Perioperative Short-term Pulmonary Rehabilitation for Patients Undergoing Lung Volume Reduction Surgery

Abstract

Although pulmonary rehabilitation is recommended for patients undergoing lung volume reduction surgery, the optimal method of pulmonary rehabilitation is unclear. The aim of this study was to determine the feasibility and safety of perioperative short-term pulmonary rehabilitation. We enrolled candidates for lung volume reduction surgery from 1999 to 2006 and retrospectively evaluated the feasibility and safety of perioperative short-term pulmonary rehabilitation for these patients. The program included the progressive exercise training on a treadmill for approximately 3 weeks. Two primary endpoints, feasibility and safety, were determined by the adherence rates of the program session and the adverse events. Pulmonary function and exercise capacity were evaluated at baseline and the termination of pre- and postoperative short-term pulmonary rehabilitation. Twenty-two patients were enrolled in this study. All patients completed our program without any serious adverse events. The mean values of adherence rates of the preoperative, postoperative, and overall period were, 89.1%, 95.1%, and 92.1%, respectively. All values of pulmonary function tests, except for forced vital capacity, significantly improved at the termination of postoperative short-term pulmonary rehabilitation in comparison to those at the termination of preoperative short-term pulmonary rehabilitation. The values of the 6-minute walk distance, total exercise time, and maximal workload on incremental exercise test were significantly improved by preoperative short-term pulmonary rehabilitation, and their values were maintained until the termination of postoperative short-term pulmonary rehabilitation. The results indicated that it is both feasible and safe to perform perioperative short-term pulmonary rehabilitation.

Keywords: :

• chronic obstructive pulmonary disease
• exercise tolerance
• exercise training
• lung volume reduction
• rehabilitation

INTRODUCTION

The National Emphysema Treatment Trial and several large case series have demonstrated that lung volume reduction surgery (LVRS) provides improvements in the survival, exercise capacity, and quality of life in selected patients with severe pulmonary emphysema (1–6). The morbidity and mortality following LVRS tended to be higher than those after other thoracic surgical procedures because of the fragile nature of these patients (7). Therefore, many centers performing LVRS have found that pulmonary rehabilitation (PR) plays an essential role during the perioperative period (1–6).

Despite the strong scientific rationale of providing comprehensive PR in patients undergoing LVRS, no formal guidelines regarding the optimal method of PR is available (8). Although the National Emphysema Treatment Trial study certainly provided an excellent example of the integration of PR into a surgical treatment program for patients with severe emphysema, the rehabilitation program was not designed specifically to evaluate PR.

There was a consensus on the period of PR in surgical candidates for LVRS. The National Emphysema Treatment Trial protocol requires all subjects to complete a comprehensive outpatient program of PR for 6 to 10 weeks (9). Other studies also reported that the period of PR before LVRS was set 6 to 12 weeks (2–6). Debigare and colleagues reported that performing a minimally supervised home-based exercise program 5 times per week for 10 to 12 weeks was feasible and effective for patients undergoing LVRS (10).

Although such a long-term rehabilitation may be suitable for fragile patients, this length potentially diminishes patients’ motivation to undergo LVRS. Obviously, a short period of program is less expensive and would also further encourage more patients to agree to participate in this program. However, an aggressive intervention may be needed to reduce the period of PR. To our knowledge, there have so far been few reports on such PR programs. We therefore enrolled candidates for LVRS and retrospectively evaluated the feasibility and safety of perioperative PR for a short period.

MATERIALS AND METHODS

Study design

Twenty-two consecutive patients undergoing bilateral LVRS and perioperative short-term PR (STPR) were enrolled between September 1999 and July 2006, and also were retrospectively analyzed. The study used internal controls (each patient served as his/her own control), and pre-STPR data were used as the baseline data for comparisons with preoperative and postoperative STPR data, which were evaluated at the end of therapy. The two primary endpoints, feasibility and safety, were determined by the adherence rates of the program session and the adverse events induced by the PR program. The secondary endpoints included pulmonary functions and exercise capacities. The institutional Review Board of Clinical Research of the hospital ethically approved this study, and informed consent for this study was obtained from all patients.

Patients

The inclusion and exclusion criteria for the study are shown in Table 1. Patients with moderate to severe bilaterally diffuse emphysema were included in this study. All studied patients had radiographic evidence of hyperinflation and heterogeneously distributed emphysema that provided target areas for resection based on high-resolution computed tomography and lung perfusion scanning.

Table 1  Inclusion and exclusion criteria for study enrollment

Inclusion Criteria

Age younger than 80 years

Cessation of cigarette smoking (>6 months)

Heterogeneously distributed emphysema

Marked hyperinflation

Marked physiologic impairment (FEV1 <35% predicted)

Mean pulmonary artery pressure <35 mm Hg

Exclusion Criteria

80 years and older

Continued cigarette smoking

Severe hypoxemia (PaO2/FiO2 ratio <150)

Markedly disordered alveolar gas exchange (DLCO <25% predicted, PaCO2 >50 mm Hg)

Significant co-morbidity

Respirator dependent state

Previous pleurodesis or thoracotomy

Homogeneously distributed emphysema

Absence of lung hyperinflation

Radiographically interstitial pulmonary disease that precludes surgery

Mean pulmonary artery pressure >35 mm Hg

FEV₁, forced expiratory volume in 1 second; PaO₂, partial pressure of arterial oxygen; FiO₂, fraction of inspired oxygen; DL_CO, diffusing capacity of carbon monoxide; PaCO₂, partial pressure of carbon dioxide.

Short-term pulmonary rehabilitation

The preoperative phase of STPR began as soon as no clinical evidence of cardiovascular disease was confirmed after hospitalization. The STPR was administered 5 times per week for approximately 3 weeks. Certified physical therapists (M. I. and K. H.) supervised all of the sessions.

The progressive exercise training was the main part of the programs that consisted of lower extremity exercise using treadmill. Each session included 30 minutes of exercise that consisted of 3 rounds of 10-min continuous walking at the target exercise level and a few minutes of rest. The exercise intensity determined by the combination of speed and grade on the treadmill were adjusted using a modified Cornell protocol. This protocol consisted of 11 stages, beginning with the equivalent of stage 0 of the Bruce protocol (1.7 mile per hour, 0% grade), and then increased in a stepwise fashion to the equivalent of stage 5 (5 mph, 18% grade) (11). Specifically, at the beginning of the session, patients began to walk for 10 minutes at the intensity corresponding to approximately 40 to 50% of the maximum intensity derived from the incremental exercise test at baseline.

We adjusted the target exercise level according to the levels of perceived exertion of dyspnea, leg fatigue, and/or general fatigue using the modified Borg scale developed by Borg (12), which has category-ratios ranging from levels of 0 to 10. The exercise intensity increased in patients with the Borg scale <5, but it was unchanged in those with the scale between 5 and 6. The intensity was decreased under the following conditions; the Borg scale was >6, attainment of age-predicted maximal heart rate (210 − 0.85 × age), and/or infeasible a bout of treadmill walking.

The patients received supplemental oxygen via a nasal cannula as was deemed necessary. Each session included lower extremity resistance training through sit-to-stand exercise as well. We instructed the patients to seat in a standard chair and then to stand up then sit down again 50 times including a short intermission following every 10 repetitions. The STPR in the postoperative phase included an early mobilization as well as the progressive exercise training, and was begun on the first postoperative day to prevent pulmonary complication and to hasten the postoperative recovery. Physical therapists provided all patients with vigorous chest physiotherapy and early mobilization that included getting out of bed, sitting on the edge of the bed, standing, and walking.

Immediately after independent ambulation, the progressive exercise training was resumed regardless of the chest tube withdrawal, as is the case with preoperative STPR. The protocol was conducted from the lowest stage of the modified Cornell protocol. The postoperative program was continued until the time of discharge.

Other PR components, including educational activities, such as instructions about disease and therapeutic interventions, instructions for chest clearance, functional training in activities of daily living, and energy-conserving strategies were provided by physical therapists during hospitalization.

Surgery

LVRS was performed by one experienced thoracic surgeon (R.N.) via a median sternotomy (MS, n = 8, September 1999 to January 2000) and video-assisted thoracic surgery (VATS, n = 14, January 2000 to July 2006).

Pulmonary function tests

Pulmonary function tests including spirometry, plethysmography, diffusing capacity of carbon monoxide (DL_CO), and resting room air arterial blood gas analysis were measured by experienced technicians.

Six-minute walk test

The 6-minute walk distance (6MWD) was identified as one of exercise capacity. This test was performed according to the published standardized guideline (13). All of the patients were informed of the purpose and methodology of this test. The distance walked in meters, oxygen saturation by pulse oximetry and the modified Borg scale were all recorded.

Incremental exercise test

The maximal exercise capacity was measured by a symptom-limited graded treadmill exercise test, the day after the 6-min walk test using the modified Cornell protocol. Technicians instructed patients to keep walking up to their individual maximum capacity. The test was stopped when the patients were exhausted, or reached a maximum heart rate, or at any signs of ischemic heart disease. The test was performed with supplemental oxygen if oxygen saturation of hemoglobin <90%, as demonstrated by pulse oximetry. We assessed the following variables: the total exercise time in minutes, the maximal workload attained in metabolic equivalents during the test, and the modified Borg scale.

Statistical analysis

The values are presented as the mean of the value ± standard deviation. We used the paired Student’ t-test and the Wilcoxon rank-sum test for comparisons of the continuous variables among baseline, preoperative, and postoperative periods. The differences were considered to be statistically significant when the p value was less than 0.05. The statistics were completed using a statistical software package (JMP 5.0.1 J; SAS Institute Japan Inc; Tokyo, Japan).

Table 2  Baseline characteristics of patients*

Age (years)	67.6 ± 7.2
Sex, male / female, No (%)	2 (9.1)/20 (90.9)
Body Mass Index (kg/m^2)	20.9 ± 3.0
Smoking history (pack-yr)	73.8 ± 35.8
Co-morbidities, No (%)	9 (40.9)
Distribution of emphysema: upper lobe/ non-upper lobe, (%)	20 (90.9)/ 2 (9.1)
Oxygen supplementation, (%)	2 (9.1)
FEV1% predicted (%)	46.4 ± 21.6
DLCO% predicted (%)	54.5 ± 23.5
PaO2 (mm Hg)	70.6 ± 12.1
PaCO2 (mm Hg)	40.3 ± 5.3
MRC dyspnea scale, 2/3/4, (%)	4 (18.2)/14 (63.6)/4 (18.2)

*Values are mean ± standard deviation or numbers (percentages) of patients.

Abbreviations: FEV₁, forced expiratory volume in 1 second; DL_CO, diffusing capacity of carbon monoxide; PaO₂, partial pressure of arterial oxygen; PaCO₂, partial pressure of carbon dioxide; MRC, Medical Research Council.

RESULTS

Feasibility, safety, and hospital course

The baseline characteristics of the patients are shown in Table 2. All patients completed STPR program with no hospital deaths. Neither injury nor any accident occurred during perioperative STPR. The mean values of adherence rates of the preoperative, postoperative, and overall period were, 89.1%, 95.1%, and 92.1%, respectively. The median number of sessions attended the progressive exercise training of the preoperative, postoperative, and overall period were, 10 sessions, 18 sessions, and 28 sessions, respectively. The median duration of the preoperative STPR, postoperative STPR, and hospital stay were 2.7 weeks (interquartile range, 2.3 − 3.5 weeks), 4.7 weeks (interquartile range, 4 − 6.3 weeks) and 8.3 weeks (interquartile range, 6.6 − 9.8 weeks), respectively. Postoperative complications developed in 9 patients (40.9%). Of these patients, 5 patients (MS, n = 3; VATS, n = 2) had postoperative pneumonia and 4 patients (MS, n = 3; VATS, n = 1) had a persistent air leak for longer than 7 days.

Pulmonary function tests

There were no differences in the pulmonary function test results between the baseline and termination of preoperative STPR. Postoperative values significantly improved in all functions except for forced vital capacity, in comparison to the preoperative values (Table 3).

Table 3  Results of pulmonary function tests at baseline, preoperative^†- and postoperative^† short-term pulmonary rehabilitation

Variables	Baseline data	P-value (baseline vs. preop. data)	Preop. STPR data	P-value (preop. vs. postop. data)	Postop. STPR data
FVC (L)	2.5 ± 1.0	NS	2.5 ± 1.1	NS	2.5 ± 0.6
FVC% predicted (%)	73.0 ± 23.8	NS	74.1 ± 25.7	NS	72.2 ± 14.6
FEV1 (L)	1.3 ± 0.65	NS	1.18 ± 0.61	0.0116	1.31 ± 0.53
FEV1% predicted (%)	46.4 ± 21.6	NS	42.6 ± 19.6	0.0082	47.3 ± 18.4
FRC% predicted (%)	157.8 ± 83.2	NS	155.7 ± 54.9	0.0096	102.4 ± 31.4
RV% predicted (%)	266.2 ± 137.9	NS	245.7 ± 106.6	0.0096	186.5 ± 64.2
TLC% predicted (%)	143 ± 48.4	NS	135.4 ± 33.7	0.007	109.7 ± 16.7

*Baseline data were measured before the initiation of STPR.

^†Preoperative and postoperative STPR denote those at the termination of preoperative STPR and postoperative STPR, respectively.

Values are mean ± standard deviation.

Abbreviations: STPR, short-term pulmonary rehabilitation; preop, preoperative; postop, postoperative; FVC, forced vital capacity; FEV₁, forced expiratory volume in 1 second; FRC, functional residual capacity; RV, residual volume; TLC, total lung capacity; NS, not significant.

Six-minute walk test

The 6MWD at the termination of preoperative STPR was significantly improved by 36.2 meters in absolute change and by 8.3% in percent change, in comparison to the baseline value, while there were no differences between preoperative and postoperative values. No significant changes were seen in the modified Borg scale during 6-min walk test among all three periods (Table 4).

Table 4  Results of exercise capacity test (the 6-minute walk test and incremental exercise test) at baseline, preoperative^†- and postoperative^† short-term pulmonary rehabilitation

Variables	Baseline	P-value (baseline vs. preop. data)	Preop. STPR data (percent change^‡ from baseline,%)	P-value (preop. vs. postop. data)	Postop. STPR data (percent change^‡ from baseline,%)
6MWD (m)	434.2 ± 87.5	0.004	470.4 ± 79.5 (8.3)	NS	460.0 ± 86.5 (7.5)
Borg scale at 6-minute walk test	5.1 ± 1.6	NS	4.9 ± 1.6	NS	5.0 ± 2.3
Total exercise time (min)	11.1 ± 4.8	<0.001	14.7 ± 4.1 (32.4)	NS	13.5 ± 4.7 (21.6)
Maximal workload (METs)	6.0 ± 2.3	<0.001	7.9 ± 2.2 (31.7)	NS	7.2 ± 2.2 (20.0)
Borg scale at incremental exercise test	6.0 ± 1.1	NS	6.1 ± 1.7	NS	5.8 ± 2.1

*Baseline data were measured before the initiation of STPR.

^†Preoperative and postoperative STPR denote those at the termination of preoperative STPR and postoperative STPR, respectively.

^‡Percent change was calculated as: (preoperative- and postoperative STPR value –baseline value) / baseline value × 100.

Values are mean ± standard deviation.

Abbreviations: STPR, short-term pulmonary rehabilitation; preop, preoperative; postop, postoperative; 6MWD, 6-minute walk distance; Borg scale, the modified Borg scale; METs, metabolic equivalents; NS, not significant.

Incremental exercise test

Both the pre- and postoperative values showed significant increases in the total exercise time in minutes and the maximal workload in comparison to the baseline, despite the lack of changes in the Borg scale during the incremental exercise test. The mean total exercise time in minutes at terminations of preoperative STPR was increased by 32.4% and 21.6% in comparison to the baseline value, respectively. Likewise, the preoperative STPR improved the maximal workload by 31.7% and 20% from the baseline values, respectively. In contrast, there were no differences in the values of incremental exercise tests between the pre- and postoperative STPR (Table 4).

DISCUSSION

The present study demonstrated 3 important clinical findings: (1) all patients completed STPR with high adherence rates and without any serious adverse events; (2) preoperative STPR for a median duration of 2.7 weeks significantly increased all of the measured variables of exercise capacity; (3) postoperative STPR for a median duration of 4.7 weeks might facilitate recovery of exercise capacities to the level at the termination of preoperative STPR.

The STPR program had 3 strategies: first, the progressive exercise training included of three courses of 10-min continuous walking; second, exercise intensity was adjusted depending on the patients’ symptomatic response by using the modified Borg scale; and third, oxygen supplementation was used during exercise training. Although the high-intensity exercise training for more than 30 minutes is recommended as the principal component of PR for patients with COPD (14), many patients failed to continue such an exhausted training for a long period due to progressive air trapping and further dynamic hyperinflation during exercise (15). Therefore, one course of the exercise training was defined as 10 minutes in the current series because metabolic and physiological responses usually can be reached a plateau within 5 to 10 minutes of exertion at a constant workload (16).

Although high-intensity training performed in an incremental exercise test was recommended for exercise prescription, Maltais and colleagues (14) have reported that few subjects are able to achieve a target exercise intensity of 80% of the peak work rate. The modified Borg scale was used to establish an appropriately prescribed exercise regimen for each patient and then to subsequently adjust it as necessary. Horowitz and colleagues (17) have reported the Borg scale to be useful for adequate training intensity.

Supplemental oxygenation during STPR was aggressively used not only to ensure safety but also as an adjunct to exercise training to train at higher intensity levels (18). These strategies made daily increases in the training intensity as safe as possible for all participating patients.

Previous studies and guidelines have stated that patients with a low exercise capacity have an increased risk for perioperative death and cardiopulmonary complications after major lung surgery (19, 20). Similarly, several studies have demonstrated that postoperative mortality and morbidity rate are inversely associated with exercise tolerance in patients who underwent LVRS (4, 5, 21, 22).

Szekely and colleagues (21) reported that patients with the baseline 6MWD <200 meters, who undergo LVRS, have a greater risk of prolonged hospital stay and higher mortality in comparison to patients with better baseline exercise capacity. Moreover, the exercise capacity had been identified as one of the independent predictors of mortality after thoracoscopic LVRS according to a multi-institutional experience (22). Patients who were too disabled to complete PR should not undergo LVRS because of the high operative risks (5).

Therefore, increasing patients’ exercise capacity during preoperative phase seems important to decrease postoperative complications and to hasten postoperative recovery. The morbidity rate of this study was similar to those in previous studies (5, 22). Emphasizing patients’ exercise capacity through aggressive intervention might result in acceptable morbidity rates.

Clinical guidelines have stated that longer period of program produce greater sustained benefits including behavioral changes into activities of daily living or psychosocial adaptation than shorter programs (23). A key goal of preoperative PR for surgical candidates, unlike that with medical COPD patients, is to gain physiological improvements of exercise capacity. Several clinical trials have demonstrated that even short duration of PR can improve exercise capacity in patients undergoing thoracic surgery for malignant disease and COPD (24, 25). In addition, a short period of program has the potential to reduce the cost per patients (25).

On the other hand, Verrill and colleagues demonstrated that 12 weeks of PR significantly increased their patients’ exercise capacity, and that an additional 12 weeks of PR improved their exercise capacity further (26). If the preoperative PR in this study had been conducted for a longer period, further improvements of exercise capacity may have occurred. However, the present study focused on the clinically meaningful changes in the patients’ exercise capacity within the short-term. The minimal important difference, which refers to the interpretation of the clinical relevance of changes in exercise capacity, may be a clinical indicator that can be used to interpret whether a patient achieved a clinically meaningful change.

Puhan and colleagues have proposed that the minimal important difference of the 6MWD had been estimated to be 35 meters which corresponded to 10% of baseline value in patients with moderate to severe COPD (27). Our preoperative STPR was able to increase by 36.2 meters in the 6MWD which corresponded to an 8.3% value and to increase by 32.4% in the total exercise time in minutes in comparison to baseline values, as shown by Table 4. Criner and colleague (2) reported that preoperative PR increased by 16 meters in the 6MWD and by 27.6% in the total exercise time in minutes in candidates for LVRS.

The improvements of exercise capacity of this study were of greater magnitude than those of other studies (2, 9), despite the shorter periods of preoperative PR of this study. Therefore, the period of our preoperative PR may be considered relevant on the basis that the patients’ preoperative improvements in their exercise capacity in this study achieved the minimal important difference.

In terms of the results of the pulmonary function test, the postoperative value of the forced expiratory volume in 1 second (FEV₁) only appeared to reach significance due to a drop in the FEV₁ during the preoperative PR. In comparison to the baseline value, the postoperative value of the FEV₁ improved by no more than 10mL in our patients. A possible explanation for such small changes in the FEV₁ in this study compared to other studies is that an improvement in FEV₁ potentially requires longer periods of time, because Ciccone and colleagues reported that it took 6 months to achieve significant gains in the FEV₁ (5).

This study suffers from some limitations, such as the small cohort of patients that were analyzed over a relatively long period of time. Although we attempted to recruit as many patients as possible within a few years, no more than 22 patients were able to be enrolled because this was a single-institution study.

Second, we have not presented the longer term outcomes. One reason for this is that the main purpose of this study was to evaluate the feasibility and safety of inpatient STPR. Moreover, there were no significant correlations between the short-term and the long-term outcomes. In addition, although the patients’ satisfaction and health-related quality of life were clinically important outcomes, both may be greatly influenced by the surgical intervention. Therefore, we did not investigate these outcomes.

Third, given the variations in the types of program settings, patient populations, and health-care systems in different countries, the generalizability of our results to other countries must be considered with caution.

Finally, although the results of the 6MWD and the incremental exercise test were significantly improved by the preoperative PR, it may be insufficient to draw conclusions whether these improvements can be considered clinically meaningful changes because of the absence of a control group. In addition, it may be necessary to consider a learning effect of the 6-minute walk test, because the majority of patients with COPD showed an increase in the 6MWD with test repetition in a previous study (28). We did not perform a preliminary test before the 6-minute walk test, as a published guideline described that a practice test is not needed in most clinical settings (13). Despite these limitations, our results indicate that a short course of preoperative exercise training can result in improvements in exercise capacity, which may potentially reduce the morbidity rates after LVRS.

Cesario and colleagues conducted a pilot trial to evaluate the effects of inpatient PR in lung cancer patients who were denied surgery on the basis of their poor pulmonary function despite a favorable clinical stage. All study patients improved their exercise capacity within 4 weeks of initiating the preoperative PR and subsequently underwent surgery without mortality (29). Although our study also was conducted in an inpatient setting to ensure the safety of the deconditioned patients undergoing LVRS, our short-term PR program might be applicable to such lung cancer patients with a poor pulmonary reserve.

In summary, all patients completed the rehabilitation program with high adherence rates and without any exercise-related serious adverse events because STPR was performed under close supervision of physical therapists. We concluded that a perioperative STPR is feasible and safe in patients undergoing LVRS.

DECLARATION OF INTEREST

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.