Clinical trial NCT05315648: Effect of General and Non-general Anesthesia on Perioperative Depression or Anxiety
Official title: The Associations Between Perioperative Depression or Anxiety, Salivary Cortisol and α-amylase, and Administered Anesthesia Type in Knee Arthroscopy With Anterior Cruciate Ligament Reconstruction (ACLR): Prospective, Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Depression, Anxiety
Keywords: perioperative anxiety or depression
general anesthesia
salivary cortisol
salivary α-amylase
Hospital Anxiety and Depression Scale
stress response
non-general anesthesia
Lead sponsor: Second Affiliated Hospital of Wenzhou Medical University
Sponsor class: OTHER
First posted: 2022-04-07
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized in a 1:1 ratio into two groups, group GA and group NGA, using a random number generator. This allocation will be written and stored in an opaque, secure envelope. Patients in group GA will receive general anesthesia followed by femoral nerve block. Patients in group NGA will receive combined spinal-epidural anesthesia followed by femoral nerve block.
Primary purpose: TREATMENT

Brief summary: Perioperative depression and/or anxiety play a critical role in patient presentation, satisfaction and outcomes. The aim of this study is to assess the level of perioperative depression and/or anxiety in patients with arthroscopic knee surgery and to evaluate their relationship with anesthesia approach (general anesthesia or non general anesthesia). The perioperative characteristic of depression or anxiety is assessed by Hospital Anxiety and Depression Scale (HADS) questionnaires and the level of salivary cortisol, salivary α-amylase (sAA) and blood glucose.

Detailed description: The incidence of perioperative anxiety has been reported to range from 11% to 80% among adult patients. Perioperative depression and/or anxiety may increase the risk of poor postoperative outcomes including increased morbidity and mortality , increased health care utilization, increased opioid consumptions and pain scores, and decreased quality of recovery. Previous studies have found that worrying about postoperative pain, unease of separation from family, loss of selfcare and work ability, fear of surgery and even death are common factors leading to perioperative anxiety symptoms.

The investigators found there were not enough studies to gain insights into the public's knowledges, attitudes, and concerns regarding the risks associated with anesthesia. To some, the fear of general anesthesia (GA) remains prevalent, especially with regard to possible brain damage, death, and intraoperative awareness. The others, neuraxial anesthesia was supposed to result in potentially complications, including postdural puncture headache, backache, transient neurological symptoms, epidural hematoma and abscess, meningitis, arachnoiditis, postoperative urinary retention, local anesthetic systemic toxicity.

Such fears can even exceed the anxiety about actual surgery. Actually, anesthesia approach can be selected based on patients and anesthesiologists preference.

The investigators assumed from clinical experiences that effects of different anesthetic approach and anesthetic drugs on stress reaction, perioperative blood glucose, immunity or neuroendocrine during surgical operation were different, which resulted different prognosis of patients.

The perioperative characteristic of depression or anxiety is assessed by Hospital Anxiety and Depression Scale (HADS) questionnaires, salivary cortisol, salivary α-amylase (sAA) and blood glucose.

Salivary cortisol and a-amylase are produced respectively by the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic-adrenomedullary (SAM) system during stress response, still not included in the routine evaluation of perioperative physiological stress response. The application of these tests require additional and definitive validation. In our study, salivary cortisol and a-amylase are measured as stress biomarkers to examine their associations with anesthetic approach.The correlation between salivary cortisol and serum cortisol was excellent in dynamic tests of adrenal function (dexamethasone suppression, adreno-cortico-tropic-hormone stimulation), in healthy subjects and in patients with adrenal insufficiency, in tests of circadian variation and in randomly collected samples. The rate of equilibrium of cortisol between blood and saliva was very fast, being less than 5 minutes. Since only free levels of cortisol are detected in saliva, salivary cortisol is suggested to be a more appropriate measure for the clinical assessment of adrenocortical function than serum cortisol. sAA has been proposed as a sensitive biomarker for stress-related changes in the body that reflect the activity of the sympathetic nervous system, and a growing body of research is accumulating to support the validity and reliability of this parameter. Numerous studies applying stress protocols have demonstrated that salivary a-amylase is highly sensitive to stress-related changes.

The investigators are trying to recruit patients who are scheduled to undergo knee arthroscopy with anterior cruciate ligament reconstruction (ACLR) for the first time. Those patients will be randomly assigned to general anesthesia (GA) group or non-general anesthesia (NGA) group. Patients in GA group will received general anesthesia combined with femoral nerve block (FNB). Patients in NGA group will received neuraxial anesthesia combined with FNB, and without sedation. All patients received routine anesthesia and surgical protocols and will be sent to the postoperative recovery unit (PACU) after surgery. Intraoperative vital signs, analgesic usage, and duration of surgery were recorded.

The primary outcomes are HADS scores , salivary cortisol, sAA, blood glucose，swelling ratings postoperatively, temperature ratings postoperatively and hospital stay. Secondary outcomes are analgesic usage intraoperative and postoperative, anesthesia induction pain score, postoperative pain score, duration of stay in the recovery unit, incidences of complications about relevant anesthesia.

The Patients Hospital Anxiety and Depression Scale (HADS), a 14-item scale (7 items each for anxiety and depression), with each item scored from 0 to 3. Salivary cortisol, sAA and blood glucose levels will be tested in the morning one day before operation (T0), on the day of operation (T1), 2 hours after operation (T2), the first morning after operation (T3), the second morning after operation (T4).

The investigators will conduct subgroup analysis based on the patients' anesthesia wishes (conform to patient's wishes, against patient's wishes, no original opinion) to address the influence of anaesthesia practice and perioperative stress response.

Eligibility criteria: Inclusion Criteria:

* Participants will be scheduled to receive anterior cruciate ligament reconstruction of knee joint for the first time
* American Society of Anesthesiologists (ASA) physical status I or II
* The operation time is less than 2 hours (from the beginning use of the tourniquet to the release)

Exclusion Criteria:

* Clinical diagnosis of anxiety or depression or mania
* Clinical diagnosis of systemic diseases (systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, rheumatoid arthritis, primary aldosteronism, Cushing syndrome)
* Medication history of cortisol or sedative hypnotic drugs
* Tumor patients
* Smoking
* Pregnancy status
* Diabetes
* Drinking coffee or alcohol drinks during perioperative period

Primary outcomes:
measure: The rate of Anxiety symptoms (HADS-A)
timeFrame: one day before surgery, 1day, 3 days after surgery and 5 days after surgery while in hospital
measure: The rate of Depression symptoms (HADS-D)
timeFrame: one day before surgery, 1day, 3 days after surgery and 5 days after surgery while in hospital
measure: The changes of salivary cortisol concentration
timeFrame: on the day of surgery (6 - 8 am), at 2 hours after surgery, the first morning after surgery (6 - 8 am) and the second morning after surgery (6 - 8 am)
measure: The changes of Saliva α- amylase activity
timeFrame: on the day of surgery (6 - 8 am), at 2 hours after surgery, the first morning after surgery (6 - 8 am) and the second morning after surgery (6 - 8 am)
measure: The changes of Blood glucose level
timeFrame: on the day of surgery (6 - 8 am), at 2 hours after surgery, the first morning after surgery (6 - 8 am) and the second morning after surgery (6 - 8 am)
Secondary outcomes:
measure: The changes of swelling rating
timeFrame: at 6, 12, 24, 48, and 72 hours after surgery
measure: Post-operative opioid consumptions
timeFrame: from arrived at PACU to the first 72 post-operative hours
measure: The changes of NRS of postoperative pain
timeFrame: at 2, 6, 12, 24, 48, and 72 hours after surgery
measure: Complications related to general anesthesia
timeFrame: started from the induction of general anesthesia to the first 72 post-operative hours
measure: Complications related to combined spinal-epidural anesthesia
timeFrame: started from the beginning of combined spinal-epidural anesthesia to the first 72 post-operative hours
measure: Complications related to femoral nerve block
timeFrame: started from the puncture of nerve block to the first 72 post-operative hours
measure: Costs of hospitalization
timeFrame: through study completion, an average of 1 week
measure: The changes of skin temperature rating
timeFrame: at 1, 3, and 5 days after surgery
measure: Length of hospital stay
timeFrame: The length of hospital stay was counted in days, about 5 to 7 days usually
Other outcomes:
Locations:
city: Wenzhou
country: China
facility: Second Affiliated Hospital of WenZhou Medical University
state: Zhejiang
Study officials:
affiliation: Second Affiliated Hospital of Wenzhou Medical University
name: CongCong Huang, Master
role: STUDY_DIRECTOR
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