Assessing The Effects of Exercise, Protein, and Electric Stimulation On Intensive Care Unit Patients Outcomes

Older, critically ill patients who survive their ICU stay frequently develop post-ICU
syndrome (PICS) - a condition manifested by sarcopenia, weakness, malnutrition and
neurocognitive decline - which occurs as a result of a critical illness, prolonged bed rest,
catabolism, and polypharmacy. PICS frequently leads to chronic disability, prolonged
mechanical ventilation (MV), functional deficits, and the need for extended rehabilitation in
long term care facilities (LTCs). As the majority of patients admitted to ICUs are ≥ 65 years
old, many of these patients are at high risk for PICS. Since the care of ICU patients is
primarily focused on the medical management of the acute critical illness, there are limited
resources and strategies available to prevent PICS. Evidence suggests mobility-based physical
rehabilitation (MPR) combined with resistive training with neuromuscular electric stimulation
(NMES) and high protein diets (HPRO) containing essential amino acids can mitigate the loss
of muscle mass and function during bed rest in the elderly. The investigators hypothesize
that preventive therapy involving the addition of both NMES and HPRO to MPR early and
throughout the ICU and hospital stay can mitigate PICS-associated sarcopenia, malnutrition,
and immobility to confer valuable health benefits toward recovery. To test this, the
investigators will use a 2x2 factorial design in which older, MV ICU patients will all
receive comprehensive ICU care and MPR, then be randomized to one of 4 groups: 1) MPR+NMES,
2) MPR+HPRO, 3) all 3 together, or 4) MPR alone (control), to determine independent and
combined effects of the interventions.

The Specific Aims are to 1) determine the effects of adding NMES and HPRO interventions to
MPR on muscle mass, strength, and mobility function in older, critically ill MV patients
while still in the ICU, and 2) determine the effects of adding NMES and HPRO interventions to
MPR on the clinical outcomes of time to weaning from MV, ICU/hospital length of stay and
discharge disposition of these patients.

This proposal capitalizes on the interdisciplinary collaboration among Pulmonary/Critical
Care Intensivists, Physical Therapists, Geriatricians, Clinical Nutritionists, Statisticians
and Nutrition and Metabolism clinical researchers examining the efficacy of the proposed
comprehensive rehabilitation approach. The investigators' primary goal is to attenuate the
severity of sarcopenia and functional decline in this older, critically ill population at
risk for severe disability. Additionally, by focusing on maintaining skeletal muscle mass,
function, and strength, the investigators hope to improve clinical outcomes. The
investigators posit this combined therapy will mitigate PICS-associated disability and speed
the recovery from critical illness in older, MV ICU patients. This project has high overall
impact as the intervention is easily administered by hospital staff and may greatly reduce
the physiological and functional declines while hastening recovery during acute ICU
hospitalization in older adults.

Inclusion Criteria:

- Age ≥ 45 years

- Respiratory insufficiency requiring mechanical ventilation (MV)

- ICU presentation < 6 days

- Patient or legally authorized representative able to provide written or witnessed
verbal informed consent in English

- All four limbs intact and mobile

- Eligible for and able to participate in physical therapy

- Pre admission Barthel Index >70

Exclusion Criteria:

- Acute kidney injury with a glomerular filtration rate < 30 ml/min

- Diagnosis of severe organ dysfunction including end stage liver disease or cirrhosis

- Diagnosis of active cancer

- Acute or chronic organ transplant rejection

- Exceedingly high mechanical ventilator settings (FiO2>60%, PEEP>12) or alternative
modes of mechanical ventilation (inverse ratio pressure control, airway pressure
release ventilation)

- Severe functional impairment or physical impairment to rehabilitation

- On high dose vasopressor agents (> 5mcg of norepinephrine or equivalent)

- Liver function tests > 2.5 x normal limits (normal reference ranges include AST
between 10 and 40 units/L or ALT between 7 and 56 units/L)

- Chronic dementia or cognitive impairment