Intravenous Acetaminophen for Postoperative Delirium in Older Patients Recovering From Major Noncardiac Surgery

Phase 3Not Yet RecruitingNCT06653465

RenJi Hospital1,930 enrolled

Overview

Investigators propose this multi-center randomised controlled study to test the preventive effect of intravenouse acetaminophen in delirium over 5 postoperative days among older patients recovering from major non-cardiac surgery.

Delirium is a common complication in elderly patients after major surgeries and can lead to poor outcomes such as neurocognitive decline. Acetaminophen is a widely used adjuvant for perioperative multimodal analgesia. It can effectively alleviate postoperative pain, promote opioid-sparing and exert anti-neuroinflammatory response, showing strong potential for preventing postoperative delirium. There is evidence that intravenous acetaminophen reduces delirium in older patients following cardiac surgery, but its effectiveness is inconclusive among non-cardiac surgical patients. Investigators propose this multi-center, randomized, placebo-controlled, parallel-group trial in patients aged \>65 years old scheduled for non-cardiac major surgery with general anesthesia expected to last at least 2 h. A total of 1930 elderly patients will be enrolled and randomized at 1:1 ratio to acetaminophen or saline placebo groups, stratified by age, education level, and trial site with random-sized blocking. Acetaminophen or saline will be given when the surgical suture begin at the end of surgery and thereafter a total of 7 doses within 48h after surgery. The primary outcome will be the incidence of delirium, assessed twice daily, through the five postoperative days. Secondary outcomes will include pain scores with movement, opioid use within the first 48 postoperative hours, severity of delirium, ICU and hospital lengths of stay.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

1,930

Conditions

Delirium in Old Age

Interventions

AcetaminophenDRUG

Acetaminophen, which has similarly effects with NSAIDs in terms of inhibition of cyclooxygenase COX1, COX2 and COX3, is widely used as adjuvant for perioperative multimodal analgesia.

SalineDRUG

Saline, a kind of crystalloid widely used in clinical treatment.

Eligibility

Sex: ALLMin age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥ 65 years. 2. Scheduled for non-cardiac major surgery with general anesthesia that is expected to last more than 2h. 3. ASA Physical Status I-III. 4. Weight \>50 kg. 5. Written informed consent. Exclusion Criteria: 1. Pre-existing neuropsychiatric diseases (Alzheimer's disease, Schizophrenia, Parkinson's Disease, Seizures, etc.). 2. Pre-existing cognitive impairment (MMSE\<18). 3. Preoperative delirium. 4. Severe circulatory instability (preoperative left ventricular ejection fraction less than 30%, unstable angina, severe coronary artery disease, sick sinus syndrome, etc.). 5. Contraindication to the acetaminophen use, including serum creatinine \> 177µmol/L or aminotransferses \> 3 times the upper limit of normal. 6. Alcohol or drug abuse within a year before surgery. 7. Inability to communicate because of severe visual/auditory dysfunction or language barrier.

Outcomes

Primary Outcomes

Incidence of postoperative delirium

Delirium will be assessed by the trained investigators twice daily, from 8-10 AM and from 5-7 PM, starting from postoperative day 1 using 3-minute Confusion Assessment Method (3D-CAM) or CAM-ICU for intubated patients. Immediately before assessing delirium, sedation or agitation was assessed using Richmond Agitation-Sedation Scale (RASS). If the patient was too deeply sedated or unarousable (RASS -4 or -5), delirium assessment was aborted and the patient was recorded as comatose.

Time frame: Participants will be followed up during the first 5 postoperative days.

Secondary Outcomes

Delirium type

Patients with delirium were classified into three motoric subtypes. Hyperactive delirium was defined when RASS was consistently positive (+1 to +4); hypoactive delirium was defined when RASS was consistently neutral or negative (-3 to 0); and mixed delirium was defined when some RASS scores were positive (+1 to +4) and some RASS scores were neutral or negative (-3 to 0).

Time frame: Participants will be followed up during the first 5 postoperative days.

Delirium severity

Delirium rating scale 98 revised (DRS-R-98) will be used to evaluate severity of delirium. DRS-R-98 consists of 16 items, including 13 items to assess severity of delirium and 3 diagnostic items. The total severity score range from zero (best) to 39 (worst).

Time frame: Participants will be followed up during the first 5 postoperative days.

Pain scores

Pain scores will be assessed using numerical rating scale (NRS) once daily, with 0 meaning "no pain" and 10 meaning "the worst pain imaginable".

Time frame: Participants will be followed up during the first 5 postoperative days.

Total opioid consumption

Amount of intravenous and/or oral opioid consumption for analgesia will be recorded.

Central Contacts

LIQUN YANG, MD

CONTACT

15921969001 lqyang72721@126.com

Data from ClinicalTrials.gov

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