The Effect of Early Neuromuscular Electrical Stimulation and Early Mobilization on Preventing the Intensive Care Unit-Acquired Weakness in Lung Cancer Resection Patients: A Randomized Controlled Trial

Abstract

Introduction

The aim of this research is to examine the impact of neuromuscular electrical stimulation (NMES) and early mobilization (EM) on preventing the intensive care unit-acquired weakness (ICU-AW) in lung cancer resection patients.

Methods

This was a single-center, parallel-group, randomized controlled trial. Participants were randomized into NMES, EM, and control groups. The main outcome measure was the occurrence of ICU-AW, with secondary outcomes encompassing differences in handgrip strength, duration of stay in the ICU, and overall hospital length of stay across the groups.

Results

Both interventions demonstrated significant reductions in ICU-AW incidence compared with the control group. The EM group had odds ratios of 0.10 (95% CI 0.03 - 0.31) at 2 days post-admission and 0.07 (95% CI 0.02 - 0.26) at ICU discharge, while the NMES group showed comparable reductions (OR 0.07; 95% CI 0.02 - 0.23 and OR 0.02; 95% CI 0.00 - 0.18, respectively). No significant between-intervention differences were observed. Compared with the control group, both intervention groups showed significantly greater handgrip strength at two days after ICU admission and at ICU discharge (P < 0.05). Neither intervention significantly affected ICU or hospital length of stay (P > 0.05).

Conclusions

EM and NMES each play a significant role in the reduction of ICU-AW incidence, enhance the handgrip strength of both upper limbs, but do not reduce ICU or hospital length of stay in lung cancer resection patients.

Keywords

early mobilization neuromuscular electrical stimulation lung cancer intensive care unit-acquired weakness handgrip strength

Introduction

Lung cancer remains a leading cause of death,¹ accounting for 18.4% of all cancer deaths worldwide in 2018.² Surgical intervention is crucial for improving survival rates, and patients typically require monitoring in the intensive care unit (ICU) following surgery.³ Intensive care unit-acquired weakness (ICU-AW) is a common issue among critically ill patients, with muscle wasting potentially leading to a loss of up to 10% of muscle mass within the first week,⁴ which is associated with functional impairment.⁵ Lung cancer patients often experience significant symptom burdens, including dyspnea, fatigue, anxiety, and pain, which can diminish their daily activity levels preoperatively.^6,7 Furthermore, studies indicate that lung cancer patients exhibit lower physical health scores compared with healthy individuals.⁸ The prolonged immobilization in critical care, combined with muscle disuse, increases the risk of ICU-AW, particularly in lung cancer patients,⁹ highlighting the need for innovative preventive strategies.

Neuromuscular electrical stimulation (NMES) is a treatment that uses tiny electric signals to activate weak or paralyzed muscles.¹⁰ Previous studies have demonstrated that NMES can inhibit muscle volume loss and increase muscle mass.^11-13 Upon applying this therapeutic approach to the target patient population, existing literature indicates that NMES significantly enhances functional outcomes in cancer patients, as evidenced by improvements in the six-minute walk test distance, 30-second sit-to-stand test score, and functional capacity.¹⁴ Additionally, NMES has been correlated with positive changes in mobility and muscle strength, which are critical indicators of physical rehabilitation.¹⁵ Concurrently, the application of NMES has been linked to enhanced emotional regulation capabilities, suggesting a potential impact on the psychosocial well-being of individuals undergoing cancer treatment.¹⁶

Early mobilization¹⁷ (EM) is another way to attenuate muscle degradation, preserve muscle mass.^18,19 EM may significantly reduce the risk of readmission and postoperative complications in patients who have undergone abdominal cancer surgery.²⁰ Furthermore, it has been shown to enhance early postoperative mobilization capabilities in individuals after major head and neck cancer surgery.²¹ Additionally, EM positively contributes to the improvement of exercise capacity in patients recovering from cancer surgery,²² thereby promoting overall functional recovery and quality of life.

To date, no studies have investigated the implementation of these two approaches separately in postoperative lung cancer patients. Therefore, the purpose of our study is to investigate the effect of NMES and EM on the incidence and severity of ICU-AW in patients after lung cancer surgery, compared with the control group. Discovering the relationship between NMES, EM, and the incidence of ICU-AW after surgery, the findings of this research may provide evidence for future guidelines on the prevention of acquired weakness in ICU patients after lung cancer resection surgery.

Material and Methods

Study Design

A computer-generated randomization schedule was utilized for number randomization, with each number being individually sealed. The experiment utilized a simple random allocation method in a 1:1:1 ratio, with the random sequence being generated by statisticians. An allocation list was generated using Excel, which included participant IDs and random numbers.

Group assignments were concealed in sequentially numbered, opaque, sealed envelopes prepared by research assistants not involved in recruitment. After eligibility confirmation, implementers opened envelopes strictly sequentially, ensuring allocation concealment. Outcome assessors were blinded to group allocation throughout data collection and trial protocol.

Study Subjects

This was a prospective, single-centre, assessor-blinded, randomized controlled trial (RCT), conducted from October 2023 to December 2024. This study was approved by the relevant institutional ethics committee prior to study initiation. The study was conducted in accordance with the Declaration of Helsinki (1975, as revised in 2024) and the CONSORT guidelines.²³

This study has been registered at the Chinese Clinical Trial Registry. Date of registration: 31 October 2023. Written informed consent was obtained from all participants prior to enrollment. The consent covered participation in the study titled “the effects of NMES and EM, compared with routine care, on the prevention of ICU-AW following lung cancer resection” including the study procedures, potential risks and benefits, and the right to withdraw at any time without penalty.

Inclusion/Exclusion Criteria

The inclusion criteria were as follows: Diagnosed with non-small cell lung cancer or small cell lung cancer, post-thoracoscopy or open thoracotomy; Age over 18 years; Initial admission to the ICU for treatment; Expected ICU stay duration of more than 2 days (According to the classification of surgical risk, the postoperative ICU stay is considered to exceed two days if any of the following factors are present: Nutrition risk screening (NRS) 2002 score ≥ 3; forced expiratory volume in one second (FEV1) < 2L, FEV1/forced vital capacity (FVC) < 70%, or percentage of predicted postoperative FEV1 (PPO-FEV1) < 1L; Hospital anxiety and depression scale (HADS) score ≥ 8; peak oxygen consumption (VO₂peak) <15 mL/kg/min, maximum metabolic equivalent < 4 METs); -1 < Richmond Agitation-Sedation Scale (RASS) score < 1; Pre-admission Barthel index (BI) > 60, indicating basic self-care abilities.

The exclusion criteria were as follows: deformity, paralysis, or surgery of limbs; a pre-existing primary systemic neuromuscular disease that affects muscle strength (e.g., Guillain Barre, Myasthenia Gravis, Amyotrophic Lateral Sclerosis); install a pacemaker; severe heart failure or cardiac arrhythmia; Limb fractures, tumors, thigh burns, or skin diseases that prevent the use of NMES; pregnancy; participants who refuse to participate.

Outcome Measurements

Before surgery, the researchers collected baseline data of the patients. Upon admission to the intensive care unit, the patients’ Medical Research Council Muscle Strength scale (MRC) score and handgrip strength were recorded two days after ICU admission, at ICU discharge and three months after the surgery, along with the time of ICU admission and the hospital length of stay.

To ensure unbiased results and enhance the reliability of the study, four physical therapists who are not affiliated with our research evaluated the outcomes of MRC score, handgrip strength, ICU length of stay, and hospital length of stay. All assessors received standardized training on the use of the MRC scale and dynamometer-based handgrip strength measurement prior to the study and demonstrated consistent inter-rater reliability during a pilot assessment session. Outcome assessors were blinded to group allocation throughout the study period.

The Incidence of ICU-AW

The incidence of ICU-AW is our primary outcome. The presence of ICU-AW is determined by the MRC score. MRC score evaluates global muscle strength. Manual strength of six muscle groups (shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion) is evaluated on both sides using MRC scale. The summation of scores gives MRC-sum score, ranging from 0 to 60. An MRC score of less than 48 indicate the presence of ICU-AW.²⁴

Secondary Outcomes

Secondary outcomes include handgrip strength (measured bilaterally using a handheld dynamometer with the patient in a supine position), ICU length of stay, and total hospital length of stay. The length of ICU stay refers to the number of days a patient spent in the ICU, while the total hospital stay includes all days spent in the hospital until discharge after operation.

Intervention

NMES Program

NMES was initiated on the first day after lung cancer surgery and continued until participants were discharged from the hospital. Participants received NMES (Model XY-K-FKZL-II; Xiangyu Medical Co., Ltd., Anyang, China) treatment at the hospital 5 days per week, for 90 minutes per day, in 30-minute sessions, targeting two pairs of muscles per session. The stimulator delivered a symmetrical biphasic current (500 microseconds, 50 Hz),²⁵ with a duty cycle of 20% (10 seconds on, 40 seconds off). The maximum output intensity of the device was 60 mA, adjustable in 2-mA increments. Electrode pads (5 x 5 cm) were placed horizontally over the muscle bellies, including the bilateral deltoids, biceps brachii, extensor carpi radialis, iliopsoas, quadriceps, and tibialis anterior muscles. Using two NMES electrical stimulators, each capable of stimulating two pairs of muscles simultaneously, the treatment was administered in a sequential manner, progressing from the upper to lower limbs and from proximal to distal regions. The intensity was adjusted to achieve muscle tetanic isometric contraction within the patients’ pain tolerance.^26,27

EM Program

EM was performed daily by physical therapists starting on the first day after lung cancer surgery and continued until discharge. Before each session, therapists assessed agitation and sedation using the RASS. For each session, interventions were determined by the score of RASS (Table 1). Before each session, physical therapists assessed the participants for any indication that could lead to unsafely performing the protocol (Supplemental. Table 1). Additionally, if a participant exhibited any other criteria for discontinuing the physical rehabilitation session such as orthostatic hypotension and dislodgment of catheters, the mobilization was stopped immediately, and the attending physician was informed of the emergency situation.

Table 1.

EM Protocol Details by RASS Score Range

RASS score	Level of consciousness	Exercise type	Exercise details	Equipment required	Frequency
-1	Drowsy but opens eyes to voice	Active-assisted ROM → Active ROM	• Upper/lower extremities •2-3 sets × 8-10 repetitions •Patient initiates movement with minimal assistance	• Therapist assistance	5 days per week
0	Alert and calm	Active ROM+ Functional training	• Sitting balance training • Standing with support • 3 sets × 8-10 repetitions • Weight-bearing exercises	• Bedside chair • Walker • Light dumbbells (1 kg)	5 days per week
+1	Restless but not aggressive	Active ROM → Light resistance training	• Full joint mobility exercises • 3 sets × 10-12 repetitions • Progressive resistance (0.5-1 kg)	•Light dumbbells (0.5-1kg) • Resistance bands	5 days per week

Control Group

The control group received standard postoperative ICU care according to institutional protocols, including routine monitoring, turning for pressure relief, basic hygiene assistance, and standard respiratory care. No structured mobilization protocols or electrical muscle stimulation were provided to control group participants during their ICU stay.

Data Analysis

Sample size calculations were based on the primary outcome of the ICU-AW incidence rates. The anticipated incidence was 8% for the group receiving EM, 13% for the group receiving NMES,²⁸ and 50% for the control group. Based on a significance level of 0.05 and a statistical power of 90%, calculations using the PASS15 software suggest that a total of 73 participants are needed across the three groups. Considering a 20% dropout rate, the final required sample size is determined to be at least 92, with a minimum of 31 participants in each group.

All continuous variables were presented as mean ± standard deviation (SD) or median (IQR). The continuous variables in the EM Group and NMES Group were compared separately with the Control Group by a two-sided independent samples t-test. Frequency data were compared between the groups using the χ² test. Statistical comparisons were adjusted for baseline measurements using analysis of covariance (ANCOVA). To account for potential confounding factors that might influence early postoperative muscle weakness, we retrospectively extracted additional clinical variables from the medical records. These included postoperative Day-1 hemoglobin levels, use of high-flow oxygen therapy, exposure to corticosteroids, incidence of sepsis, history of tracheostomy, and the use of sedatives and mechanical ventilation during the postoperative ICU stay. Continuous variables (e.g., hemoglobin levels) were compared using one-way ANOVA, and categorical variables were analyzed using the χ² test. All results were considered significant at P<0.05. Statistical analyses were performed using SPSS software V.25.0 and R version 4.3.1.

Results

Study Population and Characteristics

A total of 3,256 individuals were assessed for eligibility in this study, of which 3,151 were deemed ineligible, resulting in 105 participants being randomly allocated to the NMES, EM, and control groups. Within the intervention groups, three participants declined treatment, one opted out of surgery, and three were lost to follow-up. In the control group, one participant passed away postoperatively due to complications, and three were lost to follow-up. Further details can be found in Figure 1.

Figure 1.

Flow chart of the patients in the study

In the cohort of 94 individuals analyzed, no statistically significant differences were observed among the three groups in baseline demographic and clinical characteristics. The prevalence of COPD was the highest at 35%, followed by coronary heart disease (7%), atherosclerosis (4%), and asthma (1%). The majority of patients underwent thoracoscopic surgery (94%). The average surgery durations for the control group, EM group, and NMES group were 2.02±0.30, 2.06±0.40, and 2.16±0.41 hours, respectively. For more detailed information, please refer to Table 2.

Table 2.

Patient Characteristics

Variables	Total (n = 94)	Control group (n = 31)	EM group (n = 32)	NMES group (n = 31)	P
Age(years)	58.84 ± 9.69	59.35 ± 7.01	60.66 ± 9.73	56.45 ± 11.58	0.214
Gender (male), n (%)	47(50)	16(51)	18(56)	13(41)	0.662
Smoking(number/day×years)	273.62 ± 501.38	277.42 ± 558.40	276.25 ± 485.52	267.10 ± 473.10	0.996
BMI(kg/m2)	23.42 ± 5.24	24.24 ± 6.52	22.65 ± 4.15	23.39 ± 4.85	0.489
FEV1 value, L	2.12 ± 0.60	2.20 ± 0.62	1.92 ± 0.52	2.24 ± 0.63	0.067
FEV1/FVC% value	74.56 ± 12.39	77.68 ± 11.15	71.27 ± 11.95	74.84 ± 13.51	0.120
HADS	6.87 ± 7.26	7.42 ± 6.87	4.69 ± 5.47	8.58 ± 8.77	0.090
Postoperative day-1 hemoglobin, g/L	101.00 ± 12.59	99.26 ± 11.40	102.88 ± 13.44	100.81 ± 12.95	0.524
High-flow oxygen therapy, n (%)	37 (39.4)	14 (45.2)	15 (46.9)	8 (25.8)	0.167
Corticosteroid exposure, n (%)	46 (48.9)	15 (48.4)	17 (53.1)	14 (45.2)	0.817
VO2 peak, L/min	1.93 ± 0.76	1.99 ± 0.75	1.80 ± 0.73	2.00 ± 0.80	0.496
MaxMet	7.16 ± 2.29	6.98 ± 1.96	7.02 ± 2.11	7.50 ± 2.76	0.611
Complication, n(%)
COPD	33 (35)	7(22)	15 (46)	11(35)	0.130
Coronary disease	7(7)	1(3)	4(12)	2(6)	0.362
Atherosclerosis	4(4)	2(6)	1(3)	1(3)	0.760
Asthma	1(1)	0	0	1(3)	0.358
NRS	2.17 ± 2.02	2.00 ± 2.18	2.78 ± 1.84	1.71 ± 1.94	0.091
MRC	56.32 ± 3.45	56.65 ± 3.28	55.44 ± 3.49	56.90 ± 3.51	0.198
Surgical method,n(%)					0.817
Thoracotomy	5(5)	1(3)	2(6)	2(6)
VATS	89(94)	30(96)	30(93)	29(93)
Duration of surgery,hours	2.08 ± 0.37	2.02 ± 0.30	2.06 ± 0.40	2.16 ± 0.41	0.296
Left hand grip strength,Kg	27.62 ± 8.25	26.87 ± 7.89	28.06 ± 7.27	27.90 ± 9.65	0.828
Right hand grip strength,Kg	29.99 ± 8.67	29.45 ± 8.77	29.94 ± 8.41	30.58 ± 9.07	0.878

Abbreviations: BMI, Body Mass Index; FEV1, forced expiratory volume in one second; FVC, forced vital capacity; HADS, Hospital Anxiety and Depression Scale; VO2, maximal oxygen consumption; MET, maximum metabolic equivalent; COPD, chronic obstructive pulmonary disease; NRS, nutrition risk screening; MRC, Medical Research Council; EM, early mobilization; NMES, neuromuscular electrical stimulation; VATS, video-assisted thoracic surgery.

Regarding the potential confounding factors, no statistically significant differences were found among the three groups for postoperative Day-1 hemoglobin levels (P = 0.524), use of high-flow oxygen therapy (P = 0.167), or corticosteroid exposure (P = 0.817) (Table 2). Furthermore, our retrospective review revealed that nearly all patients received sedatives and mechanical ventilation during their routine postoperative ICU observation, while the incidences of tracheostomy and sepsis were exceedingly rare across all groups. Thus, these factors were uniformly distributed and are unlikely to have introduced systematic confounding to our primary outcomes.

The Incidence of ICU-AW

At two days after ICU admission, the incidence of the ICU-AW was 74.1% in the control group versus 21.8% in the EM group (OR 0.10, 95% CI 0.03 - 0.31) and 16.1% in the NMES group (OR 0.07; 95% CI 0.02 - 0.23; X² = 27.25, P < 0.001). At ICU discharge the incidence fell to 61.2% in controls compared with 9.3% (OR 0.07; 95% CI 0.02 - 0.26) and 3.2% (OR 0.02; 95% CI 0.00 - 0.18) in the EM and NMES groups, respectively (X² = 34.25, P < 0.001). Three months post-surgery, 16.1% of controls were still affected, whereas no cases were observed in the two intervention groups (X² = 8.06, P = 0.006) (Table 3).

Table 3.

The Incidence of ICU-AW

Group	Two days after ICU admission			Discharge from ICU			Three months after surgery
Group	Incidence n(%)	Absent n(%)	OR (95% CI)	Incidence n(%)	Absent n(%)	OR (95% CI)	Incidence n(%)	Absent n(%)	OR (95% CI)
Control group (N=31)	23(74.1)	8(25.8)	1.00 (Ref)	19(61.2)	12(38.7)	1.00 (Ref)	5(16.1)	26(83.8)	1.00 (Ref)
EM Group (N=32)	7(21.8)*	25(78.1)	0.10 (0.03 - 0.31)	3(9.3)*	29(90.6)	0.07 (0.02 - 0.26)	0(0)	32(100.0)	< 0.01 (0.00 - 1.56)
NMES Group (N=31)	5(16.1)*	26(83.8)	0.07 (0.02 - 0.23)	1(3.2)*	30(96.7)	0.02 (0.00 - 0.18)	0(0)	31(100.0)	< 0.01 (0.00 - 1.61)
X² value	27.25			34.25			8.06
P value	<0.001			<0.001			0.006

Note.* Indicates that the P value is less than 0.05 compared with the control group.

Odds ratios (OR) and 95% confidence intervals (CI) calculated via logistic regression (Ref=Control).

Abbreviations: EM, early mobilization; NMES, neuromuscular electrical stimulation.

Firth’s penalized likelihood logistic regression was applied only when one group had zero events.

Handgrip Strength

Handgrip strength data are summarized in Table 4. In all groups, handgrip strength declined significantly at two days after ICU admission and at ICU discharge compared with baseline (P < 0.05), but recovered to baseline levels by three months after surgery (P > 0.05). Compared with the control group, both the EM and NMES groups showed significantly greater left-hand handgrip strength at two days after ICU admission, at ICU discharge, and at three months after surgery (P < 0.05). For right-hand handgrip strength, the NMES group was significantly higher than the control group at all three time points (P < 0.05), whereas the EM group did not differ significantly from the control group at two days after ICU admission (95% CI, -7.19 to 0.06; P = 0.054) but showed significantly higher values at ICU discharge and three months after surgery (P < 0.05). No significant differences were observed between the EM and NMES groups at any time point (P > 0.05).

Table 4.

Hand Grip Strength in Different Groups

Groups	Baseline		Two days after ICU admission		Discharge from ICU		Three months after surgery
Groups	Left hand grip strength	Right hand grip strength	Left hand grip strength	Right hand grip strength	Left hand grip strength	Right hand grip strength	Left hand grip strength	Right hand grip strength
Control group	26.87 ± 7.88	29.45 ± 8.76	13.23 ± 6.64	14.84 ± 7.65	16.77 ± 6.78	18.32 ± 7.86	23.84 ± 7.96	25.55 ± 8.20
EM group	28.06 ± 7.27	29.94 ± 9.07	18.16 ± 5.65*#	18.41 ± 5.67#	21.41 ± 5.98*#	22.50 ± 6.97*#	28.94 ± 7.00*	30.31 ± 8.01*
NMES group	27.90 ± 9.64	30.58 ± 9.07	18.65 ± 7.91*#	21.35 ± 8.20*#	21.84 ± 7.09*#	24.74 ± 7.58*#	28.39 ± 7.70*	31.32 ± 8.01*

Note. Data are presented as mean±SD or median (IQR).

Abbreviations: EM, early mobilization; NMES, neuromuscular electrical stimulation.

*Indicates that the P value is less than 0.05 compared with the control group.

#Indicates that the P value is less than 0.05 compared with the baseline.

The Days of ICU and Hospital Length of Stay

No statistically significant differences in ICU length of stay were observed among the three groups (H = 0.93, P = 0.62). Similarly, no statistically significant differences were observed in hospital stay duration across the groups (H=1.06, P=0.58) (Table 5).

Table 5.

ICU and Hospital Length of Stay

Group	The ICU admission day, median (IQR)	The hospital length of stay, median (IQR)
Control group	3(1)	9(3)
EM group	3(1)	10(3)
NMES group	3(2)	9(4)
H	0.93	1.06
P	0.62	0.58

Abbreviations: EM, early mobilization; NMES, neuromuscular electrical stimulation.

Discussion

This study investigated the clinical effectiveness of NMES and EM compared with a control group in preventing ICU-AW after radical lung cancer surgery, providing important evidence for future clinical decision-making. Our primary finding was that both NMES and EM markedly reduced the incidence of ICU-AW compared with usual care. Compared with Zhou’s study,¹⁸ the preventive effect appeared more pronounced in our study. Several factors may account for this difference. First, the study populations were different: we enrolled postoperative lung cancer patients whose ICU admission was primarily for short-term monitoring to ensure postoperative safety,³ whereas Zhou’s study mainly included patients admitted to the ICU for emergent, life-threatening conditions, with greater illness severity and longer disease courses. Consistent with large international ICU audits, critically ill patients typically presented with significant organ dysfunction and high risks of complications and death.²⁹ Second, we excluded patients with preexisting limb motor impairment at enrollment, thereby minimizing confounding of MRC scores by baseline motor dysfunction. Consequently, the preventive efficacy against ICU-AW may be more evident in postoperative lung cancer patients.

Handgrip strength declined sharply during the first two ICU days. This marked reduction in strength over such a short period of only 48 hours can be attributed to several overlapping physiological mechanisms. First, major thoracic surgery triggers a profound systemic inflammatory and stress response, releasing catabolic cytokines that rapidly accelerate skeletal muscle protein breakdown.³⁰ Second, strict bed rest and prolonged immobilization during the initial postoperative phase drastically reduce muscle protein synthesis, with early signs of disuse atrophy appearing within days.³¹ Furthermore, factors such as postoperative pain, residual effects of anesthetics, and sedation can suppress the central motor drive, leading to an inability to fully recruit motor units voluntarily.³² However, this early muscle wasting was significantly mitigated by both interventions. EM actively engages the neuromuscular system to maintain mechanical loading and counter disuse atrophy, while NMES circumvents central motor inhibition by directly stimulating involuntary muscle contractions, thereby preserving muscle mass and local microcirculation. After three months, handgrip strength in both intervention groups had recovered to baseline levels.

Contrary to the report by Othman et al,³³ neither EM nor NMES shortened ICU length of stay or total hospital length of stay. Two factors may explain these findings. First, baseline hospital stays were already short in our cohort, likely reflecting our institution’s standardized perioperative management pathway for lung cancer resection, which has historically optimized recovery and minimized hospitalization duration. The relatively short baseline stays may have limited statistical power to detect further reductions.³⁴ Second, analyzing EM and NMES as separate monotherapies rather than combined interventions may have introduced a floor effect, where maximal benefit was already achieved with standard care alone. Future research should evaluate concurrent EM and NMES implementation within the same patient group to assess potential synergistic effects on clinical outcomes.

Furthermore, it is well established that early postoperative muscle weakness can be influenced by a variety of clinical confounding factors. For instance, reduced hemoglobin levels - a common hematological abnormality following lung cancer surgery - can lead to decreased oxygen delivery to tissues, plausibly contributing to early fatigue and muscle weakness.³⁵ Moreover, intensive care unit-acquired weakness is frequently associated with mechanical ventilation, the use of sedatives and neuromuscular blocking agents, corticosteroid exposure, and systemic complications such as sepsis. To ensure the robustness of our findings, we rigorously evaluated these potential confounders. Our retrospective analysis confirmed no significant differences among the groups in postoperative Day-1 hemoglobin levels, high-flow oxygen therapy, or corticosteroid exposure. Additionally, routine postoperative care for our cohort uniformly involved short-term mechanical ventilation and sedation during ICU observation, while the incidences of severe complications like sepsis or the need for tracheostomy were exceedingly rare. Therefore, these variables were evenly distributed across the study population and are highly unlikely to have introduced systematic bias into our primary outcomes.

Conclusions

In summary, both EM and NMES significantly reduce ICU-AW incidence and preserve early handgrip strength in post-lung cancer surgery patients. Clinically, these findings provide clinicians with two highly effective, non-pharmacological strategies to counteract early postoperative muscle wasting. EM and NMES offer flexible rehabilitation options that can be tailored to individual patient conditions, tolerance levels, and ICU resources. By integrating careful design with clear clinical endpoints, this study provides a solid foundation for future trials and the development of early rehabilitation guidelines in broader ICU populations. Furthermore, for advanced lung cancer patients complicated by distant metastases (e.g., solitary skull lesions³⁶ or leptomeningeal spread³⁷) where active EM is often contraindicated due to severe neurological deficits or fall risks, NMES serves as a valuable alternative to preserve peripheral muscle mass.

However, this study has several limitations that warrant consideration: (1) double-blinding was impossible because ICU patients cannot be realistically blinded to mobilization procedures; (2) this study focused on preventing ICU-AW, not on specific lung function metrics or respiratory rehabilitation, despite lung cancer surgery’s impact on postoperative function. These gaps are noted in the limitations and designated for future work; (3) the follow-up period was relatively short and may not capture the long-term effects of the interventions; and (4) there is an absence of detailed continuous data regarding the exact duration of sedative and vasoactive drug use, length of intubation, days on mechanical ventilation, and specific exposure dosages to neuromuscular blocking agents. Although our routine cohort management standardized most of these ICU practices, future large-scale prospective studies incorporating these precise parameters are needed to fully eliminate residual confounding.

Supplemental Material

Supplemental Material - The Effect of Early Neuromuscular Electrical Stimulation and Early Mobilization on Preventing the Intensive Care Unit-Acquired Weakness in Lung Cancer Resection Patients: A Randomized Controlled Trial

Supplemental Material for The Effect of Early Neuromuscular Electrical Stimulation and Early Mobilization on Preventing the Intensive Care Unit-Acquired Weakness in Lung Cancer Resection Patients: A Randomized Controlled Trial by Jun Wang, Lihua Huang, Chunna Lan, Na Deng, Huiling Hu, Yuzhou Hu, Aierken Nilubaier, Xiaoyue Yang, Baoyin Jiang in Technology in Cancer Research & Treatment.

Supplemental Material

Supplemental Material - The Effect of Early Neuromuscular Electrical Stimulation and Early Mobilization on Preventing the Intensive Care Unit-Acquired Weakness in Lung Cancer Resection Patients: A Randomized Controlled Trial

Supplemental Material

Supplemental Material - The Effect of Early Neuromuscular Electrical Stimulation and Early Mobilization on Preventing the Intensive Care Unit-Acquired Weakness in Lung Cancer Resection Patients: A Randomized Controlled Trial

Footnotes

Acknowledgements

Generative artificial intelligence (AI) tools were used to assist with language editing. The authors take full responsibility for the content of the manuscript, including the accuracy of the data, interpretation of results, and proper attribution of sources. No AI tool was used to generate or modify scientific data, produce figures containing research results, or draft sections reporting methodology or findings.

ORCID iD

Baoyin Jiang

Ethical Considerations

The study was conducted in accordance with the Declaration of Helsinki (1975, as revised in 2024). Institutional review board approval was obtained for the trial from Xiangya Second Hospital of Central South University, Changsha, China (No. 2023K054), on 1 September 2023.

Consent to Participate

All subjects gave their informed consent for inclusion before they participated in the study.

Author Contributions

BJ helped in the Conceptualization and the Methodology. JW and ND helped in the Formal analysis. XY helped in the Investigation. ND helped in the Project administration. JW and YH assisted in the operation of the Software. HH assisted in the supervision and validation. LH and ND assisted in the visualization. JW and LH assisted in the Writing of the original draft. JW and LH assisted with the Writing of the review & editing.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The datasets used and analyzed during the current study are available from the corresponding author upon request.*

Trial Registration

Chinese Clinical Trial Register, No. ChiCTR2300077110. Date of registration: 31 October 2023.

Supplemental Material

Supplemental material for this article is available online.

Appendix

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