CORTERAS STUDY: The Effect of Corticosteroids on Early Recovery After Major Surgery in Elderly Patients

Study Overview
=================
Brief Summary
-----------------
Major surgery induces a systemic inflammatory response, which can influence the post-operative morbidity, such as coagulation disorders and post-operative muscle weakness, hampering early recovery after surgery. Single administration of high dose corticosteroids is known to reduce this inflammatory response and could possibly improve the post-operative outcome. The CORTERAS study will evaluate the effect of administration of corticosteroids, as compared to no corticosteroids, on postoperative muscle weakness and quality of recovery after surgery in elderly patients.

Detailed Description
-----------------
The number of elderly patients undergoing surgery is expected to increase in the coming years, due to the increase in life expectancy in the developing world. Compared to younger surgical patients, the older patients are at greater risk of mortality and morbidity after surgery. Post-operative fatigue is an important complication after surgery. Not only is it reported by patients as one of the most distressing symptoms, it is also thought to be a significant contributor to delayed recovery after surgery. From a pathophysiological point of view, muscle weakness could be a major contributor to this post-operative fatigue. Recent studies showed a profound reduction in muscle strength after surgery in elderly patients, which lasted for more than 3 months after surgery. This decrease in muscle strength might be induced by an excessive inflammatory response to surgery. Glucocorticosteroids are capable of tampering an excessive inflammatory response to surgery and could improve the quality of recovery after surgery. However, a possible effect on post-operative muscle weakness hasn't been specifically investigated. Therefore, the main objective of this prospective clinical trial is to evaluate the effect of corticosteroids on early post-operative outcome, focusing on muscle weakness, in elderly patients (≥60 years) undergoing surgery.

Official Title
-----------------
CORTERAS STUDY: The Effect of Corticosteroids on Early Recovery After Major Surgery in Elderly Patients

Conditions
-----------------
Inflammatory Response, Weakness, Muscle

Intervention / Treatment
-----------------
* Drug: Methylprednisolone
* Drug: NaCl 0.9%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 60 years or older. Scheduled for one of the predefined surgical procedures: off-pump coronary bypass surgery on-pump coronary bypass surgery aortic and mitral valve replacement laparoscopic hemicolectomies thoracoscopic lung resections femoral popliteal and tibial bypass surgery and femoral profundoplasty laparoscopic radical prostatectomies Exclusion Criteria: Lack of informed consent or inability to give informed consent. Severe postoperative nausea & vomiting (PONV), needing corticosteroids as PONV prophylaxis. Urgent, not elective surgery Hypersensitivity or known allergic reactions to methylprednisolone Preoperative systemic use of steroids: Including, but not limited to, the use of corticosteroids > 4 weeks before surgery of at least 4 mg methylprednisolone equivalents. Excluding inhalational and topical steroids Preexisting muscle disease o Including, but not limited to: Steinert's disease, amyotrophic lateral sclerosis (ALS), Duchenne dystrophy, amputation of dominant arm or hand.

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>100 ml of NaCl 0,9%, not containing corticosteroids, given at induction of anaesthesia, before surgery. If a patient will receive cardiopulmonary bypass (CPB) during his operation, a repeat dose of 100 ml of NaCl 0,9% will be administered at the beginning of CPB. | Drug: NaCl 0.9%<br>* 100 ml NaCl0,9% as an IV injection at the induction of anaesthesia but before surgery. If CPB is required an additional 100ml will be given.<br>|
| Active Comparator: Methylprednisolone<br>250 mg of methylprednisolone made up with 100 ml NaCl 0,9%, given at the induction of anaesthesia, before surgery. If a patient will receive cardiopulmonary bypass (CPB) during his operation, a repeat dose of 250 mg methylprednisolone will be administered at the beginning of CPB. | Drug: Methylprednisolone<br>* 250 mg Methylprednisolone made up with 100 ml NaCl0,9% as an IV injection at the induction of anaesthesia but before surgery. If CPB is required an additional dose in 100 ml will be given.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post operative muscle weakness | decrease in muscle strength post-operatively, assessed by comparing the handgrip strength of the dominant hand, measured by the JAMAR dynamometer, on day 1 following surgery as compared to the preoperative value | Pre-operative and Post operative day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post operative muscle weakness | Decrease in muscle strength post-operatively, assessed by comparing the handgrip strength of the dominant hand, measured by the JAMAR dynamometer, on day 3 and 5 following surgery as compared to the preoperative value, if still in the hospital. | Pre-operative and Post operative day 1, 3 and 5 | 
| Maximum inspiratory pressure as measure of respiratory muscle function | Maximum inspiratory pressure on day 1, 3 and 5, as compared to pre-operative value, if still in the hospital. | Pre-operative and Post operative day 1, 3 and 5 | 
| Post operative fatigue | Assessed by the Chalder fatigue Questionnaire - 11 items, scores min 0 - max 33, higher score means worse outcome: post-operative day 1, 3, 5 and 28, as compared to preoperatively | Pre-operative and Post operative day 1, 3, 5 and 28 | 
| Quality of recovery (QOR) | Assessed by the QOR-15 scale, scores min 0 - max 150, higher score means worse outcome, assessed on day 1, 3 and 5 as compared to preoperatively | Post operative day 1, 3 and 5 | 
| Functioning at day 28 | EuroQol five dimensions of health (EQ5D), score of 1-5 on each health dimension, higher score means worse outcome + visual analogue scale from 0-100 questionning todays health, lower score means worse outcome. EQ5D is assessed on day 28, as compared to pre-operatively values | Pre-operative and Post operative day 28 | 
| Coagulation disorder | biochemical markers of coagulation postoperatively as compared to preoperatively | postoperatively first 24 hours | 
| Sleeping pattern | Assessed by the Consensus Sleep Diary (CSD) in a subset of study population | 10 consecutive nights, starting 3 days before surgery | 
| Sleep quality | Assessed by the Pittsburgh Sleep Quality Index (PSQI) in a subet of study population, score range between 0 and 21, higher scores indicate worse sleep quality | 3 days before and 10 days after surgery | 
| Sleep chronotype | Assessed by the Munich Chronotype Questionnaire (MCTQ) is a subset of study population | 3 days before surgery | 
| Sleeping EEG pattern | Assessed by EEG recording in a subset of study population | first postoperative night |