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The Diagnosis and Incidence of Critical Illness Polyneuromyopathy in Medical and Neurosurgical ICU Patients

Primary Purpose

Critical Illness

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Muscle Ultrasound

Nerve Conduction Study

Electromyography

About this trial

This is an interventional diagnostic trial for Critical Illness

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Set 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.
Admission to an intensive care unit.
Mechanical ventilation support through an endotracheal tube for greater than 48 hours.
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:

Acute respiratory failure defined as requiring invasive or non-invasive ventilation with a p/f ratio ≤ 250
Admission to an intensive care unit, in ICU for greater than 48 hours.
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.

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

Exclusion Criteria:

For Aim 1.1-1.3:

Age less than 18 years.
Diagnosis of pre-existing disease of the peripheral motor or sensory nervous system or myopathy.
Central nervous system disorder that would compromise the ability of the patient to participate in the study.
Pharmacologic paralysis.
Absence of ability to test at least one arm and one leg with NCS/EMG (e.g. due to amputation or overlying equipment).
Decremental response on repetitive nerve stimulation.
External pacemaker wire.
Pregnancy.
Initiation of mechanical ventilation (invasive or non-invasive) and admission to the ICU both >120 hours (5 days) ago.
Referral from another hospital for patients that have required mechanical ventilation for more than 48 hours.
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.

For Aim 1.4:

Isolated subdural or epidural hematoma
Age less than 18 years.
Diagnosis of pre-existing disease of the peripheral motor or sensory nervous system or myopathy.
Pharmacologic paralysis.
Absence of ability to test at least one arm and one leg with NCS/EMG (e.g. due to amputation or overlying equipment).
Decremental response on repetitive nerve stimulation.
External pacemaker wire.
Pregnancy.
Initiation of mechanical ventilation and admission to the ICU both >120 hours (5 days) ago.
Referral from another hospital for patients that have required mechanical ventilation for more than 48 hours.
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.

Sites / Locations

University of Colorado Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Medical ICU Subjects

Neuro ICU Subjects

Arm Description

All Medical ICU subjects that meet eligibility criteria and are enrolled in the study will receive muscle Ultrasounds, Nerve Conduction Studies and Electromyography (EMG).

All Neuro ICU subjects that meet eligibility criteria and are enrolled in the study will receive Nerve Conduction Studies and Electromyography (EMG).

Outcomes

Primary Outcome Measures

Aims 1.1-1.3: Number of medical ICU subjects diagnosed with CIPNM according to Moss/Quan established criteria of CIP or CIM.

Subjects have CIPNM if either Moss/Quan criteria for (CIP) or (CIM) criteria are met: CIP: SNAP amplitudes < 80% of lower norm limit of 2+ nerves, Reduced recruitment on EMG, Absence of decremental response, and MRC score < 48 or clinical weakness on exam CIM: SNAP amplitudes > 80% of the lower norm limit of 2+ nerves, CMAP amplitudes < 80% of the lower limit of normal in two or more nerves without conduction block, needle EMG with short-duration, low amplitude motor unit potentials with early recruitment, absence of a decremental response, and MRC score < 48 or clinical weakness on exam CIPNM: Absence of a decremental response, SNAP amplitudes < 80% of the lower limit of normal in two or more nerves, CMAP amplitudes < 80% of the lower limit of normal in two or more nerves without conduction block, sustained spontaneous activity and/or changes in motor unit recruitment, in at least two muscles, and MRC score < 48 or clinical weakness on exam

Aim 1.4: Number of neurosurgical ICU subjects diagnosed with CIPNM according to Moss/Quan established criteria of CIP or CIM.

Secondary Outcome Measures

ICU length of stay

ICU-free days

the number of days out of 28 that the subject is alive and out of the ICU, but remains hospitalized.

time on mechanical ventilation

hospital length of stay

hospital total length of subject stay.

hospital-free days

the number of days oout of 28 that the subject was alive and out of the acute care hospital.

in hospital mortality

Incidence of in hospital mortality through day 28

Discharge location

Subject discharge location from acute hospitalization period to home, SNF, rehab hospital, LTACH, hospice, etc.

Full Information

NCT ID

NCT02634658

First Posted

November 13, 2015

Last Updated

May 3, 2017

Sponsor

University of Colorado, Denver

1. Study Identification

Unique Protocol Identification Number

NCT02634658

Brief Title

The Diagnosis and Incidence of Critical Illness Polyneuromyopathy in Medical and Neurosurgical ICU Patients

Official Title

The Diagnosis and Incidence of Critical Illness Polyneuromyopathy in Medical and Neurosurgical ICU Patients

Study Type

Interventional

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Completed

Study Start Date

June 2009 (undefined)

Primary Completion Date

April 2014 (Actual)

Study Completion Date

September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Colorado, Denver

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Critical Illness

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

120 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Medical ICU Subjects

Arm Type

Experimental

Arm Description

All Medical ICU subjects that meet eligibility criteria and are enrolled in the study will receive muscle Ultrasounds, Nerve Conduction Studies and Electromyography (EMG).

Arm Title

Neuro ICU Subjects

Arm Type

Experimental

Arm Description

All Neuro ICU subjects that meet eligibility criteria and are enrolled in the study will receive Nerve Conduction Studies and Electromyography (EMG).

Intervention Type

Other

Intervention Name(s)

Muscle Ultrasound

Other Intervention Name(s)

US, Ultrasound

Intervention Description

Ultrasound will be performed using a linear-array transducer with standardized gain and varying depth based on the amount of overlying soft tissue and muscle size. The subjects will be examined in the supine position with extended limbs and relaxed muscles. We will perform bilateral scans of the biceps, anterior forearm, and anterior thigh at standardized sites. For muscle echogenicity measurements, we will scan the same muscles at the same points.

Intervention Type

Other

Intervention Name(s)

Nerve Conduction Study

Other Intervention Name(s)

NCS

Intervention Description

Nerve Conduction Studies will be performed using a Nicolet EDX using standard procedures. Repetitive stimulation of the median motor nerve are performed in all subjects. Bilateral sural, radial and median sensory nerves will be analyzed. We will only perform surface, not subdermal sensory recordings. The bilateral peroneal, tibial and median motor responses will be recorded over extensor digitorum brevis, abductor hallucis brevis, and abductor pollicis brevis muscles. The peroneal motor nerve will be stimulated at the fibular head and lateral popliteal fossa, recording from the tibialis anterior muscle. The compound motor action potential (CMAP) responses will be elicited from standard distal and proximal sites.

Intervention Type

Other

Intervention Name(s)

Electromyography

Other Intervention Name(s)

EMG

Intervention Description

EMG studies will be performed using standard precautions. Insertional activity, spontaneous activity, motor unit potential (MUP) morphology and recruitment/activation pattern will be recorded from some combination of the deltoid, triceps, biceps, first dorsal interosseous, abductor pollicis brevis, iliopsoas, vastus medialis, and tibialis anterior muscles. The specific muscles studied for each patient will vary according to the patient's level of consciousness and ability to activate the muscles either voluntarily or during spontaneous limb movement. If possible, we will try to examine 3 unilateral upper extremity and 3 unilateral lower extremity muscles. If a patient is not able to volitionally participate in EMG testing (by contracting their muscles on command), we will analyze insertional/spontaneous activity and potentially morphology/recruitment (e.g. stroking the sole of the foot to stimulate contraction of the tibialis anterior).

Primary Outcome Measure Information:

Title

Aims 1.1-1.3: Number of medical ICU subjects diagnosed with CIPNM according to Moss/Quan established criteria of CIP or CIM.

Description

Time Frame

Weekly up to Day 28 or hospital discharge whichever occurs first.

Title

Aim 1.4: Number of neurosurgical ICU subjects diagnosed with CIPNM according to Moss/Quan established criteria of CIP or CIM.

Description

Time Frame

Weekly through Day 28 or hospital discharge whichever occurs first

Secondary Outcome Measure Information:

Title

ICU length of stay

Description

ICU length of stay

Time Frame

upon completion of ICU stay, commonly 7-14 days.

Title

ICU-free days

Description

the number of days out of 28 that the subject is alive and out of the ICU, but remains hospitalized.

Time Frame

upon completion of inpatient period, commonly up to 28 days.

Title

time on mechanical ventilation

Description

time on mechanical ventilation

Time Frame

upon completion of ventilation period, commonly 3-14 days.

Title

hospital length of stay

Description

hospital total length of subject stay.

Time Frame

upon completion of inpatient period, commonly up to 28 days.

Title

hospital-free days

Description

the number of days oout of 28 that the subject was alive and out of the acute care hospital.

Time Frame

28 days

Title

in hospital mortality

Description

Incidence of in hospital mortality through day 28

Time Frame

28 days

Title

Discharge location

Description

Subject discharge location from acute hospitalization period to home, SNF, rehab hospital, LTACH, hospice, etc.

Time Frame

up to 28 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: For Aim 1.1-1.3, one of the following 2 sets of criteria are needed for inclusion Set 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. Admission to an intensive care unit. Mechanical ventilation support through an endotracheal tube for greater than 48 hours. 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: Acute respiratory failure defined as requiring invasive or non-invasive ventilation with a p/f ratio ≤ 250 Admission to an intensive care unit, in ICU for greater than 48 hours. Plus dysfunction in one of the following organ systems: 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. 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) Hematologic dysfunction: Platelet count < 80,000 or a decrease by 50% over the previous 3 days. 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. Non-traumatic subarachnoid hemorrhage or intracerebral (intraparenchymal) hemorrhage. Admission to a neurological or neurosurgical intensive care unit. Mechanical ventilation support through an endotracheal tube for greater than 48 hours. Exclusion Criteria: For Aim 1.1-1.3: Age less than 18 years. Diagnosis of pre-existing disease of the peripheral motor or sensory nervous system or myopathy. Central nervous system disorder that would compromise the ability of the patient to participate in the study. Pharmacologic paralysis. Absence of ability to test at least one arm and one leg with NCS/EMG (e.g. due to amputation or overlying equipment). Decremental response on repetitive nerve stimulation. External pacemaker wire. Pregnancy. Initiation of mechanical ventilation (invasive or non-invasive) and admission to the ICU both >120 hours (5 days) ago. Referral from another hospital for patients that have required mechanical ventilation for more than 48 hours. 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. For Aim 1.4: Isolated subdural or epidural hematoma Age less than 18 years. Diagnosis of pre-existing disease of the peripheral motor or sensory nervous system or myopathy. Pharmacologic paralysis. Absence of ability to test at least one arm and one leg with NCS/EMG (e.g. due to amputation or overlying equipment). Decremental response on repetitive nerve stimulation. External pacemaker wire. Pregnancy. Initiation of mechanical ventilation and admission to the ICU both >120 hours (5 days) ago. Referral from another hospital for patients that have required mechanical ventilation for more than 48 hours. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marc Moss, MD

Organizational Affiliation

University of Colorado, Denver

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Colorado Hospital

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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The Diagnosis and Incidence of Critical Illness Polyneuromyopathy in Medical and Neurosurgical ICU Patients

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