IFAD 2013

1. Nutrition after an ePanic attack
IFAD November 2013
Alexander Wilmer, M.D., Ph.D.
Medical Intensive Care
University Hospital Gasthuisberg
KU Leuven
I have no relevant disclosures for this talk

2. Casaer M et al. N Engl J Med 2011; 365: 506-517

3. EN
Day 2: start EN
Day 8
100 % of prescribed cal
Day 1+2 : Gluc 20%
Day 3: start PN
PN
Early PN group
n=2312
EN
Day 2: start EN
Day 8Day 1-7 : Gluc 5%
Late PN group
n=2328
Casaer M et al. N Engl J Med 2011; 365: 506-517

4. Total
kcal/d
1576
(d1-7)
594
(d1-7)
Average
kcal/d
0
200
400
600
800
1000
1200
1400
1600
1800
2000
d1 d2 d3 d4 d5 d6 d7 d8
EPANIC
EN+PN
EPANIC
EN
EPaNIC: Early Parenteral completing Enteral nutrition in adult
critically ill patients: calories administered

5. EPaNIC : primary endpoints
Late PN Early PN
Discharged alive within 8 days 75.2 % 71.7 % P = 0.007
ICU stay (days) median (IQR) 3 (2 – 7) 4 (2 – 9) P = 0.02
Time to alive discharge from ICU
Hazard ratio (95%CI)
Adjusted cox proportional hazard analysis
1.063 (1.002 – 1.128) P = 0.04
Outcomes adjusted for prespecified risk factors: type and severity of illness, age, BMI, NRS-
score.
Time to alive ICU-discharge: patient who died were censored at a time point after the last
surviving patient had been discharged

6. AJRCCM, 2013

7. Kaplan-Meier: safety analysis:
90 day survival
Casaer M et al. N Engl J Med 2011; 365: 506-517

8. EPaNIC : other results
Late PN Early PN
Patients with new ICU infection 22.8 % 26.2 % P = 0.008
Airway or lung 16.4 % 19.3 % P = 0.009
Bloodstream 6.1 % 7.5 % P = 0.05
Wound 2.7 % 4.2 % P = 0.006
Duration of hospital stay
days, median (IQR)
14 (9 – 27) 16 (9 – 29) P =0.004
6 Minutes Walking Distance (m)
N tested
277 (210 – 345)
624
283 (205 – 336)
603
P = 0.69
Casaer M et al. N Engl J Med 2011; 365: 506-517

9. Controversial guidelines
ESPEN 2009
“All patients who are not expected to be on normal nutrition
within 3 days should receive PN within 24–48h if EN is
contraindicated or if they cannot tolerate EN” (Grade C)
SCCM 2009
“If early EN is not feasible or available the first 7 days
following admission to the ICU, no nutrition support therapy
should be provided” (Grade C)

10. Relevant RCTs on nutrition after the
“ePanic attack”
for hypocaloric versus normocaloric feeding
• EDEN trial (Rice et al. JAMA 2012)
• SPN trial (Heidegger et al. Lancet 2013)
• Early PN Trial (Doig et al. JAMA 2013)

11. # screened # randomised intervention caloric target
EPANIC 8703 4640
EN+EPN vs
EN+ LPN
20-30 kcal/kg
EDEN 7968 1000 Trophic vs FEF
25-30 kcal/kg
SPN 2556 305 EN vs EN+PN
d1-d3=25-30 kcal/kg
D3 if < 60% target = IC
Early PN ? 1372
PN < 24 hrs vs
standard care
Harris-Benedict

12. Trophic feeding group:
10-20 kcal/h first 272 patients,
then 20 kcal/h until
d6 if still on on MV

14. Early parenteral nutrition in critically ill patients
with short-term relative contraindications to early
enteral nutrition
• Standard care (n=682)
after 1.98 d 199 (=29.2%) received EN
after 1.99 d 186 (=27,3%) received PN
after 5,58 d 19 (= 2,8%) received PN+EN
278 (=40.8%) received neither PN nor EN during 3,72 d
on average in the SC group: unfed for 2.8 d, 2.9 d of PN and 4 d of EN
• Early PN (n=681)

15. Primary endpoint Patients Age Weight APACHE II
EPANIC* Time to discharge
alive from ICU
Mixed
(61% post cardiac surg)
64 75-76 23
EDEN VF days on d28 ALI 52 86-87 -
SPN Infections d9 - 28 Mixed 61 75-77 22-23
Early PN 60d mortality Mixed
(60 % GI)
68 - 21
* 1822 patients did not have cardiac surgery. 1828 patients were still in the ICU on d5 and
1391 on day 7. 1523 patients had APACHE II > 26.

16. How many kcal? EPANIC study
Blue = EN+PN
Red = EN only
EN+PN
1576
(d1-7)
EN
594
(d1-7)
Average
kcal/d

17. How many kcal? EDEN study
1300 (d1-6)
400 (d1-6)
Average
kcal/d
Average
kcal/d

18. How many kcal? SPN study
+/- 1400 (d1-8)
+/- 1150 (d1-8)
SPN: Average
kcal/d
EN: Average
kcal/d

19. How many kcal? Early PN trial

20. Low vs
high cal
ICU
mortality
(%)
Hospital
mortality
(%)
ICU LOS
(in d)
days
MV
Infections
(%)
EPANIC 6,1 / 6,3 10,4 / 10,9 3 / 4* 2 / 2* 22,8 / 26,2*
EDEN 23,2 / 22,2
(60 d mortality)
idem idem idem
SPN 7 / 5 18 / 13 13 / 13 6,9 / 2,5 38 / 27*
Early PN
22,8 / 21,5
(60 d mortality) 9,3 / 8,6
7,73 /
7,26*
11,4 / 10,9
Needham DM et al. BMJ 2013

21. 52 43 48 71

22. Subgroup : surgical contra-indication for EN
Late PN
N= 261
Early PN
N= 256
Enteral intake day 7 (kcal/day)
Median (IQR)
0 (0-263) 0 (0-142) P = 0.54
Patients with new ICU infection 29,9% 40,2% P = 0.01
Discharged alive from ICU <= 8 days
Odds ratio (95%CI)
1.749 (1,141-2,683) + 75%
Early PN trial: any major infection: 10,9 vs 11,4

23. Late PN
Cumulative proportion of alive ICU discharge since time
of admission according to % caloric target on day 5
0-30% 30-50 50-70 70-90 >90%
669 247 378 330 92
Total population = 1716
Casaer M et al. Am J Respir Crit Care Med Vol 187, Iss. 3, pp 247–255, Feb 1, 2013

24. Hermans G et al: Effect of tolerating macronutrient deficit on the development of ICU-acquired weakness:
a subanalysis of the EPaNIC trial. Lancet/respiratory 2013 (n=600)
On day 9
Late PN: 34 % weakness
Early PN: 43% weakness

25. Nutrition after an ePanic attack: conclusions
Best evidence indicates that – for the first week of ICU stay – most
patients at risk for malnutrition do not benefit from the currently
recommended caloric goals
Best evidence indicates that tolerating macronutrient deficit
decreases morbidity