Trial of Supplemental Parenteral Nutrition in Under and Over Weight Critically Ill Patients (TOP-UP)

Background

Critically ill patients are often hypermetabolic and can rapidly become nutritionally
compromised. Malnutrition is prevalent in these patients and has been associated with
increased morbidity and mortality. Standard nutrition therapy, i.e. provision of calories,
protein and other nutrients consists primarily of enteral nutrition (via a feeding tube into
the gastrointestinal tract), parenteral nutrition (via an intravenous tube into the blood),
or occasionally a combination of both.

However, the provision of nutrition is sub-optimal and the majority of critically-ill
patients do not meet nutritional requirements. Recent studies report that average energy
intakes of critically ill patients are only 49% to 70% of calculated requirements. Despite
repeated, sustained efforts over the past few years, the investigators have not
significantly improved the amount of calories delivered via the enteral route. This leads us
to conclude that if the investigators are to be successful at increasing the provision of
calories and protein to patients at-risk, the investigators will have to supplement the
calories via the parenteral route.

Critically ill patients that are at extremes of weight are at a higher nutritional risk and
have higher mortality rates. A recent International multicenter observational study of 2772
ICU patients from 165 ICUs showed a significant inverse linear relationship between the odds
of mortality and total daily calories received. Increased amounts of calories was most
important for the BMI < 20 group followed by the BMI 20 -< 25 group and BMI > 35 group with
no benefit of increased calorie intake for patients in the BMI 25 -< 35 group. Feeding an
additional 1000 kcals almost halved the odds of 60-day mortality in patients with a BMI < 25
or > 35. Similar results were observed for feeding an additional 30 grams of protein per
day.

Thus, a prospective randomized trial is warranted to confirm our hypothesis that in patients
with a BMI of < 25 and those with a BMI > 35 increasing the provision of more energy and
protein can impact clinical outcomes. The results of this study will serve to answer some
fundamental questions with regards to impact of amount of energy and protein delivered to
nutritional at-risk ICU patients and will inform current practice.

Study Intervention:

Patients will be randomized to one of 2 interventions: enteral nutrition alone or enteral
nutrition plus parenteral nutrition (supplemental PN group).

Inclusion Criteria:

- Critically ill adult patient (≥ 18 years) admitted to ICU

- Has acute respiratory failure (ARF) i.e. expected to remain mechanically ventilated
for more than 48 hours

- Expected ICU dependency of 5 or more days

- On or expected to initiate enteral nutrition within 7 days of ICU admission

- BMI <25 or ≥ 35 based on pre-ICU actual or estimated dry weight

Exclusion Criteria:

- >72 hours from admission to ICU to time of consent

- Not expected to survive an additional 48 hrs from screening evaluation

- A lack of commitment to full aggressive care (anticipated withholding or withdrawing
treatments in the first week but isolated DNR acceptable)

- Patients already receiving PN at screening

- Absence of All gastrointestinal risk factors, defined as:

1. High Apache II Score (>20)

2. On more than 1 vasopressor or increasing doses or vasopressors

3. Receiving continuous infusion of narcotics

4. High nasogastric/orogastric output (>500 mL over 24 hours)

5. Recent surgery involving esophagus, stomach, or small bowel OR peritoneal
contamination with bowel contents

6. Pancreatitis

7. Multiple gastrointestinal investigations

8. Recent history of diarrhea/C. Difficile

9. Surgical patients with future surgeries planned

10. Ruptured or dissected abdominal aortic aneurysm

- Patients admitted with diabetic ketoacidosis or non-ketotic hyperosmolar coma

- Pregnant or lactating patients

- Patients with clinical fulminant hepatic failure

- Patients with Cirrhosis Child's Class C Liver Disease (except those on a transplant
list or transplantable)

- Dedicated port of central line not available

- Known allergy to study nutrients (soy, eggs or olive products)

- Enrolment in another industry sponsored ICU intervention study