ASPEN/SCCM Critical Care Nutrition Guidelines:

What’s New and Updated?Todd W. Rice, MD, MSc

Associate Professor of MedicineVanderbilt University

WiSPEN Annual Fall Symposium 2016September 16, 2016

Objectives1. Briefly outline some of the recommendations

which changed with the newest guidelines

2. Understand role of nutrition risk assessment in providing nutrition to ICU patients

3. Understand the data / studies investigating trophic enteral feeds in critically ill patients

4. Learn recent data on GRV and recommendation to not routinely check GRV in ICU patients

HistoricalTimeline

• 2004-2009 ASPEN SCCM Guidelines• Current 2016 Guidelines Effort

Committee convened Jan 2012 Harmonization process with Canadians over 2 yrs

Lit searches, >750 RCTs entered, DAFs completed Manuscript compiled over one year Jan-Dec 2014

Sections written, GRADE tables constructed, editing Manuscript submission Jan 19, 2015 Review process – 3 Boards 2 Journals Final acceptance June 2015 ASPEN, Sept 2015 SCCM Available online Jan 15, 2016 and in print Feb 15, 2016

Concept of Nutritional Risk

Components: Impaired nutrition status and disease severity

J Kondrup (Curr Opin Clin Nutr Metab Care 2014;17:177)

Jens Kondrup

Dosing of EN

• No EN if low nutritional risk, low dz severity(NRS 2002 ≤ 3 or Nutric Score ≤5) for first week1,2

• Trophic or full feeds appropriate for ALI/ARDS and pts expected to be on MV ≥ 72 hrs3

• Advance to goal as tolerated over 24-48 hrsIf high nutrition risk (NRS 2002 ≥5, Nutric ≥6)1,2

Attempt to provide > 80% goal4

1Kondrup J (Clin Nutr 2002) 2Heyland DK (Clin Nutr 2015) 3Rice T (JAMA 2012) 4Heyland DK (CCM 2011;39:1)

EN Benefits: Achieved at Different Doses?• Non-Nutrition benefits - Lower dose, needed in all patients

Gastrointestinal responsesGut integrity Commensal bacteriaGut/lung axis of inflamm Secretory IgA, GALT tissueMotility/contractility Trophic effect epitheliumAbsorptive capacity Reduced bact virulence

Immune responsesModulate regulatory cells Promote Th-2 >Th-1 lymphocytes Stimulate oral tolerance Maintain MALT tissue Duod colon receptors Modulate adhesion molecules

Metabolic responsesIncretin to insulin sens Reduce hyperglycemia (AGES) Attenuate stress metab Enhance fuel utilization

• Nutrition benefits – Higher dose, needed in high risk patientsProtein, calories Micronutrients, anti-oxidantsMaintain LBM Stimulate protein synthesis

S McClave, R Martindale, T Rice, D Heyland (CCM 2014;42:2600)

Nutritional AssessmentSet Goals of Therapy

• Caloric requirements25-30 Kcal/kg/dPublished predictive equations no more accurateIndirect calorimetry

• Protein requirementsGreater emphasisHigher doses1.2–2.0 gm/kg/d

Fewer restrictions

MJ Allingstrup (Clin Nutr 2012;31:462)1

P Weijs (JPEN 2012;36:60)2

28-Day Mortality2

Survival1

Monitor Tolerance and Adequacy

• GRVs should not be used as part of routine care1

Montejo Multicenter RCT 1 GI Complications %Goal Feeds500cc GRV (n=160) 47.8% * 89% *200cc GRV (n=169) 63.6% 83%

Reignier Multicenter RCT 2 VAP Infect Mortality DeficitNo GRV used (n=227) 16.7% 26.4% 27.8% 319 kcalRoutine GRV (n=222) 15.8% 27.0% 27.5% 509 kcal

1 JC Montejo (Intens Care Med 2010;36:1386) 2 J Reignier (JAMA 2013;309:249)

Formula Selection in the ICU• Start with standard polymeric isotonic formula (most ICU pts)

• Evaluate candidacy for immune-modulating formula (Surg ICU)

• Consider use of specialty formulasGut dysfunction (diarrhea)

Small peptide/MCT semi-elementalPrebiotic soluble fiber > mixed fiber formula

Obesity formulas (Class II and III)

• Cannot recommend certain formulasOrgan-failure formulas

Rarely use hepatic, renal failure Don’t use pulmonary failure

Disease-specific (diabetic)

•EN

SA McClave, B Taylor, RG Martindale (SCCM/ASPEN Guidelines 2015)

Immunonutrition and Anti-Inflammatory • Elective Surgery, SICU – Use arg/fish oil formula 1

Infection ↓ 41% (OR=0.59)Hosp LOS ↓2.38 days

• Crit Care MICU – Don’t recommend arg/FO formulaNo difference mortality, infection, LOS

• ALI/ARDS – No recommendation anti-inflammatory lipid profile formula 2-8

Gadek, Singer, Pontes-Arruda, Grau-CarmonaConstant infusion – All benefit

Rice ARDSNet, StapletonBolus infusion – Harm, no benefit

Van Zanten Meta-PlusConstant infusion - Harm

Elective Surg

Critical ICU

ARDS or ALI

1 JW Drover (JACS 2011;212(3);385) 2 JE Gadek (CCM 1999;27:1409) 3 P Singer (CCM 2006;34:1033) 4 A Pontes-Arruda (CCM 2006;34:2325)5 T Grau-Carmona (Clin Nutr 2011;30:578) 6 T Rice (JAMA 2012;307:795)7 R Stapleton (CCM 2011;39:1655) 8 A Van Zanten (JAMA 2014;312:514)

Adjunctive Therapy• Soluble fiber – Consider routine use in all pts

Use for diarrhea (Consistent 4 trials: 3 better1-3, 1 no different4)• Probiotics – Use for select patient populations

Where RCTs have shown safety and benefit 4Do not use routinely for general ICU pts

• Antioxidants – Use for all pts requiring Specialized Nutr Support Selenium, zinc, copper, Vit C, Vit E

• Enteral glutamine – Do not use1Spapen (Clin Nutr 2001;20:301) 2Heather (Heart Lung 1991;20:409)3Rushdi (Clin Nutr 2004;23:1344) 4Hart (JPEN 1988;12:465)5Zhang (World J Gastro 2010;16:3970)

• McClave, Taylor, Martindale •(SCCM ASPEN 2015 Guidelines)

•(p=0.05)

Use of Parenteral Nutrition

• Differences EN vs PN decreasing• Withhold PN in low risk

If EN not feasible (NRS 2002 ≤ 3 or Nutric Score ≤5)• Initiate exclusive PN ASAP in high risk or severely malnourished pt

if EN not feasible (NRS 2002 ≥5, Nutric Score ≥6)• Add supp PN after 7-10 days if EN < 60% goal high or low risk 1• Maximize efficacy of PN

Use protocols – Do not use parenteral glutamine 2Hypocaloric dosing (80%) first week 3Withhold soy-based lipids first weekModerate glucose control (140-180 mg/dL)Transition off PN when EN provides > 60% goal

1Heiddeger (Lancet 2012 Dec 3) 2 Heyland REDOXS Trial (NEJM2013; 368:1489)3Jiang (Clin Nutrit 2011;30:730)

Organ Failure Subsets

• Organ failure (pulmonary, renal, hepatic)

Use standard polymeric formulasPush protein to 2.0 gm/kg/d (2.5 for dialysis)

• PancreatitisAssess disease severity 1 – Use APACHE II ≥8, RC≥3,

CRP>150 to initiate SNSMild AP – Advance directly to Reg Diet per pt wishesMod-severe AP – Start gastric or jejunal within 24-48 hrs2

Probiotics – Consider use in SAP on EN 3PN – Use after one week if EN not feasible

MOF

1Tenner (Am J Gastr 2013;108:1400) 2Chang (Crit Care 2013;17:R118)3Zhang (World J Gastro 2010;16:3970)

Additional Disease Subsets• Sepsis – (support Surviving Sepsis Campaign recs)

Avoid PN regardless of nutritional risk over first weekUse trophic feeding initially, advance to full after 48 hrsArginine is safe, but don’t use Arg FO formula

Luiking, Deutz (Clinical Science 2015;128:57–67)

ASPEN/SCCM CCN Guidelines:Bundle Statements

JPEN 2016;40(2):159-211

ASPEN/SCCM Crit Care Nutr

Guidelines• Remain flexible

• Management, Rx decisions based on totality of information 1Notion that evidence can be placed in hierarchies is “illusionary”

• ASPEN SCCM GuidelinesRigorous evidence-basedExpert consensus involved (voting, recs with very low QOE)

• Guidelines never take priority over clinical judgmentShould be interpreted in context of institutional settingImportance – Organizes info, provides references, good start

1 M Rawlins [Clin Med 2008;8(6):579-88]

Rawlins

Nutritional Risk

Introduction• Not all patients derive same benefit from nutrition therapy

• Previously well nourished, mild critical illness, short stay ICULittle benefit

• Moderate to severe nutritional riskMore likely to benefitMore likely to be harmed by iatrogenic underfeeding

• Benefit of nutrition Rx depends on:Route Timing InterruptionsDosing Content Mobility

SA McClave, RG Martindale, TW Rice, DK Heyland (CCM 2014:42:2600)

Concept of Nutritional Risk

Components: Impaired nutrition status and disease severity

J Kondrup (Curr Opin Clin Nutr Metab Care 2014;17:177)

Jens Kondrup

Concept of Nutritional Risk: NRS 2002

Kondrup J (Clin Nutr 2002)Age >70 yrs : Add 1 point Score >3 Consider EN/PN

Score >5 High risk

Concept of Nutritional Risk: Nutric Score

Heyland DK (Crit Care 2011;6:1) (Clin Nutr 2015)

Six Factors :

Disease severity:AgeInitial APACHE II scoreInitial SOFA scoreInterleukin-6Comorbidities

Poor nutritional status:Hosp LOS prior to ICU

Low Risk: 0-5 pointsHigh Risk: 6-10 points

Paradigm Shift: Assess Risk-↑Therapy-↑ResponseObservational Studies

1 B Jie (Clin Nutr 2012) 2 DK Heyland (Crit Care 2011;15:R268) (Clin Nutr 2015 Jan)

• NRS-2002 Jie Study1 - High Risk patients (n=120)with NRS Score > 5 Insufficient Pre-Op Sufficient Pre-OpControls (n=77) Sufficient Nutr Rx(n=43)

Overall complications 51% 26% *Nosocomial infection 34% 16% *

No benefit (sufficient vs insufficient ) Low Risk pts (n=965) NRS < 5

• Nutric Score Heyland Study2 (n=1199) (no Interleukin-6 used)

EN Rx Effect onHigh Risk Pts (p<0.0001)

Low Risk (p=NS)

Paradigm Shift: Assess Risk-↑Therapy-↑Response

1 J Starke (Clin Nutrit 2011;30:194)

• Starke Study (NRS Score >3) (n=132)

Energy Protein Complic Antibiot Re-HospIntervent (n=66) 24 kcal/kg* 1.0 gm/kg* 6.0%* 1.5%* 25.7%*Controls (n=66) 18 kcal/kg 0.7 gm/kg 19.7% 12.1% 42.4%

Randomized Controlled Trials

Nutritional Assessment• Additional assessments

Evaluate co-morbiditiesFunction of the GI tractRisk of aspiration

• Avoid useProtein markers (albumin, transferrin, prealbumin)Selective anthropometrics (no AMC, TSF, CHI)

Use height, ABW, UBW, IBW, BMIMarkers of inflammation/infection:

Procalcitonin, IL-1, IL-6,CRP, TNF, Citrulline

• Emerging assessment toolsCT scanMid-thigh US Mourtzakis (Appl Phys Nutr Metab 2008;33:997)

How much should we feed patients?

(especially early in critical illness)

What are the data on trophic feeds?

Quantity of Feeds• Limited data suggest initiating EN

w/in 24 hrs is beneficial (esp trauma) 1

• But those data don’t address quantity of enteral feeding

• If we start enteral feeds within 24-48 hours, do we have to get to target or goal rates as soon as possible?

1. Doig et al. Intensive Care Med. 2009;35(12):2018-2027.

Full calorie Feeds in Critically Ill Patients

Haddad, et al. (Crit Care Med. 2003)1

• Prospective study of 203 critically ill patients• Decreased mortality for patients who received 20-90% of

daily goal calories

Rubinson, et al (Crit Care Med. 2004)2

• 138 MICU patients who were NPO > 96 hrs• Receiving > 25% calories was associated with

significantly lower risk of bloodstream infection (RR = 0.27; 0.11-0.68)

Difficulty: Only an Association- can’t determine cause and effect

1. Haddad SH, et al. Am J Resp Criti Care Med. 2003;31:A832. Rubinson et al. Crit Care Med. 2004;32:350-7.

Feeding VolumesClinical Outcomes: Humans

• Prospective cohort (n=187)

• Feb 1999-Oct 2000• 2 teaching hospitals• ICU LOS ≥ 96 hours• 70% EN, 20% EN/PN • 46% overall mortality

• Tertile II: 9-18 kcal/kg/dKrishnan JA, et al. Chest. 2003; 124:297

*

*

**O.R

.

* P < 0.05

00.20.40.60.8

11.21.41.61.8

<33%33-65%66+%

HormesisBeneficial or stimulatory effect obtained

via the application of an agent at a low

dose, whereas higher doses result in

detrimental effects or toxicity

–Ex: AlcoholGlade MJ, Nutrition: 2001; 17:983

“Trophic” Feeds

The minimum amount of enteral nutrition required for the mucosal benefits is unknown

As little as 10-40% of caloric requirements preserves mucosal structure in dogs1 and pigs 2

Trophic= nourishment or growth• Low volume continuous feeds for the purpose of nourishing the intestinal mucosa

1. Owens L, et al. J of Nutrition. 2002;132:2717-22. 2. Burrin DG, et al. Am J Clin Nutr. 2000;71:16

Trophic vs. Full-Calorie FeedsTrophic Feeds

Pro• Decreased feeding

intolerances/complications• Decreased cost• Less Hassle

Con• Malnutrition (weight loss,

protein loss)• Worse immune function• Loss of muscle strength

(i.e. Diaphragm weakness)

Full-Calorie Feeds Pro

• ? Slow malnutrition• Better immune function• Maintain muscle strength

Con• Increased GI

intolerances/complications• Hyperglycemia• Increased CO2 / azotemia• Increased septic

complications• Fuel for inflammatory “fire”

Rice, et al: Trophic vs. Full Feeds in Critically Ill Mechanically Ventilated Patients Acute Respiratory Failure with expected MV > 2 days Mostly MICU patients – 20% ALI; 18% Pneumonia 40% on vasopressors at enrollment Initiation of feeds on average 1 day after start of MV GRV threshold 300 cc

Trophic (N=98) vs. Full-Calorie (N=102) EN• Trophic feeding group – 10 cc/hr for up to 6 days• Full-Cal feeding group – goal feeds ASAP• Enteral Feeds started within 6 hrs of randomization in both

• More Diarrhea and Elevated GRV in Full Group

Rice TW, et al. Crit Care Med. 2011;39(5):967-974.

Rice, et al: Summary - Main Outcomes

Outcome Trophic Full-Cal P-value

Death at Hosp D/C (%) 22.4 19.6 0.62

VFD to day 28 17.9 ± 10.4 17.8 ± 10.5 0.95

ICU free days to day 28 15.8 ± 9.9 16.5 ± 9.6 0.60

Rice TW, et al. Crit Care Med. 2011;39(5):967-974.

• 1000 mech vent patients with ALI– Mostly Medical – Pneumonia (65%); Sepsis (15%)– 38% on vasopressors at enrollment– GRV threshold 400 cc

• Factorial design with n-3 fatty acid / placebo

• Trophic (N=508) vs. Goal (N=492) for first 6d

• Primary endpoint: Ventilator-free days

Enteral Feeding Timeline

+/-Vent

+/-Vent

ALI Criteria

ALI Criteria

Trophic Feeds20 kcal / hr

Full Feeds

Rampup

Rampup

Full Feeds

Day1 2 3 4 5 6 7 8 …280-1

Specimensampling

Specimensampling

Specimensampling

-2 9 10 11 12 13-3

Enteral Feeding started

6 hrs

EDEN: Enteral Feeds Delivered

* * ** * ** * ****

*P<0.001

EDEN: Percent of Feeding Days with Specific GI Intolerances

0

4

8

12

16

20

Perc

ent o

f On

Stud

y D

ays

Trophic (N=508)Full (N=492)

P=0.05P<0.001

P=0.003P=0.003

eFig 1: NHLBI ARDS Network. JAMA. 2012; 307(8):795.

EDEN: Outcomes

P=0.89

P=0.67

P=0.77

NHLBI ARDS Network. JAMA. 2012; 307(8):795.

Optimal Initial Amount of Enteral Feeding in Critically Ill Patients:

Systematic Review and Meta-Analysis

• Meta-analysis of adult ICU patients

• Initial trophic vs full feeding

• 4 RCTs (N=1540 participants total)

• Primary analyses: Mortality

Choi EY, Park DA, Park J. JPEN. 2015;39(3):291-300.

Optimal Initial Amount of Enteral Feeding in Critically Ill Patients:

Systematic Review and Meta-Analysis• No diff in Mortality (OR 0.95; 0.74-1.20; P=0.65)

• Subgroup analysis:– Trophic >33% of goal: OR 0.61 (0.39-0.97; P=0.04)

• No difference in Hospital or ICU LOS

• Serious GI Intolerance: 23% trophic vs 31% full (OR 0.66; 0.39-1.12; P=0.12)

Choi EY, Park DA, Park J. JPEN. 2015;39(3):291-300.

• 894 critically ill patients– 7 hospitals in Saudia Arabia and Canada– 75% medical, 21% non-op trauma – 96% MV, 55% on pressors

• Randomized, open label trial• 40-60% goal cal + protein vs 70-100% goal kcal

for up to 14 days• Primary Endpoint: 90 day mortality

Arabi YM, et al. NEJM. 2015;372(25):2398-2408.

Arabi YM, et al. NEJM. 2015;372(25):2398-2408.

Arabi YM, et al. NEJM. 2015;372(25):2398-2408.

Arabi YM, et al. NEJM. 2015;372(25):2398-2408.

Arabi YM, et al. NEJM. 2015;372(25):2398-2408.

Arabi YM, et al. NEJM. 2015;372(25):2398-2408.

• Long-term (to 12 mos) follow-up of EDEN pts– Two studies:

• Quality of life and mental health from all centers• Physical and cognitive function from subset of 5 ctrs

• A priori established endpoints for the trial

Needham DM, et al. BMJ. 2013;346:f1532.Needham DM, et al. AJRCCM. 2013;188(5):567-576.

Needham DM, et al. BMJ. 2013;346:f1532

Needham DM, et al. BMJ. 2013;346:f1532

Needham DM, et al. AJRCCM. 2013;188(5):567-576.

Needham DM, et al. AJRCCM. 2013;188(5):567-576.

Gastric Residual Volumes

GRV: Evidence McClave (JPEN 1992)1: 20 normals, 10 ICU pts

• GRV did not correlate with exam or X-ray findings• 15% of normals, 50% of ICU patients: GRV> 150 cc• No normals, 30% ICU patients: GRV > 200 cc

Spain (JPEN 1999)2: 75 ICU pts• 26% had one GRV > 200 cc• Only 4 pts (5.3%) had more than 1 GRV > 200 cc• 80% of pts with GRV > 200cc never had second GRV > 200cc

Mentec (CCM 2002)3: 153 med/surg ICU pts• 21/40 patients who vomited never had GRV > 150 cc• 6/19 pts vomited prior to having GRV > 150 cc• GRV > 500cc correlated with vomiting, but not GRV >150cc

1. McClave SA, et al. JPEN. 1992;16:99-105. 2. Spain DA, et al. JPEN. 1999;23:288-92.3. Mentec H, et al. Crit Care Med. 2001;29:1955-61.

GRV: Evidence Pinilla (JPEN 2001)1: GRV threshold of 250 cc vs. 150 cc

• GRV > 150cc (53%) vs. GRV > 250cc (23%) (P=0.005)• No difference in vomiting (7% vs. 6% in lower GRV)• Pts w/ higher GRV trended to reach goal rates faster

McClave (Crit Care Med 2005)2: GRV threshold of 200 cc vs. 400 cc• Calorimetric microspheres with fluorometry and blue food

coloring to assess aspiration / regurgitation• No difference in aspiration (21.6% vs. 22.6%) or regurg (35%

vs. 28%)

1. Pinilla JC, et al. JPEN. 2001;25:81-6. 2. McClave SA, et al. Crit Care Med. 2005;33:324-30.

• 449 mechanically ventilated patients– Ventilated > 2 days– EN w/in 36 hrs of MV– 9 French ICUs

• Randomized, non-inferiority design

• GRV > 250 mL q6h vs no GRV measurement

• Primary endpoint: % pts with VAPReignier J, et al. JAMA. 2013; 309(3):249-56.

Reignier J, et al. JAMA. 2013; 309(3):249-56.

Reignier J, et al. JAMA. 2013; 309(3):249-56.

Reignier J, et al. JAMA. 2013; 309(3):249-56.

Gastric Residual VolumesRecommendations:

Do not routinely measure GRVs in ICU patients Do not hold feeds for a single, elevated GRV Use GRVs in conjunction with other clinical

parameters (abd pain, cramping, distention, nausea, vomiting) to assess tolerance

Do not stop feeds for GRVs < 300-500 cc unless associated with other clinical signs

Pro-kinetic agents/post-pyloric tubes may be tried if elevated GRV

McClave SA, Snider HL. JPEN. 2002;26 (6 suppl):S43-8.

Continuing Education #1

• Which of the following is the WORST assessment of nutritional risk in critically ill patients?

A. Nutric Score

B. Serum Albumin

C. Nutritional Risk Screening (NRS) Score

D. Paraspinal Muscle mass

Continuing Education #2• Which of the following statements about targeted

caloric goals in critically ill patients is true?A. Targeting full calorie enteral feeding in the first few ICU days

is beneficial in all critically ill patients

B. Full calorie enteral feeds early in the course of critical illness results in improved physical and cognitive function at 12 months

C. Initial trophic enteral feedings resulted in similar short and long-term outcomes in patients with ARDS as initial full calorie enteral feeds

D. Initial trophic enteral feedings result in similar outcomes in patients who are malnourished

Continuing Education #3• Use of which of the following Gastric Residual Volumes

routinely in the care of critically ill patients has been shown to reduce VAP and decrease time on mechanical ventilation?A. 150 mL

B. 200 mL

C. 250 mL

D. 400 mL

E. None

Summary

• Numerous changes to the guidelines, but still use guidelines as guidelines and not as absolute dictum

• Individualize enteral (and parenteral) nutrition prescription according to nutritional risk assessment

• Initial trophic feeds are probably okay in many critically ill patients – but initiate early

• Routine, scheduled GRV checks probably not improving safety or outcomes

QUESTIONS???