Neuromuscular Electrical Stimulation in Critically Ill Patients Aged 80 and Over

A clinical trial is proposed to evaluate the effectiveness of Medium-Frequency Neuromuscular Electrical Stimulation, in combination with standard physical therapy, compared to standard physical therapy alone on muscle mass, muscle strength, and functionality in critically ill patients aged 80 and over during their hospital stay. The study will also assess the safety of the intervention and the standardization of the parameters used in the protocol.

General Aim

To evaluate the effectiveness of medium-frequency neuromuscular electrical stimulation, in combination with standard physical therapy, versus standard physical therapy alone, on muscle mass, muscle strength, and functionality in critically ill oldest old patients during their hospital stay.

Specific Objectives

To compare quadriceps femoris muscle thickness (rectus femoris-vastus intermedius) and tibialis anterior muscle thickness via ultrasonography between the study groups during hospitalization.

To compare global peripheral muscle strength using the Medical Research Council Sum Score (MRC-SS) and handgrip strength using dynamometry between the study groups during hospitalization.

To compare maximal inspiratory muscle strength using pimometry between the study groups during hospitalization.

To compare patients' functional status using the Functional Status Score for the Intensive Care Unit (FSS-ICU) between the study groups during hospitalization.

To compare differences in levels of independence in activities of daily living using the Barthel Index between the study groups during hospitalization.

To compare health-related quality of life using the SF-36 questionnaire between the study groups during hospitalization.

To compare cognitive impairment using the Montreal Cognitive Assessment (MoCA) between the study groups during hospitalization.

To compare frailty levels using the Clinical Frailty Scale (CFS) between the study groups during hospitalization.

Methodology

A prospective, randomized controlled clinical trial is proposed, consisting of the application of a standardized medium-frequency neuromuscular electrical stimulation (NMES) protocol in oldest old patients admitted to the medical and surgical Intensive Care Units of Dr. Hernán Henríquez Aravena Hospital. The sample will consist of oldest old participants (≥80 years), who will be randomly divided into two subgroups: a control group (standard physical therapy) and an experimental group (standard therapy + NMES).

The control group will receive the standard physical therapy routinely provided during hospitalization. The experimental group will receive standard physical therapy plus medium-frequency NMES, which will begin within the first 48 hours of admission to the unit.

Population and Sample

The target and accessible population will include oldest old patients admitted to the Adult Critical Care Unit (ICU) at Dr. Hernán Henríquez Aravena Hospital in Temuco, Chile. Participant selection will be non-probabilistic, with patients being included as they meet the inclusion criteria. Once eligibility is confirmed, participants will be randomized into either the control group or the intervention group.

The recruitment process will begin once approval has been obtained from the hospital administration, the ethics committee, and the head of the Adult Intensive Critical Care Unit (ICU). The ICU staff will be notified of the start of data collection for patients meeting the inclusion criteria. The invitation to participate in the study will be extended by a collaborating physiotherapist who works permanently in the Adult ICU of Dr. Hernán Henríquez Aravena Hospital in Temuco, Chile. As eligible candidates are identified, they will be recruited into the study.

The recruitment site will be the Adult ICU facilities, including both the medical and surgical units, from admission until hospital discharge.

Sample Size Calculation

The sample size (N) was calculated using a statistical power of 80% and a significance level of 0.05, using the G\*Power 3.1.9.7 software. The calculation was based on the variation in quadriceps muscle thickness (rectus femoris-vastus intermedius), measured via ultrasonography and expressed as a percentage, which was defined as the primary outcome variable.

According to previous studies, it is expected that muscle thickness will decrease significantly less in the group receiving medium-frequency NMES after the intervention period, with an estimated reduction of \~20% compared to the control group.

Based on the sample size calculation and for the purpose of assigning patients to the two described groups (control and medium-frequency NMES), a minimum of 24 patients (12 per group) is required to detect a difference in quadriceps muscle thickness changes (rectus femoris-vastus intermedius).

Considering an anticipated 20% dropout rate during the trial-due to the critical condition of the participants-the final number of participants expected to be recruited is 15 per group.

Intervention

The interventions will be carried out by the principal investigator and trained assistants during the research period. Prior to their application, pharmacological, ventilatory, and hemodynamic data will be recorded in order to assess the patient's condition and their response during mobilization and/or the application of electrical stimulation.

A. Standard Physical Therapy

All participants will receive standard physical therapy. This intervention includes passive mobilization of the lower limbs, specifically targeting the ranges of hip flexion, knee flexion and extension, and ankle flexion and extension. One set of 10 bilateral repetitions will be performed while the patient is under sedation in the ICU. Once the patient is awake, the mobilization protocol routinely used in the unit will be followed.

This intervention will be conducted twice daily: once in the morning shift (08:00-12:00 hrs) and once in the afternoon shift (14:00-18:00 hrs), consistent with routine ICU practices at Dr. Hernán Henríquez Aravena Hospital.

B. Medium-Frequency Neuromuscular Electrical Stimulation (NMES)

The NMES protocol involves the use of a 4-channel device (Enraf-Nonius®, Rotterdam, Netherlands), provided by the Muscle Mass and Strength Regulation Research Group at Universidad de La Frontera. Two sessions will be conducted daily-one in the morning (08:00-12:00 hrs) and one in the afternoon (14:00-18:00 hrs)-always after standard physical therapy.

Two electrodes will be applied to each thigh, placed at the motor point of the quadriceps muscle. This point has been identified in previous studies and is located by measuring the distance between the anterior superior iliac spine (ASIS) and the superior border of the patella. The midpoint of this measurement is identified, and from there, 5 cm proximally and 10 cm distally are marked. The electrodes will be positioned at these points, creating a 15 cm distance between them.

Electrode placement will be marked using a semi-permanent marker to ensure consistency across sessions.

The medium-frequency NMES protocol, as reported in previous studies, consists of a carrier frequency of 2,500 Hz, a treatment frequency of 100 Hz, an ON period of 5 seconds (1 second ramp-up, 3 seconds contraction, and 1 second ramp-down), and an OFF period (rest) of 10 seconds. Each session will last 20 minutes, totaling 40 minutes of NMES per treatment day.

Stimulation intensity will be set once a visible and palpable muscle contraction is achieved. The intensity will be adjusted every 3 minutes to maintain consistent stimulation throughout the session. The stimulation intensity (in mA) at the start and end of muscle contraction will be recorded in a data sheet.

Evaluations

The characteristics and progression of skeletal muscle mass (thickness of the quadriceps femoris and anterior tibialis muscles) will be assessed using ultrasonography. Handgrip strength will be measured using a digital hand dynamometer; inspiratory muscle strength will be evaluated using a pimometer; peripheral muscle strength will be assessed using the Medical Research Council Sum Score (MRC-SS); functionality will be assessed using the Functional Status Score for the Intensive Care Unit (FSS-ICU); independence in basic activities of daily living will be measured using the Barthel Index; quality of life will be assessed with the Short Form-36 Health Survey (SF-36); cognitive impairment will be evaluated using the MoCA (Montreal Cognitive Assessment); and frailty will be assessed with the Clinical Frailty Scale (CFS). These evaluations will be applied in both groups (control and experimental) from ICU admission to hospital discharge.

Quadriceps muscle thickness will be assessed at four specific time points:

ICU admission (baseline): within the first 24 hours after ICU admission (Day 1).

During ICU stay (intermediate ICU assessment): at the first occurrence when the patient reaches a level of consciousness sufficient for active participation, defined as a score ≥ 3 out of 5 on the "S5Q" scale, assessed daily (average: 5-6 days).

• Change in Handgrip Strength [Срок оценки: During ICU stay (intermediate ICU assessment): on average Day 4-6 Prior to step-down unit discharge (end-of-ICU assessment): on average Day 12-14 Prior to hospital discharge (final assessment): on average Day 18-20]
• Change in Peripheral Muscle Strength [Срок оценки: During ICU stay (intermediate ICU assessment): on average Day 4-6 Prior to step-down unit discharge (end-of-ICU assessment): on average Day 12-14 Prior to hospital discharge (final assessment): on average Day 18-20]
• Change in Inspiratory Muscle Strength [Срок оценки: During ICU stay (intermediate ICU assessment): on average Day 4-6 Prior to step-down unit discharge (end-of-ICU assessment): on average Day 12-14 Prior to hospital discharge (final assessment): on average Day 18-20]
• Change in ICU Functionality [Срок оценки: During ICU stay (intermediate ICU assessment): on average Day 4-6 Prior to step-down unit discharge (end-of-ICU assessment): on average Day 12-14]
• Change in Independence in Performing Activities of Daily Living [Срок оценки: Prior to step-down unit discharge (end-of-ICU assessment): on average Day 12-14 Prior to hospital discharge (final assessment): on average Day 18-20]
• Change in Perceived Health Status [Срок оценки: Prior to step-down unit discharge (end-of-ICU assessment): on average Day 12-14 Prior to hospital discharge (final assessment): on average Day 18-20]
• Change in Frailty [Срок оценки: ICU admission (baseline): Day 1 Prior to hospital discharge (final assessment): average: Day 18-20]
• Change in Cognitive Impairment [Срок оценки: Prior to step-down unit discharge (end-of-ICU assessment): on average Day 12-14 Prior to hospital discharge (final assessment): on average 18-20]