Perioperative Multimodal Care for Cystectomy Frail Patient
Perioperative Multimodal Care for Cystectomy Frail Patient
Major surgery in the elderly and frail patient is a challenge. Optimal perioperative
 management is essential for outcome and survival. There is a need for improved
 multidisciplinary approach to improve postoperative outcome in this patient population at
 high risk for postoperative morbidity and mortality. Here the investigators will evaluate the
 implementation of a multimodal prehabilitation program including optimization of nutrition
 (protein and carbohydrate loading), optimization of preoperative hydration and the use of
 regional anesthesia during cystectomy and urinary diversion in a series old frail patients
 and compared/matched them to a historical series of similar patients in terms of early return
 of quality of life using the Convalescence and Recovery Evaluation (CARE) instrument,
 cognition, and postoperative morbidity.

 The importance of patient-reported health status is well recognized and is a facet of
 healthcare quality. In addition it is a valuable means for quantitatively measuring the
 implication of technology adoption for the patient, who typically judges the efficacy of a
 surgical procedure by whether it improves quality of life.

 The objective of this study is to evaluate the implementation of a multimodal prehabilitation
 program in a series old frail patients and compared them to a historical series of similar
 frail patients in terms of early return of quality of life, cognition, and postoperative
 morbidity. The importance of patient-reported health status is well recognized and is a facet
 of healthcare quality. In addition it is a valuable means for quantitatively measuring the
 implication of technology adoption for the patient, who typically judges the efficacy of a
 surgical procedure by whether it improves quality of life.
In industrialized countries the average life expectancy has continuously increased during the
 last decades and this trend is expected to continue. In Switzerland, a sexagenarian now has a
 50% chance, if male, and 70% if female of reaching the age of 80. By 2050, the population of
 over 80 year-olds will have multiplied 2.7 times in Switzerland. Age is considered the
 greatest single risk factor for developing cancer, bladder cancer is no exception and
 typically affects old patients with a median age at the time of diagnosis of around 70. In
 the US 32% of patients diagnosed with bladder cancer are between 75 and 84. In addition, the
 prevalence of comorbidities in this old population is very high as hypertension is present in
 50-60%, coronary artery disease in 15%, cardiac failure in 15%, dementia in 30%, diabetes in
 10-20%, hearing and vision loss in 20-30%. The presence of advanced age, several
 comorbidities, new acute medical condition (i.e. fracture or newly diagnosed cancer) define
 the clinical condition of frailty. This medical condition is a consequence of age-related
 decline in many physiological systems, with defects accumulating with the passage of time
 (age) resulting in an increased risk of death (ageing).

 So surgery and the perioperative period can be exceptionally challenging in old and frail
 patients due to the presence of comorbidities and age-related physiological changes. In these
 patients treatment goals should focus on maintaining a good quality of life for the remaining
 time span by aiming for excellent functional results and if possible long term remission. The
 gold standard of care today for muscle invasive bladder cancer is pelvic lymph node
 dissection, cystectomy and urinary diversion which is associated with a high postoperative
 complication rate (50%). This is probably why today younger age, high stage or grade disease
 and lower comorbidity are associated with higher odds of receiving radical cystectomy.
 However, elderly alone should not preclude the indication for radical cystectomy and urinary
 diversion. In addition there is evidence that the type of anesthesia may impact cognition in
 old patients. Major cardiac and non-cardiac surgical procedures are known to affect cognitive
 function. The incidence of postoperative cognitive dysfunction (POCD) varies greatly (4% to
 41% after major surgery). POCD may persist being a risk factor for long-term cognitive
 deterioration.

 There is evidence that a multimodal prehabilitation program including optimization of
 nutrition and mobilisation can improve functional recovery after surgery, resulting in less
 complications and short length of stay. Optimizing the nutritional status of the frail
 patients before cystectomy and avoiding general anesthesia could be an alternative to
 conventional pre- and intraoperative approaches to improve outcome and quality of life,
 including pain early return of gastrointestinal function cognition and functional activities.

 The objective of this study is to evaluate the implementation of a multimodal prehabilitation
 program including optimization of nutrition (protein and carbohydrate) and hydration combined
 with the use of regional anesthesia (spinal-epidural anesthesia) during cystectomy in a
 series old frail patients and compared/matched them to a historical series of similar frail
 patients in terms of early return of quality of life using the Convalescence and Recovery
 Evaluation (CARE) instrument, cognition (CERAD test), and postoperative morbidity. As there
 is a need for a shift in the emphasis towards more patient and recovery-centric measures such
 as quality of life, the investigators decide to assess the early return of quality of life
 using the CARE instrument as the primary endpoint. The CARE instrument is a robust
 multi-dimensional measure of convalescence after major abdominal and pelvic surgery. It has
 been specifically designed and validated for patients undergoing abdominal and pelvic surgery
 (like cystectomy) with a high test retest reliability. The CARE instrument covers 4 domains
 (pain, gastrointestinal, cognition and activity). The importance of patient-reported health
 status is well recognized and is a facet of healthcare quality. In addition it is a valuable
 means for quantitatively measuring the implication of technology adoption for the patient,
 who typically judges the efficacy of a surgical procedure by whether it improves quality of
 life. The Consortium of Establish a Registry for Alzheimer's Disease (CERAD) test is a widely
 validated test packet for evaluation of old patients with dementia. However this CERAD test
 has also been validated in the perioperative setting. It consists of a test battery,
 including verbal fluency, Boston naming test, word list learning, constructional praxis, word
 list recall, word list recognition, and mini mental state examination, which can detect
 subtle changes in cognition. It is easy applicable and the investigators have expertise using
 this test in a similar cystectomy population.

 The investigators will, in a first step, start with a pilot study including 20 patients in
 order to assess the feasibility of the multimodal approach in the urologic clinic and this
 population. The sample size for the feasibility endpoint is based on convenience and no a
 priori calculation was conducted. This number of patients is comparable to published case
 series illustrating the feasibility of this anesthetic technique for cystectomy patients.

 Secondly, the investigators will add 11 patients in the intervention group and then compare
 this series with a historical series of 31 similar frail and old cystectomy patients. This is
 based on the CARE results of the historical series (mean CARE score on POD 7 of 50.68 with a
 SD ± 6.43 and considering a difference of 7 points as clinically relevant with an effect size
 of 0.7).
Inclusion Criteria:

 -  Informed Consent as documented by signature (Appendix Informed Consent Form)

 -  ≥ 75 years old

 -  Fried frailty score ≥2

 -  Cystectomy with urinary diversion

 -  No contra-indication for spinal or epidural anesthesia

 Exclusion Criteria:

 -  Contraindications to the class of drugs under study, e.g. known hypersensitivity or
 allergy to class of drugs or the investigational product,

 -  Women who are pregnant or breast feeding (not applicable as recruitment concerns
 patients with ≥75 yrs of age)

 -  Known or suspected non-compliance, drug or alcohol abuse,

 -  Inability to follow the procedures of the study, e.g. due to language problems,
 psychological disorders, dementia, etc. of the participant,

 -  Enrolment of the investigator, his/her family members, employees and other dependent
 persons,

 -  Specific exclusions for the disease under study,

 -  Specific concomitant therapy washout requirements prior to and/or during study
 participation,

 -  Dietary restrictions: milk allergy

 -  Refusal to regional anesthesia

 -  Risk of aspiration

 -  Oral fluid restriction due to any reasons (severe renal insufficiency i.e. GFR <
 20ml/min)