Intraoperative Blood Pressure Management and Dexamethasone in Lung Cancer Surgery

Study Overview
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Brief Summary
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Surgery is the front-line therapy for non-small cell lung cancer (NSCLC) but postoperative complications remains high and patients' long-term outcome is still challenging. In addition to surgery, anesthetic management particularly intraoperative blood pressure management and use of dexamethasone may affect patients' early and long-term outcomes after surgery for NSCLC. This study aims to investigate the impact of intraoperative blood pressure management and dexamethasone administration on early and long-term outcomes in patients undergoing surgery for lung cancer.

Detailed Description
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Surgical resection is the main treatment for patients with non-small cell lung cancer (NSCLC) and continuous efforts have been made to evolve surgical strategies and techniques. It has been now been realized that perioperative period is characterized with profound changes and anesthesia management may also affect outcomes of patients after cancer surgery. Even under well controlled conditions, blood pressure fluctuation frequently occurs during anesthesia and surgery. In previous studies, intraoperative hypotension was associated with increased risk of organ injuries (such as delirium, acute kidney injury, myocardial injury, and stroke) and higher 1-year mortality. Unpublished data showed that intraoperative hypotension was also associated with shortened long-term survival in patients after lung cancer surgery. In a recent trial, individualized intraoperative blood pressure management which avoided intraoperative hypotension decreased the incidence of postoperative organ injury when compared with routine practice. Avoiding intraoperative hypotension may also prolong survival after lung cancer surgery. However, evidences are lacking regarding this topic. Dexamethasone is frequently used for prevention of postoperative nausea and vomiting. Studies showed that a single low-dose dexamethasone has anti-inflammatory effect and can regulate immune function. It has been shown that perioperative dexamethasone can improve analgesia after surgery. In retrospective studies, perioperative low-dose dexamethasone was associated with less wound infection and improved long-term survival in patients after surgeries for pancreatic and lung cancer. It is hypothesized that intraoperative dexamethasone may reduce postoperative complications and improve long-term survival after lung cancer surgery. Interventional studies are required to confirm this hypothesis.

Official Title
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Impact of Intraoperative Blood Pressure Management and Dexamethasone on Patient's Outcomes After Lung Cancer Surgery: A 2 × 2 Factorial Randomized Controlled Trial

Conditions
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Lung Cancer, Surgery, Blood Pressure Management, Dexamethasone, Overall Survival, Postoperative Complications

Intervention / Treatment
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* Drug: Dexamethasone
* Other: Targeted blood pressure management
* Drug: Placebo
* Other: Routine blood presure management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged >50 years but <90 years. Diagnosed as resectable primary non-small cell lung cancer (stage IA-IIIA) and scheduled for radical surgery with an expected duration of >2 hours. Agree to participate in this study and sign the informed consent. Exclusion Criteria: Clinical examinations suggest non-resectable lung cancer or patients scheduled for a biopsy surgery. Recurrent or metastatic lung cancer. History of cancer or complicated with cancer in other organs. Long-term exposure to glucocorticoids or other immunosuppressant(s) due to autoimmune disease or organ transplantation. Uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg); or requirement of vasopressors to maintain blood pressure. Persistent atrial fibrillation, or acute cardiovascular events (acute coronary syndrome, stroke, or congestive heart failure) within 3 months. Severe hepatic dysfunction (Child-Pugh C) or renal failure (requirement of renal replacement therapy). Any other circumstances considered unsuitable for study participation by attending physicians or investigators.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: A 2 × 2 factorial randomized controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Routine blood pressure management + placebo<br>Blood pressure is maintained according to routine practice. Placebo (normal saline 2 ml) is administered before anesthesia induction. | Drug: Placebo<br>* Placebo (2 ml normal saline) is administered before anesthesia induction.<br>* Other names: Normal saline;Other: Routine blood presure management<br>* Blood pressure is maintained according to routine practice.<br>|
| Experimental: Routine blood pressure management + dexamethasone<br>Blood pressure is maintained according to routine practice. Dexamethasone (10 mg/2 ml) ia administered before anesthesia induction. | Drug: Dexamethasone<br>* Dexamethasone (10 mg/2 ml) is administered before anesthesia induction.<br>* Other names: Glucocorticoids;Other: Routine blood presure management<br>* Blood pressure is maintained according to routine practice.<br>|
| Experimental: Targeted blood pressure management + placebo<br>Blood pressure is maintained within ±10% from baseline. Placebo (normal saline 2 ml) is administered before anesthesia induction. | Other: Targeted blood pressure management<br>* Blood pressure is maintained within ±10% from baseline.<br>Drug: Placebo<br>* Placebo (2 ml normal saline) is administered before anesthesia induction.<br>* Other names: Normal saline;|
| Experimental: Targeted blood pressure management + dexamethasone<br>Blood pressure is maintained within ±10% from baseline. Dexamethasone (10 mg/2 ml) is administered before anesthesia induction. | Drug: Dexamethasone<br>* Dexamethasone (10 mg/2 ml) is administered before anesthesia induction.<br>* Other names: Glucocorticoids;Other: Targeted blood pressure management<br>* Blood pressure is maintained within ±10% from baseline.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival after surgery | Overall survival after surgery | Up to 5 years after surgery | 
| Incidence of organ injury and complications within 5 days after surgery (sub-study). | Organ injury includes delirium, acute kidney injury and myocardial injury. Postoperative complications are generally defined as newly occurred medical conditions that are harmful to patients' recovery and required therapeutic intervention, i.e., grade II or above on the Clavien-Dindo classification. | Up to 5 days after surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free survival after surgery | Recurrence-free survival after surgery | Up to 5 years after surgery | 
| Cancer-specific survival after surgery | Cancer-specific survival after surgery | Up to 5 years after surgery | 
| Event-free survival after surgery | Event-free survival after surgery | Up to 5 years after surgery | 
| Rate of intensive care unit (ICU) admission after surgery (sub-study) | Rate of ICU admission after surgery | During the day of surgery | 
| Rate of ICU admission with endotracheal intubation after surgery (sub-study) | Rate of ICU admission with endotracheal intubation after surgery | During the day of surgery | 
| Duration of mechanical ventilation in ICU after surgery (sub-study) | Duration of mechanical ventilation in ICU after surgery | Up to 30 days after surgery | 
| Length of stay in ICU after surgery (sub-study) | Length of stay in ICU after surgery | Up to 30 days after surgery | 
| Incidence of organ injury within 5 days after surgery (sub-study) | Organ injury includes delirium, acute kidney injury and myocardial injury. Delirium is assessed with the 3-minute diagnostic assessment for CAM-defined delirium (3D-CAM). Acute kidney injury is diagnosed according to the KDIGO (Kidney Disease: Improving Global Outcomes) criteria. Myocardial injury is diagnosed according to the serum cardiac troponin I level (higher than upper normal limit of the hospital's clinical laboratory). | Up to 5 days after surgery | 
| Incidence of complications within 30 days after surgery (sub-study) | Postoperative complications are defined as new-onset medical events that are harmful to patients' recovery and required therapeutic intervention, i.e., grade II or above on the Clavien-Dindo classification. | Up to 30 days after surgery | 
| Length of stay in hospital after surgery (sub-study) | Length of stay in hospital after surgery | Up to 30 days after surgery | 
| Rate of 30-day all-cause mortality (sub-study) | Death due to any cause within 30 days after surgery | Up to 30 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Cancer, Radical Resection, Blood Pressure Management, Dexamethasone, Overall Survival, Postoperative Complications