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Incentive Spirometry After Lung Resection: A Randomized Controlled Trial
Incentive Spirometry After Lung Resection: A Randomized Controlled Trial Peter R. A. Malik, BSc, Christine Fahim, PhD, Jordyn Vernon, MD, Priya Thomas, BSc, Colin Schieman, MD, Christian J. Finley, MD, MSc, John Agzarian, MD, MSc, Yaron Shargall, MD, Forough Farrokhyar, PhD, and Waël C. Hanna, MDCM, MBA Division of Thoracic Surgery, McMaster University, Hamilton, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada; and Section of Thoracic Surgery, University of Calgary, Calgary, Canada
Background. Incentive spirometry (IS) is thought to reduce the incidence of postoperative pulmonary complications (PPC) after lung resection. We sought to determine whether the addition of IS to routine physiotherapy following lung resection results in a lower rate of PPC, as compared with physiotherapy alone. Methods. A single-blind prospective randomized controlled trial was conducted in adults undergoing lung resection. Individuals with previous lung surgery or home oxygen were excluded. Participants randomized to the control arm (PHY) received routine physiotherapy alone (deep breathing, ambulation and shoulder exercises). Those randomized to the intervention arm (PHY/IS) received IS in addition to routine physiotherapy. The trial was powered to detect a 10% difference in the rate of PPC (b [ 80%). Student’s t test and chisquare were utilized for continuous and categorical variables, respectively, with a significance level of p ¼ 0.05. Results. A total of 387 participants (n [ 195 PHY/IS; n [ 192 PHY) were randomized between 2014 and 2017.
Baseline characteristics were comparable for both arms. The majority of patients underwent a pulmonary lobectomy (PHY/IS [ 59.5%, PHY [ 61.0%; p ¼ 0.84), with no difference in the rates of minimally invasive and open procedures. There were no differences in the incidence of PPC at 30 days postoperatively (PHY/IS [ 12.3%, PHY [ 13.0%; p ¼ 0.88). There were no differences in rates of pneumonia (PHY/IS [ 4.6%, PHY [ 7.8%; p ¼ 0.21), mechanical ventilation (PHY/IS [ 2.1%, PHY [ 1.0%; p ¼ 0.41), home oxygen (PHY/IS [ 13.8%, PHY [ 14.6%; p ¼ 0.89), hospital length of stay (PHY/IS [ 4 days, PHY [ 4 days; p ¼ 0.34), or rate of readmission to hospital (PHY/IS [ 10.3%, PHY [ 9.9%; p ¼ 1.00). Conclusions. The addition of IS to routine postoperative physiotherapy does not reduce the incidence of PPC after lung resection.
P
Two of the most commonly recommended postoperative interventions for mitigating the risk of PPC include routine physiotherapy and incentive spirometry (IS). Physiotherapy is widely practiced in the postoperative setting and normally includes a defined set of deep breathing and mobility exercises [7] under the direction or supervision of a physiotherapist. The addition of IS to physiotherapy is also widely practiced. A commonly used IS device is a small plastic ball-valve mechanism that allows patients to practice deep breathing and sustained maximal alveolar inflation [3]. The addition of IS to the postoperative regimen has been shown to decrease the risk of PPC by mobilizing lung secretions and maintaining alveolar expansion [8, 9]. While believed to be a useful intervention, the addition of IS to physiotherapy has not been studied with a randomized controlled trial (RCT) in patients undergoing lung resection. In the era of minimally invasive lung surgery, Enhanced Recovery Pathways After Surgery, and value-based healthcare, we question whether IS remains a useful intervention in the postoperative setting after lung resection. This current prospective RCT aimed to compare the incidence of PPC between IS plus physiotherapy and
ostoperative pulmonary complications (PPC) are the most frequent adverse events after thoracic surgery, with an incidence 25% to 49% [1, 2]. PPC are most commonly defined as atelectasis requiring bronchoscopy, pneumonia, or respiratory failure requiring invasive or noninvasive mechanical ventilation. Although most PPC are low-grade complications, some can lead to significant patient morbidity and mortality [3–5]. The most common risk factors for developing PPC after lung resection include tobacco use, older age, and the presence of comorbid pulmonary disorders [6], all of which are common amongst thoracic surgical patients. As a result, the goal of preventing PPC before they develop has been a major focus for thoracic surgeons.
Accepted for publication March 22, 2018. Presented at the Fifty-fourth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 27–31, 2018. Address correspondence to Dr Hanna, McMaster University, St. Joseph’s Healthcare Hamilton, 50 Charlton Ave E, Suite T2105, Hamilton, ON L8N 4A6, Canada; email: [email protected].
Ó 2018 by The Society of Thoracic Surgeons Published by Elsevier Inc.
(Ann Thorac Surg 2018;-:-–-) Ó 2018 by The Society of Thoracic Surgeons
0003-4975/$36.00 https://doi.org/10.1016/j.athoracsur.2018.03.051
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MALIK ET AL INCENTIVE SPIROMETRY AFTER LUNG SURGERY
physiotherapy alone in patients undergoing lung resection. The null hypothesis assumed no difference in the incidence of PPC from the addition of IS to physiotherapy, compared with physiotherapy alone.
Patients and Methods Trial Design We conducted a single-blinded, parallel, RCT at a tertiary center for thoracic oncology between August 2014 and March 2017. Eligible and consenting patients were enrolled to the trial before surgery. Treatment allocation was done using 1:1 computer-generated block randomization with the sealed envelope method. Envelopes were opened immediately after surgery and patients were assigned to either the control arm (PHY) or the intervention arm (PHY/IS). Surgeons were blinded to treatment allocation. To maintain blinding, all patients on the trial received an opaque black cardboard box to keep by their bedside. For patients who were allocated to the PHY arm, the box was empty. For patients who were allocated to the PHY/IS arm, the box contained the IS device, and patients were required to keep the device hidden in the box at all times when not in use. This study received approval by the Hamilton Integrated Review Ethics Board.
Participants Adult patients undergoing lung resection at our institution were invited to participate. Exclusion criteria were history of previous lung resection, radiological evidence of pneumonitis on preoperative imaging, the use of home oxygen before surgery, and being wheelchair bound. No restrictions were placed on the choice of surgical approach (thoracotomy versus minimally invasive surgery) or the extent of the planned lung resection.
Intervention Participants who were randomized to the PHY control arm received routine physiotherapy based on current institutional standards. This involved early ambulation on the first postoperative day and daily visits by a physiotherapist until the patient was able to ambulate independently. During these visits, patients were taught deep breathing and shoulder range-of-motion exercises. Teaching emphasized slow deep breathing, incremental increase in forceful breathing, coughing, and repetition of 10 deep breaths every waking hour. Once the patient was able to ambulate independently, he or she was encouraged to perform these exercises on his or her own, without the supervision of the physiotherapist. Patients were also provided a summary sheet outlining those exercises for future reference and were encouraged to continue these exercises for 30 days after surgery. Participants allocated to the PHY/IS intervention arm received IS in addition to the routine physiotherapy care outlined previously. Patients were given their IS device (Air-Eze Breathing Exerciser, Teleflex, Morrisville, NC) on the first postoperative day and were encouraged to start using it immediately. Instructions on the use of the
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IS device were given to the patients by the physiotherapist. Teaching emphasized slow deep breathing, sustained vacuum pressure, incremental increase in the negative pressure threshold of the device, and repetition of 10 deep breaths with the IS device every waking hour. Once the patient was able to ambulate independently, they were encouraged to perform these exercises on their own, without the supervision of the physiotherapist. Patients were also provided a summary sheet outlining those exercises for future reference and were encouraged to continue these exercises for 30 days after surgery. In keeping with the pragmatic nature of this trial, no formal monitoring of compliance was completed outside the scope of the routine physiotherapy visits.
Outcome Measures The primary outcome was the incidence of PPC within 30 days after lung resection. Using the Ottawa Thoracic Morbidity and Mortality System for Classifying Thoracic Surgical Complications [8], PPC was defined as a composite outcome that included 1 or more of the following: pneumonia treated with antibiotics, atelectasis requiring bronchoscopy, or respiratory failure requiring invasive or noninvasive mechanical ventilation. Data were collected during the hospital stay and at 2-week and 4-week time points during surveillance visits. Secondary outcomes of interest included the length of hospital stay, postoperative complications, and rates of readmission to hospital.
Statistical Analysis The trial was powered to detect a 10% difference in the rate of aggregate PPC between study arms, with a b of 0.2% (power ¼ 80%) and a of 0.05, assuming a PPC rate of 20% for the control group, and using normal approximation to binomial distribution approach. All analyses were carried out based on the intention-to-treat principle [9]. Categorical variables were reported using counts and frequencies, and compared using the chi-square test. Normally distributed continuous variables were reported using mean and standard deviation, and compared using the independent samples t test. Ordinal variables were reported using medians and interquartile ranges, and compared using the Mann-Whitney U test. Unadjusted risk ratios were calculated with 95% confidence intervals. The number of patients needed to treat with PHY/IS to prevent 1 PPC was calculated from taking the inverse of the absolute risk difference between groups. Three post hoc subgroup analyses were performed for patients who received or were converted to thoracotomy, for patients who had a lobectomy, and for patients who were diagnosed with chronic obstructive pulmonary disease (COPD). A p value of less than 0.05 was considered significant. All analyses were performed using SPSS version 22.0 (IBM Corporation, Armonk, NY) software.
Results A total of 420 patients were enrolled in the trial. Thirtythree patients were excluded after consent for reasons including voluntary withdrawal from the study, inability
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Fig 1. Consort flow diagram. (ICU ¼ intensive care unit; IS ¼ incentive spirometry; PHY ¼ routine physiotherapy; PHY/IS ¼ incentive spirometry in addition to routine physiotherapy.)
to wean from the ventilator postoperatively, inability to randomize due to logistical constraints, or cancellation of surgery. In total, 387 were randomized; 192 to the PHY arm and 195 to the PHY/IS arm (Fig 1).
Baseline and Surgical Characteristics Clinical and demographic data are presented in Table 1. The groups were balanced for age, sex, history of COPD, current smoking status, and percent predicted forced expiratory volume in 1 second and diffusion capacity of the lungs for carbon monoxide. Most patients underwent pulmonary resection for clinical stage I or II non-small cell lung cancer. The majority of patients underwent pulmonary lobectomy (PHY/IS ¼ 59.5%, PHY ¼ 61.0%; p ¼ 0.836) using a minimally invasive approach (PHY/IS ¼ 68.2%, PHY ¼ 66.2%; p ¼ 0.519). There were no significant differences between trial arms with respect to perioperative variables such as extent of resection, surgical access, or mode of analgesia (Table 2).
Postoperative Pulmonary Complications Table 3 presents the rate of composite PPC and individual outcomes with risk ratios and p values. The rate of composite PPC were similar between both study arms (PHY/IS ¼ 12.3%, PHY ¼ 13.0%; p ¼ 0.879). The control group demonstrated a higher incidence of pneumonia; however, this difference was not statistically significant (PHY ¼ 7.8%, PHY/IS ¼ 4.6%; p ¼ 0.212). There were no
significant differences in the incidence of atelectasis (PHY/IS ¼ 4.6%, PHY ¼ 4.2%; p ¼ 1.00), atelectasis requiring bronchoscopy (PHY/IS ¼ 4.1%, PHY ¼ 5.2%; p ¼ 0.637), or invasive and noninvasive mechanical ventilation (PHY/IS ¼ 2.1%, PHY ¼ 1.0%; p ¼ 0.685). Risk ratios are provided in Figure 2 for individual and composite PPC.
Secondary Outcomes Secondary outcomes are summarized in Table 3. Median length of hospital stay (PHY ¼ 4 days, PHY/IS ¼ 4 days; p ¼ 0.342), hospital readmissions or unplanned emergency room visits within 30 days (PHY ¼ 9.9%, PHY/IS ¼ 10.3%; p ¼ 1.00), and postoperative supplemental oxygen requirement at discharge from hospital (PHY ¼ 14.6%, PHY/IS ¼ 13.8%; p ¼ 0.885) were comparable for both treatment arms. The incidence of major complications (greater than Grade II) was 12.0% (n ¼ 23 of 192) in the PHY arm and 14.9% (n ¼ 29 of 195) in the PHY/IS arm, without any significant statistical difference (p ¼ 0.330). There were no mortalities in this trial.
Subgroup Analyses PATIENTS WHO RECEIVED A THORACOTOMY. A total of 141 (PHY/IS ¼ 68, PHY ¼ 73) patients were planned to receive a thoracotomy or were converted to thoracotomy from a planned minimally invasive procedure. Patients planned for upfront thoracotomy included selected complex Stage
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Table 1. Demographic and Baseline Characteristics
Demographics Male Age, years % predicted FEV % predicted DLCO Any comorbidity COPD Diabetes Preoperative chemotherapy Preoperative radiotherapy Smoking status Never Ex-smoker Current smoker Unknown Pack-year smoking Disease type Malignant Squamous Adenocarcinoma Carcinoid Small cell Metastatic disease Benign Benign pulmonary nodule Infection Spontaneous pneumothorax Other Pathological stagea Stage 1–2 Stage 3–4
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Table 2. Surgical Details
Spirometry/ Physiotherapy (n ¼ 195)
Physiotherapy (n ¼ 192)
91 (46.7) 66.6 12.1 83 20 83 20 180 (92.3) 54 (27.7) 37 (19.0) 11 (6.1)
102 (52.8) 67.5 10.4 82 18 72 18 183 (95.3) 55 (28.6) 34 (17.7) 10 (5.6)
9 (5.0)
8 (4.5)
29 105 60 1 40
(14.9) (53.8) (30.8) (0.5) (0–110)
38 97 58 1 37.5
(19.6) (50.0) (29.9) (0.5) (1–150)
165 37 91 14 1 22 8 1
(84.6) (19.0) (46.7) (7.2) (0.5) (11.3) (4.1) (0.5)
167 40 82 17 0 26 9 2
(86.1) (21.0) (42.7) (9.0) (0.0) (13.5) (4.6) (1.0)
2 (1.0) 5 (2.6)
7 (3.5) 0
22 (11.3)
18 (9.3)
124 (87.3) 18 (12.7)
123 (87.9) 17 (12.1)
Preoperative Variables Extent of resection Segmentectomy Lobectomy Bilobectomy Pneumonectomy Wedge resection Surgical approach Robotic VATS VATS converted to thoracotomy Posterolateral thoracotomy Robotic converted to thoracotomy Mode of analgesia Intercostal or paravertebral block Paravertebral catheter Epidural catheter Patient controlled intravenous analgesia
Spirometry/ Physiotherapy Physiotherapy p (n ¼ 195) (n ¼ 192) Value 22 116 7 7 43
(11.3) (59.5) (3.6) (3.6) (22.1)
26 117 5 7 37
(13.5) (61.0) (2.6) (3.6) (19.3)
0.540 0.836 0.771 1.00 0.842
38 (19.5) 89 (45.6) 6 (3.1)
47 (24.5) 72 (37.5) 8 (4.2)
0.519
56 (28.7)
60 (31.3)
6 (3.1)
5 (2.6)
80 (62.5)
81 (63.8)
7 (5.5) 41 (32.0) 67 (34.4)
7 (5.5) 39 (30.7) 65 (33.8)
0.9749
Values are n (%). VATS ¼ video-assisted thoracoscopic surgery.
PATIENTS WHO RECEIVED A LOBECTOMY. A total of 233 patients (PHY/IS ¼ 116, PHY ¼ 117) received lobectomy. For this subgroup, the composite PPC rate for the PHY/IS cohort was 13.8% (n ¼ 16 of 116) and 13.7% (n ¼ 16 of 117) in the PHY cohort (p ¼ 1.00).
Patients With COPD
Values are n (%), mean SD, or median (interquartile range).
A total of 109 patients (PHY/IS ¼ 54, PHY ¼ 55) were diagnosed with COPD before operation. For this subgroup, the composite PPC rate for the PHY/IS cohort was 9.3% (n ¼ 5 of 54) and 16.4% (n ¼ 9 of 55) in the PHY cohort. This difference was not statistically significant (p ¼ 0.392).
COPD ¼ chronic obstructive pulmonary disease; DLCO ¼ diffusion capacity of the lungs for carbon monoxide; FEV1 ¼ forced expiratory volume in 1 second.
Comment
IIIA-N2 tumors after induction chemoradiation, T4 tumors involving the mediastinum or chest wall, or tumors requiring pneumonectomy or double-sleeve resections. Minimally invasive cases were converted to posterolateral thoracotomy in the event of intraoperative complications or failure to progress with the minimally invasive approach. For this subgroup, the composite PPC rate was 22.1% in PHY/IS cohort and 20.5% in PHY cohort (p ¼ 0.840). Of the remaining 246 patients who received minimally invasive resection (robotic or video assisted), the PPC rate was for 7.1% for the PHY/IS arm and 8.4% for the PHY arm (p ¼ 0.812).
IS has been widely adopted in the postoperative setting after lung resection, despite uncertainty about its effectiveness. In the ICOUGH (Incentive spirometry, Coughing and deep breathing, Oral care, Understanding, Getting out of bed at least 3 times daily, and Head-of-bed elevation) trial, Cassidy and colleagues [10] demonstrated potential therapeutic value of IS in a bundled intervention, where IS was integrated into a multidisciplinary postoperative program that focused on patient education and physiotherapy exercises. The rates of pneumonia were reduced from 2.6% to 1.6% after administering the program, though this result was not statistically significant. This study was also limited by the integration of multiple interventions, which precludes the isolation of
a
Staging as per the American Joint Committee on Cancer, seventh edition.
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Table 3. Postoperative Morbidity Spirometry/ Physiotherapy (n ¼ 195)
Postoperative Morbidity Composite PPC with 30 days Pneumonia Atelectasis Bronchoscopy Mechanical ventilation Home oxygen use Readmission or emergency room visits within 30 days Major complications (> Grade II) Total LOS
24 9 9 8 4 27 20 29 4
(12.3) (4.6) (4.6) (4.1) (2.1) (13.8) (10.3) (14.9) (0–38)
Physiotherapy (n ¼ 192) 25 15 8 10 2 28 18 23 4
(13.0) (7.8) (4.2) (5.2) (1.0) (14.6) (9.9) (12.0) (1–38)
Relative Risk (95% CI) 0.94 0.60 1.12 0.79 1.97 0.95 1.10 1.30
(0.56–1.60) (0.26–1.31) (0.43–2.81) (0.32–1.95) (0.36–10.62) (0.60–1.50) (0.60–2.00) (0.82–2.08) NA
p Value 0.879 0.212 1.00 0.637 0.685 0.885 1.00 0.330 0.342
Values are n (%) or median (minimum, maximum), unless otherwise indicated. CI ¼ confidence interval;
LOS ¼ length of stay;
NA ¼ not applicable;
treatment effects for any single intervention. This demonstrates a common methodological challenge in previous trials since IS has been studied under a variety of designs with varying comparator interventions, durations, and outcome measures. Specifically in thoracic surgery, 2 small historical comparative trials have been performed, both of which did not demonstrate any measurable clinical benefit when IS was added to routine physiotherapy in the postoperative setting. The first trial by Vilaplana and colleagues [11] included 18 patients in the intervention arm (IS added to chest physiotherapy) and 19 patients in the control arm (chest physiotherapy only), and concluded that “the routine use of IS does not decrease the frequency of clinical events.” However, this study reported a relatively high PPC frequency (27%), and was likely severely underpowered. The second trial by Gosselink and colleagues [12] compared 32 patients in the intervention arm and 35 patients in the control arm. They demonstrated identical incidence rates of PPC of 11% (4 patients) in both trial arms. This study reported an
Fig 2. Risk ratios for composite postoperative pulmonary complications (PPC) and individual outcomes. The boxes represent risk ratios, and the lines represent 95% confidence intervals. The vertical line presents the null hypothesis of no difference in PPC rate between the intervention and control arms.
PPC ¼ postoperative pulmonary complications.
incidence of PPC that is comparable to the one we report, but was likely underpowered to detect any meaningful clinical differences between trial arms. More recently, an RCT comparing IS with routine physiotherapy after bariatric surgery has similarly shown no added benefit for IS on the incidence of postoperative hypoxemia [13]. However, the results of this trial are difficult to extrapolate to the thoracic surgery population, and the clinical outcomes studied are not necessarily of relevance to complications after lung resection. We have shown, in this adequately powered and blinded RCT, that the addition of IS to routine physiotherapy after lung resection does not reduce the rate of PPC. Similarly, we found no significant differences in length of hospital stay and readmission rates between the trial arms. We have also demonstrated that patients with thoracotomy are at a much higher risk for postoperative PPC than are patients who undergo minimally invasive resection. However, in a subgroup analysis of patients who received thoracotomy, there was also no difference in PPC rate between physiotherapy alone and physiotherapy with IS. Although this post hoc analysis may be underpowered and exploratory in nature, it does generate the hypothesis that the findings of the whole cohort are most likely applicable to thoracotomy patients. In contrast, in the subgroup of patients who suffered from COPD, we found that the incidence of PPC was lower in the PHY/IS cohort than in the PHY cohort, pointing perhaps to some clinical benefit of IS in this particular patient population. We note, however, that this difference was not statistically significant, likely due to the low incidence of COPD in this cohort. We have also independently evaluated the subgroup who had a lobectomy, and were no able to detect any differences in outcomes with the use of IS. We believe that this trial provides sound scientific impetus for abandoning the use of IS in the era of modern thoracic surgery. With the rise of minimally invasive surgery and Enhanced Recovery Pathways After Surgery protocols, a significant emphasis is being placed on eliminating redundant interventions in the postoperative setting [14]. A similar emphasis is also being placed on maximizing the value of medical care, by decreasing costs
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and improving quality. Although a cost-analysis was not planned in this trial, we do believe that eliminating IS will result in cost savings on a national level in Canada, where the majority of thoracic surgery centers still use IS. In a public healthcare system, these costs can be redirected to fund higher value interventions. There are a number of limitations associated with this trial. First, the physiotherapy program used in the control arm at our institution may not be generalizable to other institutions. However, we believe that the results of this trial are applicable to centers that utilize a postoperative regimen that includes deep breathing exercises, shoulder range-of-motion exercises, and early ambulation. Second, compliance with IS or physiotherapy was not monitored after patients were discharged from hospital. In an effort to keep the trial pragmatic and as close as possible to a real-life situation, we elected not to impose the added burden of a compliance log on patients who have been discharged from hospital. Patient compliance has historically been a challenge in RCTs evaluating the effectiveness of IS on postoperative outcomes [15]. It is known that those who report high pain scores after surgery are less likely to regularly use the IS [16]. Moreover, the maximal treatment effect of either intervention may not have been observed due to the short median length of stay of patients in our trial. However, we believe that these limitations are mitigated by the randomization effect and the pragmatism of the trial, which increases the generalizability of the findings.
Conclusion Our findings do not support the addition of IS to the postoperative care of patients after lung resection, when conventional physiotherapy and early ambulation are already being employed.
References 1. Patel RL, Townsend ER, Fountain SW. Elective pneumonectomy: factors associated with morbidity and operative mortality. Ann Thorac Surg 1992;54:84–8. 2. Stephan F, Boucheseiche S, Hollande J, et al. Pulmonary complications following lung resection: a comprehensive analysis of incidence and possible risk factors. Chest 2000;118:1263–70.
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3. Branson RD. The scientific basis for postoperative respiratory care. Respir Care 2013;58:1974–84. 4. Sabate S, Mazo V, Canet J. Predicting postoperative pulmonary complications: implications for outcomes and costs. Curr Opin Anaesthesiol 2014;27:201–9. 5. Allen MS, Darling GE, Pechet TT, et al. Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial. Ann Thorac Surg 2006;81: 1013–9; discussion 9–20. 6. Rock P, Rich PB. Postoperative pulmonary complications. Curr Opin Anaesthesiol 2003;16:123–31. 7. Agostini P, Reeve J, Dromard S, Singh S, Steyn RS, Naidu B. A survey of physiotherapeutic provision for patients undergoing thoracic surgery in the U.K. Physiotherapy 2013;99: 56–62. 8. Seely AJ, Ivanovic J, Threader J, et al. Systematic classification of morbidity and mortality after thoracic surgery. Ann Thorac Surg 2010;90:936–42; discussion 942. 9. Montori VM, Guyatt GH. Intention-to-treat principle. CMAJ 2001;165:1339–41. 10. Cassidy MR, Rosenkranz P, McCabe K, Rosen JE, McAneny D. I COUGH: reducing postoperative pulmonary complications with a multidisciplinary patient care program. JAMA Surg 2013;148:740–5. 11. Vilaplana J, Sabate A, Ramon R, Gasolibe V, Villalonga R. [Ineffectiveness of incentive spirometry as coadjuvant of conventional physiotherapy for the prevention of postoperative respiratory complications after thoracic and esophageal surgery]. Rev Esp Anestesiol Reanim 1990;37: 321–5. 12. Gosselink R, Schrever K, Cops P, et al. Incentive spirometry does not enhance recovery after thoracic surgery. Crit Care Med 2000;28:679–83. 13. Pantel H, Hwang J, Brams D, Schnelldorfer T, Nepomnayshy D. Effect of incentive spirometry on postoperative hypoxemia and pulmonary complications after bariatric surgery: a randomized clinical trial. JAMA Surg 2017;152:422–8. 14. Li S, Zhou K, Che G, et al. Enhanced recovery programs in lung cancer surgery: systematic review and meta-analysis of randomized controlled trials. Cancer Manag Res 2017;9: 657–70. 15. Narayanan AL, Hamid SR, Supriyanto E. Evidence regarding patient compliance with incentive spirometry interventions after cardiac, thoracic and abdominal surgeries: a systematic literature review. Can J Respir Ther 2016;52: 17–26. 16. Harris DJ, Hilliard PE, Jewell ES, Brummett CM. The association between incentive spirometry performance and pain in postoperative thoracic epidural analgesia. Reg Anesth Pain Med 2015;40:232–8.
Background. Incentive spirometry (IS) is thought to reduce the incidence of postoperative pulmonary complications (PPC) after lung resection. We sought to determine whether the addition of IS to routine physiotherapy following lung resection results in a lower rate of PPC, as compared with physiotherapy alone. Methods. A single-blind prospective randomized controlled trial was conducted in adults undergoing lung resection. Individuals with previous lung surgery or home oxygen were excluded. Participants randomized to the control arm (PHY) received routine physiotherapy alone (deep breathing, ambulation and shoulder exercises). Those randomized to the intervention arm (PHY/IS) received IS in addition to routine physiotherapy. The trial was powered to detect a 10% difference in the rate of PPC (b [ 80%). Student’s t test and chisquare were utilized for continuous and categorical variables, respectively, with a significance level of p ¼ 0.05. Results. A total of 387 participants (n [ 195 PHY/IS; n [ 192 PHY) were randomized between 2014 and 2017.
Baseline characteristics were comparable for both arms. The majority of patients underwent a pulmonary lobectomy (PHY/IS [ 59.5%, PHY [ 61.0%; p ¼ 0.84), with no difference in the rates of minimally invasive and open procedures. There were no differences in the incidence of PPC at 30 days postoperatively (PHY/IS [ 12.3%, PHY [ 13.0%; p ¼ 0.88). There were no differences in rates of pneumonia (PHY/IS [ 4.6%, PHY [ 7.8%; p ¼ 0.21), mechanical ventilation (PHY/IS [ 2.1%, PHY [ 1.0%; p ¼ 0.41), home oxygen (PHY/IS [ 13.8%, PHY [ 14.6%; p ¼ 0.89), hospital length of stay (PHY/IS [ 4 days, PHY [ 4 days; p ¼ 0.34), or rate of readmission to hospital (PHY/IS [ 10.3%, PHY [ 9.9%; p ¼ 1.00). Conclusions. The addition of IS to routine postoperative physiotherapy does not reduce the incidence of PPC after lung resection.
P
Two of the most commonly recommended postoperative interventions for mitigating the risk of PPC include routine physiotherapy and incentive spirometry (IS). Physiotherapy is widely practiced in the postoperative setting and normally includes a defined set of deep breathing and mobility exercises [7] under the direction or supervision of a physiotherapist. The addition of IS to physiotherapy is also widely practiced. A commonly used IS device is a small plastic ball-valve mechanism that allows patients to practice deep breathing and sustained maximal alveolar inflation [3]. The addition of IS to the postoperative regimen has been shown to decrease the risk of PPC by mobilizing lung secretions and maintaining alveolar expansion [8, 9]. While believed to be a useful intervention, the addition of IS to physiotherapy has not been studied with a randomized controlled trial (RCT) in patients undergoing lung resection. In the era of minimally invasive lung surgery, Enhanced Recovery Pathways After Surgery, and value-based healthcare, we question whether IS remains a useful intervention in the postoperative setting after lung resection. This current prospective RCT aimed to compare the incidence of PPC between IS plus physiotherapy and
ostoperative pulmonary complications (PPC) are the most frequent adverse events after thoracic surgery, with an incidence 25% to 49% [1, 2]. PPC are most commonly defined as atelectasis requiring bronchoscopy, pneumonia, or respiratory failure requiring invasive or noninvasive mechanical ventilation. Although most PPC are low-grade complications, some can lead to significant patient morbidity and mortality [3–5]. The most common risk factors for developing PPC after lung resection include tobacco use, older age, and the presence of comorbid pulmonary disorders [6], all of which are common amongst thoracic surgical patients. As a result, the goal of preventing PPC before they develop has been a major focus for thoracic surgeons.
Accepted for publication March 22, 2018. Presented at the Fifty-fourth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 27–31, 2018. Address correspondence to Dr Hanna, McMaster University, St. Joseph’s Healthcare Hamilton, 50 Charlton Ave E, Suite T2105, Hamilton, ON L8N 4A6, Canada; email: [email protected].
Ó 2018 by The Society of Thoracic Surgeons Published by Elsevier Inc.
(Ann Thorac Surg 2018;-:-–-) Ó 2018 by The Society of Thoracic Surgeons
0003-4975/$36.00 https://doi.org/10.1016/j.athoracsur.2018.03.051
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MALIK ET AL INCENTIVE SPIROMETRY AFTER LUNG SURGERY
physiotherapy alone in patients undergoing lung resection. The null hypothesis assumed no difference in the incidence of PPC from the addition of IS to physiotherapy, compared with physiotherapy alone.
Patients and Methods Trial Design We conducted a single-blinded, parallel, RCT at a tertiary center for thoracic oncology between August 2014 and March 2017. Eligible and consenting patients were enrolled to the trial before surgery. Treatment allocation was done using 1:1 computer-generated block randomization with the sealed envelope method. Envelopes were opened immediately after surgery and patients were assigned to either the control arm (PHY) or the intervention arm (PHY/IS). Surgeons were blinded to treatment allocation. To maintain blinding, all patients on the trial received an opaque black cardboard box to keep by their bedside. For patients who were allocated to the PHY arm, the box was empty. For patients who were allocated to the PHY/IS arm, the box contained the IS device, and patients were required to keep the device hidden in the box at all times when not in use. This study received approval by the Hamilton Integrated Review Ethics Board.
Participants Adult patients undergoing lung resection at our institution were invited to participate. Exclusion criteria were history of previous lung resection, radiological evidence of pneumonitis on preoperative imaging, the use of home oxygen before surgery, and being wheelchair bound. No restrictions were placed on the choice of surgical approach (thoracotomy versus minimally invasive surgery) or the extent of the planned lung resection.
Intervention Participants who were randomized to the PHY control arm received routine physiotherapy based on current institutional standards. This involved early ambulation on the first postoperative day and daily visits by a physiotherapist until the patient was able to ambulate independently. During these visits, patients were taught deep breathing and shoulder range-of-motion exercises. Teaching emphasized slow deep breathing, incremental increase in forceful breathing, coughing, and repetition of 10 deep breaths every waking hour. Once the patient was able to ambulate independently, he or she was encouraged to perform these exercises on his or her own, without the supervision of the physiotherapist. Patients were also provided a summary sheet outlining those exercises for future reference and were encouraged to continue these exercises for 30 days after surgery. Participants allocated to the PHY/IS intervention arm received IS in addition to the routine physiotherapy care outlined previously. Patients were given their IS device (Air-Eze Breathing Exerciser, Teleflex, Morrisville, NC) on the first postoperative day and were encouraged to start using it immediately. Instructions on the use of the
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IS device were given to the patients by the physiotherapist. Teaching emphasized slow deep breathing, sustained vacuum pressure, incremental increase in the negative pressure threshold of the device, and repetition of 10 deep breaths with the IS device every waking hour. Once the patient was able to ambulate independently, they were encouraged to perform these exercises on their own, without the supervision of the physiotherapist. Patients were also provided a summary sheet outlining those exercises for future reference and were encouraged to continue these exercises for 30 days after surgery. In keeping with the pragmatic nature of this trial, no formal monitoring of compliance was completed outside the scope of the routine physiotherapy visits.
Outcome Measures The primary outcome was the incidence of PPC within 30 days after lung resection. Using the Ottawa Thoracic Morbidity and Mortality System for Classifying Thoracic Surgical Complications [8], PPC was defined as a composite outcome that included 1 or more of the following: pneumonia treated with antibiotics, atelectasis requiring bronchoscopy, or respiratory failure requiring invasive or noninvasive mechanical ventilation. Data were collected during the hospital stay and at 2-week and 4-week time points during surveillance visits. Secondary outcomes of interest included the length of hospital stay, postoperative complications, and rates of readmission to hospital.
Statistical Analysis The trial was powered to detect a 10% difference in the rate of aggregate PPC between study arms, with a b of 0.2% (power ¼ 80%) and a of 0.05, assuming a PPC rate of 20% for the control group, and using normal approximation to binomial distribution approach. All analyses were carried out based on the intention-to-treat principle [9]. Categorical variables were reported using counts and frequencies, and compared using the chi-square test. Normally distributed continuous variables were reported using mean and standard deviation, and compared using the independent samples t test. Ordinal variables were reported using medians and interquartile ranges, and compared using the Mann-Whitney U test. Unadjusted risk ratios were calculated with 95% confidence intervals. The number of patients needed to treat with PHY/IS to prevent 1 PPC was calculated from taking the inverse of the absolute risk difference between groups. Three post hoc subgroup analyses were performed for patients who received or were converted to thoracotomy, for patients who had a lobectomy, and for patients who were diagnosed with chronic obstructive pulmonary disease (COPD). A p value of less than 0.05 was considered significant. All analyses were performed using SPSS version 22.0 (IBM Corporation, Armonk, NY) software.
Results A total of 420 patients were enrolled in the trial. Thirtythree patients were excluded after consent for reasons including voluntary withdrawal from the study, inability
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Fig 1. Consort flow diagram. (ICU ¼ intensive care unit; IS ¼ incentive spirometry; PHY ¼ routine physiotherapy; PHY/IS ¼ incentive spirometry in addition to routine physiotherapy.)
to wean from the ventilator postoperatively, inability to randomize due to logistical constraints, or cancellation of surgery. In total, 387 were randomized; 192 to the PHY arm and 195 to the PHY/IS arm (Fig 1).
Baseline and Surgical Characteristics Clinical and demographic data are presented in Table 1. The groups were balanced for age, sex, history of COPD, current smoking status, and percent predicted forced expiratory volume in 1 second and diffusion capacity of the lungs for carbon monoxide. Most patients underwent pulmonary resection for clinical stage I or II non-small cell lung cancer. The majority of patients underwent pulmonary lobectomy (PHY/IS ¼ 59.5%, PHY ¼ 61.0%; p ¼ 0.836) using a minimally invasive approach (PHY/IS ¼ 68.2%, PHY ¼ 66.2%; p ¼ 0.519). There were no significant differences between trial arms with respect to perioperative variables such as extent of resection, surgical access, or mode of analgesia (Table 2).
Postoperative Pulmonary Complications Table 3 presents the rate of composite PPC and individual outcomes with risk ratios and p values. The rate of composite PPC were similar between both study arms (PHY/IS ¼ 12.3%, PHY ¼ 13.0%; p ¼ 0.879). The control group demonstrated a higher incidence of pneumonia; however, this difference was not statistically significant (PHY ¼ 7.8%, PHY/IS ¼ 4.6%; p ¼ 0.212). There were no
significant differences in the incidence of atelectasis (PHY/IS ¼ 4.6%, PHY ¼ 4.2%; p ¼ 1.00), atelectasis requiring bronchoscopy (PHY/IS ¼ 4.1%, PHY ¼ 5.2%; p ¼ 0.637), or invasive and noninvasive mechanical ventilation (PHY/IS ¼ 2.1%, PHY ¼ 1.0%; p ¼ 0.685). Risk ratios are provided in Figure 2 for individual and composite PPC.
Secondary Outcomes Secondary outcomes are summarized in Table 3. Median length of hospital stay (PHY ¼ 4 days, PHY/IS ¼ 4 days; p ¼ 0.342), hospital readmissions or unplanned emergency room visits within 30 days (PHY ¼ 9.9%, PHY/IS ¼ 10.3%; p ¼ 1.00), and postoperative supplemental oxygen requirement at discharge from hospital (PHY ¼ 14.6%, PHY/IS ¼ 13.8%; p ¼ 0.885) were comparable for both treatment arms. The incidence of major complications (greater than Grade II) was 12.0% (n ¼ 23 of 192) in the PHY arm and 14.9% (n ¼ 29 of 195) in the PHY/IS arm, without any significant statistical difference (p ¼ 0.330). There were no mortalities in this trial.
Subgroup Analyses PATIENTS WHO RECEIVED A THORACOTOMY. A total of 141 (PHY/IS ¼ 68, PHY ¼ 73) patients were planned to receive a thoracotomy or were converted to thoracotomy from a planned minimally invasive procedure. Patients planned for upfront thoracotomy included selected complex Stage
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Table 1. Demographic and Baseline Characteristics
Demographics Male Age, years % predicted FEV % predicted DLCO Any comorbidity COPD Diabetes Preoperative chemotherapy Preoperative radiotherapy Smoking status Never Ex-smoker Current smoker Unknown Pack-year smoking Disease type Malignant Squamous Adenocarcinoma Carcinoid Small cell Metastatic disease Benign Benign pulmonary nodule Infection Spontaneous pneumothorax Other Pathological stagea Stage 1–2 Stage 3–4
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Table 2. Surgical Details
Spirometry/ Physiotherapy (n ¼ 195)
Physiotherapy (n ¼ 192)
91 (46.7) 66.6 12.1 83 20 83 20 180 (92.3) 54 (27.7) 37 (19.0) 11 (6.1)
102 (52.8) 67.5 10.4 82 18 72 18 183 (95.3) 55 (28.6) 34 (17.7) 10 (5.6)
9 (5.0)
8 (4.5)
29 105 60 1 40
(14.9) (53.8) (30.8) (0.5) (0–110)
38 97 58 1 37.5
(19.6) (50.0) (29.9) (0.5) (1–150)
165 37 91 14 1 22 8 1
(84.6) (19.0) (46.7) (7.2) (0.5) (11.3) (4.1) (0.5)
167 40 82 17 0 26 9 2
(86.1) (21.0) (42.7) (9.0) (0.0) (13.5) (4.6) (1.0)
2 (1.0) 5 (2.6)
7 (3.5) 0
22 (11.3)
18 (9.3)
124 (87.3) 18 (12.7)
123 (87.9) 17 (12.1)
Preoperative Variables Extent of resection Segmentectomy Lobectomy Bilobectomy Pneumonectomy Wedge resection Surgical approach Robotic VATS VATS converted to thoracotomy Posterolateral thoracotomy Robotic converted to thoracotomy Mode of analgesia Intercostal or paravertebral block Paravertebral catheter Epidural catheter Patient controlled intravenous analgesia
Spirometry/ Physiotherapy Physiotherapy p (n ¼ 195) (n ¼ 192) Value 22 116 7 7 43
(11.3) (59.5) (3.6) (3.6) (22.1)
26 117 5 7 37
(13.5) (61.0) (2.6) (3.6) (19.3)
0.540 0.836 0.771 1.00 0.842
38 (19.5) 89 (45.6) 6 (3.1)
47 (24.5) 72 (37.5) 8 (4.2)
0.519
56 (28.7)
60 (31.3)
6 (3.1)
5 (2.6)
80 (62.5)
81 (63.8)
7 (5.5) 41 (32.0) 67 (34.4)
7 (5.5) 39 (30.7) 65 (33.8)
0.9749
Values are n (%). VATS ¼ video-assisted thoracoscopic surgery.
PATIENTS WHO RECEIVED A LOBECTOMY. A total of 233 patients (PHY/IS ¼ 116, PHY ¼ 117) received lobectomy. For this subgroup, the composite PPC rate for the PHY/IS cohort was 13.8% (n ¼ 16 of 116) and 13.7% (n ¼ 16 of 117) in the PHY cohort (p ¼ 1.00).
Patients With COPD
Values are n (%), mean SD, or median (interquartile range).
A total of 109 patients (PHY/IS ¼ 54, PHY ¼ 55) were diagnosed with COPD before operation. For this subgroup, the composite PPC rate for the PHY/IS cohort was 9.3% (n ¼ 5 of 54) and 16.4% (n ¼ 9 of 55) in the PHY cohort. This difference was not statistically significant (p ¼ 0.392).
COPD ¼ chronic obstructive pulmonary disease; DLCO ¼ diffusion capacity of the lungs for carbon monoxide; FEV1 ¼ forced expiratory volume in 1 second.
Comment
IIIA-N2 tumors after induction chemoradiation, T4 tumors involving the mediastinum or chest wall, or tumors requiring pneumonectomy or double-sleeve resections. Minimally invasive cases were converted to posterolateral thoracotomy in the event of intraoperative complications or failure to progress with the minimally invasive approach. For this subgroup, the composite PPC rate was 22.1% in PHY/IS cohort and 20.5% in PHY cohort (p ¼ 0.840). Of the remaining 246 patients who received minimally invasive resection (robotic or video assisted), the PPC rate was for 7.1% for the PHY/IS arm and 8.4% for the PHY arm (p ¼ 0.812).
IS has been widely adopted in the postoperative setting after lung resection, despite uncertainty about its effectiveness. In the ICOUGH (Incentive spirometry, Coughing and deep breathing, Oral care, Understanding, Getting out of bed at least 3 times daily, and Head-of-bed elevation) trial, Cassidy and colleagues [10] demonstrated potential therapeutic value of IS in a bundled intervention, where IS was integrated into a multidisciplinary postoperative program that focused on patient education and physiotherapy exercises. The rates of pneumonia were reduced from 2.6% to 1.6% after administering the program, though this result was not statistically significant. This study was also limited by the integration of multiple interventions, which precludes the isolation of
a
Staging as per the American Joint Committee on Cancer, seventh edition.
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Table 3. Postoperative Morbidity Spirometry/ Physiotherapy (n ¼ 195)
Postoperative Morbidity Composite PPC with 30 days Pneumonia Atelectasis Bronchoscopy Mechanical ventilation Home oxygen use Readmission or emergency room visits within 30 days Major complications (> Grade II) Total LOS
24 9 9 8 4 27 20 29 4
(12.3) (4.6) (4.6) (4.1) (2.1) (13.8) (10.3) (14.9) (0–38)
Physiotherapy (n ¼ 192) 25 15 8 10 2 28 18 23 4
(13.0) (7.8) (4.2) (5.2) (1.0) (14.6) (9.9) (12.0) (1–38)
Relative Risk (95% CI) 0.94 0.60 1.12 0.79 1.97 0.95 1.10 1.30
(0.56–1.60) (0.26–1.31) (0.43–2.81) (0.32–1.95) (0.36–10.62) (0.60–1.50) (0.60–2.00) (0.82–2.08) NA
p Value 0.879 0.212 1.00 0.637 0.685 0.885 1.00 0.330 0.342
Values are n (%) or median (minimum, maximum), unless otherwise indicated. CI ¼ confidence interval;
LOS ¼ length of stay;
NA ¼ not applicable;
treatment effects for any single intervention. This demonstrates a common methodological challenge in previous trials since IS has been studied under a variety of designs with varying comparator interventions, durations, and outcome measures. Specifically in thoracic surgery, 2 small historical comparative trials have been performed, both of which did not demonstrate any measurable clinical benefit when IS was added to routine physiotherapy in the postoperative setting. The first trial by Vilaplana and colleagues [11] included 18 patients in the intervention arm (IS added to chest physiotherapy) and 19 patients in the control arm (chest physiotherapy only), and concluded that “the routine use of IS does not decrease the frequency of clinical events.” However, this study reported a relatively high PPC frequency (27%), and was likely severely underpowered. The second trial by Gosselink and colleagues [12] compared 32 patients in the intervention arm and 35 patients in the control arm. They demonstrated identical incidence rates of PPC of 11% (4 patients) in both trial arms. This study reported an
Fig 2. Risk ratios for composite postoperative pulmonary complications (PPC) and individual outcomes. The boxes represent risk ratios, and the lines represent 95% confidence intervals. The vertical line presents the null hypothesis of no difference in PPC rate between the intervention and control arms.
PPC ¼ postoperative pulmonary complications.
incidence of PPC that is comparable to the one we report, but was likely underpowered to detect any meaningful clinical differences between trial arms. More recently, an RCT comparing IS with routine physiotherapy after bariatric surgery has similarly shown no added benefit for IS on the incidence of postoperative hypoxemia [13]. However, the results of this trial are difficult to extrapolate to the thoracic surgery population, and the clinical outcomes studied are not necessarily of relevance to complications after lung resection. We have shown, in this adequately powered and blinded RCT, that the addition of IS to routine physiotherapy after lung resection does not reduce the rate of PPC. Similarly, we found no significant differences in length of hospital stay and readmission rates between the trial arms. We have also demonstrated that patients with thoracotomy are at a much higher risk for postoperative PPC than are patients who undergo minimally invasive resection. However, in a subgroup analysis of patients who received thoracotomy, there was also no difference in PPC rate between physiotherapy alone and physiotherapy with IS. Although this post hoc analysis may be underpowered and exploratory in nature, it does generate the hypothesis that the findings of the whole cohort are most likely applicable to thoracotomy patients. In contrast, in the subgroup of patients who suffered from COPD, we found that the incidence of PPC was lower in the PHY/IS cohort than in the PHY cohort, pointing perhaps to some clinical benefit of IS in this particular patient population. We note, however, that this difference was not statistically significant, likely due to the low incidence of COPD in this cohort. We have also independently evaluated the subgroup who had a lobectomy, and were no able to detect any differences in outcomes with the use of IS. We believe that this trial provides sound scientific impetus for abandoning the use of IS in the era of modern thoracic surgery. With the rise of minimally invasive surgery and Enhanced Recovery Pathways After Surgery protocols, a significant emphasis is being placed on eliminating redundant interventions in the postoperative setting [14]. A similar emphasis is also being placed on maximizing the value of medical care, by decreasing costs
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and improving quality. Although a cost-analysis was not planned in this trial, we do believe that eliminating IS will result in cost savings on a national level in Canada, where the majority of thoracic surgery centers still use IS. In a public healthcare system, these costs can be redirected to fund higher value interventions. There are a number of limitations associated with this trial. First, the physiotherapy program used in the control arm at our institution may not be generalizable to other institutions. However, we believe that the results of this trial are applicable to centers that utilize a postoperative regimen that includes deep breathing exercises, shoulder range-of-motion exercises, and early ambulation. Second, compliance with IS or physiotherapy was not monitored after patients were discharged from hospital. In an effort to keep the trial pragmatic and as close as possible to a real-life situation, we elected not to impose the added burden of a compliance log on patients who have been discharged from hospital. Patient compliance has historically been a challenge in RCTs evaluating the effectiveness of IS on postoperative outcomes [15]. It is known that those who report high pain scores after surgery are less likely to regularly use the IS [16]. Moreover, the maximal treatment effect of either intervention may not have been observed due to the short median length of stay of patients in our trial. However, we believe that these limitations are mitigated by the randomization effect and the pragmatism of the trial, which increases the generalizability of the findings.
Conclusion Our findings do not support the addition of IS to the postoperative care of patients after lung resection, when conventional physiotherapy and early ambulation are already being employed.
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3. Branson RD. The scientific basis for postoperative respiratory care. Respir Care 2013;58:1974–84. 4. Sabate S, Mazo V, Canet J. Predicting postoperative pulmonary complications: implications for outcomes and costs. Curr Opin Anaesthesiol 2014;27:201–9. 5. Allen MS, Darling GE, Pechet TT, et al. Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial. Ann Thorac Surg 2006;81: 1013–9; discussion 9–20. 6. Rock P, Rich PB. Postoperative pulmonary complications. Curr Opin Anaesthesiol 2003;16:123–31. 7. Agostini P, Reeve J, Dromard S, Singh S, Steyn RS, Naidu B. A survey of physiotherapeutic provision for patients undergoing thoracic surgery in the U.K. Physiotherapy 2013;99: 56–62. 8. Seely AJ, Ivanovic J, Threader J, et al. Systematic classification of morbidity and mortality after thoracic surgery. Ann Thorac Surg 2010;90:936–42; discussion 942. 9. Montori VM, Guyatt GH. Intention-to-treat principle. CMAJ 2001;165:1339–41. 10. Cassidy MR, Rosenkranz P, McCabe K, Rosen JE, McAneny D. I COUGH: reducing postoperative pulmonary complications with a multidisciplinary patient care program. JAMA Surg 2013;148:740–5. 11. Vilaplana J, Sabate A, Ramon R, Gasolibe V, Villalonga R. [Ineffectiveness of incentive spirometry as coadjuvant of conventional physiotherapy for the prevention of postoperative respiratory complications after thoracic and esophageal surgery]. Rev Esp Anestesiol Reanim 1990;37: 321–5. 12. Gosselink R, Schrever K, Cops P, et al. Incentive spirometry does not enhance recovery after thoracic surgery. Crit Care Med 2000;28:679–83. 13. Pantel H, Hwang J, Brams D, Schnelldorfer T, Nepomnayshy D. Effect of incentive spirometry on postoperative hypoxemia and pulmonary complications after bariatric surgery: a randomized clinical trial. JAMA Surg 2017;152:422–8. 14. Li S, Zhou K, Che G, et al. Enhanced recovery programs in lung cancer surgery: systematic review and meta-analysis of randomized controlled trials. Cancer Manag Res 2017;9: 657–70. 15. Narayanan AL, Hamid SR, Supriyanto E. Evidence regarding patient compliance with incentive spirometry interventions after cardiac, thoracic and abdominal surgeries: a systematic literature review. Can J Respir Ther 2016;52: 17–26. 16. Harris DJ, Hilliard PE, Jewell ES, Brummett CM. The association between incentive spirometry performance and pain in postoperative thoracic epidural analgesia. Reg Anesth Pain Med 2015;40:232–8.