Paracetamol and Mannitol Injection and Postoperative Delirium

Not Applicable

Not yet recruiting

• Conditions: Postoperative Delirium; Elderly; Non Cardiac Surgery
• Interventions: Drug: Acetaminophen group; Drug: Sufentanil group

• Registration Number: NCT07235995
• Lead Sponsor: Xiangya Hospital of Central South University

Brief Summary

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.

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 Timeline

• Status Verified: 2025-11
• Study First Submitted: 2025-11-13
• Study First Submitted QC: 2025-11-17
• Last Update Submitted: 2025-11-17
• Study First Posted: 2025-11-19
• Last Update Posted: 2025-11-19
• Study Start: 2025-12-01
• Primary Completion: 2027-01-31
• Study Completion: 2027-04-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 1092

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Acetaminophen group	Acetaminophen group	Intravenous acetaminophen is the analgesic of choice for patients in the acetaminophen group
Sufentanil group	Sufentanil group	Intravenous sufentanil is the analgesic of choice for patients in the sufentanil group

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Length of ICU stay	immediately after surgery	Length of ICU stay after surgery admitted to ICU
Length of hospital stay	immediately after surgery	Length of hospital stay within hospital admission
Incidence of non-delirium-related complications	30 days after surgery	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).
All-cause mortality	30-day after surgery	30-days outcome (survival or death) after surgery; Patients will be assessed via phone call if they are discharged before day 30 after surgery
Severity of pain	postoperative days 1-5	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).
Quality of life of 30-day survivors	day 30 after surgery	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.
Cognitive function of 30-day survivors	day 30 after surgery	Patients will be assessed with TICS-m via phone call if they are discharged before day 30 after surgery

Trial Locations

Locations (1)

Xiangya hospital; 🇨🇳 Changsha, Hunan, China