Effects of foot reflexology on anxiety and physiological parameters in patients undergoing coronary artery bypass graft surgery: A clinical trial

Accepted Manuscript Effects of foot reflexology on anxiety and physiological parameters in patients undergoing coronary artery bypass graft surgery: A clinical trial Yaser Abbaszadeh, Atefeh Allahbakhshian, Alehe Seyyedrasooli, Parvin Sarbakhsh, Sakineh Goljarian, Naser Safaei PII:

S1744-3881(17)30483-8

DOI:

10.1016/j.ctcp.2018.02.018

Reference:

CTCP 841

To appear in:

Complementary Therapies in Clinical Practice

Received Date: 25 October 2017 Revised Date:

25 February 2018

Accepted Date: 28 February 2018

Please cite this article as: Abbaszadeh Y, Allahbakhshian A, Seyyedrasooli A, Sarbakhsh P, Goljarian S, Safaei N, Effects of foot reflexology on anxiety and physiological parameters in patients undergoing coronary artery bypass graft surgery: A clinical trial, Complementary Therapies in Clinical Practice (2018), doi: 10.1016/j.ctcp.2018.02.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Effects of foot reflexology on anxiety and physiological parameters in patients undergoing coronary artery bypass graft surgery: A clinical trial Affiliation:

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Yaser Abbaszadeh, Atefeh Allahbakhshian, Alehe Seyyedrasooli, Parvin Sarbakhsh, Sakineh Goljarian, Naser Safaei Master of medical-surgical nursing student, Faculty of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, Iran Assistant Professor, Department of Medical-Surgical, Faculty of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, Iran

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Lecture, Department of Medical-Surgical Nursing, Faculty of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, Iran

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Assistant Professor, Department of Statistics and Epidemiology, School of Public Health, Tabriz University of Medical Sciences, Tabriz, Iran Assistant Professor, Department of physiotherapy, Faculty of Rehabilitation, Tabriz University of Medical Sciences, Tabriz, Iran Professor, Department of Cardiac Surgery, Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran E-mail addresses:

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Corresponding author: Atefeh Allahbakhshian, PhD, Faculty of Nursing & Midwifery, Tabriz University of Medical Sciences, Southern Shariati Street, Tel.:+98098414796770; fax:+98098414796969 (E-mail:[email protected]). [email protected] (Yaser Abbaszadeh), [email protected] (Atefeh Allahbakhshian), [email protected] (Alehe Seyyedrasooli), [email protected] (Parvin Sarbakhsh), [email protected] (Sakineh Goljarian), [email protected] (Naser Safaei)

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Effects of foot reflexology on anxiety and physiological parameters in patients undergoing coronary artery bypass graft surgery: A clinical trial ABSTRACT Introduction: This study aimed to investigate the effect of foot reflexology on anxiety and physiological parameters in patients after CABG surgery.

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Method: This was a single-blind, three-arm, parallel-group, randomized controlled trial with three groups of 40 male patients undergoing CABG. Participants were placed in three groups, named intervention, placebo, and control. Physiological parameters were measured including systolic and diastolic blood pressure, mean arterial pressure, heart rate, respiratory rate, percutaneous oxygen saturation, and anxiety of participants. Results: Results showed a statistically significant difference between intervention and control groups in terms of the level of anxiety (p<0.05). Also, results showed a statistically significant effect on all physiological parameters except heart rate (p<0.05).

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Conclusion: This study indicated that foot reflexology may be used by nurses as an adjunct to standard ICU care to reduce anxiety and stabilize physiological parameters such as systolic, diastolic, mean arterial pressure, and heart rate.

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Keywords: Foot reflexology; Anxiety; Physiological parameters; Coronary artery bypass graft; Nursing

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1. Introduction Coronary artery disease (CAD) is among the leading causes of mortality worldwide, and is becoming increasingly more prevalent [1]. Treatments include pharmacotherapy, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) [2]. In recent years, CABG has emerged as the standard treatment for critical cases [3], accounting for 60% of all open-heart surgeries in Iran [4]. Despite many advantages of this treatment for improving acute symptoms of the disease and increasing survival rate, evidences indicate that the diagnosis of CAD and the need for CABG arouses anxiety in patients [5]. Patients may suffer from anxiety and depression after the surgery [6, 7] and in addition to fear and mood disorders, patients undergoing heart surgery may develop other physiological dysfunctions [8]. The anxiety provoked in these patients, stimulated their sympathetic system [9, 10], and increased indices such as heart rate, blood pressure, respiratory rate [10]. Anxiety can also delay the healing of wound site [1117] and weaken immune system response [17-19]. Tully et al. (2011) showed that post-operative anxiety is one of the risk factors for atrial fibrillation [20]. After surgery, patients were transferred to the intensive care unit (ICU) and received mechanical ventilation until their cardiac and respiratory conditions stabilized [21]. In addition to the stress of undergoing heart surgery, patients experience stress and anxiety triggered by the ICU environment [10, 22] and mechanical ventilation [23]. Additionally, patients suffer more anxiety during the weaning process of recovery [24, 25]. The administration of analgesic and soporific drugs is common in ICUs [26], aiming to reduce anxiety and stress, improve the course of mechanical ventilation [27, 28], and manage pain [29]. However, the use of these medicines may result complications such as respiratory depression [30-32], and gastrointestinal problems like nausea and vomiting [29, 32, 33], gastrointestinal reflux, reduced bowel movement and constipation, dependence and addiction [32], cognitive disorders [34, 35], increased duration of mechanical ventilation, prolongation of the length of ICU stay, and a higher chance of mortality [26, 36].Today, it seems that non-pharmaceutical therapies such as complementary and alternative medicine (CAM) may be used to reduce anxiety [21, 37-40], prevent physiological reactions caused by anxiety [37, 40, 41], stabilize vital signs [42], and manage pain [43]. Since nurses play a key role in predicting psychological and physiological needs of patients and reducing their level of anxiety and stress [25], it seems that nurses can practice some CAMs to reduce stress, pain, and improve the health conditions of patients [44]. As a result, in addition to helping patients relax, nurses can lower the chance of complications by actively reducing the anxiety levels of their patients. CAM therapies is made up of different fields, such as acupuncture, herbal medicine, chiropractic, homeopathy, reflexology massage, etc. [45]. Foot reflexology is a form of CAMs administered by applying pressure at specific points on the body [46]. In fact, reflexology specialists believe that there are some reflex areas and points on feet and hands, which may relate to certain body

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parts, organs, and specific glands. In this method, pressure is applied to reflex points, specifically on feet due to their accessibility and sensitivity [47, 48]. Reflexology claims that stimulating the nerves of the points indicated on the foot or hand maps causes response from organs or glands [49]. Maybe the application of this technique can reduce stress and anxiety by reducing fluctuations in sympathetic system [38, 50, 51]. In other words, presumably reflexology can reduce the level of vital signs increased with anxiety [41]. Maybe reflexology can be a nonaggressive, simple, low-cost, and complication-free method, which can be used as a suitable complementary treatment, with pharmacotherapy and exemplary nursing skills [52, 53]. Maybe this safe and practical method can be applied to reduce the level of anxiety in patients hospitalized in hospitals and healthcare centers [54]. Based on reflexologists' claims, a number of studies have been conducted studying the effect of reflexology with regards to different situations and diseases; such as reduction of anxiety and improvement of physiological parameters in bronchoscopy candidates [55] and reduction of anxiety in cancer patients undergoing chemotherapy [56]. With respect to cardiology, studies on the effect of foot reflexology on reduction of anxiety after CABG [38] and reduction of anxiety in patients with CAD before angiography [51] can be mentioned. Despite the positive effect of this method mentioned by different studies, some studies have rejected such claims, due to: ineffectiveness of reflexology in improving the rate of arterial compliance and physiological indices of healthy people [57], ineffectiveness of reflexology in improving hemodynamic parameters of patients with chronic heart failure [58], and ineffectiveness of reflexology in improving anxiety and physiological indices of patients undergoing CABG [44]. Systematic reviews have also indicated the need for more studies on effects of reflexology [59-61]. Regarding the importance of CAD, the prevalence of medical methods such as CABG for its treatment, the creation of undesirable psychological and physiological conditions in patients, and the unique role of nurses in the course of care and progress of these patients, the use of safe, complication-free, and simple methods, could be considered as an additional skill for nurses. Nevertheless, there is no strong evidence confirming the effectiveness of reflexology, specially in these patients, in bedside. To this end, this study was conducted to investigate the effect of foot reflexology on the level of anxiety and physiological parameters of patients undergoing CABG.

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2. Method 2.1. Study design This was a single-blind, three-arm, parallel-group controlled trial with three groups.

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2.2. Setting This study was conducted between 20 January and 22 May 2017 in the Cardiac Surgery Unit of Shahid Madani teaching hospital affiliated to the Tabriz University of Medical Sciences, Iran.

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2.3. Participants Participants were selected from a pool of male patients hospitalized in Shahid Madani Hospital, who had been diagnosed with CAD, and were candidates for non-urgent CABG. Exclusion of females was due to cultural matters, as all of the massage sessions were conducted by a male masseur. Samples were selected using convenience sampling. Inclusion criteria were: participants aged 18-65 years, candidate for non-urgent bypass surgery, without previous open-heart surgery, and without psychological problems (e.g. depression or anxiety) based on their medical history clinical record of them, with normal foot soles, without foot abnormalities (e.g. corn, callus, scar, neuropathy), without any intra-aortic balloon pump or pacemaker, in SIMV/CPAP (PSV) mode, not addicted to alcohol and drugs, without history of chronic pain (for example from arthritis), without history of receiving reflexology, without facial scars, without severe visual and auditory disorders, not taking inotropic drugs, and who had not received analgesics or injections of neuromuscular inhibitors since their admission to the ICU. Exclusion criteria were: decreased level of consciousness, mitral valve repair or replacement during CABG surgery (Each type of cardiac surgery will vary from viewpoints of surgical duration, surgical site, recovery time, and duration of hospitalization, which can have an effect on patient anxiety [38]. Different physiological changes will be developed as a result of different changes in the level of anxiety.), and hemodynamic instability.

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2.4. Specification of Sample size and Randomization The sample size was specified after conducting the pilot study on 30 patients undergoing CABG (10 participants in each group). Based on the systolic blood pressure rates of the first day immediately after intervention, and the comparison of them between the three groups using pilot data (Table 1), and a formula of sample size required for the analysis of variance with α=0.05 and a power of 95%, a sample size of 32 in each group was specified. Considering 25% attrition, the sample size of 40 participants was considered in each group (Figure 1). The sample size was specified using G-power 3.1.2. Randomization was done using blocking. Participants were placed in three groups, named intervention (A), placebo (B), and control (C) using random block size of six by someone not involved in sampling. Each block included two participants from each group. Participants were placed based on the sequence of the block of the target group. The type of intervention was written on a paper and placed in an opaque envelope numbered sequentially (allocation concealment). An intervention type of each participant was stated after the surgical procedure and at the bedside for the researcher. The researcher did not have access to the allocation list. Φ = 1/σ n / r Σ (µi – µ.)² , µ. = Σ µi / r r: Number of groups=3, µ i: Mean of each group, σ:Standard deviation, n = 30

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2.5. Intervention Group A received foot reflexology in bed, while reclining in a supine position. Group B received general heel massage (superficial touch, and without any pressure.) in bed, also in supine position. Heel selected as placebo according to Ebadi et al.’s study [53]. There were not reflexology points and areas on the heels which were selected in group A. Reflexology theory declares that massaging irrelevant areas does not have therapeutic effect [62]. Also, according to the reflexologists’ belief, reflexology is the use of pressure techniques, stimulating the nerves and receiving responses from the organs [49]. Thus, no pressure was applied on heels for group B. First, the masseur washed and warmed his hands and soaked them in olive oil (which does not have a therapeutic effect and was used only for lubrication). Then, he administered foot reflexology and general foot massage. Both types of massage were applied first to the right foot and then the left one. The foot reflexology and surface heel massage of each foot lasted for 15 minutes. Foot reflexology methodology was based on a text book for reflexology [63]. Practical trainings in text book has been taught to the first author by a reflexology specialist (first author has received one year of reflexology trainings and its certificate from the reflexology specialist. Trainings was conducted in reflexology unit of Faculty of Rehabilitation, Tabriz, Iran. Reflexology specialist was certified from the Faculty of Traditional Medicine of Shahed University in Iran, and with 8 years of experience.). The intervention was supervised by the reflexology specialist and research team. According to the reflexologists' claim, the points on the sole of the foot which may be associated with reduction of anxiety and adjustment of physiological parameters were selected. Selected points on the right foot included solar plexus (It’s called the relaxation point. Perhaps it helps calm, balance, relaxation, panic reaction, and reducing anxiety and stress.), hypothalamus gland (Perhaps links the pituitary gland point to secrete hormones and balances autonomic nervous system.), pituitary gland (Probably stimulating this point causes control of other endocrine glands, secretion of hormone, creating balance in secretion of hormones, creating emotional and physical balance.), lung (Maybe stimulation of the lung area regulates breathing and Oxygen level.), and adrenal glands (Perhaps stimulating this point causes secretion of adrenaline and hydrocortisone, creating balance, combating with stress and calming stress response.). Selected points on the left foot included solar plexus, hypothalamus gland, pituitary gland, lung, heart (Probably stimulating this point regulates blood circulation.), and adrenal glands. First, initial movements of relaxation included three techniques, namely rotate the foot, stretch the Achilles, and open and stretch the chest were administered respectively, each for one minute before giving reflex point massage on each foot (less time was considered for these techniques to focus more on reflex points and areas.). In the first technique, the heel was held with the opposite hand from the below, the metatarsal arch was gripped with the hand of the same side, and rotated clockwise and counterclockwise for several times. In the second technique, the heel was pulled and released with the opposite hand in the same position. In the third technique, fingers of the both hands are placed on top of the foot in a way that the fingertips are located towards the base of toes in zone 3 (a longitudinal area that begins from above the head, passes through the eyes and reaches the middle fingers and toes), and both thumbs are placed under the metatarsal arch in this area.

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2.6. Data Collection Instrument Data collection instrument included four sections:

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Then, the pressure was applied by gliding movement outwardly. In the next stage, the given body points were equally stimulated for 12 minutes. Stimulation of solar plexus was done through placing pressure and releasing, and applying rotational pressure with thumb. Stimulation of hypothalamus gland, pituitary gland, heart, and adrenal area was performed through applying rotational pressure with thumb. Stimulation of lung area was done by pulling back the toes and executing biting movements with the thumb from above the diaphragm area on the sole of the foot towards the toes [63]. Since organs at each body side are corresponded to the foot at the same side, the respective heart point in the left foot was stimulated, and the location of the reflex points and areas in this study was selected based on the map presented in Embong et al.’s study (2015) [64].

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2.6.1. Participants Demographic Form The demographic information form of participants was completed through interviewing and reviewing clinical records of them. This form included questions related to age, body mass index, marital status, educational level, job, duration of surgery, time to regain consciousness after being transferred to ICU, history of diseases such as hypertension, hyperlipidemia, and diabetes, history of smoking, history of pulmonary diseases, and number of grafts.

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2.6.2. Faces Anxiety Scale (FAS) In this study, the faces anxiety scale (FAS) was used for collecting anxiety data of patients undergoing mechanical ventilation and after mechanical ventilation. This scale was developed by McKinley et al. (2003) [65]. FAS was used because mechanically ventilated patients were unable to communicate verbally to respond to anxiety-inducing items, as a result use of currently available anxiety measures is difficult. The correlation of FAS with non-verbal responses of patients to short questions from the Profile of Mood States Anxiety Subscale was reported as 0.64 (p<0.001). The score range between 0.4-0.8, as the validity criterion, indicates the validity of FAS as a suitable instrument for anxiety measurement [66]. McKinley et al. (2008) reported the correlation coefficient of 0.7 (p<0.005) for this scale and the Spielberger state-anxiety inventory in non-ventilated intensive care patients [67]. FAS is a single-item scale, ranked from 1 to 5, showing different levels of anxiety, from “neutral face” to “extreme fear”. As compared to the anxiety subscale of the Brief Symptom Inventory (BSI) and numeric analogue anxiety scale, the majority of intensive care patients were capable of responding to FAS [65].

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2.6.3. Short-Form of STAI In addition to FAS, the short-form of STAI was used in the second and third days (STAI was not used in the first day because the participants were under mechanical ventilation, and they were not able to answer the questionnaire due to their extremely vulnerable conditions). This instrument was comprised of six items. Responses to each item was rated on a Likert Scale anchored by “not at all,” “somewhat,” “moderately,” and “very much”. The short-form version is actually derived from the full-length scale with correlation coefficient of 96% between each of the shortform and full-length scale. It is a valid and reliable instrument. The range for the short STAI is between 6 and 24 points with (6-11), (12-17), and (18-24) signifying mild, moderate, and the severe levels of anxiety, respectively [38, 68]. The correlation coefficient of FAS with short-form STAI was computed as 0.393 (p=0.012). 2.6.4. Physiological Parameters Checklist Objective physiological data collected from the participants was recorded in the physiological parameters checklist. The physiological parameters included systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), and percutaneous oxygen saturation (SPO2) of the participants. 2.7. Measurement

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Initial measurements of objective physiological indicators during mechanical ventilation were taken for all three groups after participants had completely regained consciousness after admission to the Intensive Care Unit of the Cardiological Surgery Department, during the evening shift. During this period, participants were monitored by the research team. After performing the foot reflexology and general heel massage, the second measurement was taken. The third measurement was taken out 10 minutes after the intervention. In the second and third days of admission to ICU, foot reflexology and general heel massage sessions were held in the morning (10:00 to 12:00) and evening (16:00 to 18:00) shifts. In addition, any interference by visits of physicians and ward rounds within these periods was avoided. The measurement of indicators in these sessions was based on [specified] intervals during mechanical ventilation. The group C only received routine care (no therapeutic touch) and only their indices were measured by the first author. Demographic data was collected by the research team through interviewing and reviewing clinical records of the patients. Assessment of the level of anxiety during mechanical ventilation was done based on facial images of FAS by the first author. In the second and third days, both FAS and short-form of STAI were used in the morning and evening shift to measure the level of anxiety. Data collection was done through interviews using the short-form of STAI (the interview method was chosen for creating the same conditions among illiterate and literate participants.). In addition, the mean and standard deviation of the participants’ anxiety scores were measured with this instrument. In the current study, all physiological parameters, except respiratory rate, during mechanical ventilation were measured using Datex-Ohmeda S/5 (General Electric Co., USA) and spontaneous respiratory rate of the participants was measured using the Drager Evita 2 Dura Ventilator (Germany). In addition, the same monitoring device was used to measure the physiological parameters of the participants while they were weaned off of the mechanical ventilator. Both devices were precisely calibrated before data collection. The data collection was supervised by the research team. 2.8. Blinding None of the group members were aware of the randomized allocation through the block size of six. Participants were separated in their specific intensive care units and there was no interaction between any participants.

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2.9. Ethical Considerations This study was approved by the Ethics Committee of Tabriz University of Medical Sciences (1395.931.IR.TBZMED.REC) and registered in the Clinical Trial Registration Center of Iran under the code IRCT2016110125937N3. Then, the required permissions were granted by the Treatment Department of the University. Consent of participants was obtained by the research team the day before the surgery, after the research team explained the study and its objectives to the participants. Moreover, the participants were ensured that their information would remain confidential, they can withdraw from participation any time they want, there is no participation cost, and they will be provided with study results should they want them.

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2.10. Data Analysis Data analysis was done with SPSS 21 software. The between-group similarity of quantitative and qualitative demographic data was specified using one-way ANOVA and chi-square/Fisher exact tests, respectively. Data analysis was conducted using generalized estimating equations (GEE) method’s generalized linear models [69]. The significance level of the test was considered to be p<0.05. Normality of all variables was assessed by the groups and assessment times, using the Kolmogorov–Smirnov test. Moreover, the skewness and kurtosis indices were checked. These indices for all variables were within the range of -2 and 2. According to the test results, all variables, except SPO2, were normal at the significance level of 0.01. Since this variable had acceptable skewness and kurtosis values, it was considered normal. In addition, GEE analysis is resistant to presumption of data normality and thus a slight deviation from normality has minimal effect. 3. Findings 3.1. Demographic Specifications

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In terms of age, the mean and standard deviation of participants were 56.50±7.99. All participants were male. There was no statistically significant between-group difference with respect to demographic information (p>0.05) (Table 2).

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3.2. Anxiety Results from GEE showed a statistically significant difference between the groups A and C in terms of the level of anxiety (p<0.05) (Table 3). In contrast, there was no significant difference between the groups B and C in this regard (p>0.05). In the second and third days, the short-form STAI showed a significant reduction in the level and score of anxiety of the participants (p<0.05) (Table 4).

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3.3. Physiological Parameters GEE results showed a significant difference between the groups A and C in all physiological results, except heart rate (p<0.05). There was no significant difference between the groups A and C in terms of heart rate (p>0.05). In addition, there was no significant difference between the groups B and C in this regard (p>0.05) (Table 5).

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4. Discussion This study was conducted to determine the effect of foot reflexology on anxiety and physiological parameters of patients undergoing CABG. Findings showed that foot reflexology had a statistically significant effect on the level of anxiety and physiological parameters, such as systolic and diastolic blood pressure, mean arterial pressure, respiratory rate, and arterial oxygen saturation. In contrast, it had no statistically significant effect on heart rate. FAS showed that none of the groups showed severe or very severe levels of anxiety after mechanical ventilation. Both instruments showed a statistically significant reduction in the group A, compared to the B, in terms of anxiety level. The short-form of STAI showed that the mean anxiety scores of all three groups were within the range of a mild level of anxiety. The lowest mean score was obtained in the group A, receiving reflexology, in the evening shift of the second day. Moreover, the downward trend of scores was stronger in the group A, and consequently the minimum score was obtained in the evening shift of the third day. This result was clinically significant. Reduction in the level of anxiety was observed in all three groups. It seems that the weaning off of the ventilator, healing of incision site, gradual pain reduction in surgery site, and progressive course of improvement could reduce the level of anxiety in all three groups over time. However, this improvement was greater in the group A, and may indicate additional effectiveness of reflexology in reducing the level of anxiety. Reduction in the systolic and diastolic blood pressure, as well as mean arterial pressure in the group A was significantly higher than those of the group C. This difference can be considered clinically significant. The observed changes in respiratory rate and SPO2 in the group A, as compared to the C, were B=-2.198 and B=1.446, respectively. Despite this statistically significant difference, it is not clinically significant. This is because changes of these parameters are minimal and within the normal range. Although the reduction of heart rate in the group A was not statistically significant, it could be clinically significant. The heart rate reductions in all three groups ranged from above 100, on average, towards the normal range. Reductions in the group A were greater than the two other groups, specifically in terms of heart rate during mechanical ventilation. The downward trend of systolic and diastolic blood pressure, mean arterial pressure and heart rate in all three groups could be due to reduced level of anxiety because of above reasons. Bagheri-Nesami et al. (2014), Vardanjani et al. (2013), and Shahsavari et al. (2017) showed the significant effectiveness of foot reflexology in reducing the level of anxiety in patients after CABG, patients undergoing coronary artery angiography, and candidates for bronchoscopy [38, 51, 55]. Findings of these studies were consistent with ours, in that foot reflexology reduced the level of anxiety. In contrast, Gunnarsdottir and Jonsdottir (2007) and Kavei et al. (2015) reported that reflexology did not have a significant effect on the anxiety level of patients undergoing CABG, nor patient undergoing open heart surgery under mechanical ventilation [44, 70] . Given the very small sample size (9 patients) in Gunnardsdottir and Jonsdottir’s study, their results are not a reliable indicator of the effectiveness of reflexology in improving the anxiety levels of patients undergoing coronary artery bypass. In Kavei et al.’s study, the foot reflexology was administered only an hour after admission to the ICU, where it seems that the patients had not fully recovered from the effects of anesthesia and sedatives, and the intervention was made before the patient

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was completely conscious. Patients became aware of the operative procedure and their intubation after recovering from anesthesia, and regained consciousness over time, which resulted in a gradual increase in their anxiety levels; as such, the effect of reflexology on anxiety level was not observed. Mc Vicar et al. (2007), and Mackereth et al. (2009) showed that foot reflexology resulted in a significant reduction in cardiovascular parameters of healthy individuals and systolic pressure in patients with multiple sclerosis [71, 72]. Also, Korhan et al. Obtained evidence that foot, hand, and ear reflexology reduces SBP, DBP, HR, and RR in patients under mechanical ventilation [41]. Results of these studies are consistent with the findings of the present study, given reduced rate of physiological indices. On the other hand, some studies did not report the effectiveness of foot reflexology in improving physiological parameters. Ebadi et al. (2015), Rollinson et al. (2016), and Jones et al. (2013) reported insignificant effect of foot reflexology on physiological parameters of patients undergoing open-heart surgery, cardiac indices and arterial compliance in healthy people, and hemodynamic parameters in patients with chronic heart failure respectively [53, 57, 58]. Due to the administration of reflexology one hour after ICU admission when the patients were not fully recovered from the effects of anesthetics and sedatives, the results from Ebadi et al.’s study are not reliable, since the effects of the sedatives acted as interference for the outcomes of reflexology. Moreover, since the intervention group included all patients undergoing open-heart surgery, the differences in incision site and surgical procedure could also result in different hemodynamic effects, interfering with the outcomes of the effects of the massage. In addition, the use of two different individuals for administering the massages could affect the results, in spite of the fact that they were trained by the same specialist. It seems that inadequate sample size (12 participants) in Rollinson et al.’s study can affect the outcomes. In addition to small sample size (12 patients with heart failure) in Jones et al.'s study can affect the study outcomes. Elisabeth et al. (2012) concluded that foot reflexology can significantly increase blood pressure and heart rate in healthy people [73]. It is worth noting that different methods have been used in studies reporting consistent and inconsistent results with the current study. It seems that using different techniques can also result in different outcomes. Moreover, contradictory results and their discussions indicate that many factors together can affect reflexology results. These effects may vary based on conditions. These factors are summarized as follows: health condition of an individual, sample size, better research control, existence of different text books with different techniques, different foot charts specifically disagreeing regarding the heart area, duration of massage, number of sessions, number of masseurs in studies, difference in anxiety and hemodynamic conditions in different diseases, duration of surgery, incision site, level of pressure (gentle or mild) (This is because gentle and light massages stimulate parasympathetic and sympathetic systems, respectively [53]), time of massage starting under mechanical ventilation, chance of interference with sedatives, and different stages of the disease.

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5. Conclusion Considering this point that the improvement in anxiety and physiological parameters was greater in the group A and also the closeness of the changes in the other two groups (Group B was insignificant compared to the group C), it seems that foot reflexology may have effects on the level of anxiety and physiological parameters of male patients undergoing CABG. Thus, it may be used as an applicable, safe, and non-invasive bedside treatment administered to reduce anxiety and create stable conditions in physiological parameters such as systolic, diastolic, mean arterial pressure, and heart rate due to anxiety, specifically when these patients are under disagreeable conditions in the ICU. As a result, it seems that reflexology can be used by nurses as an adjunct to standard ICU care to reduce anxiety and stabilize some physiological parameters. But considering the clinical and non clinical effects of reflexology, existence of the limitations in this study, contradictory results in the studies, and little evidence of its efficacy [61, 74], it is recommended that the results of the study were used with caution. Also further investigation is recommended in this regard. 5.1. Limitations The major limitation of the current study was its conduction only on male patients; therefore, results are not generalizable to other groups, such as women and children. Another limitation of the study was its conduction in only one teaching center, which may limit its generalizability. It is recommended to investigate the effects of foot

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reflexology on women undergoing coronary artery bypass in future studies. Moreover, it is recommended to investigate the effect of this method in other diseases and operative procedures. Conflict of Interest The authors declare that there is no conflict of interest.

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Author contributions The first author designed and conducted intervention, wrote the manuscript, collected data, and interpreted data. The second author (corresponding author) designed intervention, wrote the manuscript, revised it for content and edited it grammatically and scientific writing. The third author revised manuscript for content and edited it grammatically and scientific writing. Fourth author analyzed data. The fifth author taught reflexology to the first author. Sixth author interpreted data.

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Acknowledgments First and foremost, we would like to thank all of the patients who participated in this study. Next, we extend our gratitude to the nurses who provided the conditions for conducting our bedside research in the ICU. Finally, we would like to appreciate the Research Department of Tabriz University of Medical Sciences for their financial support.

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Target population (CABG patient)

Enrolment

Assessed for eligibility, n = 155 Excluded (n = 35) Did not have the inclusion criteria

Randomized (n = 120)

Allocated to placebo (n = 40)

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Allocated to intervention (n = 40)

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Lost to fallow up (n = 0) Discontinued study (n = 0)

Analyzed (n = 40)

Allocation

Follow-Up Lost to fallow up (n = 0) Discontinued study (n = 0)

Lost to fallow up (n = 0) Discontinued study (n = 0) Analysis

Analyzed (n = 40) FIG. 1. CONSORT diagram.

Table 1 Participants’ systolic blood pressure rates of the first day immediately after intervention in pilot study

SBP Mean (SD) 119.3 (12.10) 138.4 (16.10) 127.8 (18.65)

Allocated to control (n = 40)

Group Intervention (A) Placebo (B) Control (C)

Analyzed (n = 40)

Table 2 Participants’ demograraphic characteristic in the foot reflexology (A), placebo (B) and control (C) group Characteristic All participant Group A

56.30 ± 7.11 27.93 ± 4.07 3.25 ± 0.57

Statistical test and p-value ANOVA, P = 0.717, F = 0.334 ANOVA, P = 0.880, F = 0.128 ANOVA, P = 0.286, F = 1.265

5.01 ± 0.92 42.37± 8.69 2.92 ± 0.47

ANOVA, P = 0.720, F = 0.329 ANOVA, P = 0.502, F = 0.694 ANOVA, P = 0.425, F = 0.862

1 (2.5) 39 (97.5)

0 (0) 40 (100)

Fisher’s Exact test P = 1.000

16 (40) 12 (30) 2 (5) 9 (22.5) 1 (2.5)

10 (25) 15 (37.5) 5 (12.5) 6 (15) 4 (10)

Fisher’s Exact test P = 0.348

1 (2.5) 10 (25) 13 (32.5) 6 (15) 10 (25)

1 (2.5) 8 (20) 24 (60) 1 (2.5) 6 (15)

2 (5) 6 (15) 23 (57.5) 3 (7.5) 6 (15)

Fisher’s Exact test P = 0.205

67 (55.8) 53 (44.2)

19 (47.5) 21 (52.5)

20 (50) 20 (50)

28 (70) 12 (30)

Chi-Square Test ᵡ² = 4.934, dƒ = 2, p = 0.85

31 (25.8) 89 (74.2)

10 (25) 30 (75)

9 (22.5) 31 (77.5)

12 (30) 28 (70)

Chi-Square Test ᵡ² = 0.609, dƒ = 2, p = 0.738

68 (56.7) 52 (43.3)

19 (47.5) 21 (52.5)

25 (62.5) 15 (37.5)

24 (60) 16 (40)

Chi-Square Test ᵡ² = 2.104, dƒ = 2, p = 0.349

39 (32.5) 81 (67.5)

12 (30) 28 (70)

16 (40) 24 (60)

11 (27.5) 29 (72.5)

Chi-Square Test ᵡ² = 1.595, dƒ = 2, p = 0.450

3(2.5) 117 (97.5)

0 (0) 40 (100)

2 (5) 38 (95)

1 (2.5) 39 (97.5)

Fisher’s Exact test P = 0.772

26 (21.7) 94 (78.3)

6 (15) 34 (85)

11 (27.5) 29 (72.5)

9 (22.5) 31 (77.5)

Chi-Square Test ᵡ² = 1.866, dƒ = 2, p = 0.393

Group B

56.50 ± 7.99 27.81 ± 4.02 3.35 ± 0.56

55.90 ± 8.31 27.95 ± 3.97 3.35 ± 0.53

57.32 ± 8.62 27.54 ± 4.12 3.45 ± 0.57

4.93 ± 0.98 43.22 ± 8.80 2.89 ± 0.54

4.96 ± 0.86 42.75 ± 10.61 2.80 ± 0.68

4.83 ± 1.16 44.55 ± 6.74 2.95 ± 0.45

Marital, n (%)

1 (0.8) 119 (99.2)

0 (0) 40 (100)

36 (30) 37 (30.8) 10 (8.3) 28 (23.3) 9 (7.5)

10 (25) 10 (25) 3 (7.5) 13 (32.5) 4 (10)

4 (3.3) 24 (20) 60 (50) 10 (8.3) 22 (18.3)

M AN U

Married Educational level, n (%) Illiterate Primary Under diploma Diploma Lisence and uper lisence Job, n (%) Worker Farmer Self-employed Employee Retired

Diabetes, n (%) Yes No Hypertension, n (%)

AC C

Yes No Hyperlipidaemia, n (%) Yes No Pulmonary diseases, n (%) Yes No Place of residence, n (%) Rural Urban

EP

Yes No

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Smoking, n (%)

Table 3 Comparison of foot reflexology (A), placebo (B) and control (C) group on anxiety (FAS). Measurement Under mechanical ventilation stage T2e T2m T3m T1b T1a T1t Variable n(%) n(%) n(%) n(%) n(%) n(%) Group

Group C

SC

Age (years) Mean ± SD Body Mass Index Mean ± SD Duration of surgery (Hours) Mean ± SD Time to regain consciousness after being transferred to ICU (Hours) Mean ± SD Ejection friction (%) Mean ± SD Grafts (n) Mean ± SD

Single

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GEE T3e n(%) P-value

B

OR

95% CI Lower Upper

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0(0) 4(10) 24(60) 8(20) 4(10) 2(5) 2(5) 15(37.5) 14(35) 7(17.5) 0(0) 1(2.5) 19(47.5) 13(32.5) 7(17.5)

16(40) 14(35) 7(17.5) 3(7.5) 0(0) 5(12.5) 15(37.5) 9(22.5) 8(20) 3(7.5) 0(0) 11(27.5) 17(42.5) 10(25) 2(5)

22(55) 11(27.5) 3(7.5) 4(10) 0(0) 9(22.5) 11(27.5) 14(35) 6(15) 0(0) 2(5) 12(30) 16(40) 8(20) 2(5)

79 (65.8) 33 (27.5) 8 (6.7) 0 (0) 0 (0) 75 (62.5) 41 (34.2 4(3.3) 0 (0) 0 (0) 47 (39.2) 66 (55.00) 7 (5.8) 0 (0) 0 (0)

102 (85.0) 13 (10.8) 5 (4.2) 0 (0) 0 (0) 95 (79.2) 21 (17.5) 4 (3.3) 0 (0) 0 (0) 78 (65.00) 42 (35.00) 0 (0) 0 (0) 0 (0)

106 (88.3) 13 (10.8) 1 (0.8) 0 (0) 0 (0) 99 (82.5) 18 (15.0) 3 (2.5) 0 (0) 0 (0) 95 (79.2) 20 (16.7) 5 (4.2) 0 (0) 0 (0)

113 (94.2) 7 (5.8) 0 (0) 0 (0) 0 (0) 99 21 0 (0) 0 (0) 0 (0) 101 (84.2) 15 (12.5) 4 (3.3) 0 (0) 0 (0)

Table 4 Comparison of foot reflexology (A), placebo (B) and control (C) group on anxiety (short form). T2m T2e T3m T3e Measurement stage Mean (SD) Mean (SD) Mean (SD) Mean (SD) Variable Group P-value B A 8.25 (2.71) 7.30 (2.23) 6.89 (1.83) 6.21 (0.82) < 0.001 -2.063 B 9.53 (1.95) 8.43 (2.01) 7.66 (1.94) 7.44 (1.92) 0.262 -0.539 C 10.81 (2.16) 9.54 (1.62) 8.70 (2.64) 7.80 (2.31) Referent (0ᵅ)

MAP

Table 5

0.026

-1.858

0.156

-3.498

-0.218

0.358

0.592

1.80

-0669

1.853

Referent (0ᵅ)

RI PT

A no mild moderate severe Very severe B no mild moderate severe very severe C no mild moderate severe very severe

GEE

OR 0.127 0.584

95% CI Lower Upper -2.808 -1.318 -1.480 0.403

SC

MAP

Under mechanical ventilation T1b T1a T1t Mean (SD) Mean (SD) Mean (SD)

127.95 (16.06) 131.55 (19.17) 131.00 (21.07) 74.60 (9.49) 77.17 (7.83) 77.07 (14.08) 92.40 (9.88) 95.30 (10.18) 94.97 (15.17) 100.90 (16.02) 100.45 (14.11) 101.12 (12.79) 16.75 (5.49) 17.02 (4.31) 17.22 (4.73) 95.92 (2.86) 95.95 (2.51) 95.35 (2.46)

121.17 (13.78) 128.57 (16.79) 128.82 (16.62) 72.12 (8.62) 76.27 (10.38) 75.40 (12.56) 88.55 (8.58) 93.65 (11.04) 93.22 (12.91) 95.30 (20.87) 98.70 (13.97) 100.22 (11.86) 16.12 (4.69) 16.80 (4.33) 17.00 (4.80) 95.52 (2.32) 95.30 (2.72) 94.82 (2.20)

120.77 (13.60) 125.62 (18.20) 127.05 (15.46) 71.45 (8.04) 75.25 (10.14) 75.57 (12.28) 87.92 (7.99) 92.02 (11.34) 92.72 (12.18) 97.30 (15.43) 97.40 (13.14) 100.55 (11.59) 16.47 (4.59) 16.02 (4.02) 17.47 (4.52) 95.80 (2.22) 95.15 (2.31) 94.37 (2.55)

T2m Mean (SD)

109.01 (13.28) 118.55 (16.70) 114.60 (15.23) 68.11 (9.21) 72.72 (9.03) 71.85 (10.55) 81.70 (9.76) 87.98 (10.44) 86.14 (11.27) 89.40 (13.86) 92.65 (11.95) 91.13 (11.73) 19.75 (4.12) 21.00 (4.40) 20.78 (3.22) 93.00 (2.68) 92.01 (2.47) 92.39 (2.37)

T2e Mean (SD)

110.46 (13.47) 116.50 (15.14) 117.59 (17.15) 68.05 (7.71) 72.15 (10.90) 73.25 (11.55) 82.29 (8.71) 86.88 (11.61) 88.01 (12.78) 88.44 (12.93) 90.53 (13.05) 90.72 (11.26) 19.82 (3.44) 20.68 (3.54) 20.11 (3.41) 93.21 (2.53) 92.41 (2.26) 92.47 (2.42

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Measurement stage Variable Group SBP A B C DBP A B C MAP A B C HR A B C RR A B C SPO2 A B C

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Comparison of foot reflexology (A), placebo (B) and control (C) group on physiologic parameters.

T3m Mean (SD)

114.57 (11.64) 118.45 (9.07) 118.63 (16.58) 71.35 (7.65) 73.17 (5.86) 75.39 (11.86) 85.77 (8.29) 88.26 (6.25) 89.81 (12.90) 87.29 (11.02) 89.67 (8.78) 89.42 (10.48) 18.58 (2.85) 19.50 (2.76) 20.28 (3.65) 93.95 (2.56) 93.32 (2.14) 93.04 (2.41)

GEE T3e Mean (SD)

114.16 (8.98) 120.56 (8.14) 119.39 (12.10) 72.24 (6.07) 75.43 (4.85) 75.69 (8.53) 86.21 (6.68) 90.44 (4.89) 90.30 (9.09) 84.45 (9.64) 89.33 (9.22) 87.10 (10.17) 17.55 (2.64) 19.05 (2.11) 19.54 (3.30) 95.01 (2.18) 93.90 (2.08) 93.76 (2.27)

P-value B 0.006 -6.546 0.836 -0.480 Referent (0ᵅ) 0.001 -5.136 0.607 -0.791 Referent (0ᵅ) 0.001 -5.652 0.647 -0.753 Referent (0ᵅ) 0.074 -3.981 0.649 1.004 Referent (0ᵅ) 0.001 -2.198 0.251 -0.742 Referent (0ᵅ) 0.002 1.446 0.675 0.203 Referent (0ᵅ)

95% CI Lower Upper -11.254 -1.838 -5.013 4.054 -8.208 -3.802

-2.064 2.221

-9.047 -3.987

-2.257 2.472

-8.354 -3.324

0.392 5.331

-3.530 -2.010

-0.866 0.525

0.512 -0.746

2.380 1.152

AC C

EP

Day 1, evening, before intervention under mechanical ventilation with consciousness (T1b) - Day 1, evening, immediately after intervention under mechanical ventilation with consciousness (T1a) - Day 1, evening, ten minutes after intervention under mechanical ventilation with consciousness (T1t) - Day2, morning, (T2m) - Day2, evening, (T2e) - Day3, morning, (T3m) - Day3, evening, (T3e) B: coefficient, CI: Confidence Interval, OR: Odds Ratio, 0ᵅ: Zero

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Effects of foot reflexology on anxiety and physiological parameters in patients undergoing coronary artery bypass graft surgery: A clinical trial ABSTRACT Introduction: This study aimed to investigate the effect of foot reflexology on anxiety and physiological parameters in patients after CABG surgery.

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Method: This was a single-blind, three-arm, parallel-group, randomized controlled trial with three groups of 40 male patients undergoing CABG. Participants were placed in three groups, named intervention, placebo, and control. Physiological parameters were measured including systolic and diastolic blood pressure, mean arterial pressure, heart rate, respiratory rate, percutaneous oxygen saturation, and anxiety of participants. Results: Results showed a statistically significant difference between intervention and control groups in terms of the level of anxiety (p<0.05). Also, results showed a statistically significant effect on all physiological parameters except heart rate (p<0.05).

SC

Conclusion: This study indicated that foot reflexology may be used by nurses as an adjunct to standard ICU care to reduce anxiety and stabilize physiological parameters such as systolic, diastolic, mean arterial pressure, and heart rate.

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Keywords: Foot reflexology; Anxiety; Physiological parameters; Coronary artery bypass graft; Nursing

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1. Introduction Coronary artery disease (CAD) is among the leading causes of mortality worldwide, and is becoming increasingly more prevalent [1]. Treatments include pharmacotherapy, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) [2]. In recent years, CABG has emerged as the standard treatment for critical cases [3], accounting for 60% of all open-heart surgeries in Iran [4]. Despite many advantages of this treatment for improving acute symptoms of the disease and increasing survival rate, evidences indicate that the diagnosis of CAD and the need for CABG arouses anxiety in patients [5]. Patients may suffer from anxiety and depression after the surgery [6, 7] and in addition to fear and mood disorders, patients undergoing heart surgery may develop other physiological dysfunctions [8]. The anxiety provoked in these patients, stimulated their sympathetic system [9, 10], and increased indices such as heart rate, blood pressure, respiratory rate [10]. Anxiety can also delay the healing of wound site [1117] and weaken immune system response [17-19]. Tully et al. (2011) showed that post-operative anxiety is one of the risk factors for atrial fibrillation [20]. After surgery, patients were transferred to the intensive care unit (ICU) and received mechanical ventilation until their cardiac and respiratory conditions stabilized [21]. In addition to the stress of undergoing heart surgery, patients experience stress and anxiety triggered by the ICU environment [10, 22] and mechanical ventilation [23]. Additionally, patients suffer more anxiety during the weaning process of recovery [24, 25]. The administration of analgesic and soporific drugs is common in ICUs [26], aiming to reduce anxiety and stress, improve the course of mechanical ventilation [27, 28], and manage pain [29]. However, the use of these medicines may result complications such as respiratory depression [30-32], and gastrointestinal problems like nausea and vomiting [29, 32, 33], gastrointestinal reflux, reduced bowel movement and constipation, dependence and addiction [32], cognitive disorders [34, 35], increased duration of mechanical ventilation, prolongation of the length of ICU stay, and a higher chance of mortality [26, 36].Today, it seems that non-pharmaceutical therapies such as complementary and alternative medicine (CAM) may be used to reduce anxiety [21, 37-40], prevent physiological reactions caused by anxiety [37, 40, 41], stabilize vital signs [42], and manage pain [43]. Since nurses play a key role in predicting psychological and physiological needs of patients and reducing their level of anxiety and stress [25], it seems that nurses can practice some CAMs to reduce stress, pain, and improve the health conditions of patients [44]. As a result, in addition to helping patients relax, nurses can lower the chance of complications by actively reducing the anxiety levels of their patients. CAM therapies is made up of different fields, such as acupuncture, herbal medicine, chiropractic, homeopathy, reflexology massage, etc. [45]. Foot reflexology is a form of CAMs administered by applying pressure at specific points on the body [46]. In fact, reflexology specialists believe that there are some reflex areas and points on feet and hands, which may relate to certain body parts, organs, and specific glands. In this method, pressure is applied to reflex points, specifically on feet due to their accessibility and sensitivity [47, 48]. Reflexology

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claims that stimulating the nerves of the points indicated on the foot or hand maps causes response from organs or glands [49]. Maybe the application of this technique can reduce stress and anxiety by reducing fluctuations in sympathetic system [38, 50, 51]. In other words, presumably reflexology can reduce the level of vital signs increased with anxiety [41]. Maybe reflexology can be a non-aggressive, simple, low-cost, and complication-free method, which can be used as a suitable complementary treatment, with pharmacotherapy and exemplary nursing skills [52, 53]. Maybe this safe and practical method can be applied to reduce the level of anxiety in patients hospitalized in hospitals and healthcare centers [54]. Based on reflexologists' claims, a number of studies have been conducted studying the effect of reflexology with regards to different situations and diseases; such as reduction of anxiety and improvement of physiological parameters in bronchoscopy candidates [55] and reduction of anxiety in cancer patients undergoing chemotherapy [56]. With respect to cardiology, studies on the effect of foot reflexology on reduction of anxiety after CABG [38] and reduction of anxiety in patients with CAD before angiography [51] can be mentioned. Despite the positive effect of this method mentioned by different studies, some studies have rejected such claims, due to: ineffectiveness of reflexology in improving the rate of arterial compliance and physiological indices of healthy people [57], ineffectiveness of reflexology in improving hemodynamic parameters of patients with chronic heart failure [58], and ineffectiveness of reflexology in improving anxiety and physiological indices of patients undergoing CABG [44]. Systematic reviews have also indicated the need for more studies on effects of reflexology [59-61]. Regarding the importance of CAD, the prevalence of medical methods such as CABG for its treatment, the creation of undesirable psychological and physiological conditions in patients, and the unique role of nurses in the course of care and progress of these patients, the use of safe, complication-free, and simple methods, could be considered as an additional skill for nurses. Nevertheless, there is no strong evidence confirming the effectiveness of reflexology, specially in these patients, in bedside. To this end, this study was conducted to investigate the effect of foot reflexology on the level of anxiety and physiological parameters of patients undergoing CABG.

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2. Method 2.1. Study design This was a single-blind, three-arm, parallel-group controlled trial with three groups. 2.2. Setting This study was conducted between 20 January and 22 May 2017 in the Cardiac Surgery Unit of Shahid Madani teaching hospital affiliated to the Tabriz University of Medical Sciences, Iran.

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2.3. Participants Participants were selected from a pool of male patients hospitalized in Shahid Madani Hospital, who had been diagnosed with CAD, and were candidates for non-urgent CABG. Exclusion of females was due to cultural matters, as all of the massage sessions were conducted by a male masseur. Samples were selected using convenience sampling. Inclusion criteria were: participants aged 18-65 years, candidate for non-urgent bypass surgery, without previous openheart surgery, and without psychological problems (e.g. depression or anxiety) based on their medical history clinical record of them, with normal foot soles, without foot abnormalities (e.g. corn, callus, scar, neuropathy), without any intra-aortic balloon pump or pacemaker, in SIMV/CPAP (PSV) mode, not addicted to alcohol and drugs, without history of chronic pain (for example from arthritis), without history of receiving reflexology, without facial scars, without severe visual and auditory disorders, not taking inotropic drugs, and who had not received analgesics or injections of neuromuscular inhibitors since their admission to the ICU. Exclusion criteria were: decreased level of consciousness, mitral valve repair or replacement during CABG surgery (Each type of cardiac surgery will vary from viewpoints of surgical duration, surgical site, recovery time, and duration of hospitalization, which can have an effect on patient anxiety [38]. Different physiological changes will be developed as a result of different changes in the level of anxiety.), and hemodynamic instability. 2.4. Specification of Sample size and Randomization

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The sample size was specified after conducting the pilot study on 30 patients undergoing CABG (10 participants in each group). Based on the systolic blood pressure rates of the first day immediately after intervention, and the comparison of them between the three groups using pilot data (Table 1), and a formula of sample size required for the analysis of variance with α=0.05 and a power of 95%, a sample size of 32 in each group was specified. Considering 25% attrition, the sample size of 40 participants was considered in each group (Figure 1). The sample size was specified using G-power 3.1.2. Randomization was done using blocking. Participants were placed in three groups, named intervention (A), placebo (B), and control (C) using random block size of six by someone not involved in sampling. Each block included two participants from each group. Participants were placed based on the sequence of the block of the target group. The type of intervention was written on a paper and placed in an opaque envelope numbered sequentially (allocation concealment). An intervention type of each participant was stated after the surgical procedure and at the bedside for the researcher. The researcher did not have access to the allocation list. Φ = 1/σ n / r Σ (μi – μ.)² , μ. = Σ μi / r r: Number of groups=3, µi: Mean of each group, σ:Standard deviation, n = 30

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2.5. Intervention Group A received foot reflexology in bed, while reclining in a supine position. Group B received general heel massage (superficial touch, and without any pressure.) in bed, also in supine position. Heel selected as placebo according to Ebadi et al.’s study [53]. There were not reflexology points and areas on the heels which were selected in group A. Reflexology theory declares that massaging irrelevant areas does not have therapeutic effect [62]. Also, according to the reflexologists’ belief, reflexology is the use of pressure techniques, stimulating the nerves and receiving responses from the organs [49]. Thus, no pressure was applied on heels for group B. First, the masseur washed and warmed his hands and soaked them in olive oil (which does not have a therapeutic effect and was used only for lubrication). Then, he administered foot reflexology and general foot massage. Both types of massage were applied first to the right foot and then the left one. The foot reflexology and surface heel massage of each foot lasted for 15 minutes. Foot reflexology methodology was based on a text book for reflexology [63]. Practical trainings in text book has been taught to the first author by a reflexology specialist (first author has received one year of reflexology trainings and its certificate from the reflexology specialist. Trainings was conducted in reflexology unit of Faculty of Rehabilitation, Tabriz, Iran. Reflexology specialist was certified from the Faculty of Traditional Medicine of Shahed University in Iran, and with 8 years of experience.). The intervention was supervised by the reflexology specialist and research team. According to the reflexologists' claim, the points on the sole of the foot which may be associated with reduction of anxiety and adjustment of physiological parameters were selected. Selected points on the right foot included solar plexus (It’s called the relaxation point. Perhaps it helps calm, balance, relaxation, panic reaction, and reducing anxiety and stress.), hypothalamus gland (Perhaps links the pituitary gland point to secrete hormones and balances autonomic nervous system.), pituitary gland (Probably stimulating this point causes control of other endocrine glands, secretion of hormone, creating balance in secretion of hormones, creating emotional and physical balance.), lung (Maybe stimulation of the lung area regulates breathing and Oxygen level.), and adrenal glands (Perhaps stimulating this point causes secretion of adrenaline and hydrocortisone, creating balance, combating with stress and calming stress response.). Selected points on the left foot included solar plexus, hypothalamus gland, pituitary gland, lung, heart (Probably stimulating this point regulates blood circulation.), and adrenal glands. First, initial movements of relaxation included three techniques, namely rotate the foot, stretch the Achilles, and open and stretch the chest were administered respectively, each for one minute before giving reflex point massage on each foot (less time was considered for these techniques to focus more on reflex points and areas.). In the first technique, the heel was held with the opposite hand from the below, the metatarsal arch was gripped with the hand of the same side, and rotated clockwise and counterclockwise for several times. In the second technique, the heel was pulled and released with the opposite hand in the same position. In the third technique, fingers of the both hands are placed on top of the foot in a way that the fingertips are located towards the base of toes in zone 3 (a longitudinal area that begins from above the head, passes through the eyes and reaches the middle fingers and toes), and both thumbs are placed under the metatarsal arch in this area. Then, the pressure was applied by gliding movement outwardly. In the next stage, the given body points were equally stimulated for 12 minutes. Stimulation of solar plexus was done through placing

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2.6. Data Collection Instrument Data collection instrument included four sections:

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pressure and releasing, and applying rotational pressure with thumb. Stimulation of hypothalamus gland, pituitary gland, heart, and adrenal area was performed through applying rotational pressure with thumb. Stimulation of lung area was done by pulling back the toes and executing biting movements with the thumb from above the diaphragm area on the sole of the foot towards the toes [63]. Since organs at each body side are corresponded to the foot at the same side, the respective heart point in the left foot was stimulated, and the location of the reflex points and areas in this study was selected based on the map presented in Embong et al.’s study (2015) [64].

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2.6.1. Participants Demographic Form The demographic information form of participants was completed through interviewing and reviewing clinical records of them. This form included questions related to age, body mass index, marital status, educational level, job, duration of surgery, time to regain consciousness after being transferred to ICU, history of diseases such as hypertension, hyperlipidemia, and diabetes, history of smoking, history of pulmonary diseases, and number of grafts.

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2.6.2. Faces Anxiety Scale (FAS) In this study, the faces anxiety scale (FAS) was used for collecting anxiety data of patients undergoing mechanical ventilation and after mechanical ventilation. This scale was developed by McKinley et al. (2003) [65]. FAS was used because mechanically ventilated patients were unable to communicate verbally to respond to anxiety-inducing items, as a result use of currently available anxiety measures is difficult. The correlation of FAS with non-verbal responses of patients to short questions from the Profile of Mood States Anxiety Subscale was reported as 0.64 (p<0.001). The score range between 0.4-0.8, as the validity criterion, indicates the validity of FAS as a suitable instrument for anxiety measurement [66]. McKinley et al. (2008) reported the correlation coefficient of 0.7 (p<0.005) for this scale and the Spielberger state-anxiety inventory in non-ventilated intensive care patients [67]. FAS is a single-item scale, ranked from 1 to 5, showing different levels of anxiety, from “neutral face” to “extreme fear”. As compared to the anxiety subscale of the Brief Symptom Inventory (BSI) and numeric analogue anxiety scale, the majority of intensive care patients were capable of responding to FAS [65].

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2.6.3. Short-Form of STAI In addition to FAS, the short-form of STAI was used in the second and third days (STAI was not used in the first day because the participants were under mechanical ventilation, and they were not able to answer the questionnaire due to their extremely vulnerable conditions). This instrument was comprised of six items. Responses to each item was rated on a Likert Scale anchored by “not at all,” “somewhat,” “moderately,” and “very much”. The short-form version is actually derived from the full-length scale with correlation coefficient of 96% between each of the short-form and full-length scale. It is a valid and reliable instrument. The range for the short STAI is between 6 and 24 points with (6-11), (12-17), and (18-24) signifying mild, moderate, and the severe levels of anxiety, respectively [38, 68]. The correlation coefficient of FAS with short-form STAI was computed as 0.393 (p=0.012). 2.6.4. Physiological Parameters Checklist Objective physiological data collected from the participants was recorded in the physiological parameters checklist. The physiological parameters included systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), and percutaneous oxygen saturation (SPO2) of the participants. 2.7. Measurement Initial measurements of objective physiological indicators during mechanical ventilation were taken for all three groups after participants had completely regained consciousness after admission to the Intensive Care Unit of the Cardiological Surgery Department, during the evening shift. During this period, participants were monitored by the

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research team. After performing the foot reflexology and general heel massage, the second measurement was taken. The third measurement was taken out 10 minutes after the intervention. In the second and third days of admission to ICU, foot reflexology and general heel massage sessions were held in the morning (10:00 to 12:00) and evening (16:00 to 18:00) shifts. In addition, any interference by visits of physicians and ward rounds within these periods was avoided. The measurement of indicators in these sessions was based on [specified] intervals during mechanical ventilation. The group C only received routine care (no therapeutic touch) and only their indices were measured by the first author. Demographic data was collected by the research team through interviewing and reviewing clinical records of the patients. Assessment of the level of anxiety during mechanical ventilation was done based on facial images of FAS by the first author. In the second and third days, both FAS and short-form of STAI were used in the morning and evening shift to measure the level of anxiety. Data collection was done through interviews using the short-form of STAI (the interview method was chosen for creating the same conditions among illiterate and literate participants.). In addition, the mean and standard deviation of the participants’ anxiety scores were measured with this instrument. In the current study, all physiological parameters, except respiratory rate, during mechanical ventilation were measured using Datex-Ohmeda S/5 (General Electric Co., USA) and spontaneous respiratory rate of the participants was measured using the Drager Evita 2 Dura Ventilator (Germany). In addition, the same monitoring device was used to measure the physiological parameters of the participants while they were weaned off of the mechanical ventilator. Both devices were precisely calibrated before data collection. The data collection was supervised by the research team. 2.8. Blinding None of the group members were aware of the randomized allocation through the block size of six. Participants were separated in their specific intensive care units and there was no interaction between any participants.

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2.9. Ethical Considerations This study was approved by the Ethics Committee of Tabriz University of Medical Sciences (1395.931.IR.TBZMED.REC) and registered in the Clinical Trial Registration Center of Iran under the code IRCT2016110125937N3. Then, the required permissions were granted by the Treatment Department of the University. Consent of participants was obtained by the research team the day before the surgery, after the research team explained the study and its objectives to the participants. Moreover, the participants were ensured that their information would remain confidential, they can withdraw from participation any time they want, there is no participation cost, and they will be provided with study results should they want them.

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2.10. Data Analysis Data analysis was done with SPSS 21 software. The between-group similarity of quantitative and qualitative demographic data was specified using one-way ANOVA and chi-square/Fisher exact tests, respectively. Data analysis was conducted using generalized estimating equations (GEE) method’s generalized linear models [69]. The significance level of the test was considered to be p<0.05. Normality of all variables was assessed by the groups and assessment times, using the Kolmogorov–Smirnov test. Moreover, the skewness and kurtosis indices were checked. These indices for all variables were within the range of -2 and 2. According to the test results, all variables, except SPO2, were normal at the significance level of 0.01. Since this variable had acceptable skewness and kurtosis values, it was considered normal. In addition, GEE analysis is resistant to presumption of data normality and thus a slight deviation from normality has minimal effect. 3. Findings 3.1. Demographic Specifications In terms of age, the mean and standard deviation of participants were 56.50±7.99. All participants were male. There was no statistically significant between-group difference with respect to demographic information (p>0.05) (Table 2). 3.2. Anxiety

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Results from GEE showed a statistically significant difference between the groups A and C in terms of the level of anxiety (p<0.05) (Table 3). In contrast, there was no significant difference between the groups B and C in this regard (p>0.05). In the second and third days, the short-form STAI showed a significant reduction in the level and score of anxiety of the participants (p<0.05) (Table 4).

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3.3. Physiological Parameters GEE results showed a significant difference between the groups A and C in all physiological results, except heart rate (p<0.05). There was no significant difference between the groups A and C in terms of heart rate (p>0.05). In addition, there was no significant difference between the groups B and C in this regard (p>0.05) (Table 5).

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4. Discussion This study was conducted to determine the effect of foot reflexology on anxiety and physiological parameters of patients undergoing CABG. Findings showed that foot reflexology had a statistically significant effect on the level of anxiety and physiological parameters, such as systolic and diastolic blood pressure, mean arterial pressure, respiratory rate, and arterial oxygen saturation. In contrast, it had no statistically significant effect on heart rate. FAS showed that none of the groups showed severe or very severe levels of anxiety after mechanical ventilation. Both instruments showed a statistically significant reduction in the group A, compared to the B, in terms of anxiety level. The shortform of STAI showed that the mean anxiety scores of all three groups were within the range of a mild level of anxiety. The lowest mean score was obtained in the group A, receiving reflexology, in the evening shift of the second day. Moreover, the downward trend of scores was stronger in the group A, and consequently the minimum score was obtained in the evening shift of the third day. This result was clinically significant. Reduction in the level of anxiety was observed in all three groups. It seems that the weaning off of the ventilator, healing of incision site, gradual pain reduction in surgery site, and progressive course of improvement could reduce the level of anxiety in all three groups over time. However, this improvement was greater in the group A, and may indicate additional effectiveness of reflexology in reducing the level of anxiety. Reduction in the systolic and diastolic blood pressure, as well as mean arterial pressure in the group A was significantly higher than those of the group C. This difference can be considered clinically significant. The observed changes in respiratory rate and SPO2 in the group A, as compared to the C, were B=-2.198 and B=1.446, respectively. Despite this statistically significant difference, it is not clinically significant. This is because changes of these parameters are minimal and within the normal range. Although the reduction of heart rate in the group A was not statistically significant, it could be clinically significant. The heart rate reductions in all three groups ranged from above 100, on average, towards the normal range. Reductions in the group A were greater than the two other groups, specifically in terms of heart rate during mechanical ventilation. The downward trend of systolic and diastolic blood pressure, mean arterial pressure and heart rate in all three groups could be due to reduced level of anxiety because of above reasons. Bagheri-Nesami et al. (2014), Vardanjani et al. (2013), and Shahsavari et al. (2017) showed the significant effectiveness of foot reflexology in reducing the level of anxiety in patients after CABG, patients undergoing coronary artery angiography, and candidates for bronchoscopy [38, 51, 55]. Findings of these studies were consistent with ours, in that foot reflexology reduced the level of anxiety. In contrast, Gunnarsdottir and Jonsdottir (2007) and Kavei et al. (2015) reported that reflexology did not have a significant effect on the anxiety level of patients undergoing CABG, nor patient undergoing open heart surgery under mechanical ventilation [44, 70] . Given the very small sample size (9 patients) in Gunnardsdottir and Jonsdottir’s study, their results are not a reliable indicator of the effectiveness of reflexology in improving the anxiety levels of patients undergoing coronary artery bypass. In Kavei et al.’s study, the foot reflexology was administered only an hour after admission to the ICU, where it seems that the patients had not fully recovered from the effects of anesthesia and sedatives, and the intervention was made before the patient was completely conscious. Patients became aware of the operative procedure and their intubation after recovering from anesthesia, and regained consciousness over time, which resulted in a gradual increase in their anxiety levels; as such, the effect of reflexology on anxiety level was not observed. Mc Vicar et al. (2007), and Mackereth et al. (2009) showed that foot reflexology resulted in a significant reduction in cardiovascular parameters of healthy individuals and systolic pressure in patients with multiple sclerosis [71, 72]. Also, Korhan et al. Obtained evidence that foot, hand, and ear reflexology reduces SBP, DBP, HR, and RR in patients under mechanical

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ventilation [41]. Results of these studies are consistent with the findings of the present study, given reduced rate of physiological indices. On the other hand, some studies did not report the effectiveness of foot reflexology in improving physiological parameters. Ebadi et al. (2015), Rollinson et al. (2016), and Jones et al. (2013) reported insignificant effect of foot reflexology on physiological parameters of patients undergoing open-heart surgery, cardiac indices and arterial compliance in healthy people, and hemodynamic parameters in patients with chronic heart failure respectively [53, 57, 58]. Due to the administration of reflexology one hour after ICU admission when the patients were not fully recovered from the effects of anesthetics and sedatives, the results from Ebadi et al.’s study are not reliable, since the effects of the sedatives acted as interference for the outcomes of reflexology. Moreover, since the intervention group included all patients undergoing open-heart surgery, the differences in incision site and surgical procedure could also result in different hemodynamic effects, interfering with the outcomes of the effects of the massage. In addition, the use of two different individuals for administering the massages could affect the results, in spite of the fact that they were trained by the same specialist. It seems that inadequate sample size (12 participants) in Rollinson et al.’s study can affect the outcomes. In addition to small sample size (12 patients with heart failure) in Jones et al.'s study can affect the study outcomes. Elisabeth et al. (2012) concluded that foot reflexology can significantly increase blood pressure and heart rate in healthy people [73]. It is worth noting that different methods have been used in studies reporting consistent and inconsistent results with the current study. It seems that using different techniques can also result in different outcomes. Moreover, contradictory results and their discussions indicate that many factors together can affect reflexology results. These effects may vary based on conditions. These factors are summarized as follows: health condition of an individual, sample size, better research control, existence of different text books with different techniques, different foot charts specifically disagreeing regarding the heart area, duration of massage, number of sessions, number of masseurs in studies, difference in anxiety and hemodynamic conditions in different diseases, duration of surgery, incision site, level of pressure (gentle or mild) (This is because gentle and light massages stimulate parasympathetic and sympathetic systems, respectively [53]), time of massage starting under mechanical ventilation, chance of interference with sedatives, and different stages of the disease.

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5. Conclusion Considering this point that the improvement in anxiety and physiological parameters was greater in the group A and also the closeness of the changes in the other two groups (Group B was insignificant compared to the group C), it seems that foot reflexology may have effects on the level of anxiety and physiological parameters of male patients undergoing CABG. Thus, it may be used as an applicable, safe, and non-invasive bedside treatment administered to reduce anxiety and create stable conditions in physiological parameters such as systolic, diastolic, mean arterial pressure, and heart rate due to anxiety, specifically when these patients are under disagreeable conditions in the ICU. As a result, it seems that reflexology can be used by nurses as an adjunct to standard ICU care to reduce anxiety and stabilize some physiological parameters. But considering the clinical and non clinical effects of reflexology, existence of the limitations in this study, contradictory results in the studies, and little evidence of its efficacy [61, 74], it is recommended that the results of the study were used with caution. Also further investigation is recommended in this regard. 5.1. Limitations The major limitation of the current study was its conduction only on male patients; therefore, results are not generalizable to other groups, such as women and children. Another limitation of the study was its conduction in only one teaching center, which may limit its generalizability. It is recommended to investigate the effects of foot reflexology on women undergoing coronary artery bypass in future studies. Moreover, it is recommended to investigate the effect of this method in other diseases and operative procedures. Conflict of Interest The authors declare that there is no conflict of interest. Author contributions

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The first author designed and conducted intervention, wrote the manuscript, collected data, and interpreted data. The second author (corresponding author) designed intervention, wrote the manuscript, revised it for content and edited it grammatically and scientific writing. The third author revised manuscript for content and edited it grammatically and scientific writing. Fourth author analyzed data. The fifth author taught reflexology to the first author. Sixth author interpreted data.

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Acknowledgments First and foremost, we would like to thank all of the patients who participated in this study. Next, we extend our gratitude to the nurses who provided the conditions for conducting our bedside research in the ICU. Finally, we would like to appreciate the Research Department of Tabriz University of Medical Sciences for their financial support.

Enrolment

Target population (CABG patient) Assessed for eligibility, n = 155

Excluded (n = 35) Did not have the inclusion criteria

Randomized (n = 120)

Lost to fallow up (n = 0) Discontinued study (n = 0)

Analyzed (n = 40)

Allocated to placebo (n = 40)

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Allocated to intervention (n = 40)

Lost to fallow up (n = 0) Discontinued study (n = 0)

Follow-Up

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Analyzed (n = 40)

Analyzed (n = 40)

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Table 1 Participants’ systolic blood pressure rates of the first day immediately after intervention in pilot study

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Allocated to control (n = 40)

Analysis

FIG. 1. CONSORT diagram.

SBP Mean (SD) 119.3 (12.10) 138.4 (16.10) 127.8 (18.65)

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Group Intervention (A) Placebo (B) Control (C)

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Table 2 Participants’ demograraphic characteristic in the foot reflexology (A), placebo (B) and control (C) group Characteristic All participant Group A 56.50 ± 7.99 27.81 ± 4.02 3.35 ± 0.56

55.90 ± 8.31 27.95 ± 3.97 3.35 ± 0.53

57.32 ± 8.62 27.54 ± 4.12 3.45 ± 0.57

56.30 ± 7.11 27.93 ± 4.07 3.25 ± 0.57

4.93 ± 0.98 43.22 ± 8.80 2.89 ± 0.54

4.96 ± 0.86 42.75 ± 10.61 2.80 ± 0.68

4.83 ± 1.16 44.55 ± 6.74 2.95 ± 0.45

5.01 ± 0.92 42.37± 8.69 2.92 ± 0.47

ANOVA, P = 0.720, F = 0.329 ANOVA, P = 0.502, F = 0.694 ANOVA, P = 0.425, F = 0.862

1 (0.8) 119 (99.2)

0 (0) 40 (100)

1 (2.5) 39 (97.5)

0 (0) 40 (100)

Fisher’s Exact test P = 1.000

36 (30) 37 (30.8) 10 (8.3) 28 (23.3) 9 (7.5)

10 (25) 10 (25) 3 (7.5) 13 (32.5) 4 (10)

16 (40) 12 (30) 2 (5) 9 (22.5) 1 (2.5)

10 (25) 15 (37.5) 5 (12.5) 6 (15) 4 (10)

Fisher’s Exact test P = 0.348

4 (3.3) 24 (20) 60 (50) 10 (8.3) 22 (18.3)

1 (2.5) 10 (25) 13 (32.5) 6 (15) 10 (25)

1 (2.5) 8 (20) 24 (60) 1 (2.5) 6 (15)

2 (5) 6 (15) 23 (57.5) 3 (7.5) 6 (15)

Fisher’s Exact test P = 0.205

67 (55.8) 53 (44.2)

19 (47.5) 21 (52.5)

20 (50) 20 (50)

28 (70) 12 (30)

Chi-Square Test ᵡ² = 4.934, dƒ = 2, p = 0.85

10 (25) 30 (75)

9 (22.5) 31 (77.5)

12 (30) 28 (70)

Chi-Square Test ᵡ² = 0.609, dƒ = 2, p = 0.738

19 (47.5) 21 (52.5)

25 (62.5) 15 (37.5)

24 (60) 16 (40)

Chi-Square Test ᵡ² = 2.104, dƒ = 2, p = 0.349

12 (30) 28 (70)

16 (40) 24 (60)

11 (27.5) 29 (72.5)

Chi-Square Test ᵡ² = 1.595, dƒ = 2, p = 0.450

3)5.2( 117 (97.5)

0 (0) 40 (100)

2 (5) 38 (95)

1 (2.5) 39 (97.5)

Fisher’s Exact test P = 0.772

26 (21.7) 94 (78.3)

6 (15) 34 (85)

11 (27.5) 29 (72.5)

9 (22.5) 31 (77.5)

Chi-Square Test ᵡ² = 1.866, dƒ = 2, p = 0.393

68 (56.7) 52 (43.3) 39 (32.5) 81 (67.5)

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Group C

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31 (25.8) 89 (74.2)

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Age (years) Mean ± SD Body Mass Index Mean ± SD Duration of surgery (Hours) Mean ± SD Time to regain consciousness after being transferred to ICU (Hours) Mean ± SD Ejection friction (%) Mean ± SD Grafts (n) Mean ± SD Marital, n (%) Single Married Educational level, n (%) Illiterate Primary Under diploma Diploma Lisence and uper lisence Job, n (%) Worker Farmer Self-employed Employee Retired Smoking, n (%) Yes No Diabetes, n (%) Yes No Hypertension, n (%) Yes No Hyperlipidaemia, n (%) Yes No Pulmonary diseases, n (%) Yes No Place of residence, n (%) Rural Urban

Statistical test and p-value ANOVA, P = 0.717, F = 0.334 ANOVA, P = 0.880, F = 0.128 ANOVA, P = 0.286, F = 1.265

Group B

Table 3 Comparison of foot reflexology (A), placebo (B) and control (C) group on anxiety (FAS).

0(0) 4(10) 24(60) 8(20) 4(10) 2(5) 2(5) 15(37.5) 14(35) 7(17.5) 0(0) 1(2.5) 19(47.5) 13(32.5) 7(17.5)

16(40) 14(35) 7(17.5) 3(7.5) 0(0) 5(12.5) 15(37.5) 9(22.5) 8(20) 3(7.5) 0(0) 11(27.5) 17(42.5) 10(25) 2(5)

AC C

A

Under mechanical ventilation T1b T1a T1t n(%) n(%) n(%)

22(55) 11(27.5) 3(7.5) 4(10) 0(0) 9(22.5) 11(27.5) 14(35) 6(15) 0(0) 2(5) 12(30) 16(40) 8(20) 2(5)

EP

MAP

Measurement stage Variable Group A no mild moderate severe Very severe B no mild moderate severe very severe C no mild moderate severe very severe

T2m n(%)

GEE

T2e n(%)

79 (65.8) 33 (27.5) 8 (6.7) 0 (0) 0 (0) 75 (62.5) 41 (34.2 4(3.3) 0 (0) 0 (0) 47 (39.2) 66 (55.00) 7 (5.8) 0 (0) 0 (0)

T3m n(%)

102 (85.0) 13 (10.8) 5 (4.2) 0 (0) 0 (0) 95 (79.2) 21 (17.5) 4 (3.3) 0 (0) 0 (0) 78 (65.00) 42 (35.00) 0 (0) 0 (0) 0 (0)

106 (88.3) 13 (10.8) 1 (0.8) 0 (0) 0 (0) 99 (82.5) 18 (15.0) 3 (2.5) 0 (0) 0 (0) 95 (79.2) 20 (16.7) 5 (4.2) 0 (0) 0 (0)

T3e n(%) 113 (94.2) 7 (5.8) 0 (0) 0 (0) 0 (0) 99 21 0 (0) 0 (0) 0 (0) 101 (84.2) 15 (12.5) 4 (3.3) 0 (0) 0 (0)

P-value B 0.026 -1.828

OR 0.621

95% CI Lower Upper -3.498 -0.218

0.328

1.88

-0669

0.295

Referent (0ᵅ)

Table 4 Comparison of foot reflexology (A), placebo (B) and control (C) group on anxiety (short form).

MAP

T2m Measurement stage Mean (SD) Variable Group A 8.25 (2.71) B 9.53 (1.95) C 10.81 (2.16)

T2e Mean (SD)

7.30 (2.23) 8.43 (2.01) 9.54 (1.62)

T3m Mean (SD)

6.89 (1.83) 7.66 (1.94) 8.70 (2.64)

T3e Mean (SD)

6.21 (0.82) 7.44 (1.92) 7.80 (2.31)

GEE

P-value B < 0.001 -2.063 0.262 -0.539 Referent (0ᵅ)

OR 0.127 0.584

95% CI Lower Upper -2.808 -1.318 -1.480 0.403

1.853

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Table 5

Comparison of foot reflexology (A), placebo (B) and control (C) group on physiologic parameters. Under mechanical ventilation T1b T1a T1t Mean (SD) Mean (SD) Mean (SD)

127.92 (16.06) 131.22 (19.61) 131.00 (21.81) 74.18 (9.99) 77.61 (7.83) 77.07 (14.08) 95.98 (9.88) 95.30 (10.68) 94.91 (15.61) 100.98 (16.02) 100.92 (14.66) 101.65 (12.19) 16.12 (5.99) 17.02 (4.36) 17.55 (4.13) 95.95 (2.81) 95.92 (2.26) 95.32 (2.91)

121.61 (13.18) 128.21 (16.19) 128.85 (16.15) 72.65 (8.15) 76.51 (10.38) 75.90 (12.21) 88.55 (8.58) 93.12 (11.04) 93.55 (12.96) 95.38 (20.81) 98.10 (13.91) 100.55 (11.81) 16.65 (4.19) 16.88 (4.33) 17.00 (4.80) 95.25 (2.35) 95.30 (2.15) 94.85 (2.58)

120.11 (13.10) 125.15 (18.50) 127.05 (15.91) 71.92 (8.04) 75.52 (10.69) 75.21 (12.58) 87.95 (7.99) 92.02 (11.39) 92.15 (12.68) 97.38 (15.93) 97.90 (13.69) 100.22 (11.29) 16.91 (4.29) 16.02 (4.02) 17.91 (4.25) 95.80 (2.55) 95.62 (2.36) 94.31 (2.22)

GEE T2m Mean (SD)

109.01 (13.28) 118.55 (16.70) 114.60 (15.23) 68.11 (9.21) 72.72 (9.03) 71.85 (10.55) 81.70 (9.76) 87.98 (10.44) 86.14 (11.27) 89.40 (13.86) 92.65 (11.95) 91.13 (11.73) 19.75 (4.12) 21.00 (4.40) 20.78 (3.22) 93.00 (2.68) 92.01 (2.47) 92.39 (2.37)

T2e Mean (SD)

110.46 (13.47) 116.50 (15.14) 117.59 (17.15) 68.05 (7.71) 72.15 (10.90) 73.25 (11.55) 82.29 (8.71) 86.88 (11.61) 88.01 (12.78) 88.44 (12.93) 90.53 (13.05) 90.72 (11.26) 19.82 (3.44) 20.68 (3.54) 20.11 (3.41) 93.21 (2.53) 92.41 (2.26) 92.47 (2.42

T3m Mean (SD)

T3e Mean (SD)

114.57 (11.64) 118.45 (9.07) 118.63 (16.58) 71.35 (7.65) 73.17 (5.86) 75.39 (11.86) 85.77 (8.29) 88.26 (6.25) 89.81 (12.90) 87.29 (11.02) 89.67 (8.78) 89.42 (10.48) 18.58 (2.85) 69.50 (2.76) 20.28 (3.65) 93.95 (2.56) 93.32 (2.14) 93.04 (2.41)

114.16 (8.98) 120.56 (8.14) 119.39 (12.10) 72.24 (6.07) 75.43 (4.85) 75.69 (8.53) 86.21 (6.68) 90.44 (4.89) 90.30 (9.09) 84.45 (9.64) 89.33 (9.22) 87.10 (10.17) 17.55 (2.64) 19.05 (2.11) 19.54 (3.30) 95.01 (2.18) 93.90 (2.08) 93.76 (2.27)

P-value B 0.006 -6.291 0.831 -0.988 Referent (0ᵅ) 0.001 -5.631 0.181 -0.196 Referent (0ᵅ) 0.001 -5.125 0.191 -0.123 Referent (0ᵅ) 0.074 -3.986 0.199 1.009 Referent (0ᵅ) 0.001 -2.698 0.526 -0.195 Referent (0ᵅ) 0.002 1.991 8.112 0.583 Referent (0ᵅ)

RI PT

Measurement stage Variable Group SBP A B C DBP A B C MAP A B C HR A B C RR A B C SPO2 A B C

SC

u

95% CI Lower Upper -11.254 -1.838 -5.013 4.054 -8.208 -3.802

-2.064 2.221

-9.047 -3.987

-2.257 2.472

-8.354 -3.324

0.392 5.331

-3.530 -2.010

-0.866 0.525

0.512 -0.746

2.380 1.152

M AN U

Day 1, evening, before intervention under mechanical ventilation with consciousness (T1b) - Day 1, evening, immediately after intervention under mechanical ventilation with consciousness (T1a) - Day 1, evening, ten minutes after intervention under mechanical ventilation with consciousness (T1t) Day2, morning, (T2m) - Day2, evening, (T2e) - Day3, morning, (T3m) - Day3, evening, (T3e) B: coefficient, CI: Confidence Interval, OR: Odds Ratio, 0ᵅ: Zero

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