Personalised Prehabilitation in High-risk Patients Undergoing Elective Major Abdominal Surgery. A Randomised Blinded Controlled Trial.

 Annals of Surgery 2018;267(1):50-56 doi:10.1097/SLA.0000000000002293

Presented by: Rebeca Harris ST4

Background

  • Major abdominal surgery is associated with a high rate of postoperative complications, particularly in elderly patients with multiple comorbidities.
  • Aerobic capacity determines postoperative functional reserve, which is negatively associated with postoperative morbidity and mortality.
  • Prehabilitation exercise programmes are postulated to improve aerobic capacity, and thereby reduce postoperative complications.
  • Previous studies have shown a bias towards low-risk patients, and lack of evidence on postoperative clinical outcomes.
  • Prehabilitation is defined as a preparatory intervention aiming to increase aerobic capacity. Methods include supervised endurance exercise training and the promotion of physical activity.

Design & Setting

  • Single centre: Hospital Clinic de Barcelona
  • Patients were blindly randomized
  • Collaborating anaesthetists and surgeons were blinded to patient’s allocation
  • Ethics approved
  • Sample size prospectively powered (as standard, accepting risks of: α 0.05 and β 0.2), based on:
    • the reduction rate of patients with postoperative complications as the main outcome
    • considering the local colorectal complication rate (30%), and
    • anticipating up to 20% drop out
    • Intention-to-treat analysis

Subjects

High risk patients for elective major abdominal surgery

Inclusion criteria:

  • Elective major abdominal surgery
  • High risk defined by all of the following:
    • Age > 70 and/or ASA III/IV
    • Duke Activity Status Index Score < 46
    • Preop schedule allowed at least 4 weeks for the prehabilitation intervention

Exclusion criteria:

  • Non-elective surgery
  • Unstable cardiorespiratory disease
  • Locomotor limitations precluding exercise training
  • Cognitive deterioration impeding adherence to the programme

Intervention

  • Baseline assessment within 1 week of preoperative assessment
  • Reassessment 1 week before surgery

Standard care:

  • Physical activity, nutritional and smoking cessation advice
  • IV iron if indicated for anaemia
  • Nutritional intervention if high-risk for malnutrition

Intervention:

  • Personalised prehabilitation programme based on health and social circumstances
  • Mostly community based
  • 3 major aspects
    • Motivational interview to assess adherence profile. Tailored physical activity programme then co-designed with the patient
    • Personalised daily physical activity programme
      • Pedometer to measure steps, then feedback and optimization
    • Supervised high intensity endurance exercise programme
      • 1-3 per week
      • Exercise bike interval training, tailored to increase intensity over time, based on work rate
      • Pulse oximetry and self-perceived exertion measured

Outcomes

Primary

  • Number of patients with a complication

Secondary

  • Number and severity of postoperative complications
  • Hospital and ICU length of stay

Other

  • Endurance time
  • Distance covered in 6 minute walking test
  • Physical activity (by validated patient survey)
  • Self perceived health status (by validated patient survey)
  • Psychological status (by HADS patient survey)
  • Pulmonary function tests
  • Cardiorespiratory exercise tests

 Results

Baseline characteristics

  • 209 assessed over 3 years – 144 eligible and randomised (> 70 per group, as per power analysis minimum)
  • Comparable patient characteristics between groups
  • 19 did not receive operation, so excluded mid-trial
  • Control: 1 unable to perform exercise testing, 6 abandoned
  • Intervention: 4 unable to perform exercise testing, 4 abandoned
  • 56 (Control) and 54 (Intervention) completed trial (< 70 per group, and > 20% dropout rate, thus underpowered)

 Control

  • No change in baseline characteristics at start vs 1 week pre-surgery

 Prehabilitation intervention

  • Mean duration 6 weeks + 12 supervised exercise session
  • PRMIARY OUTCOME
    • 50% reduction in number of patients with complications: 31% vs 62%, RR 0.5 (95% CI 0.3-0.8), p = 0.001
  • SECONDARY OUTCOMES:
    • Increasein Endurance Time (135%, p < 0.001)
    • Increasein Physical Activity Index (37 points, p< 0.001)
    • No significant difference in intraoperative parameters, but trend towards lower requirement of vasoactive drugs (p=0.053)
    • Lower mean number of complications per patient : Cardiovascular(p = 0.03, RR 0.1, 95% CI 0.1-1.0), Infection of uncertain source (p = 0.013, RR not possible), Paralytic ileus (p = 0.001, RR not possible)
    • In patients with complications, intervention reducedrisk of having more than one complication (RR 0.6, but 95% CI 0.3-1.1), but no effect on severity of complications.
    • Reduced length of ICU stay (3 vs 12 days, p = 0.046)

 Conclusions

  • High intensity endurance exercise training is feasible and safe in elderly and/or multimorbid candidates for major abdominal surgery
  • Prehabilitation enhanced clinical outcomes in high-risk candidates for elective major abdominal surgery, which can be explained by the increase in aerobic capacity
  1. Reduced complication rate
  2. Prevents > 1 complication
  3. Reduced ICU length of stay

Strengths

  • Randomised blinded controlled trial
  • High risk patient group selected, reflecting patient population
  • Initially adequately powered
  • Performed within realistic preoperative timeframe for urgent surgery
  • Highly personalised, patient-centred prehabilitation programme. Well detailed for reproducibility
  • Interesting secondary outcomes, validated tools used
  • Appropriate statistical analysis employed
  • Number of patients abandoning intervention arm < control, thus patient engagement good

Weaknesses

  • Single centre
  • Blinding of clinicians following interaction with patients may have been difficult
  • Underpowered following dropouts – still able to demonstrate statistically significant difference in primary outcome, however may have ‘missed’ other significant differences in secondary outcomes
  • ? Blinding of exercise tester
  • Primary outcome extremely broad – ‘any complications’ postoperatively. Not specific, and therefore clinical significance and importance of question reduced.
  • Survival and functional recovery not assessed
  • Underpowered to assess effect on specific and important post operative complications
  • Did not demonstrate a difference in the severity of postoperative complications
  • Claims significant reduction in CV complications and the number of patients having > 1 complication, but:
    • Reduction in CV complications 95% CI 0.1-1, wide and includes ‘no effect’
    • Reduction in number of patients having more than 1 complication 95% CI 0.3-1.1, wide and includes ‘no effect’
  • Endurance time rather than familiar, objective CPEX data e.g. Anabolic threshold, formed basis of measure of aerobic capacity
  • Intensive, highly tailored programme
    • ? Sustainability on larger scale
    • No cost analysis

Implications

  • Prehabilitation in elderly, multimorbid patients appears to be feasible, safe and ‘acceptable’ to patients
  • Prehabilitation can increase preoperative exercise endurance in high risk patients
  • Postoperative complication rates can be reduced by this strategy
  • However, larger trials are required to further characterise and assess the clinical significance of postoperative complication benefits, and to determine the effect on functional recovery and survival

Potential for impact

  • Important step towards assessing the potential benefits and characterising the design of prehabilitation exercise programmes in high risk patients undergoing high risk elective surgery
  • Important and exciting emerging field of research with potential for significantly improving patient outcomes