Effect of Neoadjuvant Anti-PD-1 Immunotherapy on Perioperative Analgesia and Postoperative Delirium

Study Overview
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Brief Summary
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To observe the effect of preoperative anti-PD-1 monotherapy combined with chemotherapy on patients' perioperative pain and opioid analgesia, and evaluate its effect on the incidence and severity of patients' postoperative delirium.

Detailed Description
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In this study, the investigators intend to select patients with resectable NSCLC treated with immuno-neoadjuvant therapy in combination with chemotherapy, systematically observe the effect of preoperative anti-PD-1 monotherapy on patients' perioperative pain and opioid analgesia, and evaluate its effect on the incidence and severity of patients' postoperative delirium, in order to provide a clinical basis for the perioperative management of patients treated with immuno-neoadjuvant therapy and promote their postoperative recovery.

Official Title
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Clinical Observation of the Effect of Neoadjuvant Anti-PD-1 Immunotherapy on Perioperative Analgesia and Postoperative Delirium in Patients With Non-small Cell Lung Cancer

Conditions
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Immunotherapy, Analgesia, NSCLC, Delirium

Intervention / Treatment
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* Drug: neoadjuvant immunotherapy
* Drug: Neoadjuvant chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed stage II or stage IIIA non-small cell lung cancer (NSCLC) and meet the requirements for R0 resection; American Society of Anesthesiologists (ASA): I-III, age ≥18 years, body mass index (BMI): 18.5-30; Normal function of Coagulation and vital organs such as heart, lungs, kidney, and liver; Eligible to receive platinum-containing two-drug chemotherapy; Sign the informed consent form Exclusion Criteria Prior treatment of any kind for current lung cancer, including chemotherapy, radiation or targeted therapy; Preoperative opioid analgesia; Severe chronic or active infection requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection; History of antipsychotic medication in the last 6 months; Preoperative Mini-mental state examination (MMSE) score <23

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| neoadjuvant immunotherapy group<br>Anti-PD-1 monoclonal antibody (Nivolumab，Pembrolizumab, Sintilimab, or Sugemalimab) 200 mg intravenously in combination with cis-platinum and paclitaxel/pemetrexed | Drug: neoadjuvant immunotherapy<br>* Anti-PD-1 antibody was added to the conventional neoadjuvant chemotherapy.<br>* Other names: anti-PD-1 therapy;|
| control group<br>platinum-containing dual-agent chemotherapy(cis-platinum and paclitaxel/pemetrexed) | Drug: Neoadjuvant chemotherapy<br>* Cis-platinum combined with paclitaxel or pemetrexed<br>* Other names: Cis-platinum combined with paclitaxel or pemetrexed;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| perioperative opioids consumption | the amount of sufentanil, remifentanil and morphine application. | from beginning of surgery to day 3 after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| postoperative delirium | record the occurrence of postoperative delirium after surgery using the 3D-CAM test. Patient with postoperative delirium means worse outcome. | within 3 days after surgery | 
| score of Numerical Rating Scale | Record the patient's resting and motor Numerical Rating Scale (NRS) scores, range from 0 to 10, and higher score means more pain. | at the time of admission to the operating room, immediately after and at 24 hour, 48 hour, and 72h after entering the PICU | 
| analgesic pump press in PICU | the time of first analgesic pump press and no. of total press in PICU | day 1, 2 and 3 after surgery | 
| Percent of patients with moderate to severe pain within 72 hours | Moderate to severe pain is defined as any NRS pain score of 4 or higher. | up to 72 hours after surgery | 
| intraoperative opioid consumption | the amount of sufentanil and remifentanil | from the beginning to the end of the surgery | 
| postoperative opioid consumption | opioid usage in PCIA and supplemental analgesics within 72 h | up to 72 hours after surgery |