Intensive Nutrition in Critically Ill Adults
Intensive Nutrition in Critically Ill Adults
Despite the widespread use of nutrition therapy, no large scale randomized controlled trials
 (RCTs) have demonstrated positive outcomes with delivery of nutrition therapy early in
 critical illness, with some showing no effect with delayed nutrition or even harm.

 There are several possible reasons for the lack of observed benefit from RCTs to date;
 interventions have been short in duration (usually 3-10 days after intensive care unit (ICU)
 admission), perhaps applied at the incorrect time in regards to the patients metabolism and
 recovery, do not consider the patients nutrition risk, and have not addressed what happens to
 nutrition intake post ICU in critically ill individuals. This may explain why RCTs to date
 have not observed any positive associations with the delivery of nutrition; our focus to date
 may have been on the wrong stage of illness. A future study is thus urgently needed, which
 addresses the deficiencies in current RCTs by optimizing nutrition delivery for the whole
 hospital stay and collecting meaningful clinical, process and outcome data, which will
 potentially inform a larger trial of a similar nature.

 This initial study aims to determine whether optimization of energy using a pre-tested
 supplemental parenteral nutrition (PN) strategy in the Intensive Care Unit (ICU) and an
 intensive nutrition intervention in the post ICU period will deliver more total energy than
 standard nutrition care during hospital admission in a group of critically ill patients with
 at least one organ system failure.
Background:

 Nutrition is a commonly provided therapy in critical illness, but data about effectiveness is
 sparse. Best practice guidelines recommend enteral nutrition (EN), a specialised solution
 delivered into the gastrointestinal tract, as the first line of nutrition therapy. The
 majority of best practice guidelines also recommend delivery of energy and protein amounts
 close to predicted requirements in critical illness over the course of Intensive Care Unit
 (ICU) admission, however the only evidence to support this is from observational data.
 Although recommended that energy and protein requirements be met, and observational data
 suggests this is of benefit, there are practical challenges with the provision of EN.
 International practice surveys report the average energy and protein provided is
 approximately 59% of the patients predicted requirements, for multifactorial reasons. The
 addition of parenteral (intravenous) nutrition has been proposed as a method to provide
 additional energy when EN is insufficient, termed supplemental parenteral nutrition (PN). The
 ability of this strategy to deliver additional energy and protein to patients during critical
 illness has been proven in several feasibility/pilot trials, but the benefit on clinical and
 functional outcomes is unknown.

 Despite observational data suggesting benefit when energy and protein delivery is optimised
 close to requirements, no large scale randomised controlled trials (RCTs) have confirmed
 improved clinical outcomes in critical illness, with some showing no effect with delayed
 nutrition or even harm. There are several possible reasons for the lack of observed benefit
 from RCTs to date; the interventions may have been applied at a time when the patient's
 metabolism is not in a phase of recovery; interventions have been short in duration and;
 studies have not addressed what happens to nutrition intake in the post ICU period of
 hospitalisation in critically ill individuals.

 Aims:

 To determine whether the use of a pre-tested supplemental PN strategy in the ICU and an
 intensive nutrition intervention after discharge to the hospital ward is feasible and will
 deliver more total energy than standard nutrition care over the entire hospital stay, in
 critically ill patients with at least one organ system failure.

 A further aim is to develop a research program that will determine whether optimisation of
 energy to critically ill patients over the entire period of hospitalisation improves
 clinically-meaningful outcomes.

 Hypothesis:

 In critically ill patients with at least one organ failure, the use of a supplemental PN
 strategy in ICU and an intensive nutrition intervention on the hospital ward will lead to an
 increase in daily energy delivery of at least 15% over the entire hospital stay when compared
 to standard care.

 Fifteen percent has been estimated as the minimum acceptable clinical difference between the
 two groups.

 Objectives:

 The major objectives are:

 1. To determine whether the whole hospital nutrition intervention leads to increased
 amounts of total energy delivered over the period of hospital stay

 2. To determine if the whole hospital nutrition intervention is safe in regards to adverse
 effects

 3. To determine if the post-ICU nutrition intervention is practically feasible when applied
 in multiple hospitals, across multiple wards

 4. To measure the clinical outcomes in patients and provide information to assist design of
 a larger randomised controlled trial
Inclusion criteria

 Patients in intensive care who meet all of the following will be eligible:

 1. Admitted to intensive care between 72 hours and 120 hours

 2. Receiving invasive ventilator support

 3. At least 18 years of age

 4. Have central venous access suitable for PN solution administration

 5. Have 1 or more organ system failure (respiratory, cardiovascular or renal) related to
 their acute illness defined as:

 -  PaO2/FiO2 ≤ 300 mmHg

 -  Currently on 1 or more continuous inotrope/vasopressor infusion which were
 started at least 4 hours ago at a minimum dose of:

 1. Noradrenaline ≥ 0.1mcg/kg/min

 2. Adrenaline ≥ 0.1 mcg/kg/min

 3. Any dose of vasopressin

 4. Milrinone > 0.1 mcg/kg/min

 -  Renal dysfunction defined as:

 1. Serum creatinine 2.0-2.9 times baseline OR

 2. Urine output 0.5ml/kg/hr for ≥ 12 hours OR

 3. Currently receiving renal replacement therapy

 -  Currently has an intracranial pressure monitor or ventricular drain in situ

 Exclusion criteria

 Patients will be excluded if:

 -  Both EN and PN cannot be delivered at enrolment (i.e. either an enteral tube or a
 central venous catheter cannot be placed or clinicians feel that EN or PN cannot be
 safely administered due to any other reason)

 -  Currently receiving PN

 -  Clinician believes a specific parenteral formula is indicated

 -  Death is imminent in the next 96 hours

 -  There is a current treatment limitation in place or the patient is unlikely to survive
 to 6 months due to underlying/chronic illness

 -  More than 80% of energy requirements have been satisfactorily delivered via the
 enteral route in the last 24 hours

 -  Dialysis dependent chronic renal failure

 -  Suspected or known pregnancy

 -  Product contraindication

 -  The treating clinician does not believe the study to be in the best interest of the
 patient