Liesl wandrag controversies in enternal nutrition research [compatibility mode]
Current Controversies in ICU Nutrition Research Liesl Wandrag NIHR Clinical Doctoral Research Fellow Imperial College London
Outline• Route Controversy (EpaNIc trial)ICU nutrition research at Imperial:• Gut hormones• Energy deficit• Metabolism & muscle wasting study
Route: EN vs PN3 Meta-analysis:• Heyland et al, 2003: No mortality difference, EN signiﬁcant ↓ infecƟons.• Gramlich et al, 2004: No mortality difference, EN signiﬁcant ↓ infecƟons.• Simpson & Doig, 2005: PN signif ↓ mortality, also signif infections. (EN delayed by 48h in study). ⇒ Concluded EN route of choice
Guidelines• ESPEN: Early EN but supplement with PN if target not met within 2 days.• ASPEN: No PN if patient not malnourished for first 7 days. Start PN on day 8.
Differences in guidelines usually lead to more…
Differences in guidelines usually lead to more… research!• EPaNIC trial, early PN (within 48h) vs late (after day 8). Casaer et al, 2011 NEJM.• CALORIES trial, multi-centre UK based. Early EN vs early PN for 5 days despite gut function.• TOP-UP trial, Canadian, US, European. Pilot RCT in patients with BMI of <25 or ≥35. Energy and protein via EN or PN.
EPaNIC trial Casaer et al, 2011 NEJM Early PN (within 48h) vs late (after day 8) Research Question• To compare the effect of late PN (ASPEN) versus early PN (ESPEN) on:• Rates of death• Complications• Belgian study in adult ICU patients, not malnourished but nutritionally at risk
InterventionEarly:• EN and 20% glucose• Day 3: PN started if EN failed• When 80% of caloric goal reached via EN, PN was ↓ and then eventually stopped.Late:• EN + 5% glucose in volume equal to PN• If EN not successful after 7 days, PN was started on day 8• Maximum caloric goal: 2880kcal
Results• Similar rates of death: ICU, hospital and 90 days• Nutrition related complications similar• Discharge alive from ICU within 8 days and hypoglycaemia ↑ in Late group• Median ICU LOS 1 day shorter in Late group (Hazard ratio, 1.06, 95% CI 1.00-1.13, P=0.04)• Fewer infections and less days on CRRT in late group
Limitations:• Multi-centre, Belgium ICU’s only• 60% Cardiac ICU patients, not representative of most ICU’s• Tight glycaemic control no longer used internationally• High upper end kcal target: 2880kcal• Dextrose kcal?• Fairly small change in primary outcome: 1 day less on ICU. ICU Intensivists report this is enough change.• ? Fair comparison: 578 patients in Late PN group (started ≥ 8 days) versus 2300 patients in early group (Table 2) is ITT so groups won’t look comparable?
Nutrition Research in our ICU• Changes in appetite related gut hormones in intensive care unit patients: a pilot study. M Nematy, J O’Flynn, L Wandrag, A Brynes, S Brett, M Patterson, M Ghatei, S Bloom, G Frost Critical Care, 2006: Vol 10, Issue 1.
Pattern of plasma ghrelin during ICU stay * p<0.05 ** p<0.001
Pattern of Plasma Peptide Y during ICU stay * p<0.05
Nutrition Research in our ICU• Identifying the factors which influence energy deficit in the adult intensive care unit: A mixed linear model analysis L Wandrag, B.Siddiqui, F. Gordon, J O’Flynn, M. Hickson. Journal of Human Nutrition & Dietetics, 2011.
Energy Deficit: Methodology• N= 56 ICU patients LOS > 3 days for 30 days over a 2 consecutive years• 530 records of feeding days• Collected ICU and nutritional data• Used mixed linear models for longitudinal data• Energy deficit = Energy received – Energy requirement (estimated)
Energy Deficit: ResultsFactors associated with a significant Energy deficit:• Day when feeding initiated (p<0.001)• Fed within 24h (p<0.001)• Whether sedated (p<0.001)Three combined effects found:• Ventilation mode & Aspirate volume (p<0.007)• Fed within 24h & ventilation mode (p<0.001)• Fed within 24h & sedation (p<0.017)
Inflammatory and nutritionalchanges during critical illness with a method of attenuating muscle loss
AimsPart 1:• Understanding the relationship between inflammatory and nutritional markers will help to:• Identify a “nutritional tipping point” where anabolism starts to exceed catabolism.• Identify a simple tool that could be used to identify this anabolic point.Part 2:• Pilot RCT of an Essential Amino Acid (EAA) supplement to minimise muscle mass loss in ICU patients.
Muscle breakdown & potential building strategies on ICU ICU Muscle Mass Breakdown Immobility & Disuse Atrophy Building Age Infection/ Sepsis Steroids, Insulin, Growth Hormone Hypoxia induced inflammation “Novel” (Arginine, Glutamine, Cytokines Creatine, BCAA, EAA ROS/NO HMB, Leucine via mTOR) Hormonal effect (Catecholamines Early mobilisation Glucocorticoids) Electrical Muscle Stimulus Drugs (NMBA(?), sedation, corticosteroids) Mechanical Loading ↓Nutrition (GI problems, ↑GRV, sedation, delays)L Wandrag, unpublished
Interventional Study Pilot RCT: ICU trauma patients 28 daysN=20 Interventional N=20 Control PatientsGroupEAA supplement Standard feed only+ standard feed
Essential Amino Acid supplementation•Branched Chain Amino Acid•EAA•Valine:Leucine:Isoleucine = 1:5:1•Leucine → mTOR → Muscle Protein SynthesisPreliminary work: (EAA)•Elderly patients with sarcopenia (Borsheim et al, ClinicalNutrition’08)•Bed rest + cortisol infusion (Paddon-Jones et al, AJP ’03)
N=32 on ICU for 7 days or more • Muscle loss in this group: Mean loss of 10.4% over 7 days Equates to 1.5% loss per day (L Wandrag, unpublished)
Centre for Altitude, Space & Extreme Environment Medicine• Everest 2007: “Xtreme Everest” (Metabolic and body composition studies)• Everest 2009 (Appetite study)• Alps 2010 (Muscle wasting at altitude pilot study)• Everest 2013: “Xtreme Everest 2” (Muscle wasting at altitude: a Comparative study between Westerners and Sherpa volunteers)