Postoperative pulmonary complications (PPCs) are the most commonly reported complications after esophagectomy. The aim of this study was to examine the effect and feasibility of preoperative inspiratory muscle training-high intensity (IMT-HI), and IMT-endurance (IMT-E) on the incidence of PPCs in patients following esophagectomy for esophageal cancer (EC).
A single-blind, randomized, clinical pilot study was conducted between 2009 and 2012. Forty-five participants were assigned to either IMT-HI or IMT-E. Effectiveness was assessed by analyzing PPCs, length of hospital stay (LOS), duration of mechanical ventilation, stay on the intensive care unit, and number of reintubations. Maximal inspiratory pressure and lung function changes were recorded pre- and post-training. Feasibility was assessed by IMT-related adverse events, training compliance, and patients’ satisfaction.
Thirty-nine patients could be analyzed, 20 patients in the IMT-HI arm and 19 patients in the IMT-E arm. The incidence of PPCs differed significantly between groups and was almost three times lower for the IMT-HI group (4 vs. 11 patients; p = 0.015). Other differences in favor of the IMT-HI group were LOS (13.5 vs. 18 days; p = 0.010) and number of reintubations (0 vs. 4 patients; p = 0.030). Both interventions proved to be equally feasible.
Preoperative IMT-HI showed to be a promising, effective, and feasible intervention to reduce PPCs in EC patients undergoing esophagectomy. Further research with a larger sample size is recommended.
The risk of postoperative pulmonary complications (PPCs) following esophagectomy is generally high (27–57 %) and PPCs frequently result in morbidity and mortality.1–7 PPCs are the most commonly reported complications after esophagectomy4 and contribute to a prolonged length of hospital stay (LOS) and stay on the intensive care unit (ICU), with increased costs of care.4,6
Research regarding the prediction of PPCs following esophagectomy usually focuses on intra- and postoperative management. Although these developments have led to a reduction in PPCs, the incidence remains high. Previous efforts in esophageal cancer (EC) patients have not considered the potential of preoperative interventions.1 Improving general physical fitness preoperatively may reduce PPCs, but it is questionable whether it can be achieved in the limited timeframe with current use of neoadjuvant chemoradiotherapy (CRT) prior to esophagectomy. Alternatively, preoperative pulmonary training may offer a similar risk reduction in a shorter time period.4
A recent systematic review showed significant risk reduction of developing PPCs in patients after cardiac or abdominal surgery when preoperative inspiratory muscle training-endurance (IMT-E) was provided.8 Preoperative IMT-E in high-risk patients undergoing coronary artery bypass graft has shown a reduction of nearly 50 % in PPCs and an improvement of 18 % in maximal inspiratory pressure (MIP).9 One recently published study focused on the effects of preoperative IMT-E in patients undergoing esophagectomy.10 In this prospective, non-randomized study, preoperative IMT-E showed no significant effect on the occurrence of postoperative pneumonia. However, these results cannot be interpreted straightforward due to significant baseline differences and insufficient maximal resistance of the training device.
While the studies described above focused on IMT-E, another available modality, i.e. high intensity (IMT-HI), has been shown to be feasible and beneficial in healthy adults,11 chronic obstructive pulmonary disease (COPD) patients,12 and chronic heart failure,13 with an increase of MIP by 41, 29, and 31 %, respectively. As the improvement in MIP seems to be greater than in IMT-E, this modality may be more effective in reducing PPCs. Until now, IMT-HI has not been used preoperatively and its effects on PPCs are not clear.
Therefore, the primary objective of this pilot study was to examine the effect of preoperative IMT-HI on PPCs compared with preoperative IMT-E in EC patients awaiting esophagectomy. The secondary objective is to investigate the effect on LOS, stay on the ICU, number of reintubations, MIP and preoperative lung function, and to examine the feasibility of both training modalities.
Patients and Methods
Patients and Design
The study was performed between December 2009 and September 2012 at the University Medical Center Groningen, after approval by the local Medical Ethics Committee (M09.071587). Eligibility was assessed by the following criteria: histologically proven EC and selected for standard esophagectomy ± neoadjuvant CRT, age between 18 and 85 years, able to perform a valid spirometry test, and knowledge of the Dutch language. Exclusion criteria were neuromuscular disorder, unstable asthma, history of spontaneous pneumothorax, cognitive disorder, inability to travel to the hospital, and emotional instability. Eligible patients received written and oral information and written informed consent was obtained from participants prior to the study.
Randomization and Allocation
In this single-blind, randomized pilot study, patients were randomized to one of the two intervention groups using a block-wise randomization. The physical therapist was informed about the allocated intervention. Researchers assessing the outcomes were blinded to the intervention. Type of intervention was released after registration of all data.
Patients received preoperative IMT-HI or IMT-E. The intention was to provide a minimum training period of 3 weeks that ended the day before surgery. In case of receiving neoadjuvant CRT, training started 1–2 weeks after finishing CRT (depending on experienced side effects).
IMT-HI was based on the program described by Enright et al.11 Patients performed three supervised training sessions per week, each consisting of six cycles of six inspiratory maneuvers on an inspiratory threshold-loading device (Respifit S®, Biegler GmbH, Mauerbach, Austria). Resting time between cycles was progressively reduced from 60 to 45, 30, 15, and 5 s. MIP was measured weekly to adjust intensity adequately. Initial intensity was 60 % of MIP and increased to 80 % during the first week. In consecutive sessions, training intensity was 80 % of MIP and increased with 5 % if a Borg score14 for perceived exertion <5 was reached.
IMT-E was based on the program of Hulzebos et al.9 and contained seven training sessions a week, three supervised and four unsupervised (performed at home). Each session consisted of 20 min of breathing through an inspiratory threshold-loading device (Threshold-IMT®, Respironics) at 30 % of the MIP measured before the first session. Training load was increased with 5 % when a Borg score of <5 was reached. To perform IMT at home, patients received instructions and kept a training log (intensity, experience, and perceived exertion).
A skilled physiotherapist guided the supervised training sessions. All patients received the usual postoperative physical therapy (breathing exercises, coughing techniques, and early mobilization).
Patient characteristics, disease-related variables, and postoperative outcome measures were prospectively registered. PPCs were recorded using the criteria described by Kroenke et al.15 (Appendix 1) at a 4-point ordinal scale. The highest rate of PPC scored during admission was selected. PPCs were considered clinically relevant when one or more items in grade 3 or 4 were scored.
Secondary outcome measures were LOS (number of days admitted since day of surgery), stay on the ICU (in days), number of reintubations, and preoperative change in MIP and lung function. MIP and lung function were measured before (T0) and after (T1) the training period. MIP was measured with a portable respiratory pressure meter (Micro Medical RPM, PT Medical, Leek, The Netherlands) and according to the ATS/ERS protocol.16 Lung functions (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], FEV1/FVC, and peak inspiratory flow [PIF]) were measured according to the ATS/ERS protocol.17 Feasibility was assessed by the number of IMT-related adverse events, compliance to training, and self-estimated load of participation (on a 10-point scale).
Statistical analyses were performed using SPSS statistical software, version 20.0 (IBM Corporation, Armonk, NY, USA). Two-sided significance tests were used (α < 0.05). Data are presented as mean and standard deviation (SD), or median and interquartile range (IQR) for variables with a skewed distribution. Differences between groups in categorical variables were tested with Chi square or Fisher’s exact test, for continuous data the student’s t test or the Mann–Whitney U test was used. The Wilcoxon signed rank test was used to compare MIP and lung function tests at T0 and T1. Relative risk was calculated for PPCs and occurrence of pneumonia.
Eighty-four patients were assessed for eligibility, of which 39 were excluded (16 not meeting inclusion criteria, 23 declined). Of the 45 participants, 23 were allocated to IMT-HI, of which three were lost to follow-up (one non-resectable tumor at surgery, one unrelated lung embolism, and one discontinuation of training due to personal reasons). Twenty-two patients were allocated to IMT-E, of which two did not receive the intervention (one unrelated transient ischemic attack during intake, and one provocation of severe tension headache) and one was lost to follow-up (non-resectable tumor at surgery; Fig. 1). None of the included patients had pulmonary or other possible interfering comorbidities. The median number of weeks trained was 3.7 (2.9–4.4) for the IMT-HI group and 3.7 (3.0–4.4) for the IMT-E group (U = 169.50; p = 0.564; r = −0.09).
All patients received optimal pain management postoperatively (epidural analgesia, patient controlled analgesia, or a combination). No significant differences in baseline characteristics (Table 1) and perioperative characteristics (Table 2) were found between groups.
Postoperative Pulmonary Complications
A significant difference in PPCs was observed between groups (χ2 = 5.91; p = 0.015; Table 3). Focusing on the clinically relevant PPCs, i.e. grade 3 and 4, a relative risk of 2.9 to develop a PPC was found for patients in the IMT-E group (IMT-HI: 4 [20.0 %] vs. IMT-E: 11 [57.9 %]). Specified for pneumonia, the difference was equally large (IMT-HI: 3 [15 %] vs. IMT-E: 8 [42.1 %]), with patients in the IMT-E group being 2.81 times as likely to develop a pneumonia, although this result failed to reach significance (χ2 = 3.54; p = 0.060).
Length of Hospital Stay
Patients in the IMT-HI group had a significantly shorter duration of LOS compared with patients in the IMT-E group (U = 98.50; p = 0.010; r = −0.41). Patients scoring a PPC grade 1 or 2 had a significant shorter LOS compared with patients with a PPC grade 3 or 4 (U = 37.50; p = 0.000; r = −0.66).
Number of Reintubations and Stay on Intensive Care Unit
Significantly less reintubations were required in the IMT-HI group than in the IMT-E group (χ2 = 4.69; p = 0.030). Patients in the IMT-HI group tended to show a shorter duration of ICU stay compared with the IMT-E group; this difference just failed to reach significance (U = 130.50; p = 0.071; r = −0.29).
Maximal Inspiratory Pressure and Lung Function
The median MIP (IQR) in cmH2O for the IMT-HI group showed a significant increase of 12 % from T0 to T1 (z = −3.24; p = 0.001; r = −0.76). The IMT-E group showed a significant increase of 35 % (z = −3.82; p = <0.001; r = −0.88). No significant difference in change from T0 to T1 was found between groups (U = 138.00; p = 0.316; r = −0.17).
A significant decrease over time was found on median FEV1 in the IMT-HI group (z = −2.36; p = 0.018; r = −0.57). PIF increased significantly over time in the IMT-E group (z = −3.00; p = 0.003; r = −0.75), resulting in a significant difference between groups for PIF on T1 (U = 65.50; p = 0.011; r = −0.44) [Table 4].
Of the earlier described reasons for dropout, only tension headache was possibly related to the IMT intervention. The other reasons for dropout were determined as unrelated by an independent physician. No further adverse events occurred during training. Average compliance for the IMT-HI and the IMT-E groups were 98.0 % (minimum 84.6–maximum 100 %) and 99.4 % (minimum 93.6–maximum 100 %), respectively (U = 170.00; p = 0.240; r = −0.14). Self-estimated load of participation was graded with a median score of 5 (IQR 3–7) in both groups. No significant differences between groups were found.
This pilot study showed that PPCs occurred significantly and approximately three times less in the IMT-HI group compared with the IMT-E group. Additionally, patients in the IMT-HI group had a significantly shorter LOS and a lower number of reintubations. IMT-HI showed to be equally feasible as IMT-E for patients awaiting esophagectomy and proved to be a promising preoperative intervention to reduce PPCs.
Although the study population was small, the results strongly indicate in favor of IMT-HI, which may offer a significant contribution in reducing PPCs over IMT-E. The results in the IMT-E group match the results of a previous study on IMT-E which did not show a significant reduction of pneumonia in patients after esophagectomy.10 The shorter LOS and fewer reintubations in the IMT-HI group are positive from the patients’ perspective and may lead to a considerable cost reduction in care for this population.
When comparing the results with the earlier reported rates of PPCs following esophagectomy of 27–57 %, it is shown that the incidence in this study, especially in the IMT-E group, was relatively high. In a previous study of the same institute, an incidence of PPCs of 42 % (aged <70 years) and 56 % (aged ≥70 years) was found after esophagectomy without neoadjuvant chemoradiation therapy (NCRT).18 Compared with this reference group, the IMT-E group showed an even higher rate of PPCs (57.9 %), whereas patients in the IMT-HI group showed a considerably lower rate (20 %). It should be noted that the current population received NCRT, which may have induced more PPCs. As shown in a recent study, there is an increased incidence of cardiopulmonary complications in patients receiving NCRT prior to esophagectomy when compared with surgery alone.19
The relation between PPCs, MIP, lung function and LOS remains indefinite. Where Hulzebos et al.9 assumed that the significant increase of MIP might be related to a reduction of PPCs, the results of the present study cannot confirm this. No significant difference in MIP between groups was found in the present study, yet a significant difference in PPCs in favor of IMT-HI occurred. Moreover, the influence of lung function on PPCs seems to be questionable, which is also supported by the study of Feeney et al.20 who found no significant difference in lung function between patients with or without a PPC after esophagectomy.
The feasibility of preoperative IMT-E was previously shown in patients undergoing coronary artery bypass surgery and abdominal surgery 9,21,22 and in patients selected for esophagectomy.10 The present study confirmed these findings and additionally showed IMT-HI to be equally feasible in patients undergoing esophagectomy. As IMT-HI is less time-consuming (IMT-HI: 3 sessions a week vs. IMT-E: 7 sessions a week), this modality might be preferable, particularly in patients receiving NCRT, considering their full treatment schedule.
The main limitation of this pilot study was the small sample size due to limited inclusion during the study period. Primary reasons to decline participation were overall exhaustion from the pre-treatment period and travelling distance to the hospital. This may have caused selection bias. The study group seems to have a high level of functioning, which is also reflected in the absence of possible interfering comorbidities. Therefore, the generalizability of the results may be restricted. However, it can be expected that patients with lower initial functioning benefit even more from this intervention. Another limitation was the earlier-described maximal load of the threshold trainer (41 cmH2O),10 which resulted in suboptimal training for 6 of the 19 IMT-E patients. However, considering the results of this study, it remains questionable whether a further increase in MIP would have influenced the effect on reducing PPCs.
Based on the significant results of this pilot study, IMT-HI proved to be a promising and effective intervention in reducing PPCs in patients undergoing esophagectomy. Further research, including a randomized controlled trial in a larger population, is needed. Decentralizing the HI training with use of a portable training device would potentially increase inclusion rate and feasibility. The optimal HI-training modality and the relation between PPCs, MIP, and lung function need clarification.
Ferguson MK, Durkin AE. Preoperative prediction of the risk of pulmonary complications after esophagectomy for cancer. J Thorac Cardiovasc Surg. 2002;123(4):661-669.
Jiao WJ, Wang TY, Gong M, Pan H, Liu YB, Liu ZH. Pulmonary complications in patients with chronic obstructive pulmonary disease following transthoracic esophagectomy. World J Gastroenterol. 2006;12(16):2505-2509.
Avendano CE, Flume PA, Silvestri GA, King LB, Reed CE. Pulmonary complications after esophagectomy. Ann Thorac Surg. 2002;73(3):922-926.
Ferguson MK, Celauro AD, Prachand V. Prediction of major pulmonary complications after esophagectomy. Ann Thorac Surg. 2011;91(5):1494-1501.
Fagevik Olsén M, Wennberg E, Johnsson E, Josefson K, Lönroth H, Lundell L. Randomized clinical study of the prevention of pulmonary complications after thoracoabdominal resection by two different breathing techniques. Br J Surg. 2002;89(10):1228-1234.
Hulscher JBF, Van Sandick JW, De Boer AGEM, Wijnhoven BP, Tijssen JG, Fockens P, et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med. 2002;347(21):1662-1669.
Feeney C, Hussey J, Carey M, Reynolds JV. Assessment of physical fitness for esophageal surgery, and targeting interventions to optimize outcomes. Dis Esophagus. 2010;23(7):529-539.
Valkenet K, Van De Port IGL, Dronkers JJ, De Vries WR, Lindeman E, Backx FJG. The effects of preoperative exercise therapy on postoperative outcome: a systematic review. Clin Rehabil. 2011;25(2):99-111.
Hulzebos EHJ, Helders PJM, Favié NJ, De Bie RA, Brutel de la Riviere A, Van Meeteren NLU. Preoperative intensive inspiratory muscle training to prevent postoperative pulmonary complications in high-risk patients undergoing CABG surgery. JAMA. 2006;296(15):1851.
Dettling DS, Van der Schaaf M, Blom RL, Nollet F, Busch OR, Van Berge Henegouwen MI. Feasibility and effectiveness of pre-operative inspiratory muscle training in patients undergoing oesophagectomy: a pilot study. Physiother Res Int. 2013;18(1):16-26.
Enright SJ, Unnitham VB, Heward C, Withnall L, Davies DH. Effect of high-intensity inspiratory muscle training on lung volumes, diaphragm thickness, and exercise capacity in subjects who are healthy. Phys Ther. 2006;86(3):345-354.
Hill K, Jenkins SC, Philippe DL, Cecins N, Shepherd KL, Green DJ, et al. High-intensity inspiratory muscle training in COPD. Eur Respir J. 2006;27(6):1119-1128.
Laoutaris ID, Dritsas A, Brown MD, et al. Immune response to inspiratory muscle training in patients with chronic heart failure. Eur J Cardiovasc Prev Rehabil. 2007;14(5):679-685.
Borg GA. Perceived exertion. Exerc Sport Sci Rev. 1974;2:131-153.
Kroenke K, Lawrence VA, Theroux JF, Tuley MR. Operative risk in patients with severe obstructive pulmonary disease. Arch Intern Med. 1992;152(5):967-971.
Green M, Road J, Sieck GC, Similowski T. Tests of respiratory muscle strength. Am J Respir Crit Care Med. 2002;166(4):528-547.
Wanger J, Clausen JL, Coates A, et al. Standardisation of the measurement of lung volumes. Eur Respir J. 2005;26(3):511-522.
Pultrum BB, Bosch DJ, Nijsten MWN, et al. Extended esophagectomy in elderly patients with esophageal cancer: minor effect of age alone in determining the postoperative course and survival. Ann Surg Oncol. 2010;17(6):1572-1580.
Bosch DJ, Muijs CT, Mul VE, et al. Impact of neoadjuvant chemoradiotherapy on postoperative course after curative-intent transthoracic esophagectomy in esophageal cancer patients. Ann Surg Oncol. 2014;21(2):605-11.
Feeney C, Reynolds JV, Hussey J. Preoperative physical activity levels and postoperative pulmonary complications post-esophagectomy. Dis Esophagus. 2011;24(7):489-494.
Dronkers J, Veldman A, Hoberg E, van der Waal C, van Meeteren N. Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study. Clin Rehabil. 2008;22(2):134-142.
Weiner P, Zeidan F, Zamir D, et al. Prophylactic inspiratory muscle training in patients undergoing coronary artery bypass graft. World J Surg. 1998;22(5):427-431.
We thank the participants who made this study possible. We also thank Mariska C. Leegte, PT, Michiel C. Nagel, PT, MSc, and Joyce M.A. Stel, PT, Department of Rehabilitation, for providing the supervised training sessions. None of the persons named received compensation for their contribution. This study was Funded by a Grant from the University Medical Centre Groningen (UMCG).
Conflict of interest
The authors declare no conflicts of interest.
Trial Registration: ‘Nederlands Trial Register’ identification number: NTR2921 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2921).
See the Table 5.
About this article
Cite this article
van Adrichem, E.J., Meulenbroek, R.L., Plukker, J.T.M. et al. Comparison of Two Preoperative Inspiratory Muscle Training Programs to Prevent Pulmonary Complications in Patients Undergoing Esophagectomy: A Randomized Controlled Pilot Study. Ann Surg Oncol 21, 2353–2360 (2014). https://doi.org/10.1245/s10434-014-3612-y
- Esophageal Cancer
- Lung Function
- Esophageal Cancer Patient
- Maximal Inspiratory Pressure
- Postoperative Pulmonary Complication