Effect of EPA and HMB on Strength in ICU Patients

The investigators will determine if administration of HMB (hydroxymethylbutyrate) or EPA (eicosapentaenoic acid) will increase diaphragm and limb muscle strength for patients on breathing machines in an intensive care unit. The investigators will first measure the strength of the diaphragm and a limb muscle. Patients will then be randomized to receive either placebo (saline 30 ml every 12 hours via the GI tract, EPA (1000 mg given every 12 hours via the GI tract), or HMB (1500 mg given every 12 hours via the GI tract). Drugs will be given for 7 days; at the end of this time, strength measurements will be repeated.

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), or HMB (enteral HMB). Drugs will be administered for 7 days and measurements of diaphragm strength and tibialis anterior strength will be performed immediately before and immediately after the period of drug administration. The investigators will also perform a chart review and assess ventilator mechanics (respiratory system static compliance and inspiratory airway resistance) at the time of strength assessment. The investigators would expect that mean diaphragm strength and limb muscle strength measurements will be similar for three 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 tibialis anterior strength, 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)
3. continue drugs for 7 days then
4. remeasure magnetic stimulated Pdi twitch and tibialis anterior strength, determine respiratory system compliance, determine airway resistance, and perform a 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 100 patients into the study over a 12 month period (10 patients/month). 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.

• Drug: HMB, hydroxymethylbutyrate
  Hydroxymethylbutyrate will be given as 1500 mg powder dissolved in 30 ml saline given enterally every 12 hours for 7 days
  Other Name: This agent is an over the counter biopharmaceutical
• Drug: EPA, eicosapentaenoic acid
  EPA given as 1000 mg solution in saline (30 ml) administered enterally every 12 hours for 7 days
  Other Name: This is an over the counter biopharmaceutical

• Placebo Comparator: Control, to be given saline solution
  Intervention: This group will be given saline (30 ml every 12 hours) for 7 days
  Interventions:

  • Drug: HMB, hydroxymethylbutyrate
  • Drug: EPA, eicosapentaenoic acid
• Experimental: EPA, eicosapentaenoic acid
  This group will be given 1000 mg EPA every 12 hours for 7 days
  Intervention: Drug: EPA, eicosapentaenoic acid
• Experimental: HMB, hydroxymethylbutyrate
  This arm will be given HMB (1500 mg) every 12 hours for 7 days.
  Intervention: Drug: HMB, hydroxymethylbutyrate

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.