This study is testing whether a non-invasive nerve monitoring device (TetraGraph) can accurately detect early signs of ICU-acquired weakness by comparing readings from the device with standard nerve conduction/EMG tests done by a specialist to see if they match. They will focus on muscle response signals in the hand and leg over about 10 days in three groups: healthy volunteers, ICU patients who are not on ventilators, and ICU patients who are on ventilators.

This is a prospective, parallel-cohort controlled pilot trial involving adults who are either 1) healthy volunteers, 2) non-intubated critically ill Endeavor Health ICU patients, or 3) intubated critically ill Endeavor Health ICU patients. Each cohort will have 8 total participants for a total of 24 patients from Endeavor Health. The testing done in this study (EMG/NCS and TetraGraph) is not part of standard of care procedures for critically ill patients. These tests are being performed for research purposes only.

Participants in cohorts 2 and 3 (non-intubated ICU patients and intubated ICU patients) will be enrolled in the trial from the time they (or their LAR) sign the consent form to 90 days post-hospital discharge to allow for data collection regarding outcomes after their ICU stay. Enrollment of ICU patients will be within the first 72 hours of their ICU stay as our preliminary data suggested the CMAP amplitudes started to drop after this time. Healthy volunteers will be enrolled in the trial from the time they sign their consent form to 10 days after their first visit. Each patient will serve as their own control with regards to changes, if any, in amplitude and/or duration.

Neurological EMG/NCS Testing Methods. The investigators will sequentially record the handheld quantitative neuromuscular monitor data and standard EMG/NCS data on the following study days: 1, 5, 10. The standard EMG and NCS sessions will be conducted by a neurologist and four muscles will be tested during the EMG portion (all on same side): the abductor digiti minimi (hand), biceps (upper arm), vastus medialis (upper leg), and tibialis anterior (lower leg). The four muscles will be tested to confirm if the weakness is neurogenic, myopathic, or a mixed process in origin. These specific muscles were chosen to ensure that at least one proximal and one distal muscle group is tested in each limb in order to help clarify the diagnosis and cause of the weakness, if any exists. The landmarks to apply the surface electrodes for standard NCS testing will be as follows. To test the tibialis anterior, the research staff will place the active electrode at the proximal one-third of the line between the tip of the fibular head and the tip of the lateral malleolus. This is roughly one-third of the way down the shin, slightly lateral (2-3 cm) to the shin bone. The reference electrode will be placed 3-4 cm distal to the recording electrode on the tibial boney prominence. The ground electrode will be placed between the active electrode and stimulation probe. The cathode of the bipolar stimulating probe will be placed just inferior to the fibular head about 9-10 cm proximal to the recording electrode. For testing the abductor digiti minimi, the research staff will place the active electrode directly on the muscle belly of the ADM. This is on the ulnar border of the palm, approximately halfway between the wrist crease and the base of the little finger. The reference electrode will be placed over the distal joint (the fifth MCP joint) or on the proximal phalanx of the fifth digit, while the ground electrode will be placed on the dorsum of the hand between the active and reference electrodes. The cathode of the bipolar stimulating probe will be placed 7-8 cm proximal to the active electrode along the medial aspect of the anterior wrist over the ulnar nerve.

The skin temperature of the limbs will first be measured with a temporal infrared temperature device to record the temperature prior to testing. The participant's limb will be warmed using hot packs to at least 32-34 degrees celsius per AANEM guidlines to ensure proper nerve conduction velocity. These measurements will be taken at supramaximal stimulation current for consistency of measurements. More specifically, investigators will be using a polar probe to apply a current in the milliamp (mA) range. Investigators will start at 15 mA, stimulating at least 1-3 times before increasing stimulation by 5-20 mA and stimulating again three times. Investigators will continue to increase the current until the response amplitude stops growing (supramaximal stimulation) or investigators reach the maximum current intensity of 80 mA. If needed, investigators will also increase the duration of the stimulus from 0.1 milliseconds (ms) up to a maximum of 1 ms, usually by increments of 0.1-0.2 ms. The EMG/NCS measurements will be done one time and by a trained neurologist. No desensitization is expected between series of EMG tests conducted on the patients enrolled.

Peripheral Nerve Monitor (TetraGraph) Testing Methods Then, all participants will have the handheld quantitative neuromuscular monitor applied to the skin over the nerve distribution of two muscles (all on same side of body), the abductor digiti minimi (ADM) and tibialis anterior, to obtain CMAP amplitudes and duration. These specific muscles were chosen to ensure that at least one muscle from each limb is tested, and to correlate with the muscles tested in the EMG/NCS testing. To test the ADM and the tibialis anterior using the TetraGraph device, the surface electrodes will be placed as follows. For testing of the ADM, the research staff will place the two stimulating pads along the ulnar nerve on the volar aspect of the distal forearm. The recording pad will be placed over the muscle belly of the ADM, e.g., the outside edge of the palm near the fifth finger. The fourth (reference) electrode will be placed on the 5th finger. The response should be that the fifth finger should spread away from the rest of the fingers.

For testing of the tibialis anterior, the research staff will find the top of the muscle just below the knee and the bony prominence at the point called the tibial tubercle. The proximal surface sticker will be placed approximately 2 finger-widths below the lateral portion of the tibial tubercle. The distal two surface stickers (recording and reference) will be placed further down the lateral aspect of the calf muscle, as far as they can extend distally from the proximal surface stimulating electrodes. The appropriate response to stimulation of the tibialis anterior nerve should be dorsiflexion of the foot.

The handheld quantitative neuromuscular monitor (TetraGraph) will perform three measurements (within a minute of one another to ensure reproducibility). The handheld quantitative neuromuscular device will not be testing the biceps or vastus medialis as these muscles will only be tested via the EMG testing to help clarify the diagnosis. The investigators also want to limit stimulation to muscles that would be practical to use in real time. When the monitor is started, it then delivers a set of single twitches at 1 Hz, starting at 0 mA (milliamperes) and increasing in 5 mA steps until the cMAP amplitude no longer increases. The maximum current it can deliver is 80 mA. At the point where the amplitude no longer increases, the current value (in mA) is considered "maximal" - and 20% higher current is set as "supramaximal" level, to account for potential changes in skin resistance over time that may falsely decrease the cMAP amplitude. The handheld quantitative neuromuscular monitor will go through the series of stimulations and automatically stop stimulations once the supramaximal current is identified - the procedure takes 10-15 seconds. If the cMAP amplitude detected has not reached a plateau (and keeps increasing), the monitor defaults to the highest output, 80 mA/0.3 ms (24 µC). For tibialis anterior (leg) testing, the procedure is identical to that of the hand, and the pain scores should be similar to those at the hand. Discomfort from the electrical impulses is mild and feels similar to hitting participant's funny bone. If for whatever reason a patient experiences pain of 7 or higher on the Defense and Veterans Pain Rating Scale (DVPRS) (0 = "no pain", 10 = "as bad as it could be, nothing else matters"), or an ICU patients on sedation or on a mechanical ventilator score greater than or equal to 6 (equates to severe pain) using the Critical Care Observation Tool (CPOT) participants will be withdrawn from the study. A member of the research team will be present at all time to monitor the patients and at which pain can be assessed. A member of the research team will also monitor the patient for up to 10 minutes after tests have been performed.

Inclusion Criteria:

• Cohort 1: Healthy volunteers

Inclusion criteria:

• Subjects must be > 18 years old and < 90 years old.
• Subjects must consent to participate. Cohort 2: Non-intubated critically ill patients

Inclusion criteria:

• Subjects may be male or female.
• Subjects must be > 18 years old and < 90 years old.
• Subjects must have a POA or next of kin who is able to consent (for those in the ICU and who are unable to consent themselves).

Cohort 3: Intubated critically ill patients

Inclusion criteria:

• Subjects may be male or female.
• Subjects must be > 18 years old and < 90 years old.
• Subjects must have a POA or next of kin who is able to consent (for those in the ICU and who are unable to consent themselves).
• For the Subjects in the ICU that are intubated, they must be planned to be intubated for at least 24 hours.
• Subjects must be intubated for no longer than ≥ 72 hours before enrollment.

Exclusion Criteria:

• Cohort 1: Healthy volunteers

Exclusion criteria:

• Subjects with previous paralysis or neuromuscular disease.
• Subjects with spinal cord or brain injuries that impact motor function.
• Subjects with an allergy to clinical adhesive or hydrogel. Cohort 2: Non-intubated critically ill patients

Exclusion criteria:

• Subjects with previous paralysis or neuromuscular diseases.
• Subjects with previous peripheral nerve injuries to the tested limbs.
• Subjects with spinal cord or brain injuries (including stroke) that impact motor function.
• Subjects without a POA or next of kin for those patients that are unable to consent themselves.
• Subjects with an allergy to clinical adhesive or hydrogel. Cohort 3: Intubated critically ill patients

Exclusion criteria:

• Subjects with previous paralysis or neuromuscular disease
• Subjects with previous peripheral nerve injuries to the tested limbs.
• Subjects with spinal cord or brain injuries that impact motor function.
• Subjects without a POA or next of kin for those patients that are in the intubated arm.
• Subjects with intubations expected to last less than 24 hours.
• Subjects who have already been intubated for > 72 hours.
• Subjects with an allergy to clinical adhesive or hydrogel.

Individual participant data will not be shared due to institutional policies and to protect participant privacy.