EFFECTS OF RESPIRATORY MUSCLE TRAINING ON QUALITY OF LIFE IN HEMODIALYSIS PATIENTS: BLINDED RANDOMIZED CLINICAL TRIAL

Authors:
Andrey de Borba Guimarães¹, Ana Gabrielle Espindola de Freitas¹, Juliana Ribeiro Deves¹, Kauana Neves Selister¹, Vicente de Almeida Brito¹

¹ Universidade Luterana do Brasil – ULBRA, RS, Brazil.

Corresponding author:
Vicente de Almeida Brito
Rua Manoel Fortunato de Souza, 694, Torres, RS 95560-000, Brasil
E-mail: vicentebrito09@gmail.com

Keywords: Chronic kidney disease, quality of life, inspiratory muscle training, intradialytic exercise.

ABSTRACT

Introduction: Hemodialysis patients have low levels of quality of life due to associated disorders such as altered lung function, sarcopenia, decreased functional capacity and increased fall risk. This study aims to evaluate the effects of respiratory muscle training associated with kinesiotherapy versus the effects of kinesiotherapy on quality of life in hemodialysis patients. Methods: This is a blinded randomized clinical trial with hemodialysis patients, randomized in two groups: conventional kinesiotherapy (CKG) and conventional kinesiotherapy + RMT (RMTG). Respiratory muscle strength, sustained maximal inspiration, quadriceps muscle strength, hand grip, fall risk and quality of life were measured pre and post intervention. Results: There was an increase in the general heath domain in the CKG, while RMTG had significant improvement in physical functioning, pain, mental health, emotional well-being, energy/fatigue and effects of kidney disease domains. However, only CKG showed gains in maximal inspiratory pressure. Conclusion: Respiratory muscle training associated with kinesiotherapy improves quality of life in patients on dialysis.

INTRODUCTION

Chronic kidney disease (CKD) is defined as the end stage of kidney disease, when there is an irreversible loss of renal function and structure of the kidney.¹ CKD is defined by a decreased renal function based on the glomerular filtration rate (GFR) less than 60mL/min, renal biomarkers, abnormal sedimentoscopy elements, electrolyte disturbances due tubulopathy and/or histological or structural abnormalities.^2,3 According to World Health Organization (WHO), kidney disease was responsible for 1.179.839 deaths in the world, about 2.1% of the total.⁴ Currently is the 12th biggest cause of deaths, but it is estimated that in 2060 it will be the 7th.⁴ In Brazil the numbers are still inaccurate, but it is estimated that there are 3 to 6 million people affected with CKD.⁵

Due to renal disability, patients with CKD need to undergo a kidney transplant or a renal replacement therapy (RRT), where hemodialysis is the most used.⁶ This is a procedure where a machine receive the patient’s blood through a vascular access and is driven by a pump to the dialysis filter.⁷ The blood is exposed to a dialysis solution, removing excess fluid and toxins, returning totally clean to the patient.⁷ The countless consequences caused by kidney disease as muscle weakness, sarcopenia, increased fall risk, dyspnea and changes in lung function are commonly increased due to the high physical and psychological stress resulting from treatment.^8-10

The adverse effects of CKD associated with hemodialysis have a great impact in the lives of these patients, verified through the decrease of their quality of life.^6,11,12 Through specific questionnaires, it is possible to state that the quality of life of hemodialysis patients is reduced in more than one domain, surpassing only the biological perspective and also involving the social and psychological scope.¹³

Given the above, physiotherapy interventions through resistance exercises, aerobic exercises and respiratory muscle training shows improvement in several aspects of this population.¹⁴ The benefits of physiotherapy are not limited to primary issues such as increased peripheral muscle strength, respiratory muscle strength and functional capacity, but they also reflect on important points like the improvement of the quality of life and decrease of the mortality.^15-17

Therefore, the aim of this study was to evaluate the effects of respiratory muscle training associated with kinesiotherapy versus the effects of kinesiotherapy on quality of life in hemodialysis patients.

METHODS

This is a blinded randomized controlled trial and data were acquired from january to march 2020 at Nefrotorres Clínica de Doenças Renais, city of Torres, Rio Grande do Sul, Brazil. This research met the criteria in accordance with resolution number 466/2012 of the Brazilian Ministry of Health, was approved by the Research and Ethics Committee of Universidade Luterana do Brasil (ULBRA) with reference number 3.738.209, registered in the Brazilian Registry of Clinical Trials with reference number RBR-8M62Y2 and all participants signed the Free Research Informed Consent Form.

We included patients of both genders, aged between 18 and 75 years, undergoing hemodialysis for more than 6 months with regular frequency of three times a week. Exclusion criteria was follow: patients who practiced some type of physical exercise and/or who had uncontrolled systemic arterial hypertension, ischemic heart disease, amputation, deep vein thrombosis, severe dyspnea, femoral fistula, stage 3 chronic obstructive pulmonary disease (COPD), decompensated congestive heart failure, cardiac arrhythmia, severe pneumopathy, acute systemic infection, pregnancy, decompensated diabetes mellitus and any orthopedic, neurological or cognitive impairment that compromises the understanding and execution of exercise programs.

DATA COLLECTION, EVALUATION AND RANDOMIZATION PROCEDURE

After meeting the eligibility criteria, the study participants received information about the survey and were evaluated by a blind evaluator using an evaluation form for collecting sociodemographic data, maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), sustained maximum inspiratory capacity, quadriceps muscle strength, hand grip strength, fall risk and quality of life. After undergoing the initial assessment, the patient was allocated to one of the intervention groups through randomization performed by a collaborating researcher. Previously, we had written the names of the groups in pieces of paper and placed them inside a sealed envelope for the collaborating researcher to pick up at random. There were two treatment groups: conventional kinesiotherapy group (CKG) and conventional kinesiotherapy + RMT group (RMTG).

MIP and MEP were measured using the -300 / + 300 CMH2O Murenas® analog manovacuometer. The evaluation was carried out with the participant sitting in a reclining chair (knees and hips at 90º) using a nasal clip. MIP was based on the residual volume and MEP on the total lung capacity. The effort should be maintained for at least 1,5 seconds, allowing a 1-minute rest between the maneuvers, which were repeated 3 times. The highest value of these three maneuvers was registered.¹⁸

To evaluate sustained maximum inspiratory capacity we used a Voldyne 5000®. The participant remained seated in the chair using the nasal clip and was instructed to perform a sustained maximal inspiration after a maximal expiration.

Muscle strength was measured with a SH – Saehan® hydraulic hand dynamometer and maximum voluntary isometric contraction was defined as the average value of three measures. For quadriceps strength, the patient was in a seated position (with 45º of knee flexion) and received the command to perform the extension movement with maximum contraction. For handgrip strength, the patient remained seated with elbows bent to 90 degrees and forearms in mid-position and received the command to perform a maximum hand grip contraction.

Timed Up and Go Test (TUG Test) was used to evaluate the fall risk, with the quantification in seconds of mobility and functional balance.^19,20 The patient needed to stand up from a chair, walk for 3 meters in a straight line, turn 180º, walk back and sit down. A stopwatch starts when the patient gets up and stops when he sits down.

Quality of life was measured by the Kidney Disease and Quality of Life – Short Form 1.3 (KDQOL-SF 1.3), translated and validated into portuguese.^21,22 The questionnaire was applied in the form of an interview and the result was calculated according to the manual.²³

After the end of the intervention program, the patient was reevaluated by the same evaluator.

INTERVENTION PROGRAM

The intervention program was intradialytic, performed 3 times per week during 1 month, totalizing 10 sessions. The interventions had an average duration of 45 minutes and were performed according to the group the patient was allocated to. The application of the intervention program was carried out by researchers previously trained and familiarized with the program.

The patients allocated in CKG received a adapted kinesiotherapy program, based on previous studies.^24-28 The program consisted of aerobic exercise (cycling) for 10 minutes on a WCT Fitness 60820® portable cycle ergometer in the front of patient chair, pedaling progressively and individually according to the subjective perception of effort measured by the Borg Scale, which should be between 3 and 6; and resistance exercises composed by three series of 15 repetitions of hand grip (for strengthening of finger flexors) with a ACTE® handgrip, knee extension (for strengthening of knee extensors) with ankle weights from 1 to 2 kgs (according to patient tolerance) and elbow flexion (for strengthening of elbow flexors) with dumbbells from 1 to 2kgs (according to patient tolerance).

The patients allocated in RMTG received the same kinesiotherapy program of CKG with the addition of a respiratory training based on previous studies, using a Powerbreathe Plus Light® respiratory trainer.^29-31 The patients were instructed to perform three series of 30 breaths with 1 minute rest between series. The linear load was adjusted to 30% of MIP.

In both groups, participants did not perform elbow flexion exercises on the limb where the fistula was located.

DATA ANALYSIS

The sample size was calculated from a study of Gianaki et al (2005).³² Using a power of 80% and alpha of 5% with a confidence interval of 95% and a sample size ratio of 1:1 (CKG:RMTG) we reached the number of 11 participants for each intervention group. Believing that losses and refusals will be around 10%, we reached the final number of 12 individuals for each study group, totaling 24 individuals.

The SPSS (Statistical Package for Social Science) 17.0 statistic program was used for statistical analysis. The Shapiro-Wilk test was used to verify the normality of data. For the parametric data, we used Student’s t-test (within-group variables) and one-way ANOVA (between-group variables) For non-parametric variables, Wilcoxon signed-rank test (within-group) and Kruskal–Wallis test (between-group) was used. A statistical significance of 5% was set (p<0,05).

RESULTS

As described in Figure 1, a total of 24 patients were evaluated, seven were excluded for not meeting the eligibility criteria, eight did not complete the intervention program due to the COVID-19 pandemic and were not included in the analysis. Therefore, nine patients were analyzed after 10 sessions.

Figure 1. Study flow diagram.

Table 1 shows the basic characteristics of patients, where 6 were women and 3 were men and had an average age of 53.50 ± 8.44 years in the CKG and 57 ± 18.53 years in the RMTG, average dialysis duration was 30 ± 15.87 months in the CKG and 22.75 ± 7.63 months in the RMTG, average height was 1,64 ± 0,06 meters in the CKG and 1,64 ± 0,15 meters in the RMTG, average weight was 69,54 ± 9,85 kilograms in the CKG and 87,5 ± 22,53 kilograms in the RMTG and the average body mass index (BMI) was 25,9 ± 2,65 kilogram per square centimetre (kg/cm²) in the CKG and 31,3 ± 6,46 in the RMTG.

Using the Student t-test for independent samples (Levene’s Test for Equality variance) in the intergroup relationship, the distribution of the participants demonstrated homogeneity in dialysis duration, gender, height and weight, however, it showed a significant (p<0,05) difference for age and BMI.

Table 1. Characteristics of the sample.

Variables	RMTG	CKG	P-value
Gender (M/F)	2/2	1/4	0,22
Age (years)	57,00 + 18,52	53,20 + 8,43	0,04*
HD time (months)	22,75 + 7,63	30 + 15,87	0,20
Height (meters)	1,63 + 0,14	1,63 + 0,06	0,16
Weight (kilograms)	84,62 + 24,92	69,54 + 9,85	0,13
BMI (kg/m2)	31,32 + 6,46	25,92 + 2,64	0,08

Regarding the quality of life (QoL) index (Figure 2), the CKG showed significant improvement in general health domain (55 ± 18,71 vs 66 ± 21,04, p = 0,043). The RMTG showed significant increase in the following domains: physical functioning (25 ± 31,36 vs 40 ± 42,23, p = 0,04), pain (29,37 ± 12,14 vs 69,37 ± 35,73, p = 0,036), mental health (54 ± 38,99 vs 69 ± 32,06, p = 0,018), energy/fatigue (32,5 ± 16,58 vs 50 ± 18,71, p = 0,001) and effects of kidney disease (37,5 ± 19,60 vs 46,87 ± 19,26, p = 0,035).

At the end of the intervention program, in the intragroup analysis only the CKG group showed a significant increase in MEP (48 ± 32,71 vs 65 ± 40,31 cmH2O, p = 0,026), according to table 2. There were no significant differences in the intergroup analysis.

Table 2. Differences within and between groups.

Variables	RMTG	CKG	P-value
Pre MIP (cmH2O)	-60,00 + 28,28	-54,00 + 39,11	0,80
Post MIP (cmH2O)	-62,50+ 20,61	-60,00 + 43,01	0,91
Pre MEP (cmH2O)	67,50+ 27,53	48,00+ 32,71	0,37
Post MEP (cmH2O)	60,00 + 29,43	65,00 + 40,31$	0,84
Pre SMIC (ml)	5000,00 + 0,00	4000,00 + 2236,06	0,40
Post SMIC (ml)	5000,00 + 0,00#	5000,00 + 0,00#	–
Pre RQS (kg)	10,50 + 3,69	15,4400 + 4,05	0,10
Post RQS (kg)	11,25 + 2,50	14,92 + 7,65	0,39
Pre LQS (kg)	10,75 + 3,69	15,44 + 4,05	0,11
Post LQS (kg)	10,75 + 4,34	14,72 + 8,14	0,41
Pre RHG (kg)	25,08 + 13,42	22,04 + 14,15	0,75
Post RHG (kg)	26,50 + 9,93	25,38 + 13,14	0,89
Pre LHG (kg)	22,40 + 10,58	19,84 + 14,49	0,77
Post LHG (kg)	26,25 + 15,10	22,46 + 15,73	0,72
Pre TUG (s)	21,94 + 14,57	17,27 + 11,028	0,60
Post TUG (s)	19,61 + 12,54	15,71 + 9,63	0,61

Both groups showed lower MIP values than predicted (CKG: -54 ± 39,12 vs 90,52 ± 16,46 cmH2O, 59,65% of predicted – p = 0,017; RMTG: -60 ± 28,28 vs -98,41 ± 27,40 cmH2O, 60,97% of predicted – p = 0,020), as well as the MEP values (CKG: 48 ± 32,71 vs 91,29 ± 21,44 cmH2O, 52,58% of predicted – p = 0,004; RMTG: 67,50 ± 27,54 vs 101,48 ± 34,82 cmH2O, 66,52% of predicted – p = 0,013), as shown in figure 3.

DISCUSSION

Patients on hemodialysis have worse QoL of life levels when compared to the normative population, according to the evaluative findings of the present research.⁶ Recent studies have analyzed the effects of intradialytic peripheral muscle exercise, whether aerobic and/or resisted, in the QoL levels of this population, showing improvement in the domains of cognitive function, quality of social interactions, pain and physical functioning.^33,34 Similarly, Pellizzaro et al.³⁰ studied these same effects, through a respiratory muscle training (RMT) program and, after 10 weeks, there was an improvement in the domains of sleep, pain and energy/fatigue. Corroborating the findings in the literature, in the present study the group that performed only peripheral exercise (CKG) showed significant improvement in the general health domain, while the group that performed the peripheral muscle training in addition with respiratory muscle training (RMTG) showed significant improvement in the domains of physical functioning, pain, mental health, energy/fatigue and effects of kidney disease. Even without statistically significant differences, both groups showed an improvement trend in the other domains, as found in systematic reviews.^35,36 We believe that there was an improvement in these levels due to physical activity increase muscle blood flow and open the capillary surface area, increasing the flow of urea and other toxic agents, promoting an improvement in the dialysis treatment adequacy (Kt/V) and also as a result of the fact that respiratory muscle training attenuates the respiratory metaboreflex mechanism, providing several systemic effects.^37,38

In the study conducted by Da Silva et al.³⁹ the effects of RMT on MIP and MEP of patients with chronic kidney disease were evaluated using a 24-session program and didn\’t show statistically significant improvements. However Medeiros et al.³⁶ has demonstrated in a research with 40 sessions comparing the RMT group with a control group, indicating improvement in MIP and MEP values for both groups. In this study, only the control group showed a significant improvement in the MEP value.

In our study, there was no evidence of improvement in quadriceps muscle strength. Diverging from these findings, Abdo et al.⁴⁰ showed an increase in quadriceps strength through a 24-session training program using a cycle ergometer, as well as Simo et al.⁴¹ who found an increase after 12 weeks of low intensity exercise. Still about the muscular strength, but now of hand grip, Simo et al.⁴¹ also found positive effects, the same way that Olvera-Soto et al,⁴² who concluded that 24 sessions of resistance exercise represented an opportunity to increase this strength. In 10 sessions, our study found no evidence of improvement in handgrip muscle strength. Maynard et al.⁴³ demonstrated a significant reduction in the time taken to perform the TUG Test through a 12-week program of aerobic and resistance exercises associated with virtual reality in individuals undergoing hemodialysis. Despite not showing significant differences in the average time of execution of the TUG Test after the period of 10 sessions, in our study both groups showed an average decrease of 1.56 seconds in the CKG and 2.33 seconds in the RMTG. The impact of this improvement is positive given the weakness of this population, since TUG Test performance is also an assessment of functional capacity and is directly related as a predictor of mortality. According to Roshanravan et al,⁴⁴ each second slower in test performance is associated with an 8% higher risk of death.

The progressive degeneration of renal function in patients with CKD causes several metabolic disorders such as mitochondrial activity, increased production of pro-inflammatory cytokines, oxidative stress and insulin resistance.^45,46 Due to these disorders, associated with what we find in the literature in relation to the number of interventions, we consider that 10 sessions may not have been sufficient to present significant changes.

LIMITATIONS

It was not possible to reach a larger number of participants due to the pandemic of COVID-19 and the consequent social distancing precautions defined by WHO, resulting in a small sample. There was also a variability in relation to the age group of the sample, which may have induced a smaller change in the results due to a greater association of comorbidities.

CONCLUSION

The results of our study suggest that a respiratory muscle training program associated with kinesiotherapy results in a greater improvement in the QoL levels of hemodialysis patients when compared to a conventional kinesiotherapy program. As it is a population with a chronic condition that generates several comorbidities, including important metabolic disorders, we believe that more interventions would bring more expressive results. Thus, we suggest future studies with a greater number of consultations.

CLINICAL MESSAGES

• Respiratory muscle training in association with kinesiotherapy is effective to increase quality of life levels in patients undergoing hemodialysis.
• Patients with CKD have lower MIP and MEP values than predicted.

ACKNOWLEDGEMENTS

The authors would like to thank the Clínica de Nefrologia NefroTorres, the nurse staff, the medical staff and the patients for making possible the realization of this project. We appreciate the valuable contributions of Ana Gabrielle Espindola de

Freitas, Juliana Ribeiro Deves, Kauana Neves Selister and Murilo Gomes Della Nina.

DECLARATION OF CONFLICTING INTERESTS

The authors declare that there is no conflict of interest.

FUNDING SUPPORT

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

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