Delirium in Old Age
Conditions
Keywords
postoperative delirium, acetaminophen, elderly patient
Brief summary
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.
Detailed description
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.
Interventions
DRUGAcetaminophen
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.
DRUGSaline
Saline, a kind of crystalloid widely used in clinical treatment.
Sponsors
RenJi Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of postoperative delirium | Participants will be followed up during the first 5 postoperative days. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Delirium severity | Participants will be followed up during the first 5 postoperative days. | 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). |
| Pain scores | Participants will be followed up during the first 5 postoperative days. | Pain scores will be assessed using numerical rating scale (NRS) once daily, with 0 meaning no pain and 10 meaning the worst pain imaginable. |
| Total opioid consumption | Participants will be followed up during the first 5 postoperative days. | Amount of intravenous and/or oral opioid consumption for analgesia will be recorded. |
| Delirium duration | Participants will be followed up during the first 5 postoperative days. | Time to onset of delirium. |
| Delirium type | Participants will be followed up during the first 5 postoperative days. | 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| All cause mortality | one month | — |
| Length of days in ICU and hospital after surgery | one month | Length of stay in ICU and hospital after surgery will be collected from electronic medical records. |
| Cognitive function | Cognitive function will be evaluated on the fifth day after operation. | Cognitive function will be evaluated with Mini-Mental State Examination (MMSE) score that ranges from zero (worst) to 30 (best). |
Contacts
Primary ContactLIQUN YANG, MD
Outcome results
None listed