Dexamethasone, Flurbiprofen Axetil and Delirium After Lung Cancer Surgery

Sponsor

Peking University First Hospital (Other)

Overall Status

Terminated

CT.gov ID

NCT03200600

Collaborator

Peking University Cancer Hospital & Institute (Other)

126

Enrollment

Locations

Arms

16.8

Actual Duration (Months)

Patients Per Site

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Delirium is a common complication in elderly patients after surgery. And its occurrence is associated with worse outcomes. The causes of delirium are multifactorial but may include pain, stress response and inflammation. Dexamethasone is commonly used to prevent the occurrence of postoperative nausea and vomiting. In a randomized controlled trial, small-dose dexamethasone (8 mg) administered before anesthesia induction improved the quality of recovery in patients after cardiac surgery. Flurbiprofen axetil is commonly used to improve postoperative analgesia while decreasing the requirement of opioids. In a randomized trial of the investigators, combined use of flurbiprofen axetil with sufentanil for postoperative analgesia reduced delirium in elderly patients after orthopedic surgery. The purpose of this 2 plus 2 factorial randomized controlled trial is to test the hypothesis that combined use of dexamethasone and flurbiprofen axetil may reduce delirium in elderly patients after lung cancer surgery.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung Surgery--Complications Dexamethasone Flubiprofen Axetil Delirium	Drug: Dexamethasone Drug: Normal saline Drug: Flurbiprofen axetil Drug: Lipid microsphere	Phase 4

Detailed Description

Delirium is an acutely occurred, transient and fluctuating central nervous system dysfunction which is characterized by cognitive dysfunction, decreased level of consciousness, decentralized attention, and/or disturbed perception. It is a common complication in elderly patients after surgery. Systematic reviews showed that 5% to 54.4% of patients developed delirium after noncardiac surgery, and the incidences increase with age.

The development of postoperative delirium is associated with worse outcomes. For example, patients with delirium had increased postoperative complications, prolonged hospital stay, and increased in-hospital mortality; they also had worse long-term outcomes, including declined cognitive function, decreased quality of life, and increased post-hospital mortality.

The causes of delirium are multifactorial and may include pain, stress response and inflammation. Studies showed that postoperative pain is an important risk factor of delirium, whereas good postoperative analgesia reduces the incidence of delirium. Furthermore, the studies found that surgery related inflammatory response also plays an important role in the development of delirium. However, measures that can effectively prevent the occurrence of postoperative delirium are still lacking.

Dexamethasone is commonly used to prevent the occurrence of postoperative nausea and vomiting. In a randomized controlled trial, small-dose dexamethasone (8 mg) administered before anesthesia induction improved the quality of recovery in patients after cardiac surgery. Flurbiprofen axetil is commonly used to improve postoperative analgesia while decreasing the requirement of opioids. In a randomized trial of the investigators, combined use of flurbiprofen axetil with sufentanil for postoperative analgesia reduced delirium in elderly patients after orthopedic surgery.

The purpose of this 2 plus 2 factorial randomized controlled trial is to test the hypothesis that combined use of dexamethasone and flurbiprofen axetil may reduce delirium in elderly patients after lung cancer surgery.

Study Design

Study Type:

Interventional

Actual Enrollment :

126 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Impact of Perioperative Dexamethasone and Flurbiprofen Axetil on Delirium After Surgery for Non-small Cell Lung Cancer: A 2x2 Factorial Randomized Controlled Trial

Actual Study Start Date :

Aug 2, 2017

Actual Primary Completion Date :

Dec 26, 2018

Actual Study Completion Date :

Dec 26, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexamethasone and flurbiprofen axetil Dexamethasone 10 mg is administered before anesthesia induction. Flurbiprofen axetil 50 mg is administered before the start of surgery. Postoperative analgesia is provided with a patient-controlled analgesia pump, which is established with 100 ml of 1.25 μg/ml sufentanil and 2 mg/ml flurbiprofen axetil, programmed to deliver a 2 ml bolus with a lockout interval of 6-8 min and a background infusion of 1 ml/h.	Drug: Dexamethasone Dexamethasone 10 mg is administered before anesthesia induction. Other Names: Dexamethasone sodium phosphate injection Drug: Flurbiprofen axetil Flurbiprofen axetil 50 mg is administered before the start of surgery. Postoperative analgesia is provided with a patient-controlled analgesia pump, which is established with 100 ml of 1.25 μg/ml sufentanil and 2 mg/ml flurbiprofen axetil, programmed to deliver a 2 ml bolus with a lockout interval of 6-8 min and a background infusion of 1 ml/h. Other Names: Flurbiprofen axetil injection
Experimental: Dexamethasone and lipid microsphere Dexamethasone 10 mg is administered before anesthesia induction. Lipid microsphere 5 ml is administered before the start of surgery. Postoperative analgesia is provided with a patient-controlled analgesia pump, which is established with 100 ml of 1.25 μg/ml sufentanil and 20 ml lipid microsphere, programmed to deliver a 2 ml bolus with a lockout interval of 6-8 min and a background infusion of 1 ml/h.	Drug: Dexamethasone Dexamethasone 10 mg is administered before anesthesia induction. Other Names: Dexamethasone sodium phosphate injection Drug: Lipid microsphere Lipid microsphere 5 ml is administered before the start of surgery. Postoperative analgesia is provided with a patient-controlled analgesia pump, which is established with 100 ml of 1.25 μg/ml sufentanil and 20 ml lipid microsphere, programmed to deliver a 2 ml bolus with a lockout interval of 6-8 min and a background infusion of 1 ml/h. Other Names: Lipid microsphere injection
Experimental: Normal saline and flurbiprofen axetil Normal saline 2 ml is administered before anesthesia induction. Flurbiprofen axetil 50 mg is administered before the start of surgery. Postoperative analgesia is provided with a patient-controlled analgesia pump, which is established with 100 ml of 1.25 μg/ml sufentanil and 2 mg/ml flurbiprofen axetil, programmed to deliver a 2 ml bolus with a lockout interval of 6-8 min and a background infusion of 1 ml/h.	Drug: Normal saline Normal saline 2 ml is administered before anesthesia induction. Drug: Flurbiprofen axetil Flurbiprofen axetil 50 mg is administered before the start of surgery. Postoperative analgesia is provided with a patient-controlled analgesia pump, which is established with 100 ml of 1.25 μg/ml sufentanil and 2 mg/ml flurbiprofen axetil, programmed to deliver a 2 ml bolus with a lockout interval of 6-8 min and a background infusion of 1 ml/h. Other Names: Flurbiprofen axetil injection
Experimental: Normal saline and lipid microsphere Normal saline 2 ml is administered before anesthesia induction. Lipid microsphere 5 ml is administered before the start of surgery. Postoperative analgesia is provided with a patient-controlled analgesia pump, which is established with 100 ml of 1.25 μg sufentanil and 20 ml lipid microsphere, programmed to deliver a 2 ml bolus with a lockout interval of 6-8 min and a background infusion of 1 ml/h.	Drug: Normal saline Normal saline 2 ml is administered before anesthesia induction. Drug: Lipid microsphere Lipid microsphere 5 ml is administered before the start of surgery. Postoperative analgesia is provided with a patient-controlled analgesia pump, which is established with 100 ml of 1.25 μg/ml sufentanil and 20 ml lipid microsphere, programmed to deliver a 2 ml bolus with a lockout interval of 6-8 min and a background infusion of 1 ml/h. Other Names: Lipid microsphere injection

Outcome Measures

Primary Outcome Measures

Incidence of delirium during the first five postoperative days. [From postoperative day 1 to postoperative day 5.]
Delirium is assessed twice daily with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).

Secondary Outcome Measures

Daily prevalence of delirium during the first five days after surgery. [From postoperative day 1 to postoperative day 5.]
Delirium is assessed twice daily with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).
Length of stay in hospital after surgery. [From end of surgery until hospital discharge or 30 days after surgery.]
Length of stay in hospital after surgery.
Incidence of postoperative complications within 30 days after surgery. [From end of surgery until 30 days after surgery.]
Incidence of postoperative complications within 30 days after surgery.
All-cause mortality within 30 days after surgery. [From end of surgery until 30 days after surgery.]
All-cause mortality within 30 days after surgery.
Cognitive function at 30 days after surgery. [At 30 days after surgery.]
Cognitive function is assessed with Telephone Interview for Cognitive Status-Modified (TICS-m)
Quality of life at 30 days after surgery. [At 30 days after surgery.]
Quality of life is assessed with the World Health Organization Quality of Life-short version (WHOQOL-Bref).

Other Outcome Measures

Richmond agitation sedation scale. [From postoperative day 1 to postoperative day 5.]
Assessed with Richmond agitation sedation scale twice daily.
Severity of pain. [From postoperative day 1 to postoperative day 5.]
Assessed twice daily with Numeric Rating Scale (NRS, an 11-score scale where 0 = no pain and 10 = the worst pain.
Cumulative analgesics consumption. [Until postoperative day 3.]
Cumulative analgesics consumption at different timepoints after surgery.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age from 18 to 85 years old;
Diagnose as non-small-cell lung cancer (stage IA-IIIA);
Plan to undergo surgical resection;
Provide written informed consents.

Exclusion Criteria:

Clinical evidences suggest remote metastasis of the primary cancer; have received radiotherapy, chemotherapy or targeted therapy before surgery; have received previous surgery for lung cancer; diagnosed with other cancer (other than lung cancer) currently or previously;
History of therapy with glucocorticoids or immunosuppressants within 1 year, or therapy with non-steroidal anti-inflammatory drugs (NSAIDs) within 1 month;
Allergy to glucocorticoids or NSAIDs;
Contraindications to dexamethasone or flurbiprofen axetil, such as asthma or hives urticaria induced by aspirin or other NSAIDs; active digestive tract ulcer or bleeding, or history of repeated digestive tract ulcer or bleeding; coagulopathy (platelet count < 50*10^9/L, International Normalized Ratio > 1.4, or activated partial thromboplastin time > 4 seconds above upper limit); current therapy with lomefloxacin, norfloxacin, or enoxacin; severe cardiac dysfunction (New York heart association class 3 or above, or Left Ventricular Ejection Fraction less than 30%) or myocardial infarction within 3 months; liver injury (transaminase higher than 2 times of upper limit); kidney injury (creatinine higher than 1.5 times of upper limit); uncontrolled severe hypertension before surgery (> 180/120 mmHg);
American Society of Anesthesiologists (ASA) physical status class IV or higher;
Refuse to use patient-controlled analgesia pump after surgery;
Other conditions that are considered unsuitable for study participation.