEJM article on trial of route of nutrition in critically ill

1. Presenter: Dr. Venugopalan.G
Preceptor: Dr. Navinath.M
Department of Geriatric Medicine, AIIMS

3. Critical illness is typically associated with a catabolic
stress state in which patients commonly demonstrate a
systemic inflammatory response
Proper nutrition is mandatory to…
Preserve lean body mass,
Maintain immune function, and
Avert metabolic complications

4. EN is the preferred route of feeding over parenteral
nutrition (PN) for the critically ill patient who requires
nutrition support therapy (Grade B)
EN started early within the first 24–48 hours following
admission (Grade C)
Robert G. Martindale et al. Crit Care Med 2009 Vol. 37, No. 5

5. If there is evidence of PEM at admission and EN is not
feasible, initiate PN as soon as possible (Grade C)
PN should be delayed for 7 days for patients without
evidence of PEM and EN not feasible (Grade E)
PN provided for a duration of 5–7 days would be
expected to have no outcome effect and may result in
increased risk.
Robert G. Martindale et al. Crit Care Med 2009 Vol. 37, No. 5

6. Can GIT be
used safely and
effectively?
Support for >6
weeks is
required?
Tube
Enterostomy
Nasoenteric
Nasoduodenal Nasogastric
Parenteral
Nutrition
Central Line PICC
Yes
Yes
No
No

7. Resting energy expenditure:
REE (kcal/min) = (3.6*VO2)+(1.1*VCO2)-16
REE (kcal/day) = (25 to 30) * Body weight (Kg)
Indirect calorimetry vs Predictive equation
> 200 predictive equations
Nitrogen Balance= Nitrogen Intake – Nitrogen Excretion
Nitrogen Balance= Protein Intake/6.25 – [UUN+(4-6)]
The ICU book-4th ed. Paul L. Marino

8. Daily energy should be provided by non-protein calories
Protein intake is for essential enzymatic and structural
protein
Goal for Positive N2 balance of 4 to 6 gm
Calories from non-nutritional source should be
considered along with supplement (e.g. propofol in 10%
lipid emulsion gives 1.1 kcal/mL)
Carbohydrate 70% of REE 3.7 kcal/g
Lipid 30% of REE 9.1 kcal/g
Protein 1.2 to 1.6 g/kg --- (4.0 kcal/g)

9. Standard Enteral
Nutrition
AIIMS Feed
(Special Feed)
Calories 1 kcal/ml 1.4 kcal/ml
Protein 20 g/500 ml 30 g/500 ml (0.06 g/ml)
Feed Contents
Special Feed Milk + Corn starch + High
Protein + oil + egg + sugar
Coma feed Only calories, no protein
Diabetic feed Less carbs
Renal feed Less protein (38.75/ 1 L)
Curd feed
Dal feed
Half and full strength milk
feed

10. Start within 24 to 48 hours
Gastric feeding: begin at target rate
Small bowel feed: start low (10 – 20 ml/hr) and gradually
increase to target rate in 4 to 6 hours
Absolute Contraindications:
Complete bowel obstruction
Bowel ischemia
Ileus
Circulatory shock with high dose vasopressors

11. 1. Calculate REE (kcal/day) and protein requirement(1.2
to 1.6 g/kg/day)
2. Select feeding formula (1 kcal/mL to 1.5 kcal/mL)
3. Infusion rate= feeding volume/ feeding time
Feeding volume= Calorie required(kcal/day)
Feeding formula(kcal/mL)
4. Adjust protein intake
Start at rate of 10-30 ml/hr infusion for first few
days and titrate to reach target infusion rate
within a week
The ICU book-4th ed. Paul L. Marino

12. Head of the bed should be elevated 30°– 45° (Grade C).
For high-risk patients/ intolerant to gastric feeding, delivery of
EN should be continuous infusion (Grade D).
Agents promoting motility (prokinetics, narcotic antagonists)
initiated where clinically feasible (Grade C).
Post-pyloric tube placement (Grade C).
Chlorhexidine mouthwash bid to reduce risk of VAP (Grade C)
Robert G. Martindale et al. Crit Care Med 2009 Vol. 37, No. 5

13. No benefits in mortality or complications for routine
use of…
Arginine
Glutamine
Omega 3 fatty acids
Antioxidants
Fibres
Prokinetics

14. 1. Calculate REE
2. Standard mixture of 10% amino acids (A10)-500 ml
and 50% Dextrose (D50)-500 ml
Calculate Volume of A10D50 and Infusioin rate
3. Determine Non-protein calories and correct deficit
with lipid emulsion
Final TPN order for 60 kg male will look like this:
• A10D50 to run at 80 ml/hr
• 10% intralipid, 150 ml over 3 hours
• Add standard electrolytes, multivitamins and
trace elements
• Dedicated line, infusion pump, in-line filters
The ICU book-4th ed. Paul L. Marino

15. Total volume 1000 ml
Total Energy (kcal) 1022
Non protein energy 9kcal) 862
Dextrose (g) 120
Lipids (g) 40
Nitrogen (g) 5.4
Aminoacids (g) 40
Osmolarity 1158

16. Catheter related:
CLABSI, misdirection, thrombosis, pneumothorax..…
Metabolic:
Hyperglycemia, hypophosphatemia, hypokalemia
Hypercapnia, hyperosmolar dehydration
Metabolic acidosis
Hepatic steatosis, cholestasis
Bowel ischemia

17. Early initiation of parenteral nutrition (European Guidelines)-
initiated within 48 hours after ICU admission - In 2312
patients
Late initiation of parenteral nutrition (ASPEN and Canadian
guidelines)- not initiated before day 8- In 2328 patients
Casaer MP et al. NEJM 2011

18. Late initiation of parenteral nutrition was associated with faster recovery and fewer
complications, as compared with early initiation
Casaer MP et al. NEJM 2011

19. Heidegger CP et al. Lancet 2013;381:385-93

20. Heidegger CP et al. Lancet 2013;381:385-93

21. Heidegger CP et al. Lancet 2013;381:385-93
Individually optimised energy supplementation with SPN starting 4 days after ICU
admission could reduce nosocomial infections and should be considered as a
strategy to improve clinical outcome for whom EN is insufficient

22. Early PN (started within 24 hours) and to achieve target by
day 3 vs standard nutrition (according to ICU protocols)
686 to standard care, 686 to early PN

23. The provision of early PN to critically ill adults with relative contraindications to early EN,
compared with standard care, did not result in a difference in day-60 mortality.
The early PN strategy resulted in significantly fewer days of invasive ventilation but not
significantly shorter ICU or hospital stays

24. Nutrition in the Acute Phase of Critical Illness. N Engl J Med 2014;370:1227-36

25. No consensus on timing, route, duration and type of
nutrition supplementation in critically ill
Meta analysis have varying results and affected by
small sample size and inconsistent study methods
Need of time to know whether Parenteral nutrition
(PN) is superior to enteral nutrition

27. Open
Multi-center (33 ICU)
Parallel-group
Randomized controlled trial

28. North West London Research Ethics Committee
approved the study protocol
Grant from the Health Technology Assessment
Program of the United Kingdom National Institute for
Health Research (project no. 07/52/03)

29. At least 18 years of age
Unplanned admission
Expected to require nutritional support for at least 2
days, as determined by a clinician within 36 hours after
an unplanned ICU admission
Not expected discharge in at least 3 days

30. Could not be fed through either PN or EN/ contraindications
Received nutritional support in the past 7 days
Had a gastrostomy/PEG or jejunostomy in situ
Pregnant
Not expected to be in the UK for next 6 months
Previously randomised into CALORIES
In ICU for > 36 hours
Patients admitted to ICU for treatment of thermal injury/ palliative care

31. Nutrition initiated as soon as possible after
randomization (within 36 hours)
Used exclusively for 5 days (120hours) or until
transition to exclusive oral feeding, discharge from
ICU, or death
Oral feeding could be initiated if clinically indicated
during the intervention period

32. Energy targets : 25 kcal/kg/day
Goal of reaching the target within 48 to 72 hours
Protein or AA targets were set according to local practice.
Glycemic control: <180 mg/dl
Enteral Nutrition according to local hospital supply
Total volume of EN and PN adjusted according to fluid
status

33. Calories from non-nutritional sources (e.g., Propofol)
were included in calculation.
All other treatments and nutritional support were
provided according to local practice guidelines
Constituent of PN Per standard bag Per ml
Energy (total kcal) 1365 – 2540 0.9 – 1.1
Nitrogen (g) 7.2 – 16.0 0.005 – 0.007

36. Primary outcome: (at 30 days)
All-cause mortality at 30 days.
Secondary outcomes: (at 90 days)
Duration of organ support,
Treated infectious and non infectious complications,
Length of stay in the ICU and hospital,
Duration of survival, and
Mortality at the time of discharge from the ICU and from the
hospital, at 90 days, and at 1 year.
Adverse events were monitored for 30 days

39. Estimated to enrol 2400 patients
With a power of 90% to detect a 20% relative risk
reduction (absolute risk reduction, 6.4 percentage
points) in the parenteral group
With a two sided alpha level of 0.05
Assuming that 2% of patients would cross over to the other
group or have a protocol violation and that 2% of patients
would be lost to follow-up or withdraw from the study

40. All analyses using the intention-to-treat principle on the
basis of a pre specified statistical analysis plan
Fisher’s exact test to compare b/w group difference in
primary outcome
For secondary outcomes: Fisher’s exact test, t-test,
Wilcoxon rank-sum (Mann-Whitney) test were used

42. Primary outcome: 33.1 % in PN vs 34.2% in EN
(p=0.57)
No significant difference in infectious complications,
90 day mortality, mechanical ventilation
Hypoglycemia: 3.7% in PN vs 6.2% in EN (p=0.006)
Vomiting: 8.4% in PN vs 16.2% in EN (p<0.001)

46. No significant difference in outcome between the two
study groups
No significant difference in effective nutritional
delivery, since patients in the two groups did not
receive the caloric targets

47. Suggest that early nutritional support through the
parenteral route is neither more harmful nor more
beneficial than such support through the enteral route

48. Start EN as early as possible
Use PN only when EN is contraindicated
Try to achieve target energy level within pre-specified
time (according to local ICU policy)
Individualize treatment choices