Impact of Acetaminophen on Postoperative Delirium Elderly Patients After Non-cardiac Surgery

Impact of Oral Acetaminophen Analgesia on Postoperative Delirium and Long-term Survival in Elderly Patients After Non-cardiac Surgery: A Randomized Controlled Trial

To investigate the impact of acetaminophen analgesia on the frequency of postoperative delirium and 28 days mortality in elderly patients after noncardiac surgery.

Study Overview

• Status: Unknown
• Conditions: Delirium in Old Age; Acetaminophen
• Intervention / Treatment: Drug: Acetaminophen; Drug: Sufentanil

Detailed Description

Background: Delirium is a common complication following surgery contributes to adverse outcomes, including increased mortality and morbidity, longer length of ICU stays, prolonged mechanical ventilation, and costlier hospitalizations. Previous studies showed that, the incidence of delirium for seniors patients admitted to ICU can reach up to 58%-75.6% depending on the patient population and screening instrument. The current protocols for perioperative opioid use and postoperative pain management may influence the occurrence of delirium. We hypothesize that the use of oral acetaminophen (OVA) may lead to reduced opioid consumption and decreased incidence of postoperative delirium.

Objectives: To investigate the impact of acetaminophen analgesia on the frequency of postoperative delirium and 28 days mortality in elderly patients after noncardiac surgery.

Study design: A randomized and controlled trial. Setting: Departments of critical care medicine of tertiary hospital (Xiangya) in China.

Patients: 164 elderly patients (≥ 65 years) who are scheduled to admitted to ICU after major surgery (predicted duration ≥ 2 hours) Intervention: For patients in the acetaminophen group, oral acetaminophen supplemented dexmedetomidine sedation will be provided after surgery. For patients in the control group, sufentanil supplemented dexmedetomidine sedation will be provided after surgery. the other analgesia drugs will be provided as back up in study group.

Primary outcome: Early primary endpoint is the frequency of delirium in the first 5-days post-surgery. Secondary endpoints include biomark and NeuroMonitoring of delirium, 28days and in-hospital mortality, length of stay days in ICU and hospital, complication in hospital.

Predicted duration of the study: 2 years.

• Study Type: Interventional
• Enrollment (Anticipated): 164
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yuhang Ai, Prof.; Phone Number: 8613908480631; Email: ayhicu1978@sina.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410000
      • Recruiting
      • Xiangya Hospital, Central South University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Scheduled to ICU after non-cardiac surgery for any reasons；
2. Report having moderate to severe acute pain as determined by a pain score ≥ 5 from the 11-point Numeric Pain Rating Scale (NPRS) scale after postsurgery；
3. Able to take oral medication or by stomach tube；
4. Provide written informed consent.

Exclusion Criteria:

• Patients who meet any of the following criteria will be excluded.

  1. Preoperative history of schizophrenia, epilepsy, Parkinsonism, or myasthenia gravis;
  2. Inability to communicate in the preoperative period because of coma, profound dementia or language barrier;
  3. Brain injury or neurosurgery;
  4. Severe hepatic dysfunction (eg, aspartate aminotransferase, alanine aminotransferase, or bilirubin greater than or equal to 3.0 times the upper limit of normal), active hepatic disease, evidence of clinically significant liver disease, or other condition (eg, alcoholism, cirrhosis, or hepatitis) that suggests the potential for an increased susceptibility to hepatic toxicity with study drug exposure.
  5. Subject has a positive test result for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methamphetamine, methadone, or methylenedioxy-methamphetamine) at Screening.
  6. Subject has participated in another clinical study within 30 days prior to day-of-surgery or plans to participate in another clinical study while concurrently enrolled in this study.
  7. Subject has a history of any drug allergy, hypersensitivity, or intolerance to acetaminophen or morphine or to any of the excipients in the IV or oral formulations used.
  8. Subject has intra- or postoperative complications, which in the view of the investigator, makes the subject unsuitable for the participation of the study.
  9. Subject has a history of any drug allergy, hypersensitivity, or intolerance to acetaminophen or opioid or to any of the excipients in the IV or oral formulations used.
  10. Unable to take medications orally or by stomach tube

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: acetaminophen; For patients randomized to OVA group, OVA 500mg was given every 8 hours for the first 48 hours postoperatively. Numeric Pain Rating Scale pain score is assessed every 15 minutes during the 1 hour of ICU stay and when needed.	Drug: Acetaminophen; For patients in the acetaminophen group, oral acetaminophen supplemented dexmedetomidine sedation will be provided after surgery.
ACTIVE_COMPARATOR: Sufentanil; Sufentanil injection 500μg /10ml in normal saline, total volume 50 ml.Constant infusion dosage is 0.05μg/kg/h. Numeric Pain Rating Scale pain score is assessed every 15 minutes during the 1 hour of ICU stay and when needed.	Drug: Sufentanil; For patients in the control group, sufentanil supplemented dexmedetomidine sedation will be provided after surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of delirium	evaluate the occurence of delirium by using Confusion Assessment Method for The Intensive Care Unit (CAM-ICU)	within the first 5 postoperative days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness of analgesia	to assess the effect of analgesia by using Numerical Rating Scale (NRS)；This method is composed of 0 to 10, a total of 11 Numbers. Patients with 0 to 10 this digital describe pain intensity, the greater the number the pain degree is more serious.0 painless, 1 ~ 3 mild pain (pain does not affect sleep), 4 ~ 6 moderate pain, 7 ~ 9 severe pain (couldn't sleep), 10 severe pain. We should ask the patient pain degree, tag, or let the patient draw one of the most can represent their own pain degree of digital.	during postoperative days 1-5
Length of days in ICU and hospital stay after surgery	evaluate the length of days in ICU and hospital stay from postoperative to discharge	from day 1 after surgery to discharge (up to 24 weeks)
Incidence of non-delirium complications	Incidence of non-delirium complications with 28 days after surgery	with 28 days after surgery
All-cause28-day mortality	All-cause28-day mortality	day 28 after surgery
life-Quality evaluation of 28-day survivors	evaluate the quality of life by using the world health organization quality of life measurement scale(WHOQOL-BREF). WHOQOL-BREF contains 26 items, summarizes the physiological, psychological, social relations, the environment in the field of four content.Consists of two independent analysis problem items: question 1 (G1) ask individual about their quality of life of the general subjective feeling, question 2 (G4) individual asked the total subjective feeling bout their own health. Domain scores are the positive (i.e., the higher the score, the better the quality of life).Field scoring through the calculation of average of their entries 4 times. and patients will be assessed via phone call if they are discharged before day 28 after surgery	day 28 after surgery
Cognitive function of 28-day survivors	evaluate the cognitive function of 28-day survivors by using modified version of the telephone questionnaire for cognitive function questionnaire (TICS-m);It contains 21 items, total score 50 points, can be divided into three parts: the memory part (score 20), directional force (score 13), the capablity of language, and pay attention (score 17). TICS -m total score 50 points, scored < 28 divided into dementia, 28 and 33 were divided into mild cognitive dysfunction, ≥33 were divided into normal. Patients will be assessed via phone call if they are discharged before day 28 after surgery	day 28 after surgery

Collaborators and Investigators

• Sponsor: Xiangya Hospital of Central South University
• Collaborators: Yale University

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 15, 2019
• Primary Completion (ANTICIPATED): February 1, 2020
• Study Completion (ANTICIPATED): November 1, 2020

Study Registration Dates

• First Submitted: December 2, 2018
• First Submitted That Met QC Criteria: December 2, 2018
• First Posted (ACTUAL): December 4, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 8, 2019
• Last Update Submitted That Met QC Criteria: March 6, 2019
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: delirium; acetaminophen; analgesia
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Antipyretics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Acetaminophen; Sufentanil
• Other Study ID Numbers: 2018071027

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes