Effects of three pulmonary ventilation regimes in patients undergoing coronary artery bypass graft surgery: a randomized clinical trial

The aim was to compare the effect of diaphragmatic breathing exercise (DBE), flow- (FIS) and volume-oriented incentive spirometry (VIS) on pulmonary function- (PFT), functional capacity-6-Minute Walk Test (6 MWT) and Functional Difficulties Questionnaire (FDQ) in subjects undergoing Coronary Artery Bypass Graft surgery (CABG). The purpose of incorporating pulmonary ventilator regimes is to improve ventilation and avoid post-operative pulmonary complications. CABG patients (n = 72) were allocated to FIS, VIS and DBE groups (n = 24 each) by block randomization. Preoperative and postoperative values for PFT were taken until day 7 for all three groups. On 7th postoperative day, 6 MWT and FDQ was analyzed using ANOVA and post-hoc analysis. PFT values were found to be decreased on postoperative day 1(Forced Vital Capacity (FVC) = FIS group—65%, VIS group—47%, DBE group—68%) compared to preoperative day (p < 0.001). PFT values for all 3 groups recovered until postoperative day 7 (FVC = FIS group—67%, VIS group—95%, DBE group—59%) but was found to reach the baseline in VIS group (p < 0.001). When compared between 3 groups, statistically significant improvement was observed in VIS group (p < 0.001) in 6 MWT and FDQ assessment. In conclusion, VIS was proven to be more beneficial in improving the pulmonary function (FVC), functional capacity and FDQ when compared to FIS and DBE.


Results
A total of 72 patients who were posted for Coronary Artery Bypass Graft surgery meeting the inclusion criteria were selected for the study with 24 patients in each intervention group. Baseline demographic characteristics of the participants such as age, height, weight, BMI, risk factors, type of surgery and duration of surgery are presented in Table 1. There were no statistically significant differences between the groups. Forced vital capacity (FVC) was compared within the intervention groups before and after surgery, and the same is summarized in Fig. 3. In all groups there was found to be a statistically significant decrease in FVC in the period between postoperative day 1 and postoperative day 7, when compared to the preoperative period. The FVC values for volume incentive spirometry group almost reached the baseline on postoperative day 7 (p = 1.00) ( Table 2).
Forced Expiratory Volume in one second (FEV1) was compared within the intervention groups before and after the surgery and is summarized in Fig. 4. In all groups there was a statistically significant decrease in forced expiratory volume in one second (FEV1) in the period between post-operative day 1 and postoperative day 7, when compared with the preoperative period. The forced expiratory volume in one second values for the volumeincentive spirometry group almost reached the baseline on postoperative day 7 (p = 0.69) ( Table 2).
Peak expiratory flow rates (PEFR) were compared with the intervention groups before and after surgery and are summarized in Fig. 5. In all groups there was a statistically significant decrease in peak expiratory flow rates (PEFR) in the period between post-operative day 1 and postoperative day 7, when compared with the preoperative period. The peak expiratory flow rates values for volume-incentive spirometry group almost reached the baseline on postoperative day 7 (p = 0.81) ( Table 2).
The functional capacity i.e. 6-Minute Walk Test (6 MWT) was compared between the intervention groups on postoperative day 7 and is summarized in Table 3. As observed on postoperative day 7, there was a statistically significant increase in the distance walked in the volume-incentive spirometry group as compared to the diaphragmatic breathing exercise group and the flow-incentive spirometry group (p = 0.01) (Fig. 6).
On the postoperative day 7 a comparative evaluation of the functional difficulty questionnaire (FDQ) was made among the three interventional groups. This is summarized in Table 4. Upon comparison among the three intervention groups, a significant improvement was observed on postoperative day 7 in the volume-incentive spirometry group as compared to the diaphragmatic breathing exercise group and the flow-incentive spirometry group (p < 0.001) (Fig. 7).
In the period between the preoperative day and postoperative days 5 and 7 forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and peak expiratory flow rate (PEFR) were compared among the three intervention groups. The findings are summarized in Tables 5 and 6. There was statistically significant difference among the three intervention groups in terms of forced vital capacity (FVC), the said variables being significantly lower in the flow-incentive spirometry group than in the volume-incentive spirometry group and the diaphragmatic breathing exercise group (Tables 5 and 6).

Discussion
In our study we found that Volume-incentive Spirometry improved pulmonary function, functional capacity and functional difficulty in patients who underwent coronary artery bypass graft surgery as compared to flowincentive spirometry and diaphragmatic breathing exercises.  Our results are in conjunction with Renault et al., who concluded that there was a mean significant decrease in pulmonary function (FVC, FEV1) after CABG on postoperative day 7 in the flow-incentive spirometry group 3 . Dias et al., found that in the flow-incentive spirometry group there was reduction in pulmonary function (FVC) after CABG surgery on postoperative day 1 which partially normalized by postoperative day 5 18 . Oikkonen et al., found that in the volume-incentive spirometry group after coronary artery bypass graft surgery there was reduction in pulmonary function (FVC, PEF) on postoperative day 1 which recovered (FVC, PEF) on postoperative day 7 19 .
In patients undergoing coronary artery bypass graft surgery the possible reasons for a decrease in pulmonary function (FVC, FEV1, PEFR) during the post-operative period are pain, the effect of anaesthesia, analgesia, insertion of intercostal drains. During the postoperative period, ventilation to the dependent region of the lungs is decreased since the patient performs shallow breathing without intermittent sighs due to the pain associated with median sternotomy and insertion of intercostal drains 3,18,20 .
General anaesthesia may have an effect on the ventilation and lung mechanics, which might lead to reduced ventilation-perfusion, increase in dead space and hypoxemia. Analgesics and other drugs affect the central regulation of breathing and alter the neural drive of the upper airway and muscles of the chest wall resulting in reduced ventilation, decreased sensitivity of the respiratory centres to the stimulation of CO 2 , suppression of the cough reflex and improper production of mucous [19][20][21] . Table 2. Mean difference and percentage change of pulmonary function test values between pre-operative day and post-operative day 1-7 among the three groups. p < 0.001 highly significant, POD postoperative day.   Figure 5. Comparison of peak expiratory flow rate (PEFR) before and after coronary artery bypass graft surgery between three groups. Table 3. Comparison of 6-Minute Walk Test, on post-operative day 7, between three intervention groups. p < 0.001 highly significant.

6-Minute Walk Test (6 MWT) (m) Flow-incentive spirometry group Diaphragmatic breathing exercise group Volume-incentive spirometry group
Post-operative day 7 (mean ± SD) 91. 25  www.nature.com/scientificreports/ Diaphragm dysfunction is caused due to injury to the phrenic nerve due to dissection of the internal mammary artery with electrocauterization and the insertion of chest tubes for pleural and mediastinal drainage after an open heart surgery. This leads to reflex inhibition of the phrenic nerve causing functional disruption of the movement of the diaphragm 3,18-20 .
The possible reason for improved pulmonary function in the volume-incentive spirometry group might be that it is a mechanical device which opens the alveoli and maintains its patency upon the patient's taking long deep breaths which, again, encourages the patient to breathe until total lung capacity has been achieved. Thereby lung inflation is maintained 5 . Volume-incentive spirometry thus has definite advantages over flowincentive spirometry since it improves the activity of the diaphragm and reduces the work of breathing. In   www.nature.com/scientificreports/ volume-incentive spirometry, the training volume is kept fixed by the physiotherapist until the maximal inspiratory capacity is achieved. Diaphragm fatigue is minimized since volume spirometry provides a low level of resistance training 22,23 .
Our study is in accordance with Agostini et al. who stated that 'volume-incentive' spirometry improves the lung function and also helps in lung re-expansion following CABG surgery 23 . Yamaguti et al., suggested that volume-incentive spirometry and diaphragmatic breathing exercises improve pulmonary function and promote greater diaphragmatic mobility than flow-incentive spirometry 24 . Carvalho et al., stated that the use of 'volumeincentive' spirometry promotes early re-expansion of the lungs and also reduces the chances of postoperative pulmonary complications 25 .
The secondary outcome measures in the present study showed that the volume-oriented incentive spirometry group exhibited improved functional capacity demonstrated by the fact that members of the group covered a greater distance in the 6-Minute Walk Test than members of the diaphragmatic breathing exercise group and the flow-incentive spirometry group (mean difference of 35 m). Also, there was an improvement in the scores obtained in the Functional Difficulty Questionnaire (FDQ) by the volume-incentive spirometry group (mean difference = 45 points).
The Six-Minute Walk Test (6MWT) has been validated for use in preoperative and postoperative periods as a measure of recovery and functional capacity in flow-and volume-incentive spirometry groups, members of which have undergone abdominal and thoracic surgeries. Mobilization of postoperative patients with low intensity exercise aims at eliciting cardiopulmonary responses which enhances oxygen transport, assists in reduction of postoperative pulmonary complications and improves the Quality of Life [26][27][28][29] . Early mobilization is recommended to patients undergoing coronary artery bypass graft surgery. It has proven to enhance lung volumes and gas exchange 28 . Our results are similar to the findings of Stein t al., who concluded that a 6-day rehabilitation program attenuated the postoperative reduction in respiratory muscle strength and also improved the recovery of functional capacity in the Inspiratory muscle training group after CABG 28 .
Hirschhorn et al., concluded that incorporation of moderate intensity inpatient cardiac rehabilitation improved the distance walked in 6 min by CABG patients on postoperative day 7 29 . Haeffener et al., concluded that flow-incentive spirometry coupled with expiratory positive airway pressure brought about an improvement in the distance walked by patients one week and one month post-CABG 20 . Table 5. Shows the difference between preoperative and postoperative day 5 between the three intervention groups of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR). p < 0.001 highly significant.   Table 6. Show the difference among the three intervention groups in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) between preoperative day and postoperative day 7. p < 0.001 highly significant. Sequencing was done using a computer generated random numbered tables. Block randomization was done. The participants will be divided into 12 blocks with 6 participants in each block. Allocation was done using sequentially numbered, opaque sealed envelopes. Group information was concealed in a sealed opaque envelope and was revealed to the patients only after they are recruited into the treatment group by an investigator who was a physiotherapist. The inpatient cardiac rehabilitation program was delivered to the patients by another investigator who is also a physiotherapist and was blinded to allocation and also to the assessment of outcome measures. The outcome measures were assessed by the primary investigator.

Pre-operative day minus postoperative day 7 (mean difference) Forced vital capacity (FVC) (L) Forced expiratory volume in 1 s (FEV1) (L) Peak expiratory flow rate (PEFR) (L/s)
Following the allocation to groups, the patients in all the three treatment groups were visited one day prior to surgery. Pre-operative information was offered and based on his/her group; flow-oriented incentive spirometer, volume-oriented incentive spirometer or diaphragmatic breathing exercises were taught to each patient. Use of ventilatory devices (i.e. either flow-oriented incentive spirometer/volume-oriented incentive spirometer/ diaphragmatic breathing exercise-as per the group allotted), airway clearance techniques (huffing, coughing, mucous clearance devices), circulation (ankle toe movements, upper limb and lower limb range of motion exercises), thoracic expansion exercises, mobilization (edge of bed sitting, walking, stair climbing) were provided. A standard 7-day Inpatient Cardiac Rehabilitation protocol was taught to the patient 15,16 (Fig. 8).
Pulmonary function tests (PFT) measured the following variables: forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak expiratory flow rate (PEFR).These were taken on the preoperative day and on the 1st, 2nd, 3rd, 4th, 5th, 6th and 7th postoperative days, for all the groups. These measurements were taken by the primary investigator.
The 6-Minute Walk Test (6MWT) was performed according to the American Thoracic Society's guidelines 17 . The 6-Minute Walk Test was taken on the day of discharge, for all the groups. These investigations were taken by the primary investigator.
Pulmonary Function Test. Pulmonary Function Test procedures were carried out according to the American Thoracic Society/European Respiratory Society guidelines. The following variables were recorded: forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and peak expiratory flow rate (PEFR). The best value of the three tests was taken 5 .

6-Minute Walk
Test. The 6MWT was performed according to the American Thoracic Society's guidelines. Participants were instructed to walk as far as they could along a 30-m corridor for six minutes with the aim of achieving their maximum possible walking distance in 6 min time. Standardized instructions were provided each minute. Subjects were permitted to stop and rest if required but were encouraged to continue walking as soon as they were able to do so 17 . www.nature.com/scientificreports/ Heart rate (HR), respiratory rate (RR) and oxygen saturation (SPO 2 ) were measured using pulse oxymeter; dyspnea (modified Borg scale) and fatigue were measured at the beginning and immediately after the test. The outcome of the test was the covered distance: the longer the distance covered by the patient, the better their functional performance 17 .

Scientific Reports
The Functional Difficulties Questionnaire (FDQ) is a paper-based questionnaire that contains generic instructions for completion. The Functional Difficulties Questionnaire (FDQ) comprised 13 separate functional tasks which are necessary in everyday life and involve movements associated with the thoracic region. These tasks included upright sitting, walking with arms swinging freely, coughing/sneezing, rolling over in bed, getting out of bed, washing hair, scratching the back, picking up an object off the ground, turning to reach backward, doing the clasp of a bra or tucking in a shirt at the back of pants, putting on a dressing gown/cardigan/jacket, drying the back with a towel, and pushing a set of drawers shut 9 .
The FDQ was administered to patients on the day of discharge. The FDQ is a paper-based questionnaire that includes generic instructions for completion. After reading these, on unmarked 10-cm visual analogue scales (VAS), participants can grade 13 different tasks according to the level of difficulty experienced when completing each task. The VAS end points were "No difficulty" and "maximum difficulty". In accordance with a standardized administration procedure, the therapist was present to aid with the execution of the questionnaire. Individual VAS scores, measured to the nearest millimeter, were then aggregated to form a potential number of 130, with higher scores reflecting greater functional difficulty encountered. If a given task could not be accomplished by the participant, it was automatically graded as a 10 to reflect maximum difficulty. These investigations were supervised by the primary investigator. The CONSORT flow diagram is mentioned in Fig. 9.
Step 1 • Diaphragmatic breathing exercise/ Flow incentive spirometry/ Volume incentive spirometry -5 repetitions, 3 sets, 4 times/ day • AAROM for bilateral upper limbs and lower limbs -5 repetition, 3 sets, 4 times/ day • Ankle toe movements -5 repetitions, 3 sets, 4 times/ day • Thoracic mobility exercises -5 repetitions, 2 sets, 4 times/ day • Splinted huffing-3-4 huffs, 3 times/ day Step 2 • Repeat step 1 • Edge of the bed sitting • Cane chair sitting • AROM for bilateral upper limbs and lower limbs-5 repetitions, 4 sets, 4 times/ day Step 3 • Repeat step 1 • Repeat step 2 • Splinted coughing • Supported room ambulation (1 round, 2 times/ day) Step 4 • Repeat step 3 (including step 1 and step 2) • Trunk mobility exercises (5 repetitions, 3 sets, 2 times/ day) • Unsupported ward ambulaltion (2 rounds, 2 times/day) Step 5 • Repeat step 4 • Downstairs-1 flight (2 times/ day) • Progression of ambulation (Unsupported ward ambulaltion-2 rounds, 2 times/day) Step 6 • Repeat step 5 • Downstairs -2 flights (2 times/ day) • Upstairs-1 flight (2 times/ day) Step 7 • Repeat step 6 • Up and Down Stairs-1 flight (2 times/ day) The patient was instructed to inhale with a slow and deep sustained breath, holding it for a minimum of 5 s and then was asked to exhale passively in order to avoid any forceful expiration. Initially, the patient was given a demonstration and then was asked to perform the procedure. The patient was instructed to hold the spirometer upright and to perform flow-oriented incentive spirometry by inhaling slowly which would lead to raising the ball in the spirometer. The same procedure was followed for the volume-oriented incentive spirometry, but the patient was asked to inhale in order to raise the piston or plate in the chamber to the set target 5 .
The patient was instructed to perform 3 sets of 5 repeated deep breaths. This was performed by the patient every waking hour. The therapist administered the exercise four times a day and the patient was instructed to perform the same for the rest of the day. The patient was asked to keep a record of the exercises performed by him/her by entering these in a log book which was provided beforehand 5 .
Method to perform diaphragmatic breathing exercise (DBE). The patient was asked to sit in a half lying position (back and head were fully supported and abdominal wall was relaxed) and diaphragmatic breathing was performed. The therapist placed her hands just below the anterior costal margin, on the rectus abdominus muscle, while the patient was be asked to inhale slowly and deeply through the nose, with a three second inspiratory hold from the functional residual capacity to total lung capacity. The patient was then instructed to relax the shoulders and keep the upper chest quiet so that the abdomen may be a little raised. The patient was then asked to exhale slowly though the mouth 5 .
The patient was asked to experience a slight raise and subsequent fall of the abdomen by placing his/her hand below the anterior coastal margin, during inspiration and expiration. The patient was asked to perform 3 sets of 5 deep breaths, with the therapist administering them four times in a day, and the patient was instructed  www.nature.com/scientificreports/ to perform the same every waking hour for the rest of the day. The patient was asked to breathe normally, in between the repetitions of the diaphragmatic breathing exercise. The patient was asked to keep a record of the exercise performed by entering it in the log book provided beforehand 5 .
Statistical analysis. Data was analyzed using IBM SPSS package version 25.0. Armonk, NY: IBM corp.
ANOVA and post hoc analysis (Bonferroni's t-test) were carried out to verify the within-groups differences. Between groups differences were compared using two-factor ANOVA.
Limitations. The duration and type of anaesthesia and analgesia were not recorded and this could probably affect the outcomes. The patients were provided with log books in which to make an entry every time they performed the technique. This was meant to enable the researcher check their adherence to the prescribed regimen. But there was no way to verify the authenticity of these entries.
Future research. Future studies can be carried out in a similar way with a large sample size, on patients who have undergone valve replacement surgeries. Future research on the use of alternative techniques can be carried out by assessing respiratory muscle strength and the comfort of patients who have undergone cardiac surgery. The effect generated by a combination of diaphragmatic breathing exercise and incentive spirometry can be studied in cases of thoracic and abdominal surgeries.
Clinical implication. Volume-oriented incentive spirometry can be recommended for all the patients postoperatively and preoperatively over flow-oriented incentive spirometry and diaphragmatic breathing exercise as an intervention for the generation and improvement of pulmonary function, functional capacity and functional difficulty questionnaire (FDQ) in the management of coronary artery bypass graft surgery. For general CABG population, family members need to assist the patient in this regimen of inpatient cardiac rehabilitation for better recovery.

Conclusion
• The conclusion obtained from our study is that in patients undergoing coronary artery bypass graft surgery there is decrease in the pulmonary function (FVC, FEV1, PEFR) in all the three intervention groups from postoperative day 1 to postoperative day 7, when compared with preoperative values. • Pulmonary function values (FVC, FEV1, PEFR) reached baseline on postoperative day 7, and functional capacity and functional difficulty questionnaire (FDQ) showed an improvement in the volume incentive spirometry group. • From the present study we concluded that Volume-oriented Incentive Spirometry proved to be beneficial in improving pulmonary function (forced vital capacity-FVC), functional capacity and functional difficulty questionnaire (FDQ) when compared to flow-oriented incentive spirometry and diaphragmatic breathing exercises.

Data availability
The data used to support the findings of this study are available from the corresponding author upon request.