Effect of General and Non-general Anesthesia on Perioperative Depression or Anxiety

Depression, Anxiety Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05315648
• Other study ID #: SAHoWMU-CR2021-03-109
• Status: Completed
• Phase: N/A
• Start date: October 20, 2021
• Est. completion date: January 30, 2024

Study information

• Verified date: June 2024
• Source: Second Affiliated Hospital of Wenzhou Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 162
• Est. completion date: January 30, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Anxiety Disorders
• Depression
• Depression, Anxiety
• Depressive Disorder

Intervention

Procedure:
• anesthesia approach (general anesthesia or non-general anesthesia)
patients in group GA received general anesthesia followed with FNB. patients in group NGA received CSEA followed with FNB

Locations

Country	Name	City	State
China	Second Affiliated Hospital of WenZhou Medical University	Wenzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital of Wenzhou Medical University

Country where clinical trial is conducted

China, 

References & Publications (31)

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* Note: There are 31 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The rate of Anxiety symptoms (HADS-A)	The HADS scale includes two dimensions of anxiety and depression, with a total of 14 items, 7 items for anxiety and 7 items for depression.; The score for each individual item could vary from 0 to 3, so that the total score for each scale about anxiety (HADS-A) ranges from 0 to 21. If the score was 0-7, indicating that there was no anxiety; the score was 8-10, suspected anxiety; 11-14, moderate anxiety; the score was 15-21, severe anxiety. If the score is = 8, it will be rated as positive, otherwise it will be rated as negative.	one day before surgery, 1day, 3 days after surgery and 5 days after surgery while in hospital
Primary	The rate of Depression symptoms (HADS-D)	The HADS scale includes two dimensions of anxiety and depression, with a total of 14 items, 7 items for anxiety and 7 items for depression.; The score for each individual item could vary from 0 to 3, so that the total score for each scale about depression (HADS-D) ranges from 0 to 21. If the score was 0-7, indicating that there was no depression; the score was 8-10, suspected depression; 11-14, moderate depression; the score was 15-21, severe depression. If the score is = 8, it will be rated as positive, otherwise it will be rated as negative.	one day before surgery, 1day, 3 days after surgery and 5 days after surgery while in hospital
Primary	The changes of salivary cortisol concentration	Enzyme immunoassay for the quantitative determination of free Cortisol in human saliva.The patient should not eat, drink, chew gums or brush teeth for 30 min before sampling.Otherwise rinse mouth thoroughly with cold water 5 min prior to sample collection.A minimum of 0.5 mL liquid should be collected. Saliva flow can be stimulated by chewing on a piece of Parafilm.	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)
Primary	The changes of Saliva a- amylase activity	Enzymatic assay for the determination of alpha amylase activity in human saliva.The patient should not eat, drink, chew gums or brush teeth for 30 min before sampling.Otherwise rinse mouth thoroughly with cold water 5 min prior to sample collection.A minimum of 0.5 mL liquid should be collected. Saliva flow can be stimulated by chewing on a piece of Parafilm.	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)
Primary	The changes of Blood glucose level	Using a glucose meter to check and monitor blood sugar via finger stick	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	The changes of swelling rating	The postoperative knee swelling rating on the surgical side is defined as the knee circumference on the surgical side minus the knee circumference on the non-suigical side, both measured in centimeters (cm) at 5.08 cm above the superior border of the patella, 6 h, 12 h, 24 h, 48 h, and 72 h postoperatively. The larger value means more severe swelling after surgery.	at 6, 12, 24, 48, and 72 hours after surgery
Secondary	Post-operative opioid consumptions	postoperative opioid consumption including sufentanil consumptions in PACU and the rescue analgesics (morphine 0.05 mg/kg) when NRS > 3. (sufentanil will be converted into morphine equivalents)	from arrived at PACU to the first 72 post-operative hours
Secondary	The changes of NRS of postoperative pain	Patients evaluate the pain at rest and on knee flexion after surgery. NRS will be used to assess the intensity of pain, ranged from 0-10, 0 means no pain and 10 means severe pain.	at 2, 6, 12, 24, 48, and 72 hours after surgery
Secondary	Complications related to general anesthesia	Number of Participants with the complications relaterd to general anesthesia such as intraoperative hypoxemia, postoperative nausea and vomiting , postoperative deliriums, postoperative cognitive dysfunction in each group	started from the induction of general anesthesia to the first 72 post-operative hours
Secondary	Complications related to combined spinal-epidural anesthesia	Number of Participants with the complications relaterd to combined spinal-epidural anesthesia such as postdural puncture headache, backache, transient neurological symptoms, epidural hematoma and abscess, meningitis, arachnoiditis, postoperative urinary retention, local anesthetic systemic toxicity and infection in each group	started from the beginning of combined spinal-epidural anesthesia to the first 72 post-operative hours
Secondary	Complications related to femoral nerve block	Number of Participants with the complications relaterd to femoral nerve block such as nerve injury, hematoma, local anesthetic systemic toxicity and infection in each group	started from the puncture of nerve block to the first 72 post-operative hours
Secondary	Costs of hospitalization	Costs will be calculated about total standardized costs before healthcare coverage,such as social medical reimbursement or health insurance.Costs will be evaluated in 2022 renminbi (RMB) yuans.	through study completion, an average of 1 week
Secondary	The changes of skin temperature rating	Skin temperature of the knee is measured at the center of the anterior patella on postoperative days 1, 3, and 5. Limbs will be exposed to room temperature for 5 minutes bilaterally and then the skin temperature was measured with a skin temperature gun. The skin temperature on the surgical side was defined as the skin temperature on the surgical side minus the skin temperature on the unsurgical side, both measured in degrees centigrade (°C) .	at 1, 3, and 5 days after surgery
Secondary	Length of hospital stay	from the day when the patients arrived at the ward for reception to the day when the patients discharged, based on the electronic medical record system	The length of hospital stay was counted in days, about 5 to 7 days usually