Precision implementation of early ambulation in elderly patients undergoing off-pump coronary artery bypass graft surgery: a randomized-controlled clinical trial

China faces a tsunami in the aging population, and it is estimated that by the end of 2019, the number of adults aged over 60 years had reached 230 million. By 2050, it is expected that there will be 400 million Chinese citizens aged over 65 years, including 150 million aged over 80 years [1]. The older an individual patient, the higher a surgeon’s threshold is for performing a more extensive or complicated operation [2, 3]. Coronary heart disease is now the leading cause of death, with the mortality in China at 9.2% per year for men and 7.0% for women. Off-pump coronary artery bypass grafting (OPCABG) surgery is regarded to be an ideal approach for elderly patients with coronary heart disease [4, 5]. Despite advances in cardiac surgery resulting in safer procedures, postoperative complications are still frequent, and a determinant of length of hospital stay and functional recovery [6]. It is worth noting that prolonged bed rest is recognized as a well-established contributor to delayed recovery.

Enhanced recovery after surgery (ERAS) is an approach generated from evidence-based medicine that aims to achieve an uneventful recovery after surgery [7, 8]. Early ambulation (EA) following surgery has multiple benefits, enhancing not only recovery of functional exercise capacity and self-perceived functional status, but also muscle force [9]. However, bed rest is prescribed after surgery, with on average, 83% of the patient’s time spent lying in bed, 13% of the time spent seated, and 4% of the time spent walking [10]. Although early mobilization is implemented for patients after cardiac surgery, no consensus exists regarding the optimal intensities, durations and types of EA [11, 12].

Studies of aerobic and resistance exercise have been conducted to maximize physical recovery and minimize the associated side-effects. Hong reported that heart failure patients could not tolerate physical activities at a monitored heart rate of 70% of the age-predicted maximal heart rates (APMHR) [13]. Maximal oxygen uptake (VO_2max) and its closely related clinical correlate, cardiorespiratory fitness, are key determinants of both elite performance in endurance excise and mortality in the general population, and the physiological mechanisms associated with aging appear to be responsible for a decline in the V̇O_2max of older men [14, 15]. However, exercise-based cardiac rehabilitation after surgery has failed to exploit these valuable parameters for postoperative rehabilitation. Therefore, we hypothesized that formulating an individualized security threshold of exercise for elderly patients based on APMHR and VO_2max will provide improved ambulation outcomes.

The aim of this study was to design a precision early ambulation (PEA) programs by focusing on the APMHR and VO_2max as a security threshold for cardiac rehabilitation and to clarify the specific effects on postoperative length of stay (PLOS) in hospital, postoperative complications, and physiological and psychological functional return.

This study was reported in accordance with the CONSORT 2010 Statement using the template for intervention description and replication (TIDieR).

To the best of our knowledge, this is the first trial of the formulation of early ambulation programs with precision intensity, duration and individualized security thresholds based on APMHR and VO_2max in elderly patients after cardiac surgery. By individualized implementation of this protocol, significant and favorable associations were found to exist between PEA and clinical outcomes, such as PLOS. Multivariate logistic regression analyses confirmed the effect of PEA on early discharge.

The characteristics of the participants in this study were consistent with the predominance of coronary heart disease in elderly patients. It was commonly noted that aged patients undergoing CABG were at a higher risk of perioperative complications and death, and that EA was difficult to be implement in this population. Our data showed that advanced age was an independent risk factor for early discharge. Frustratingly, there is no real consensus among clinicians regarding the definition and implementation of “early” in elderly patients. Few studies provided a clear definition of EA after cardiac surgery. David reported that the gradual increase in activity should be started on the first postoperative day until independent ambulation on the fifth postoperative day [21]. However, Jans et al. reported that EA might lead to a high incidence of postoperative OH and OI, especially in the elderly population [22]. We recommend that a progressive program, starting with standing by the bed within 24 h and walking after 24 h was safe and helpful for function recovery. Our findings appear to support the importance of avoiding bed rest for the safety of elderly patients after cardiac surgery.

EA should constitute a continuum of care and multiple therapy techniques. The Heart Failure Quality Program define EA as the patient’s ambulation without assistance [23]. In some superior ICUs, patients engage in novel mobilization techniques, such as cycle ergometer, upper body exercises, Kinarm robotic exoskeleton and supported treadmill training [24, 25]. Andrew et al. reported that walking provided a well-tolerated and clinically effective alternative to stationary cycling in the early postoperative period after CABG [26]. However, there is no evidence that one technique is superior to another. Another important factor regarding early mobilization is the intensity of EA. Moradian et al. showed that patients who received low-frequency monitored exercise programs had higher discharge rates and shorter ICU stay [27]. The expected goal in another study was 100 m of walking with assistance on day 2 after CABG, and a 10-min physiotherapy-supervised walking exercise session on day 3 [26]. Our data showed that 83% patients completed a low-intensity exercise implemented in a step-by-step process on day 3 after surgery with a low incidence of OH and OI, which was much better than that observed in the Control group. According to our clinical experience, excessive exercise is more of a hindrance than a help. Therefore, exercise physiology values such as APMHR and VO_2max are implicated as novel and efficient “warning lines” for physiological responses [13, 28]. We believe low-frequency exercises based on VO_2max and APMHR monitoring could be beneficial and accurately reflect an elderly patient’s tolerance in the early postoperative period while guaranteeing their safety.

Future efforts directed at evaluating perioperative care for elderly patients will need to be comprehensive and include traditional outcome measures, such as mortality and complications, as well as focusing more attention on quality measures, such as PLOS and readmission. Shorter hospital stays lead to benefits for patients, their families, and the hospital, contributing to net healthcare costs savings. However, prolonged hospital stay after surgery predisposes patients to clinical complications and increases medical costs. There is growing evidence that early mobilization of patients in the ICU can reduce the length of hospital and ICU stays [29]. Cacau et al. reported that an early mobility protocol decreased the length of stay from 12.2 days to 9.4 days [30]. Schaller et al. reported that the length of ICU/hospital stay was 7/15 days in the early intervention group and 10/21.5 days in the control group, respectively [31]. Therefore, it is understandable that the length of hospital stay is the outcome most frequently used to assess the effectiveness of early mobilization in elderly patients. However, in contrast with these results, some other trials did not identify this effect of early mobilization. Klein noted that there was insufficient evidence on the effect of early mobilization of critically ill people in the ICU on physical function or performance, adverse events, muscle strength and health-related quality of life at this time [32]. Although our results are consistent with the previous findings that PEA shortens the length of PLOS stay, we showed conflicting results in that the length of ICU stay was reduced by EA. We speculated that the mainly elderly population of patients enrolled in our study faced a slower early recovery as a result of organic aging during the period in the ICU. Factors affecting early discharge destination in elderly patients is potentially confounded by multiple factors. Some studies showed that a higher level of independence in activities of daily living or less degree of frailty was significantly related to early discharge among younger patients, better functional and cognitive status [33, 34]. In our study, we found that EA was an independent factor that was as important as age and Euro score in achieving an early discharge.

EA is also beneficial in terms of functional capacity and prevention of postoperative complications. Li et al. reported that ERAS effectively brought forward the time of first bowel movement by approximately 1.0 day [11]. Our data also confirmed that PEA promoted gastrointestinal function recovery, with an average reduction in the time of first bowel movement to 0.7 day. In our study, the incidence of pulmonary atelectasis and pulmonary infection in the PEA group was reduced by 7 and 2%, respectively. In contrast, Moradian et al. showed that EA reduced the incidence of pleural effusion and atelectasis by approximately 34 and 29%, respectively [27]. However, arterial oxygen level was significantly improved in the PEA group, suggesting that early ambulation could contribute to lung recovery, and improvement of circulatory function.

Growing evidence highlights that positive affectivity is associated with better cardiac rehabilitation adherence and plays a role as an independent factor influencing cardiac outcomes. Approximately 20–51% of patients with coronary heart disease are affected by clinical psychological symptoms [35]. PTSD is an abnormal psychological reaction characterized by a series of anxious manifestations such as avoidance, and a state of high alert. Gao et al. have proposed that 25.8% of patients with myocardial infarction had PTSD [36]. Deng et al. reported that the incidence of post-operative PTSD in 134 adults with congenital heart disease was 21% [37]. Our study confirmed a strong negative association of PTSD with EA, which indicated that positive psychological functioning, such as positive attitude and optimism, stimulates goal-striving activities that encourage protective health behaviors and to adherence to therapies.

Our study has some limitations. First, there was a low power of the study for the secondary endpoint due to the small sample size and clinical limitation of early ambulation. Therefore, a larger sample size should help to increase the power. Second, the narrow inclusion criteria of age and type of surgery applied in this study may increase the risk of bias due to selective reporting. Broader inclusion criteria will help to increase the generalizability of our results. However, clinical experience shows that ERAS may be more beneficial for aged patients, and cardiopulmonary bypass in cardiac surgery may have a potential negative impact on the recovery of patients. Therefore, we enrolled elderly patients undergoing OPCABG to identify significant clinical differences. Third, a blinded randomized controlled trial would provide more robust evidence; however, it was impossible to blind participants and therapists from the intervention in our study and we could not avoid the subjective implementation of the EA protocols by rehabilitation therapists and nurses in this study. Fourth, although early ambulation is an important part of ERAS, the clinical effect of early ambulation is not only determined by the effectiveness of the intervention, but also by the quality of the usual EA procedure and the clinical skill of the rehabilitation therapists as well as patient compliance in different hospitals. This study was a component of a protocol registered for ERAS that included several interventions such as respiratory exercise, acupuncture, and early ambulation. The interaction of multiple interventions has produced variable phenotypes of recovery of patients. This fact also limits the generalizability of the results to other hospitals with different standards of routine care. Fifth, although missing data were uncommon in this study, the chosen strategy of replacement of missing values with the mean value and negative results also may decrease the variability and act as a bias that decreases differences.

In summary, our data confirmed that PEA can shorten the PLOS, reduce postoperative complications, and accelerate physiological and psychological rehabilitation of elderly patients after OPCABG surgery. Our study also revealed that APMHR and VO_2max are valuable for implementation of PEA according to an established security threshold. Further investigations are required to improve the formulation and implementation of EA by focusing on factors such as cross-disciplinary integration, systematic training and individualized treatment.