This randomized clinical trial will investigate the effects of neuromuscular electrical stimulation (NMES) in critically ill patients undergoing invasive mechanical ventilation. Participants will be randomly assigned to two groups: a control group receiving conventional physical therapy alone and an intervention group receiving conventional physical therapy combined with NMES.
The control group will receive individualized conventional physical therapy, adjusted daily based on each patient's physiological status and following protocols supported by current literature. Interventions may include progressive mobility, such as bed exercises, rolling, sitting at the edge of the bed, standing, chair transfers, and ambulation, as well as respiratory physiotherapy techniques including bronchial hygiene, pulmonary re-expansion, and management of mechanical ventilation. Sessions will last approximately 20 minutes and continue throughout hospitalization, except in cases of clinical contraindications or refusal by the patient/family.
The NMES group will receive the same conventional physical therapy described above, plus NMES applied once or twice daily to both lower limbs for up to 14 consecutive days or until hospital discharge, whichever comes first.
Rectangular electrodes (90 × 50 mm) will be placed bilaterally on the vastus lateralis, vastus medialis, tibialis anterior, hamstrings, and gastrocnemius muscles. If hair interferes with electrode adhesion, the area will be shaved.
NMES will be delivered using the ReCARE® device (Visuri, MG, Brazil) with the following parameters:
Frequency: 60 Hz
Pulse duration: 500 µs
Intensity: adjusted to produce visible muscle contractions during the first two days and, from day three onward, contractions sufficient to generate movement against gravity.
Contraction (on) and relaxation (off) times and the number of contractions will be progressively adjusted according to the 14-day protocol:
Days 1-2: On = 9s, Off = 22s, 30 contractions, 1x/day
Days 3-6: On = 9s, Off = 20s, 40 contractions, 1x/day
Days 7-9: On = 9s, Off = 18s, 50 contractions, 1x/day
Days 10-14: On = 9s, Off = 15s, 60 contractions, 1x/day
NMES sessions will be postponed if the participant exhibits any of the following clinical findings within three hours prior to the session:
Acidosis (arterial pH \< 7.25 or venous pH \< 7.20)
Hypotension or hypertension (mean arterial pressure \< 60 mmHg or \> 140 mmHg)
Use of a single vasopressor at \>50% of the ICU maximum dose (e.g., dopamine \>12.5 µg/kg/min, phenylephrine \>2 µg/kg/min, vasopressin ≥0.02 U/min, norepinephrine \>1 µg/kg/min)
Use of two vasopressors at ≥40% of the ICU maximum dose
New diagnosis of pulmonary embolism or deep vein thrombosis without anticoagulation for more than 48 hours
Other signs of physiological instability, including temperature \<34°C or \>41°C, lactate \>3.0 mmol/L, creatine kinase \>400 U/L, platelet count \<20,000/mm³, or suspected muscle inflammation (e.g., rhabdomyolysis, myositis, neuroleptic malignant syndrome, or serotonin syndrome).
This study aims to determine whether NMES, as an early adjunct therapy, can improve recovery and clinical outcomes in critically ill mechanically ventilated patients when combined with conventional physical therapy.
Protocol Amendment and Rationale The study protocol was amended following study initiation due to operational and feasibility constraints identified during the early recruitment phase (from the second enrolled participant onwards), particularly related to limited availability of research personnel required for intervention delivery as originally designed.
Amendments implemented:
1. Study duration and intervention schedule The intervention duration was reduced from 20 to 14 days. In addition, the original protocol of two daily sessions during the initial phase was modified to a single daily session throughout the intervention period. Stimulation parameters were also adjusted, including optimization of on/off time and number of contractions, resulting in a shorter and more feasible protocol while maintaining the intended neuromuscular stimulation dose.
2. Eligibility criteria modification The exclusion criterion related to baseline mobility was refined. The original criterion excluding patients unable to independently leave the bed was modified to exclude patients who were either unable to leave the bed independently or had pre-existing dependence for mobility prior to hospital admission, in order to improve baseline functional homogeneity and recruitment feasibility.
3. Blinding procedures Outcome assessor blinding was removed. Although initially planned, blinding was not feasible due to limited research personnel and logistical constraints associated with intervention delivery.
Rationale:
These amendments were introduced to ensure study feasibility under resource and staffing constraints while maintaining protocol integrity and alignment with the physiological objectives of the intervention.
Importantly, these changes were implemented early in the recruitment process and reflect an adaptation toward a more feasible and clinically applicable protocol.
Impact:
These modifications do not affect the study objectives, primary or secondary outcomes, or participant safety. The intervention remains within established safety parameters for neuromuscular electrical stimulation, and no additional risk to participants has been introduced.
