This study plans to learn more about whether simpler diagnostic tests can be used to identify the development of acute neuromuscular loss of function in patients with critical illness and respiratory failure receiving mechanical ventilation. ICU patients admitted to the University of Colorado Hospital will be screened for eligibility and enrollment in the study to receive weekly measurements of nerve and muscle function through nerve conduction studies (NCS), muscle ultrasound tests, and concentric needle electromyography (EMG) tests.

This study plans to learn more about whether simpler diagnostic tests can be used to identify the development of acute neuromuscular loss of function in patients with critical illness and respiratory failure receiving mechanical ventilation. ICU patients admitted to the University of Colorado Hospital will be screened for eligibility and enrollment in the study to receive weekly measurements of nerve and muscle function through nerve conduction studies (NCS), muscle ultrasound tests, and concentric needle electromyography (EMG) tests.

Collected data includes the subject's age, gender, race, ethnicity, length of stay in ICU, time on mechanical ventilation and pertinent medical history that could indicate baseline neuromyopathy (CNS disease, diabetes, HIV, alcohol use disorder). Baseline neurological examination will be performed within 48 hours of meeting the inclusion criteria. This examination will include the level of consciousness, muscle tone, motor strength using the Medical Research Council (MRC) Scale, sensory function, muscle stretch reflexes, and plantar responses. For MRC testing, six muscle groups will be tested bilaterally: shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and foot dorsiflexion. Clinical weakness on examination (which is necessary to make the diagnosis of CIPNM (Critical Illness Polyneuropathy and Myopathy)) is defined as an MRC score equal to or less than 48 (maximum score is 60). If a subject cannot participate in any MRC strength testing (e.g. due to sedation or encephalopathy) they will be coded at the lowest level (most severe clinical weakness). Nerve conduction studies (NCS) and concentric needle electromyography (EMG) will be performed (as described below) on the same day as the initial neurological examination. The neurological examination and NCS/EMG will be repeated on a weekly basis until CIPNM is diagnosed or the subject is discharged from the ICU.

SPECIFIC AIM #1:

Aim 1.1: To determine whether amplitude reductions in the peroneal and sural nerve action potentials on NCS can serve as accurate screening tests for CIPNM in patients with acute respiratory failure.

Aim 1.2: To determine whether increased duration of the CMAP on NCS can serve as an accurate screening test for CIPNM in patients with acute respiratory failure.

Aim 1.3: To determine whether changes in muscle ultrasound echogenicity and/or thickness can serve as accurate screening tests for CIPNM in patients with acute respiratory failure.

Aim 1.4: To determine the incidence of CIPNM in patients with neurological critical illness (such as intraparenchymal and subarachnoid hemorrhage), which requires prolonged length of stay in a neurosurgical intensive care unit.

Inclusion Criteria:

For Aim 1.1-1.3, one of the following 2 sets of criteria are needed for inclusion

Set 1:

1. Acute respiratory failure defined as a Pa02 < 60 mm Hg on room air, the requirement of supplemental oxygen, or a PaC02 > 45 mm Hg.
2. Admission to an intensive care unit.
3. Mechanical ventilation support through an endotracheal tube for greater than 48 hours.
4. Severe sepsis (suspected or documented infection + at least 2/4 SIRS criteria + organ dysfunction) or septic shock (sepsis plus hypotension refractory to intravenous fluids or plasma lactate > 1.5 times the upper limit of normal)

Set 2:

1. Acute respiratory failure defined as requiring invasive or non-invasive ventilation with a p/f ratio ≤ 250

2. Admission to an intensive care unit, in ICU for greater than 48 hours.

3. Plus dysfunction in one of the following organ systems:

   1. Cardiovascular dysfunction: (at least one of the following) i. SBP ≤ 90 mm Hg or MAP ≤ 70 mm Hg for at least one hour despite adequate fluid resuscitation. Adequate fluid resuscitation is defined as the patient receiving intravenous fluid resuscitation of ≥ 30 mL/kg administered at any time during the 4 hours before a hypotensive blood pressure.

      ii. The use of vasopressors in an attempt to maintain a SBP of ≥ 90 mm Hg or a MAP of ≥ 65 mm Hg despite adequate intravascular volume status. Adequate intravascular volume status is defined as intravenous fluid resuscitation of ≥ 30 mL/kg administered at any time during the 4 hours before or after initiation of vasopressor therapy. Vasopressive therapy is defined as any one of the following: Norepinephrine, Phenylephrine, Epinephrine, Dopamine ≥ 5 mcg/kg/min, or Vasopressin ≥ 0.03 units/min.

   2. Kidney dysfunction: Urine output < 0.5 ml/kg of body weight/hr for 1 hour despite adequate fluid resuscitation or adequate intravascular volume status (as defined above)

   3. Hematologic dysfunction: Platelet count < 80,000 or a decrease by 50% over the previous 3 days.

   4. Acidosis: (at least one of the following) i. pH ≤ 7.30 ii. Plasma lactate > 1.5 times the upper limit of normal

For Aim 1.4, all of the following criteria are needed for inclusion.

1. Non-traumatic subarachnoid hemorrhage or intracerebral (intraparenchymal) hemorrhage.
2. Admission to a neurological or neurosurgical intensive care unit.
3. Mechanical ventilation support through an endotracheal tube for greater than 48 hours.

Exclusion Criteria:

For Aim 1.1-1.3:

1. Age less than 18 years.
2. Diagnosis of pre-existing disease of the peripheral motor or sensory nervous system or myopathy.
3. Central nervous system disorder that would compromise the ability of the patient to participate in the study.
4. Pharmacologic paralysis.
5. Absence of ability to test at least one arm and one leg with NCS/EMG (e.g. due to amputation or overlying equipment).
6. Decremental response on repetitive nerve stimulation.
7. External pacemaker wire.
8. Pregnancy.
9. Initiation of mechanical ventilation (invasive or non-invasive) and admission to the ICU both >120 hours (5 days) ago.
10. Referral from another hospital for patients that have required mechanical ventilation for more than 48 hours.
11. Inability to obtain informed consent or refusal to participate in the study.
12. Known steroid-induced myopathy prior to ICU admission resulting from chronic systemic glucocorticoid therapy.

For Aim 1.4:

1. Isolated subdural or epidural hematoma
2. Age less than 18 years.
3. Diagnosis of pre-existing disease of the peripheral motor or sensory nervous system or myopathy.
4. Pharmacologic paralysis.
5. Absence of ability to test at least one arm and one leg with NCS/EMG (e.g. due to amputation or overlying equipment).
6. Decremental response on repetitive nerve stimulation.
7. External pacemaker wire.
8. Pregnancy.
9. Initiation of mechanical ventilation and admission to the ICU both >120 hours (5 days) ago.
10. Referral from another hospital for patients that have required mechanical ventilation for more than 48 hours.
11. Inability to obtain informed consent or refusal to participate in the study. Known steroid-induced myopathy prior to ICU admission resulting from chronic systemic glucocorticoid therapy.