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.

Study Overview

• Status: Completed
• Conditions: Muscle Weakness; Anesthesia, Local; Surgery; Anesthesia
• Intervention / Treatment: Drug: Spinal anesthesia; Drug: General anesthesia; Drug: General anesthesia and epidural analgesia

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Genk, Belgium, 3600
    • Ziekenhuis Oost-Limburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Hip surgery: spinal anesthesia; Patients scheduled to undergo elective total hip arthroplasty will receive spinal anesthesia in combination with monitored anesthesia care (MAC).	Drug: Spinal anesthesia; The level of puncture will be L4 - L5. 10 mg bupivacaine will be injected in the subarachnoid space, after spontaneous surge of cerebrospinal fluid
EXPERIMENTAL: Hip surgery: general anesthesia; Patients scheduled to undergo elective total hip arthroplasty will receive general anesthesia	Drug: General anesthesia; The induction of general anesthesia will be delivered in a standardized manner with the intravenous administration of fentanyl 2µg/kg and propofol
EXPERIMENTAL: Colectomy: general anesthesia and epidural analgesia; Patients scheduled to undergo elective laparoscopic hemicolectomy will receive general anesthesia combined with epidural analgesia (EA).	Drug: General anesthesia and epidural analgesia; 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).
EXPERIMENTAL: Colectomy: general anesthesia; Patients will receive general anesthesia.	Drug: General anesthesia; The induction of general anesthesia will be delivered in a standardized manner with the intravenous administration of fentanyl 2µg/kg and propofol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in post-operative peripheral limb muscle weakness	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	Pre-operative (Day 0) and postoperatively (Day 1, Day 7 and Day 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in general health status	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)	Pre-operative (Day 0) and postoperatively (Day1, Day7 and Day28)
Change in post-operative lung function: vital capacity	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).	Pre-operative (Day 0) and postoperatively (Day 1, Day 7 and Day 28)
Change in post-operative lung function:forced expiratory volume	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).	Pre-operative (Day 0) and postoperatively (Day 1, Day 7 and Day 28)
Change in the neuro-endocrine stress response: Cortisol	Blood samples will be taken at the start, end of surgery and the day after surgery to measure cortisol (nmol/L) in the samples	Pre-operative (Day 0), end of surgery and postoperatively (Day 1)
Change in the neuro-endocrine stress response: ACTH	Blood samples will be taken at the start, end of surgery and the day after surgery to measure ACTH (nmol/L) in the samples	Pre-operative (Day 0), end of surgery and postoperatively (Day 1)
Change in the neuro-endocrine stress response: Noradrenaline	Blood samples will be taken at the start, end of surgery and the day after surgery to measure noradrenaline (nmol/L) in the samples	Pre-operative (Day 0), end of surgery and postoperatively (Day 1)
Change in glycemia levels	Measurement of glycemia in the blood.	Pre-operative (Day 0), end of surgery and postoperatively (Day 1)

Collaborators and Investigators

• Sponsor: Ziekenhuis Oost-Limburg
• Investigators: Principal Investigator: Dimitri Dylst, MD, Ziekenhuis Oost-Limburg

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2018
• Primary Completion (ACTUAL): December 18, 2019
• Study Completion (ACTUAL): December 30, 2019

Study Registration Dates

• First Submitted: June 14, 2018
• First Submitted That Met QC Criteria: July 24, 2018
• First Posted (ACTUAL): July 26, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 7, 2020
• Last Update Submitted That Met QC Criteria: January 6, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Weakness; Paresis; Asthenia; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: 18/0010U

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No