Postoperative inspiratory muscle training in addition

European Journal of Cardio-Thoracic Surgery Advance Access published October 20, 2015

ORIGINAL ARTICLE

European Journal of Cardio-Thoracic Surgery (2015) 1–9 doi:10.1093/ejcts/ezv359

Postoperative inspiratory muscle training in addition to breathing exercises and early mobilization improves oxygenation in high-risk patients after lung cancer surgery: a randomized controlled trial Barbara Cristina Brockia,b,*, Jan Jesper Andreasenc,d, Daniel Langere,f, Domingos Savio R. Souzab and Elisabeth Westerdahlb a b c d e f

Department of Physiotherapy and Occupational Therapy, Aalborg University Hospital, Aalborg, Denmark Faculty of Medicine and Health, Surgery, Örebro University, Örebro, Sweden Department of Cardiothoracic Surgery, Aalborg University, Aalborg, Denmark Department of Clinical Medicine, Aalborg University, Aalborg, Denmark KU Leuven Faculty of Kinesiology and Rehabilitation Sciences, Leuven, Belgium Respiratory Rehabilitation and Respiratory Division, University Hospital Leuven, Leuven, Belgium

* Corresponding author. Department of Physiotherapy and Occupational Therapy, Aalborg University Hospital, Hobrovej 18-22, 9000 Aalborg, Denmark. Tel: +45-97664238; fax: +45-97664385; e-mail: [email protected] (B.C. Brocki). Received 5 June 2015; received in revised form 4 September 2015; accepted 10 September 2015

Abstract OBJECTIVES: The aim was to investigate whether 2 weeks of inspiratory muscle training (IMT) could preserve respiratory muscle strength in high-risk patients referred for pulmonary resection on the suspicion of or confirmed lung cancer. Secondarily, we investigated the effect of the intervention on the incidence of postoperative pulmonary complications. METHODS: The study was a single-centre, parallel-group, randomized trial with assessor blinding and intention-to-treat analysis. The intervention group (IG, n = 34) underwent 2 weeks of postoperative IMT twice daily with 2 × 30 breaths on a target intensity of 30% of maximal inspiratory pressure, in addition to standard postoperative physiotherapy. Standard physiotherapy in the control group (CG, n = 34) consisted of breathing exercises, coughing techniques and early mobilization. We measured respiratory muscle strength (maximal inspiratory/expiratory pressure, MIP/MEP), functional performance (6-min walk test), spirometry and peripheral oxygen saturation (SpO2), assessed the day before surgery and again 3–5 days and 2 weeks postoperatively. Postoperative pulmonary complications were evaluated 2 weeks after surgery. RESULTS: The mean age was 70 ± 8 years and 57.5% were males. Thoracotomy was performed in 48.5% (n = 33) of cases. No effect of the intervention was found regarding MIP, MEP, lung volumes or functional performance at any time point. The overall incidence of pneumonia was 13% (n = 9), with no significant difference between groups [IG 6% (n = 2), CG 21% (n = 7), P = 0.14]. An improved SpO2 was found in the IG on the third and fourth postoperative days (Day 3: IG 93.8 ± 3.4 vs CG 91.9 ± 4.1%, P = 0.058; Day 4: IG 93.5 ± 3.5 vs CG 91 ± 3.9%, P = 0.02). We found no association between surgical procedure (thoracotomy versus thoracoscopy) and respiratory muscle strength, which was recovered in both groups 2 weeks after surgery. CONCLUSIONS: Two weeks of additional postoperative IMT, compared with standard physiotherapy alone, did not preserve respiratory muscle strength but improved oxygenation in high-risk patients after lung cancer surgery. Respiratory muscle strength recovered in both groups 2 weeks after surgery. CLINICAL TRIALS.GOV ID: NCT01793155. Keywords: Inspiratory muscle training • Lung cancer • Surgery • Pulmonary complications • Postoperative • Physiotherapy

INTRODUCTION Pulmonary resection is currently the most effective form of curative treatment for lung cancer. However, lung cancer surgery is associated with a high incidence of postoperative pulmonary

complications (PPCs), influencing patient morbidity and mortality [1, 2]. Although the causes of PPC are multifactorial, respiratory muscle dysfunction has been proposed as a contributing factor in the development of PPC, explained by changes in respiratory muscle

© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

THORACIC

Cite this article as: Brocki BC, Andreasen JJ, Langer D, Souza DSR, Westerdahl E. Postoperative inspiratory muscle training in addition to breathing exercises and early mobilization improves oxygenation in high-risk patients after lung cancer surgery: a randomized controlled trial. Eur J Cardiothorac Surg 2015; doi:10.1093/ ejcts/ezv359.

2

B.C. Brocki et al. / European Journal of Cardio-Thoracic Surgery

mechanics and function due to the surgery [3, 4]. Furthermore, respiratory muscle weakness might have been present before surgery [5, 6], and together with poor preoperative physical functioning and pre-existing comorbidities can make patients more vulnerable to postoperative complications [7]. Preoperative inspiratory muscle training (IMT) for a period of at least 2 weeks has been shown to significantly improve respiratory muscle and lung function in the early postoperative period following cardiothoracic or upper abdominal surgery, significantly reducing the risk of PPC [8]. Randomized controlled trials after pulmonary resection via thoracotomy have so far failed to detect the effects of postoperative respiratory physiotherapy in reducing PPC [9–11], although Agostini et al. [11] described a trend towards lower frequency of PPC in a high-risk subgroup of patients. There is a scarcity of studies investigating the effects of postoperative IMT on respiratory muscle strength after lung cancer surgery, and potential effects have not been adequately documented in a randomized controlled setting. To our knowledge, only one randomized controlled trial has investigated the effect of postoperative IMT on respiratory muscle strength after lung cancer surgery [6]. This study included 32 patients with chronic obstructive pulmonary disease, where IMT was performed 2 weeks preoperatively, continuing for 2 months after the surgery. The authors reported a 13% increase in respiratory muscle strength in the active arm, whereas a significant decrease was detected in controls. However, the authors did not report on differences between groups [6]. Furthermore, this study did not evaluate the effects on PPC or functional outcomes, which are endpoints that could influence recovery after surgery. The impact of surgery on postoperative respiratory muscle strength is unclear and the clinical importance of respiratory muscle dysfunction regarding the occurrence of PPC has been poorly addressed in the literature. Thus, the primary aim of this study was to investigate the effect of 2 weeks of postoperative IMT on respiratory muscle strength in high-risk patients referred for pulmonary resection on the suspicion of or confirmed lung cancer. Secondarily, we investigated the effect of the intervention on the incidence of PPCs. The main hypothesis was that postoperative IMT in addition to breathing exercises and early mobilization would preserve respiratory muscle strength, compared with a control group (CG) not performing IMT.

MATERIALS AND METHODS The study was approved by the Research Ethics Committee in Denmark—Region Nord (N-20120027) and the Danish Data Protection Agency (N-2008-58-0028). The trial was registered in the Clinicaltrials.gov database (NCT01793155), and reporting was guided by the principles outlined in the CONSORT 2010 statement [12]. We conducted an assessor-blinded, 1 : 1 parallel-group, randomized controlled trial. Eligible participants were patients scheduled for pulmonary resection at the Department of Cardiothoracic Surgery, Aalborg University Hospital, on the suspicion of or a confirmed lung tumour regardless of the surgical approach (thoracotomy or video-assisted thoracic surgery [VATS]) and at high risk of developing PPC. High risk was defined as one or more of the following: age ≥70 years [5, 13], forced expiratory volume in 1 s (FEV1) ≤ 70%predicted [14], carbon monoxide diffusion capacity (DLCO) ≤ 70%predicted [2, 13] or scheduled pneumonectomy [15]. Exclusion criteria were physical or mental deficits adversely influencing physical performance, inability to understand written and

spoken Danish, previous ipsilateral lung resection, tumour activity in other sites or organs, pancoast tumour and major surgery within 1 year. We used a computer-generated randomization list with alternate blocks of 4–6. Group allocations were placed and kept by an independent person in sequentially numbered sealed opaque envelopes and released to the main researcher individually and in sequential order at the point of randomization. Patients were allocated to either intervention group (IG) or CG after the written consent was obtained and the baseline measurements had taken place, 1 working day prior to the surgery. Randomization results were disclosed by the main researcher (Barbara Cristina Brocki).

Interventions Prior to surgery, both groups received standard physiotherapy treatment. This consisted of a preoperative instruction in breathing exercises emphasizing deep inspiration with a breath-hold before expiration using a positive expiratory pressure device, with 3 × 10 breaths every waking hour after surgery, coughing and huffing technique. The physiotherapist assessed the patients once daily for the first 2 postoperative days (PODs). Patients sited at the bedside on the day of surgery and ambulated 15 m or more the first day after surgery. Supplementary physiotherapy in both groups was given at the discretion of the ward physiotherapist. Additionally, the IG was instructed on IMT twice daily using the POWERbreathe K3® (HaB Ltd, UK), starting 1 working day before surgery and continuing for 2 weeks after surgery; no sessions were performed on the day of surgery. Each session consisted of two sets of 30 breaths with a 2-minute pause between each set on target intensity before surgery of 30% of maximal inspiratory pressure (MIP). IMT was performed sitting in a chair and wearing a nose clip; patients were instructed to breathe in as strongly and deeply as possible and then breathe out as slowly and deeply as possible. After surgery, the intensity started with 15% and incrementally increased by 2 cmH2O daily, according to the patients’ capability to train with the targeted training load. The training load was graded 3 on a 0–10 modified Borg exertion scale. Patients graded their perceived exertion in a training diary and registered adverse effects such as muscle soreness and pain (0–10 numeric rating score, NRS). Most training sessions were supervised during hospital stay and unsupervised after discharge. Patients were coached by telephone once after discharge. Compliance to training, measured as the number of performed training sets (each set consists of 30 breaths) performed at the targeted intensity, was stored electronically in the device.

Perioperative procedure Pulmonary resections were performed either by VATS or by the open technique using a muscle-sparing lateral or postero-lateral thoracotomy at the surgeons’ choice. At the end of surgery, a single chest tube was placed in the pleural space, connected to a suction system with a negative pressure of minus 5–10 cmH2O column (Thopaz chest drainage system®, Medela, Switzerland). The chest tube was removed when air leak was under 10–20 ml/min for 8 consecutive hours. No drainage was used after pneumonectomy. Pain management was primarily achieved by continuous thoracic epidural infusion of bupivacaine 2.5 mg and morphine 0.050 mg/ml at a dosage of 2–7 ml per hour, depending on the pain level, over a period of 2–5 days. As a supplement, the patients received per-oral non-steroid anti-inflammation drugs and paracetamol. Routine


Outcomes Outcomes were assessed the day before surgery (baseline), 3–5 days after surgery (POD5) and 2 weeks after surgery by assessors unaware of the individual randomization allocation. The primary outcome measure was change in inspiratory muscle strength from baseline to 2 weeks after surgery. Secondary outcomes were incidence of PPC, lung volumes, physical performance, dyspnoea levels and oxygen saturation.

Respiratory muscle strength The assessment of respiratory muscle strength at the mouth was performed according to the guidelines [16] by a physiotherapist who was unaware of the individual randomization allocation. We used a hand-held electronic transducer (Micro RPM®; MicroMedical/ CareFusion, Kent, UK) with a flanged mouth piece, and the patient sat in a chair and wore a nose clip. Measurements were performed from total lung capacity for maximal expiratory pressure (MEP) and from residual volume for MIP. The highest 1-s value for at least three consecutive attempts lying within 10 cmH2O of each other was used, and the percentage of predicted values was calculated [17]. Patients rated pain in the chest on a 0–10 NRS before and during the assessment. An inter-rater reliability test with 10 healthy individuals aged 55–75 years performed prior to the study showed an intraclass correlation coefficient (ICC) of 0.87, 95% CI [0.49; 0.96], P = 0.03 for MIP and ICC 0.98, 95% CI [0.91; 0.99], P < 0.001 for MEP.

Postoperative pulmonary complications The incidence of PPC was assessed retrospectively 2 weeks after surgery by a cardiothoracic surgeon who was unaware of the patients’ randomization allocation. Table 1 depicts PPC criteria used in this study, which was modified from Kroenke et al. [18] and Hulzebos et al. [19]. PPC was classified as 1 (minor) to 3 (severe), and a clinically relevant PPC was defined as two or more items in the grade 1 complication or one item in the grade 2 or 3 complication. Peripheral oxygen saturation (SpO2) was measured by the nurse in charge of the patient and who was not blinded to the patients’ randomization allocation. Measurements were performed each morning up to 5 days postoperatively. Hypoxaemia was defined as SpO2 1 grade 2 or >1 grade 3 criteria. All variables were assessed retrospectively 2 weeks after surgery, except for hypoxaemia (SpO2: peripheral oxygen saturation), which was assessed daily up to 5 days postoperatively. Modified from Kroenke et al. [18] and Hulzebos et al. [19].

modified 0–10 Borg scale) was assessed after the 6MWT. Higher rates correspond to higher levels of dyspnoea or experienced exertion. FEV1 and forced vital capacity (FVC) were measured using a calibrated portable spirometer, the Spirovit SP-2® (Schiller, Switzerland). The best of three measurements with the patient sitting and wearing a nose clip were recorded [22]. FEV1/FVC was calculated and values were compared with reference values. For safety considerations, we reported the incidence of pneumothorax and pleural drainage time. The thoracic surgeon was contacted in case of a persistent air leak in the pleural drainage, and as a rule of thumb, IMT continued if the registered air leak in the Thopaz drain did not exceed the leak produced during a coughing manoeuvre. As adverse events, we registered additional medical symptoms that the attending thoracic surgeon considered to be related to IMT.

Secondary outcomes

Statistical analysis

The 6-min walk test (6MWT) was used to assess functional performance. The test was performed twice (except for assessment at POD5), according to guidelines [20], in a 20-m corridor. Patients were instructed to walk at their fastest pace and cover the longest possible distance. No encouragement was given during the test. The better of two tests, separated by a recovery time of 30 min, was used and related to reference values [21]. Heart rate, SpO2 (Riester ri-fox N® pulse oximeter, Germany) and experienced dyspnoea (Borg CR10 scale) were assessed before and after the test. Perceived exertion (a

For sample size calculation, we used data from a study performed in high-risk patients scheduled for major upper abdominal surgery [23]. To find a mean difference in MIP between the two groups of 15 ± 20 cmH2O with a power of 80% and a significance level of 0.05, 29 subjects in each group were needed. A total of 70 subjects were randomized to compensate for an anticipated 15% dropout. The distribution of the variables was given as mean ± standard deviation and median (minimum–maximum) for continuous variables

THORACIC

chest X-ray was performed within 24 h after removal of the chest tube and again at the medical follow-up 2 weeks after surgery.

3

4


and as number and percentage for categorical variables. For comparison between two groups, the Mann–Whitney U-test was used for continuous variables, and the Mantel–Haenszel χ 2 test for nominal or ordered categorical variables. Fisher’s exact test was used for dichotomous variables with