Effect of EPA and HMB on Strength in ICU Patients

Objectives. There is a single objective for this study, namely, to determine if early
administration of either EPA or HMB can prevent or reverse the development of respiratory
muscle weakness in critically ill, mechanically ventilated patients. The investigators plan
to randomize patients accepted into this protocol to administration of either a control
(saline enteral control solution), EPA administration (enteral EPA), HMB (enteral HMB), or a
combination of EPA and HMB. Drugs will be administered for 10 days and measurements of
diaphragm and quadriceps strength and size will be performed immediately before (day 0) and
immediately after (day 11) the period of drug administration. A third set of measurements
(diaphragm and quadriceps strength and size) will be performed on day 21. Vastus lateralis
muscle biopsies will also be taken on days 0 and 11; no biopsy will be performed for day 21
assessments. The investigators will also perform a chart review and assess ventilator
mechanics (respiratory system static compliance and inspiratory airway resistance) at the
time of the initial strength assessment. Patient outcomes (time on mechanical ventilation and
mortality) will also be recorded. The investigators would expect that mean diaphragm strength
and limb muscle strength measurements will be similar for four groups immediately before
initiation of drug administration. The hypothesis will be supported if, post drug
administration, diaphragm and limb muscle strength are higher for patients receiving EPA
and/or HMB than the control group receiving no active drug.

Study Design.

The basic study design is to:

1. measure magnetic stimulated Pdi twitch and quadriceps strength and size, obtain a muscle
biopsy from the vastus lateralis of the quadriceps, determine respiratory system
compliance, determine airway resistance, and perform a chart review,

2. randomize patients to treatment with either: control solutions (30 ml of enteral saline
solution every 12 hours), EPA (30 ml of enteral solution containing 1000 mg of EPA every
12 hours), HMB (30 ml of enteral solution containing 1500 mg HMB every 12 hours) or both
EPA (30 ml of enteral solution containing 1000 mg of EPA every 12 hours) and HMB (30 ml
of enteral solution containing 1500 mg HMB every 12 hours).

3. continue drugs for 10 days then

4. on day 11 remeasure magnetic stimulated Pdi twitch and quadriceps strength, repeat
measurements of diaphragm and quadriceps size (i.e. thickness), repeat the vastus
lateralis muscle biopsy, determine respiratory system compliance, determine airway
resistance, and perform a chart review.

5. on day 21 remeasure magnetic stimulated Pdi twitch and quadriceps strength, and repeat
measurements of diaphragm and quadriceps size (i.e. thickness), and perform another
chart review.

For each chart review the investigators will obtain the following information: age, sex,
diagnoses, reason for institution of mechanical ventilation, vital signs, bedside parameters
of mechanical ventilation use (including mode of ventilation, duration of ventilation, level
of oxygen, breath volume and rate, % triggered breaths), most recent arterial blood gas
values, chest radiograph readings, recorded assessments of limb muscle strength and mental
status.

Study Population. Adult patients requiring mechanical ventilation for more than 24 hours in
one of the University of Kentucky adult ICU's will be asked to participate. Patients will be
excluded if: (a) the physician caring for the patient determines that the patient is too
unstable to tolerate these measurements, (b) if the patient requires high dose pressors (more
than 15 mcg/min of norepinephrine or more than 15 mg/kg/min of dopamine), (c) if the patient
requires more than 80% FiO2 or more than 15 cm H2O of PEEP, (d) if the patient has a cardiac
pacemaker or implanted defibrillator, (e) if the patient has received neuromuscular blocking
agents within the 48 hours preceding testing or has a known preexisting muscular disease, (f)
if the patient has a recent history of variceal bleeding, and (g) if the patient is
excessively sedated or mentally obtunded as judged by an inability to follow verbal commands.
The investigators will also not study pregnant females, prisoners, or institutionalized
decisionally impaired patients.

The goals are to recruit 80 patients into the study over a 24 month period (5 patients/month,
20 patients per experimental group). The investigators will study patients regardless of sex,
race, or adult age. It is hoped that sufficient minorities and women will be studied so that
the subject population is representative of the general patient population, but the
investigators will be somewhat constrained by the numbers of available patients and the day
to day makeup of the patient population in the UK ICU's. Inclusion of minorities and women
will make the study results more generally applicable.

Inclusion Criteria:

- Adult patients requiring mechanical ventilation for more than 24 hours in one of the
University of Kentucky adult ICU's

Exclusion Criteria:

- The physician caring for the patient determines that the patient is too unstable to
tolerate these measurements,

- If the patient requires high dose pressors (more than 15 mcg/min of norepinephrine or
more than 15 mg/kg/min of dopamine),

- If the patient requires more than 80% FiO2 or more than 15 cm H2O of PEEP,

- If the patient has a cardiac pacemaker or implanted defibrillator,

- If the patient has received neuromuscular blocking agents within the 48 hours
preceding testing or has a known preexisting muscular disease,

- If the patient has a recent history of variceal bleeding,

- If the patient is excessively sedated or mentally obtunded as judged by an inability
to follow verbal commands.

- We will not study pregnant females, prisoners, or institutionalized decisionally
impaired patients.