Prehabilitation

Over 8 million surgical procedures are performed each year in the UK. Despite an ageing and increasingly co-morbid surgical population, the overall risk of death and major complications remains low at just under 2%.¹ Conversely, poor outcomes are seen in patients with impaired preoperative functional capacity. This ‘high-risk’ subgroup consists typically of elderly, multiply co-morbid patients undergoing major surgery and accounts for over 80% of postoperative deaths while representing only 12.5% of surgical admissions.

Much work has been done, in recent years, to improve outcomes in this high-risk group. Emphasis has been placed mainly on intraoperative and postoperative measures, such as intraoperative goal-directed fluid therapy, better utilization of critical care resources, and widespread delivery of rehabilitation and enhanced recovery programmes. These efforts have been bolstered by improved surgical and anaesthetic techniques.

Prehabilitation is the practice of enhancing a patient’s functional capacity before surgery, with the aim of improving postoperative outcomes.² A growing body of evidence has shown improvements in length of stay, postoperative pain, and postoperative complications.³ Still in the domain of proof of concept, prehabilitation programmes are becoming more prevalent and are likely, in due course, to become an established element of the preoperative workup of high-risk patients undergoing major surgery. As such, it is important for anaesthetists to have an understanding of this burgeoning field.

Components of a prehabilitation programme

Several weeks may elapse between the decision to proceed with surgery and the surgery itself. This represents a so-called ‘teachable moment’. An opportune time to positively impact a patient’s health behaviour, which may in turn effect long-term survival. Instituting an exercise programme at this juncture may provide a welcome distraction to impending major surgery. Furthermore, patients may feel physically more capable of exercise than at any other point during the perioperative period. Many of the programmes described in the literature span 4–8 weeks in duration. Shorter programmes may be ineffective, while compliance may be a problem with longer programmes. More recently, the benefits of a multimodal approach are now being realized,⁴ producing lifestyle modification through:

• Medical optimization

• Physical exercise

• Nutritional support

• Psychological support.

These interventions are provided by a multidisciplinary team consisting of surgeons, anaesthetists, physicians, geriatricians, physiotherapists, nutritionists, and psychologists. At the outset, basic anthropometric measurements such as height, weight, and percentage body fat are obtained. Functional capacity, nutritional status, and mood are also assessed and monitored intermittently throughout the programme. Interventions should be continued into the postoperative period.

Medical optimization

Preoperative smoking cessation, reduction in alcohol intake, and weight optimization benefit the patient in the postoperative period. Carbon monoxide (CO) and nicotine produce most of the acute harm from smoking. CO reduces tissue oxygen delivery, and nicotine, because of its sympathomimetic properties, increases the work of the heart. It has long been accepted that preoperative smoking cessation is beneficial, reducing the risk of cardiopulmonary complications, wound infections, impaired wound healing and bone fusion, prolonged hospitalization, and death.⁵ The optimal timing of preoperative cessation is yet to be determined, but the deleterious effects of CO and nicotine disappear within 24–48 h, with longer periods producing greater benefits. Concerns that short periods of cessation (less than 4 weeks) increase pulmonary complication rates are unfounded.

Alcohol misuse increases postoperative morbidity, exhibiting a dose–response relationship. Postoperative infections, cardiopulmonary complications, and bleeding episodes are the most frequently occurring complications. Underlying mechanisms include immunosuppression, cardiac insufficiency, haemostatic imbalance, and an exaggerated surgical stress response. Postoperative morbidity declines with as little as 4 weeks of preoperative abstinence.⁶

The risk of major postoperative complications is greatest in the underweight patient. Normal weight patients experience fewer wound infections, less intraoperative blood loss, and shorter operation times than the obese. Interestingly, the latter have better 30 day and long-term survival rates—this is the obesity paradox.⁷

Management of anaemia, control of blood glucose, and optimization of pharmacological therapy are also addressed as part of a comprehensive prehabilitation programme. Preoperative anaemia is common in patients undergoing major surgery. Even mild anaemia may impair functional capacity and increase the risk of perioperative blood transfusion, postoperative morbidity, and mortality. Diagnosis and treatment of the cause are management priorities and elective surgery should be delayed, if necessary. Therapeutic options include iron supplementation—parenteral iron is an option when oral preparations are ineffective, not tolerated, or a rapid response is required. Blood transfusion should be reserved for patients with, or at risk of, cardiac instability. The aim of pharmacological optimization is to gain optimal control of chronic conditions such as chronic obstructive pulmonary disease, heart disease, hypertension, and diabetes, which, if poorly controlled, increase the risk of pulmonary infections, acute coronary syndrome, and stroke.

Physical exercise programme

A baseline assessment of functional capacity is performed. Two frequently used tests are the cardiopulmonary exercise test (CPET) and the 6 min walk test. The latter is a simple, inexpensive submaximal exercise test that evaluates how far a patient can walk in 6 min. The patient laps a long, flat 30 m course as many times as possible at his or her own pace, stopping to rest, if necessary. The supervising technician records heart rate, dyspnea, and fatigue levels at the beginning and end of the test, total distance walked, if the test was terminated prematurely, and the reasons why (e.g. angina and severe dyspnoea). Repeat testing on completion of the exercise programme enables quantification of any change in functional capacity.

The optimal exercise regime has not been defined, which most likely explains the diversity of regimes seen throughout the literature. Typically, the regimes consist of anything from one to five sessions per week, each 30–60 min in duration including warm-up and cool-down phases. A combination of strength and aerobic exercises are important as both muscle strength and cardiorespiratory fitness decline in the postoperative period. Optimization of exercise intensity can be done through heart rate monitoring or the use of the Borg scale (see Fig. 1).

The Borg scale is a subjective tool used during exercise testing and training to estimate effort based on how strenuous the exercise feels. Exercise intensity is adjusted to achieve a target rating—typically 12–16 in the prehabilitation setting. The scale correlates well with heart rate, ventilatory frequency, serum lactate, and percentage maximal oxygen consumption (VO2max). The Borg scale may have an advantage over heart rate monitoring in patients taking medications, such as beta blockers, that modify the heart rate response to exercise. The target for a heart rate-based approach is 70–80% of maximum heart rate—the so-called aerobic training zone. Studies have started to look at high-intensity interval training (HIIT) programmes, where the workout alternates between short work intervals at 70–90% of maximum heart rate and rest periods at 60–65% of maximum heart rate. Strength training utilizes weights or resistance exercises and should target all major muscle groups. Home-based programmes are cheaper and more convenient, both for patients and institutions. They obviate the need for costly travel arrangements and resource allocation for regular prehabilitation workshops. Patients can exercise at a time suitable to them, in their own home or at a local sports facility with remote support via telephone. Compliance rates, however, and overall improvements in functional capacity are demonstrably better with hospital-based programmes.⁸

Despite the well-documented health benefits of exercise, patients often have perceived barriers to engaging in these activities—pain associated with exercise, financial burden associated with logistics, and a fixed negative mindset to physical activity. Programmes should aim to reduce these barriers by creating an environment that facilitates engagement; they should be clear, well-defined, and provide a structure where individuals can see their progress.

Nutritional support

It is clear from the literature that poor nutritional status is associated with poor postoperative outcomes;⁹ length of stay, infectious complications, readmission rates, and mortality are all adversely affected. Pre-existing nutritional status, severity of the surgical insult, and the nature of the surgery (e.g. major gastrointestinal resection) all contribute to nutrition risk. Episodes of starvation during the perioperative period only serve to exacerbate the problem. Formal screening for nutrition risk should take place before any major surgery, and malnourished patients should receive 7–10 days of ideally enteral nutritional support preoperatively.¹⁰

The patients most likely to benefit from preoperative nutrition therapy are the malnourished, irrespective of the grade of surgery, and the well-nourished undergoing high-risk major surgery. Interventions include preoperative carbohydrate loading, which reduces insulin resistance and promotes an anabolic state, minimizing loss of protein, lean body mass, and muscle function. Taken a few hours before exercise, carbohydrates increase liver and muscle glycogen and facilitate completion of the exercise session.⁴ The European Society for Clinical Nutrition and Metabolism recommends a daily protein intake of 1.5 g kg⁻¹ ideal body weight in surgical patients to limit nitrogen losses—double the normal daily requirement.¹⁰ Whey protein is under consideration as a high-quality, highly bioavailable source of essential amino acids.

There is some evidence that immunonutrition, the ingestion of amino acids (e.g. glutamine and arginine), omega-3 fatty acids, and nucleotides counteracts the hyperinflammation and immune impairment caused by the surgical stress response, promoting wound healing, reducing infection rates, and shortening length of stay.¹⁰ Such a regime is optimally commenced 5–7 days before operation and should be continued for a similar period after operation in the malnourished.

Psychological support

The aetiology of fear in the patient awaiting surgery is manifold. The underlying diagnosis, surgery, anaesthesia, pain, survival, and recovery are all causes for concern. These psychosocial stressors produce immunological dysregulation through the immune–brain loop, acting via the same pathways that produce the surgical stress response.¹¹ The aim of psychological support is two-fold. Firstly, to reduce psychological distress and anxiety associated with diagnosis and surgery, both of which contribute to greater postoperative pain, delayed recovery, postoperative complications, and impaired wound healing. Secondly, to maximize patients’ motivation and empower them to comply with the exercise and nutritional aspects of the programme.

Psychological interventions proved to be effective include providing sensory information (i.e. what the perioperative experience will feel like), cognitive interventions, e.g. development of positive attitudes, behavioural instruction on what can be done to improve outcome, and relaxation techniques such as hypnosis and progressive muscle relaxation (sequential tensing and relaxing of each muscle group). Other interventions of benefit include providing procedural information (i.e. details regarding all aspects of the patient journey) and emotion-focused interventions involving the discussion of emotions.¹² The latter may be facilitated through the support and camaraderie experienced by meeting other participants of the prehabilitation programme.

Physiological basis of prehabilitation

Studies have shown cardiorespiratory fitness to be a strong and independent predictor of all-cause mortality, possibly a more powerful predictor than traditional risk factors such as hypertension, diabetes, smoking, and obesity. The response to training is an increase in cardiac output, arteriovenous oxygen difference, and thus VO2max. Skeletal muscle adaptations include increased mitochondrial content and oxygen uptake capacity. Overall, functional reserve increases, permitting the patient to meet the increased metabolic demands of surgery and the postoperative period.

The response to surgical stress is an amplification of the ‘fight-or-flight’ reaction. Neuroendocrine, metabolic, and immunological changes produce an increase in oxygen consumption, metabolic rate, protein catabolism, and negative nitrogen balance. The severity of this catabolic response depends on both the degree of injury and the patient’s response to injury and influences the duration of recovery. Prolonged bed rest and relative inactivity during the recovery period produce a deconditioned state with muscle atrophy, loss of contractility, and strength. Cardiac deconditioning produces a reduction in VO2max, stroke volume, and cardiac output. Combined, the patient experiences a decline in functional capacity.

Theoretically, by increasing the functional capacity before operation, the prehabilitated patient retains a higher level of functional ability perioperatively when compared with the non-prehabilitated patient and more rapidly recovers to a minimal level of functional independence after operation (see Fig. 2). The difference in functional ability is a function of the intensity, frequency, and duration of prehabiliatation.

Prehabilitation in the literature

The first published article on prehabilitation dates back to 1946.¹³ ‘Prehabilitation, rehabilitation, and “revocation” in the army’ recounts how many of the men presenting for enlistment during the Second World War were rejected on account of their poor physical and mental conditioning—a by-product of poverty, malnutrition, and poor education—and how over a period of 2 months, these substandard recruits were transformed by a programme of educational, physical, and nutritional interventions into standard recruits. Of the 12 000 men who passed through prehabilitation centres, more than 85% improved both physically and mentally.

Not until the 1980s did we again see articles on prehabilitation. These, however, originated mainly from the sports medicine community and focused on prehabilitation as a means of injury prevention in athletes. The turn of the century saw growth in interest in prehabilitation as a means of improving surgical outcomes, with a growing number of small, promising, but in a number of cases inconclusive, studies being published. In recent years, systematic reviews have emerged as investigators seek to make sense of the available data and draw robust conclusions from them.

One of the earliest systematic reviews was published in 2011.¹⁴ The review of 1245 patients recruited to 12 randomized controlled trials found that patients undergoing cardiac and abdominal surgery experienced shorter hospital stays and reduced postoperative pulmonary complication rates if they had received preoperative exercise therapy. Outcomes in prehabilitated joint arthroplasty patients showed no such improvement. It was impossible, however, to identify whether training intensity in this subgroup was sufficient because of lack of supplied data. The authors concluded that preoperative exercise therapy should be considered as standard preoperative care in patients undergoing cardiac or abdominal surgery.

In contrast, Lemanu et al.¹⁵ found prehabilitation to confer only limited benefit, with only one of the eight studies reviewed showing an improvement in physiological function and clinical outcome with preoperative exercise. The authors conceded that the lack of positive findings may have been influenced by a lack of appropriate physiological measures of training effect and poor compliance with the exercise regimens. A more recent review by Santa Mina et al.³ looked at 21 trials involving 1371 patients who had undergone either orthopaedic, abdominal, cardiac, or thoracic surgery. In the majority of the trials, preoperative exercise improved physical function and reduced postoperative complications, postoperative pain, and length of hospital and intensive care stay. Reduction in length of stay was found to be statistically significant on meta-analysis. The authors also reported an overall adverse event rate of just 0.5%, demonstrating that preoperative exercise is safe. This was attributable to two patients in one of the studies experiencing a fall in systolic blood pressure in excess of 20 mm Hg during exercise.

The earliest comprehensive meta-analyses were published by Wang et al.¹⁶ and Moran et al.¹⁷ who reviewed patients who had undergone joint replacement surgery and intra-abdominal surgery, respectively. Wang et al. found statistically significant improvements in postoperative function and pain in patients who had undergone prehabilitation but felt that the improvements were too small and too short-lived to be clinically important. The main statistically significant findings in the Moran et al. study were improved preoperative fitness and reduced postoperative complications. Neither meta-analysis could demonstrate a significant reduction in length of stay.

Cancer prehabilitation is a developing area in its own right. Patients with cancer face a unique set of circumstances not experienced by other surgical populations. Chemotherapy and chemoradiotherapy are cardiotoxic and may substantially impair cardiorespiratory fitness. In conjunction with the functional decline prefer original text: due to major surgery, this results in a significant ‘dual hit’.¹⁸ With survival adversely affected by delays in cancer treatment, the time-critical nature of the cancer pathway may preclude the institution of an effective prehabilitation programme in a population that could arguably benefit the most.

Loughney et al.¹⁸ conducted the first systematic review of the effects of exercise training on patients scheduled for ‘dual-hit’ cancer treatment (i.e. neoadjuvant chemotherapy or chemoradiotherapy plus cancer surgery). The authors found that exercise training in the neoadjuvant setting was both safe and feasible in patients awaiting breast and rectal cancer surgery, and compliance rates were acceptable. Significant improvements in physical fitness were achieved but the effect on other outcomes, such as health-related quality of life and fatigue, was inconclusive.

Another area into which prehabilitation is being diversified is in the management of frailty syndrome. This is a state of increased vulnerability to stressors, prefer original text: due to the cumulative effect of age, co-morbidity, and reduced physiological reserve and cognition. Gill et al.¹⁹ found that in moderately frail, elderly community-dwelling individuals, who were neither ill, injured, nor awaiting surgery, functional decline could be slowed and possibly prevented by a 6-month programme of home-based exercise therapy.

Despite positive findings, many investigators agree that the existing studies need to be viewed with caution. High-quality data are lacking because of the availability of mainly small, inadequately powered studies, which are frequently of poor or uncertain methodology and have high bias levels. Pooling of data is problematic because of heterogeneity of the study populations, methodologies, interventions, and outcome parameters. Low intervention adherence and reporting bias only compound the problem, making it difficult to generalize findings and combine data for meta-analysis. To firmly move beyond the realm of proof of concept, large-scale, high-quality randomized controlled studies are needed and the focus on multimodal prehabilitation strategies needs to be amplified.

Conclusion

Prehabilitation is a promising paradigm. Conceptually intuitive, and based on sound theoretical principles, the emerging evidence is encouraging. Even so, we are yet to establish how best to utilize this tool, which combination of interventions is the most effective, whether they need to be tailored to the type of surgery to be performed, and whether prehabilitation, on the whole, is cost-effective. In the near future, as interest grows and knowledge accumulates, prehabilitation may play as significant a role in the management of the high-risk surgical patient as rehabilitation and enhanced recovery protocols, bringing benefits to patients and the National Health Service (NHS) through shorter hospital stays, reduced readmission rates, reduced dependence on social care, and swifter functional recovery.

Declaration of interest

None declared.

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References