New Onset Weakness in Critically Ill Patients and the Risk of Death and Recurrent ICU Admission

Study Overview: This study will enroll patients requiring prolonged mechanical ventilation
to identify the presence of newly acquired weakness in the ICU. Eligible patients are those
that require the use of mechanical ventilation for greater than or equal to five days,
because this is a significant risk factor for weakness. These patients will be enrolled and
followed to detect the true relative mortality between weak and strong patients in the ICU.

To identify patients with relevant and significant weakness, this study identifies weakness
in patients who survive and return to a state of normal consciousness. As such these
patients, once enrolled, need to be screened daily for awakening. Once awake an assessment
of peripheral muscle strength will be performed with a standard bedside neuromuscular exam
and handgrip manometry.

Initial Data Collection: After consent, demographic information and risk factors for
neuromuscular disease for each patient will be recorded. Blood pressure values and other
data regarding the subjects' severity of illness will be collected. Any previous use of
medicines during the current hospitalization that are associated with the development of
weakness will be collected as well. Also any previous history of other chronic disease known
to be associated with weakness (e.g. diabetes, immune system deficiency, end-stage liver
disease or kidney disease) will be noted.

Screen for awakening (SA):Once daily the patient will be assessed for awakening using a
standard (RASS). When the patient awake and able to follow commands they will be assessed
for muscle strength exam.

Medical Research Council Strength Exam:The examiner will perform their exam on the first day
that the patient is eligible by RASS screening. This same examiner will return at least
twenty hours, but no more than forty-eight hours later to perform a repeat exam. The exam
will be based on the Medical Research Council standard exam. Functions assessed:Upper
extremity: wrist flexion, arm flexion, shoulder abduction. Lower extremity: ankle
dorsiflexion, knee extension and hip flexion. Handgrip assessment: On the same day as the
MRC exam the patient will be asked to perform a handgrip maneuver using the Jamar® handgrip
manometer.

Clinical outcomes:

Ventilator use, Re-intubation, Recurrent ICU admission, Tracheostomy use, ICU Length of Stay
and Hospital LOS

Inclusion Criteria:

- Adult (age > or = 18) patients admitted to the Medical ICU

- Respiratory failure requiring mechanical ventilation > or = 5 days

- Reasonable expectation for a subsequent return of mental status

Exclusion Criteria:

- Patient's family, physician, or both not in favor of aggressive treatment of patient
or presence of an advanced directive to withhold life-sustaining treatment

- Pregnancy

- Admitted to ICU from outside hospital

- New or pre-existing diagnosis causing current neuromuscular weakness

- Profound and uncorrectable hypokalemia or hypophosphatemia [K < 2.5 or P < 1.0
throughout enrollment window]

- Inability to assess muscle strength in more than six muscle groups in at least two
extremities [Bilateral amputation (BKA or AKA), severe burns, skin lesions or
dressings limiting ability of examiner to access and forcibly resist movement of the
patients extremities]

- Inability to communicate or follow commands of the examiner [persistent coma, severe
MRDD (mental retardation and developmental disabilities) or continuing necessary
medication use that impairs consciousness (i.e. narcotics), non-English speaker]

- Concurrent enrollment in another clinical trial involving steroids > 20 mg/day
prednisone equivalent for > 3 days, neuromuscular blockade for > 24 hours or any
aminoglycosides.

- Prisoner or other subject where legal surrogate decision maker is in question