The Effect of Anesthesia on Perioperative Muscle Weakness and Neuro-endocrine Stress Response (MUSCLE)

The effect of surgery, in contrary to critical illness, on muscle weakness hasn't been thoroughly investigated. Recent data suggest that elective surgery may also induce muscle weakness. The neuro-endocrine stress response could be involved in the pathophysiology. Whether the mode of anesthesia/analgesia can influence muscle weakness, by influencing the neuro-endocrine stress response is unknown. Gaining insight in this matter could affect quality of care and benefit patient recovery and satisfaction.

In this study, the investigators want to demonstrate whether the application of neuraxial anesthesia for elective surgery diminishes perioperative muscle weakness. Since spinal and epidural anesthesia/analgesia have been shown to influence the neuro-endocrine stress response, the possible underlying mediator of perioperative muscle weakness, the investigators will perform two different, but complementary, studies. In one study, patients scheduled for elective total hip arthroplasty will receive spinal anesthesia, without losing consciousness and maintaining a free airway, as compared to receiving general anesthesia. In another study, patients scheduled for a laparoscopic hemicolectomy will receive epidural anesthesia/analgesia during and after the surgery as compared to receiving no epidural anesthesia/analgesia. These studies allow the investigators to identify whether the application of neuraxial anesthesia/analgesia could diminish perioperative weakness and allow us to identify other possible mediators of perioperative muscle weakness, such as losing consciousness or receiving neuromuscular blockade. This study has the potential to help to identify a new side-effect of elective surgery, namely perioperative muscle weakness, and to identify a possible treatment for this possible new complication, namely neuraxial anesthesia and analgesia, which might benefit many patients in the future. Furthermore, investigating the possible mediating role of the neuro-endocrine stress response might identify new therapeutic targets, such as glucagon modulation.

Two independent, but complimentary, studies will be performed to evaluate the primary objective and the secondary objectives in this prospective trail. Group 1: The effect of spinal anesthesia as compared to general anesthesia for total hip arthroplasty Group 2: The effect of epidural analgesia compared to general anesthesia alone for major abdominal surgery

Patients will be randomized using a computer-generated permuted block randomization sequence (variable block-size, 1:1 allocation). The randomization will be determined on the preoperative anesthesia assessment. After the randomisation, the investigator will inform the patient which anesthesia he/she will get during the operation

Patients scheduled to undergo elective total hip arthroplasty will receive spinal anesthesia in combination with monitored anesthesia care (MAC).

Patients scheduled to undergo elective laparoscopic hemicolectomy will receive general anesthesia combined with epidural analgesia (EA).

The induction of general anesthesia will be delivered in a standardized manner with the intravenous administration of fentanyl 2µg/kg and propofol

The level of puncture will be L4 - L5. 10 mg bupivacaine will be injected in the subarachnoid space, after spontaneous surge of cerebrospinal fluid

The induction of general anesthesia will be delivered in a standardized manner with the intravenous administration of fentanyl 2 µg/kg and propofol. A thoracic epidural catheter will be placed with 3 ml of xylocaine 2% (with epinephrine 1/200.000).

The strength will be measured in the dominant hand using a Camry handgrip Dynamometer. The measurement will take place on the first day postoperatively, at day 7 and day 28 and will be compared to the preoperative measurement during the preoperative assessment

Measuring generic health status by the EQ-5D questionnaire preoperatively and at day 1, 7 and 28 after surgery. The general health status is scored by severity ranging from 0 (no problems) to 5 (severe problems)

Post-operative lung function at day 1, 7 and 28. The investigators will measure vital capacity (VC). These measurements will take place preoperatively and day 1, 7 and 28 after surgery, using a portable pulmonary function testing machine (PPFTM).

Post-operative lung function at day 1, 7 and 28. The investigators will measure forced expiratory volume in 1 second (FEV1). These measurements will take place preoperatively and day 1, 7 and 28 after surgery, using a portable pulmonary function testing machine (PPFTM).

Blood samples will be taken at the start, end of surgery and the day after surgery to measure cortisol (nmol/L) in the samples

Blood samples will be taken at the start, end of surgery and the day after surgery to measure ACTH (nmol/L) in the samples

Blood samples will be taken at the start, end of surgery and the day after surgery to measure noradrenaline (nmol/L) in the samples

Inclusion Criteria: Aged 18 years or older. Scheduled for elective total hip arthroplasty or hemicolectomy. Exclusion Criteria: Lack of informed consent or inability to give informed consent. Urgent surgery, such as hip fracture. Contra-indications for spinal or epidural analgesia, including but not limited to: Infection at the site of puncture. Coagulopathy. Severe hypovolemia. Severe aortic valve stenosis (cross sectional area < 1,3 cm2). Severe mitralis valve stenosis (cross sectional area < 1,0 cm2). Increased intracranial pressure. Pre-existing neurological condition. Severe spine deformity. Sepsis. Body mass index (BMI) > 35 kg/m2 Hypersensitivity or known allergic reactions to any products used for anesthesia. History of chronic opioid analgesics use. Preoperative use of steroids: Including, but not limited to: injection of hydrocortisone < 3 months before surgery. Preexisting muscle disease Including, but not limited to: Steinert's disease, amyotrophic lateral sclerosis (ALS), Duchenne dystrophy, amputation of dominant arm or hand.