Postoperative Delirium
Conditions
Keywords
Postoperative delirium, Intravenous acetaminophen, Elderly, Noncardiac surgical patients
Brief summary
The aim of this multicenter randomized controlled study is to evaluate the effect of an intravenous acetaminophen-mannitol opioid-sparing analgesic strategy on the cumulative incidence of POD, compared with an intravenous sufentanil-based opioid analgesic strategy.
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 older noncardiac surgical patients admitted to ICU remains inadequately studied. Objectives: To evaluate the effect of an intravenous acetaminophen-mannitol opioid-sparing analgesic strategy on the cumulative incidence of POD, compared with an intravenous sufentanil-based opioid analgesic strategy, in older noncardiac surgical patients admitted to ICU. Study design: A randomized controlled trial. Setting: 34 ICUs from different regions across China. Patients: 1092 older 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 outcomes include the duration of delirium occurring within postoperative days 1-5 ;analgesic effect within postoperative days 1-5; cumulative opioid exposure during the 48-hour intervention will be reported as drug-specific cumulative doses, including scheduled sufentanil and all rescue opioids; sleep quality within postoperative days 1-5; length of postoperative ICU stay and hospital stay; incidence of non delirium complications within 30 days after surgery; in hospital and 30 day postoperative all cause mortality, and quality of life and cognitive function in 30 day postoperative survivors. Exploratory outcomes include delirium related biomarkers and neurological function tests measured on postoperative day 1.Safety outcomes include the Hepatic adverse events ,adverse event and Serious adverse event . Predicted duration of the study: 24 months.
Interventions
The pain in this group is controlled using acetaminophen-mannitol (Paracetamol and Maninitol Injection, Yichang Renfu Medicine Co., Ltd., China), 500 mg, intravenous bolus, every 6 hours for the first 48 hours after randomization. The severity of pain is assessed using NRS/CPOT every 15 minutes during the first hour after randomization with study drug infusion and then once every 12 hours needed.The NRS will be used for awake patients, and the CPOT will be used for mechanically ventilated patients.
DRUGSufentanil group
The 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/CPOT every 15 minutes during the first hour after randomization with study drug infusion and then once every 12 hours needed.The NRS will be used for awake patients, and the CPOT will be used for mechanically ventilated patients.
Sponsors
Xiangya Hospital of Central South University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Masking description
The principal investigators and final data analysts will remain blinded to treatment allocation until completion of the primary analysis.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 60 years; * Admitted to ICU after a noncardiac surgical procedure * Signed informed consent form
Exclusion criteria
Patients who meet any of the following criteria will be excluded. * Preoperative medical history: schizophrenia, epilepsy, Parkinson's disease, end stage renal disease, or end stage liver disease. * Inability to communicate preoperatively due to coma, severe dementia, or language disorder. * Patients with traumatic brain injury or undergoing neurosurgical procedures. * Positive screening result for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methamphetamine, methadone, or methylenedioxymethamphetamine). * Participation in another clinical study within 30 days prior to surgery, or planned concurrent participation in another clinical study. * Positive preoperative CAM-ICU assessment indicating delirium. * Occurrence of intraoperative or postoperative complications before randomization, and the investigator deems the subject unsuitable for study participation. * Hepatic dysfunction at screening, defined as ALT or AST \>3× the local laboratory upper limit of normal (ULN). * Intolerance or contraindication to acetaminophen or the protocol analgesics.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence 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
| Measure | Time frame | Description |
|---|---|---|
| Duration of delirium | postoperative 1- 5 days | Duration of delirium, defined as the number of postoperative days/hours during which delirium is present.Delirium assessed using CAM-ICU every 12 hours (8am, 8 pm) during postoperative days 1-5 and RASS transform at any time. |
| Severity of pain | postoperative days 1-5 | Severity of pain assessed using numeric rating scale (NRS)/the Critical-Care Pain Observation Tool (CPOT) , 8am and 8pm, twice a day, for 5 day.The NRS will be used for awake patients, and the CPOT will be used for mechanically ventilated patients.The NRS 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).The CPOT (Critical-Care Pain Observation Tool): Total score range 0-8, where 0 indicates no pain and 8 indicates the worst pain. |
| opioid exposure | 48-hour after drug infusion | Cumulative opioid exposure during the 48-hour intervention will be reported as drug-specific cumulative doses, including scheduled sufentanil and all rescue opioids. |
| Sleep quality | postoperative days 1-5 | 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 |
| 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 |
| Length of ICU stay | From postoperative ICU admission until ICU discharge, assessed for up to 12 months. | Postoperative length of ICU stay, defined as the number of days (or hours) from ICU admission to ICU discharge. |
| Length of hospital stay | From the day of surgery until hospital discharge, assessed for up to 12 months. | Postoperative length of hospital stay, defined as the number of days/hours from surgery to hospital discharge. |
| 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). |
| 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 |
Countries
China
Contacts
CONTACTLina Zhang, Dr.
CONTACTMilin Peng, Dr.
STUDY_CHAIRYixiong Li
Central South University
Outcome results
None listed