Dexamethasone, Flurbiprofen Axetil and Delirium After Lung Cancer Surgery

NCT03200600 | Terminated Phase 4 DMC

• 1 other identifier: 2017[1359]-1
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Incidence of delirium during the first five postoperative days.

  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 Outcomes (6)

• Daily prevalence of delirium during the first five days after surgery.

  From postoperative day 1 to postoperative day 5.

• 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.

  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.

  At 30 days after surgery.

Other Outcomes (3)

• Richmond agitation sedation scale.

  From postoperative day 1 to postoperative day 5.

• Severity of pain.

  From postoperative day 1 to postoperative day 5.

• Cumulative analgesics consumption.

  Until postoperative day 3.

Study Arms (4)

Dexamethasone and flurbiprofen axetil

EXPERIMENTAL

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; Drug: Flurbiprofen axetil

Dexamethasone and lipid microsphere

EXPERIMENTAL

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; Drug: Lipid microsphere

Normal saline and flurbiprofen axetil

EXPERIMENTAL

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: Normal saline; Drug: Flurbiprofen axetil

Normal saline and lipid microsphere

EXPERIMENTAL

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: Normal saline; Drug: Lipid microsphere

Interventions

Dexamethasone DRUG

Dexamethasone 10 mg is administered before anesthesia induction.

Also known as: Dexamethasone sodium phosphate injection

Dexamethasone and flurbiprofen axetil; Dexamethasone and lipid microsphere

Normal saline DRUG

Normal saline 2 ml is administered before anesthesia induction.

Normal saline and flurbiprofen axetil; Normal saline and lipid microsphere

Flurbiprofen axetil DRUG

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.

Also known as: Flurbiprofen axetil injection

Dexamethasone and flurbiprofen axetil; Normal saline and flurbiprofen axetil

Lipid microsphere DRUG

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.

Also known as: Lipid microsphere injection

Dexamethasone and lipid microsphere; Normal saline and lipid microsphere

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University First Hospital: lead
• Peking University Cancer Hospital & Institute: collaborator

Study Sites (2)

Peking University First Hospital

Beijing, Beijing Municipality, 100035, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Related Publications (12)

• Scholz AF, Oldroyd C, McCarthy K, Quinn TJ, Hewitt J. Systematic review and meta-analysis of risk factors for postoperative delirium among older patients undergoing gastrointestinal surgery. Br J Surg. 2016 Jan;103(2):e21-8. doi: 10.1002/bjs.10062. Epub 2015 Dec 16.

  PMID: 26676760 BACKGROUND

• Ben-David B. Anaesthesia in Cancer Surgery: Can it Affect Cancer Survival? Curr Clin Pharmacol. 2016;11(1):4-20. doi: 10.2174/1574884711666160122093154.

  PMID: 26638975 BACKGROUND

• Bin Abd Razak HR, Yung WY. Postoperative Delirium in Patients Undergoing Total Joint Arthroplasty: A Systematic Review. J Arthroplasty. 2015 Aug;30(8):1414-7. doi: 10.1016/j.arth.2015.03.012. Epub 2015 Mar 14.

  PMID: 25818653 BACKGROUND

• Murphy GS, Sherwani SS, Szokol JW, Avram MJ, Greenberg SB, Patel KM, Wade LD, Vaughn J, Gray J. Small-dose dexamethasone improves quality of recovery scores after elective cardiac surgery: a randomized, double-blind, placebo-controlled study. J Cardiothorac Vasc Anesth. 2011 Dec;25(6):950-60. doi: 10.1053/j.jvca.2011.03.002. Epub 2011 May 11.

  PMID: 21565530 BACKGROUND

• Roberts B, Rickard CM, Rajbhandari D, Turner G, Clarke J, Hill D, Tauschke C, Chaboyer W, Parsons R. Multicentre study of delirium in ICU patients using a simple screening tool. Aust Crit Care. 2005 Feb;18(1):6, 8-9, 11-4 passim. doi: 10.1016/s1036-7314(05)80019-0.

  PMID: 18038529 BACKGROUND

• Balas MC, Happ MB, Yang W, Chelluri L, Richmond T. Outcomes Associated With Delirium in Older Patients in Surgical ICUs. Chest. 2009 Jan;135(1):18-25. doi: 10.1378/chest.08-1456. Epub 2008 Nov 18.

  PMID: 19017895 BACKGROUND

• Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T, Truman B, Dittus R, Bernard R, Inouye SK. The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med. 2001 Dec;27(12):1892-900. doi: 10.1007/s00134-001-1132-2. Epub 2001 Nov 8.

  PMID: 11797025 BACKGROUND

• Ansaloni L, Catena F, Chattat R, Fortuna D, Franceschi C, Mascitti P, Melotti RM. Risk factors and incidence of postoperative delirium in elderly patients after elective and emergency surgery. Br J Surg. 2010 Feb;97(2):273-80. doi: 10.1002/bjs.6843.

  PMID: 20069607 BACKGROUND

• Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62. doi: 10.1001/jama.291.14.1753.

  PMID: 15082703 BACKGROUND

• Vaurio LE, Sands LP, Wang Y, Mullen EA, Leung JM. Postoperative delirium: the importance of pain and pain management. Anesth Analg. 2006 Apr;102(4):1267-73. doi: 10.1213/01.ane.0000199156.59226.af.

  PMID: 16551935 BACKGROUND

• Halaszynski TM. Pain management in the elderly and cognitively impaired patient: the role of regional anesthesia and analgesia. Curr Opin Anaesthesiol. 2009 Oct;22(5):594-9. doi: 10.1097/ACO.0b013e32833020dc.

  PMID: 19623056 BACKGROUND

• Rudolph JL, Ramlawi B, Kuchel GA, McElhaney JE, Xie D, Sellke FW, Khabbaz K, Levkoff SE, Marcantonio ER. Chemokines are associated with delirium after cardiac surgery. J Gerontol A Biol Sci Med Sci. 2008 Feb;63(2):184-9. doi: 10.1093/gerona/63.2.184.

  PMID: 18314455 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Delirium

Interventions

Dexamethasone; dexamethasone 21-phosphate; Saline Solution; flurbiprofen axetil

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Dong-xin Wang, Wang

  Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chairman, Department of Anesthesiology and Critical Care Medicine

Study Record Dates

• First Submitted: June 25, 2017
• First Posted: June 27, 2017
• Study Start: August 2, 2017
• Primary Completion: December 26, 2018
• Study Completion: December 26, 2018
• Last Updated: July 13, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)