Dexamethasone, Flurbiprofen Axetil and Delirium After Lung Cancer Surgery

Peking University

Status and phase: Terminated; Phase 4

Conditions: Flubiprofen Axetil; Delirium; Surgery--Complications; Carcinoma, Non-Small-Cell Lung; Dexamethasone

Treatments: Drug: Normal saline; Drug: Dexamethasone; Drug: Flurbiprofen axetil; Drug: Lipid microsphere

Study type: Interventional

Funder types: Other

Identifiers

NCT03200600

2017[1359]-1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 126 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

1. 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;
2. History of therapy with glucocorticoids or immunosuppressants within 1 year, or therapy with non-steroidal anti-inflammatory drugs (NSAIDs) within 1 month;
3. Allergy to glucocorticoids or NSAIDs;
4. 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);
5. American Society of Anesthesiologists (ASA) physical status class IV or higher;
6. Refuse to use patient-controlled analgesia pump after surgery;
7. Other conditions that are considered unsuitable for study participation.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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126 participants in 4 patient groups

Dexamethasone and flurbiprofen axetil

Experimental group

Description:

1. Dexamethasone 10 mg is administered before anesthesia induction. 2. 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.

Treatment:

Drug: Flurbiprofen axetil

Drug: Dexamethasone

Dexamethasone and lipid microsphere

Experimental group

Description:

1. Dexamethasone 10 mg is administered before anesthesia induction. 2. 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.

Treatment:

Drug: Lipid microsphere

Drug: Dexamethasone

Normal saline and flurbiprofen axetil

Experimental group

Description:

1. Normal saline 2 ml is administered before anesthesia induction. 2. 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.

Treatment:

Drug: Normal saline

Drug: Flurbiprofen axetil

Normal saline and lipid microsphere

Experimental group

Description:

1. Normal saline 2 ml is administered before anesthesia induction. 2. 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.

Treatment:

Drug: Lipid microsphere

Drug: Normal saline