Dexamethasone, Flurbiprofen Axetil and Delirium After Lung Cancer Surgery

July 9, 2021 updated by: Dong-Xin Wang, Peking University First Hospital

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

126

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100142
        • Beijing Cancer Hospital
      • Beijing, Beijing, China, 100035
        • Peking University First Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: FACTORIAL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Dexamethasone and flurbiprofen axetil
  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.
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
  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.
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
  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.
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
Drug: Normal saline
Normal saline 2 ml is administered before anesthesia induction.
EXPERIMENTAL: Normal saline and lipid microsphere
  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.
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
Drug: Normal saline
Normal saline 2 ml is administered before anesthesia induction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of delirium during the first five postoperative days.
Time Frame: 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).
From postoperative day 1 to postoperative day 5.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Daily prevalence of delirium during the first five days after surgery.
Time Frame: 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).
From postoperative day 1 to postoperative day 5.
Length of stay in hospital after surgery.
Time Frame: From end of surgery until hospital discharge or 30 days after surgery.
Length of stay in hospital after surgery.
From end of surgery until hospital discharge or 30 days after surgery.
Incidence of postoperative complications within 30 days after surgery.
Time Frame: From end of surgery until 30 days after surgery.
Incidence of postoperative complications within 30 days after surgery.
From end of surgery until 30 days after surgery.
All-cause mortality within 30 days after surgery.
Time Frame: From end of surgery until 30 days after surgery.
All-cause mortality within 30 days after surgery.
From end of surgery until 30 days after surgery.
Cognitive function at 30 days after surgery.
Time Frame: At 30 days after surgery.
Cognitive function is assessed with Telephone Interview for Cognitive Status-Modified (TICS-m)
At 30 days after surgery.
Quality of life at 30 days after surgery.
Time Frame: At 30 days after surgery.
Quality of life is assessed with the World Health Organization Quality of Life-short version (WHOQOL-Bref).
At 30 days after surgery.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Richmond agitation sedation scale.
Time Frame: From postoperative day 1 to postoperative day 5.
Assessed with Richmond agitation sedation scale twice daily.
From postoperative day 1 to postoperative day 5.
Severity of pain.
Time Frame: 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.
From postoperative day 1 to postoperative day 5.
Cumulative analgesics consumption.
Time Frame: Until postoperative day 3.
Cumulative analgesics consumption at different timepoints after surgery.
Until postoperative day 3.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University First Hospital

Collaborators

Peking University Cancer Hospital & Institute

Investigators

  • Principal Investigator: Dong-xin Wang, Wang, Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 2, 2017

Primary Completion (ACTUAL)

December 26, 2018

Study Completion (ACTUAL)

December 26, 2018

Study Registration Dates

First Submitted

June 25, 2017

First Submitted That Met QC Criteria

June 25, 2017

First Posted (ACTUAL)

June 27, 2017

Study Record Updates

Last Update Posted (ACTUAL)

July 13, 2021

Last Update Submitted That Met QC Criteria

July 9, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017[1359]-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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