Paracetamol and Mannitol Injection and Postoperative Delirium (PAPOD-ES)

Impact of Paracetamol and Mannitol Injection Analgesia on Postoperative Delirium in Elderly Patients After Non-cardical Surgery: A Randomized Controlled Trial

The aim of this multi-center RCT is to investigate the effect of intravenous acetaminophen (paracetamol and mannitol injection) on postoperative delirium, comparing with intravenous sufentanil, in elderly noncardiac surgical patients admitted to ICU.

Study Overview

• Status: Not yet recruiting
• Conditions: Postoperative Delirium; Elderly; Non Cardiac Surgery
• Intervention / Treatment: Drug: Acetaminophen group; Drug: Sufentanil group

Detailed Description

Delirium is a common complication after surgery. It is associated with increased morbidity and mortality, longer intensive care unit (ICU) and hospital stay, prolonged mechanical ventilation, higher risk of institutionalization, and higher healthcare cost. Depending on patient population and screening method, the incidence of delirium in elderly patients admitted to ICU can be as high as 58-76%. The choice of analgesics and the adequacy of pain control are among the modifiable precipitating factors for postoperative delirium (POD). Whether the use of intravenous acetaminophen decreases the occurrence of POD in elderly noncardiac surgical patients admitted to ICU remains inadequately studied.

Objectives: To investigate the effect of intravenous acetaminophen (paracetamol and mannitol injection) on postoperative delirium, comparing with intravenous sufentanil, in elderly noncardiac surgical patients admitted to ICU.

Study design: A randomized controlled trial. Setting: 34 ICUs from different regions across China. Patients: 1092 elderly patients (≥ 60 years), having noncardiac surgery and admitted to ICU after surgery, are eligible.

Intervention: Patients are randomly assigned to intravenous acetaminophen or sufentanil groups. Intravenous acetaminophen is the analgesic of choice for patients in the acetaminophen group. Intravenous sufentanil is the analgesic of choice for patients in the sufentanil group (control).

Outcomes: The primary endpoint is the incidence of delirium within the first 5 days after surgery. Delirium is assessed using the confusion assessment method for the intensive care unit (CAM-ICU). The secondary endpoints include the level of pain assessed using the Numeric Rating Scale (NRS) on postoperative day 1 to 5 and day 30, 30-day mortality, length of ICU and hospital stay, quality of life assessed on postoperative day 30, cognitive function assessed on postoperative day 30, and biomarkers and neurofunctional testing for delirium.

Predicted duration of the study: 24 months.

• Study Type: Interventional
• Enrollment (Estimated): 1092
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lina Zhang, Dr.; Phone Number: 86+15874875763; Email: zln7095@163.com
• Study Contact Backup: Name: Milin Peng, Dr.; Phone Number: 86+15211040348; Email: pengmilin@csu.edu.cn

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410000
      • Xiangya Hospital
      • Contact: Milin Peng, Dr.; Phone Number: 86+15211040348; Email: pengmilin@csu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 60 years;
• Admitted to ICU after a noncardiac surgical procedure
• Moderate to severe acute pain, with a postoperative pain score ≥ 5 based on the 11-point Numerical Pain Rating Scale (NPRS)
• Signed informed consent form

Exclusion Criteria:

• Preoperative medical history: schizophrenia, epilepsy, Parkinson's disease, or severe myasthenia gravis
• History of psychiatric disease or significant neurocognitive disorder such as dementia or retardation, making POD assessment impossible
• Language or communication barrier making POD assessment impossible
• Intracranial surgery
• Severe hepatic dysfunction prohibiting the use of acetaminophen per the standard of care
• Participation in a competing study within 30d
• Patients experienced intraoperative or postoperative complications, and the investigator determined the subject was unsuitable to continue participation in the study
• Intolerant to paracetamol or opioid drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acetaminophen group; Intravenous acetaminophen is the analgesic of choice for patients in the acetaminophen group	Drug: Acetaminophen group; The pain in this group is controlled using acetaminophen (Paracetamol and Maninitol Injection, Yichang Renfu Medicine Co., Ltd., China), 500 mg, intravenous bolus, every 6 hours for the first 48 hours postoperatively. The severity of pain is assessed using NRS every 15 minutes during the first hour following ICU admission and then once every 12 hours needed.
Active Comparator: Sufentanil group; Intravenous sufentanil is the analgesic of choice for patients in the sufentanil group	Drug: Sufentanil group; he pain in this group is controlled using sufentanil (Yichang Renfu Medicine Co., Ltd., China) intravenous infusion with a rate of 0.05 μg/kg/h. The severity of pain is assessed using NRS every 15 minutes during the first hour following ICU admission and then once every 12 hours needed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of delirium	Delirium assessed using CAM-ICU every 12 hours (8am, 8 pm) during postoperative days 1-5 and RASS transform at any time	postoperative 1- 5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	30-days outcome (survival or death) after surgery; Patients will be assessed via phone call if they are discharged before day 30 after surgery	30-day after surgery
Severity of pain	Severity of pain assessed using numeric rating scale (NRS), 8am and 8pm, twice a day, for 5 day The scale consists of 11 points from 0 to 10, where 0 indicates "no pain" and 10 indicates "severe pain". Patients select the corresponding number based on their pain level. <4 points indicate mild pain (no impact on sleep), 4-6 points indicate moderate pain, and ≥7 points indicate severe pain (pain prevents sleep or causes waking).	postoperative days 1-5
Length of ICU stay	Length of ICU stay after surgery admitted to ICU	immediately after surgery
Length of hospital stay	Length of hospital stay within hospital admission	immediately after surgery
Quality of life of 30-day survivors	Patients will be assessed with World Health Organization Quality of Life Assessment Instrument Short Form (WHOQOL-BREF) via phone call if they are discharged before day 30 after surgery The scale contains 26 items covering four domains: physiological, psychological, social relations, and environmental. It uses a 1-5-point Likert scale for scoring, and the original scores are converted into a standard score of 0-100. The higher the score, the better the quality of life.	day 30 after surgery
Cognitive function of 30-day survivors	Patients will be assessed with TICS-m via phone call if they are discharged before day 30 after surgery	day 30 after surgery
Incidence of non-delirium-related complications	Complications unrelated to delirium occurring within 30 days postoperatively (e.g., cardiovascular events, cerebrovascular events, renal impairment, GI complications, infections, etc.) are defined as any newly developed complications that may affect patient recovery and require therapeutic intervention (including hospital admission).	30 days after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep quality	Subjective quality of sleep assessed using NRS (an 11-point scale where 0 = the best sleep and 10 = the worst sleep) once daily (8:00-10:00 am) during postoperative days 1-5	postoperative days 1-5
Biomarker of delirium	Biomarker of delirium including S100b and NSE on postoperative day 1	Postoperative day 1
Neuro monitoring of delirium	Monitoring of neurophysiological function, with detecting SctO2 during postoperative days 1-5	Postoperative days 1-5

Collaborators and Investigators

• Sponsor: Xiangya Hospital of Central South University
• Investigators: Study Chair: Yixiong Li, Central South University

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: November 13, 2025
• First Submitted That Met QC Criteria: November 17, 2025
• First Posted (Actual): November 19, 2025

Study Record Updates

• Last Update Posted (Actual): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Elderly; Postoperative delirium; Intravenous acetaminophen; Noncardiac surgical patients
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Emergence Delirium
• Other Study ID Numbers: 202510115 (Other Identifier: Xiangya Hospital)

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