PANDORA: Delirium Prevention After Cardiac Surgery Using IV Acetaminophen to Prevent Postoperative Delirium in Older Cardiac Surgical Patients
- Conditions
- Delirium in Old AgeDeliriumCoronary Artery Disease
- Interventions
- Other: Placebo
- Registration Number
- NCT04093219
- Lead Sponsor
- Beth Israel Deaconess Medical Center
- Brief Summary
Our objective is to find an effective prophylactic intervention by evaluating IV acetaminophen's impact in reducing the frequency of postoperative delirium, one of the most common and detrimental complications of cardiac surgery in older adults.
- Detailed Description
This project will study the impact of scheduled administration of IV acetaminophen on the incidence, duration, and severity of postoperative delirium and other important hospital outcomes. Additionally, this trial will evaluate the effects of IV acetaminophen on longer-term postoperative cognitive dysfunction and functional status and develop a biorepository of perioperative samples as a future resource to probe the mechanisms of postoperative delirium.
The investigators propose three specific aims by conducting a randomized, triple-blind clinical trial that enrolls 900 patients 60 years of age or older undergoing cardiac surgery. Through this trial, the investigators will determine the effect of IV acetaminophen on;
1. the incidence, duration, and severity of postoperative delirium,
2. the use of opioids and other rescue analgesics in the first 48 postoperative hours, daily pain scores at rest and exertion, and length of stay in the Intensive Care Unit and overall hospital length of stay
3. longer-term (one, six, 12 months) cognitive, physical, and self-care functional recovery after surgery.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 900
- ≥ 60 years of age
- Patients undergoing cardiac surgery [coronary artery bypass grafting (CABG) with or without valve, isolated valve surgery] requiring cardiopulmonary bypass
- Pre-operative left ventricular ejection fraction (LVEF) < than 30%
- Emergent procedures
- Isolated aortic surgery
- Liver dysfunction (liver enzymes > 3 times the baseline, all patients will have a baseline liver function test information), history and exam suggestive of jaundice
- Hypersensitivity to the study drugs
- Active (in the past year) history of alcohol abuse (≥5 drinks per day for men or ≥ 4 drinks per day for women)
- Any history of alcohol withdrawal or delirium tremens
- Delirium at baseline
- Non-English speaking
- Prisoners
- Physician Refusal
- COVID-19 Positive, symptomatic
- Co-enrollment with non-approved interventional trial
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Volume of the placebo (saline) will match that of IV acetaminophen at 100ml 0.9% NaCl IV Acetaminophen IV acetaminophen 1 g IV acetaminophen every 6 hours for 48 hours during the first 2 days postoperatively
- Primary Outcome Measures
Name Time Method Incidence of postoperative delirium Participants will be followed for the duration of the hospital stay, an average of 5 days Occurrence of delirium on any postoperative day, as assessed using the CAM, 3D CAM, CAM Only, or CAM-ICU daily until hospital discharge.
- Secondary Outcome Measures
Name Time Method Length of stay in the Intensive Care Unit (ICU) Measured in days admitted in the ICU, an average of 2 days Defined by the number of days admitted in the ICU prior to transfer to the general cardiac surgical floor
Additional postoperative analgesic requirements First 48 hours postoperatively Amount of opioid (IV morphine or hydromorphone) and oral analgesics required for pain control, reported as overall morphine equivalents. Total Morphine Equivalent is calculated as the sum of (fentanyl dose × 2.4) + (hydromorphone dose × 4) + morphine dose + (oxycodone dose × 1.5).
Duration of delirium Participants will be followed for the duration of the hospital stay, an average of 6 days, and at 1 month, 6 month and 1- year following the date of surgery Total number of in-hospital postoperative days in which delirium is present
Time to onset of delirium Participants will be followed for the duration of the hospital stay, an average of 5 days Measured in days
Worst daily pain scores at rest Participants will be followed for the duration of the hospital stay, an average of 5 days Pain scores will be collected three times daily using a numeric rating scale (0, no pain, to 10, worst possible pain).
Trajectory of cognitive function over time Participants will be followed for the duration of the hospital stay, an average of 6 days, and at 1 month, 6 month and 1- year following the date of surgery Neurocognition will be reported using the Montreal Cognitive Assessment (MoCA) score that ranges from zero (worst possible score) to 30 (best). At one, six, and twelve months postoperatively a telephonic MoCA will be assessed over the phone. The t-MoCA scores range from zero \[worst\] to 22 \[best\]. A hierarchical linear regression model will be used to characterize the trajectory of t-MoCA scores over time.
Incidence of Charted Delirium Participants will be followed for the duration of the hospital stay, an average of 5 days Charted Delirium will be used as a key secondary outcome in addition to the CAM diagnosis. Incidence in patient's chart for diagnoses synonymous with delirium or a change to the patient's baseline mental status as indicated by trigger words associated with a predictive value for delirium
Severity of delirium Participants will be followed for the duration of the hospital stay, an average of 5 days Delirium severity is evaluated both as the peak (highest) and sum CAM-S score over all hospital days
Worst daily pain scores with exertion (deep breathing and cough) Participants will be followed for the duration of the hospital stay, an average of 5 days Pain scores will be collected three times daily using a numeric rating scale (0, no pain, to 10, worst possible pain).
Trajectory of physical function over time. Participants will be followed at 1 month, 6 month and 1- year following the date of surgery Physical function will be assessed using the Medical Outcomes Study Short Form 12 questionnaire (SF-12) physical composite score at one, six, and twelve months postoperatively assessed over the phone. A hierarchical linear regression model will be used to characterize the trajectory of SF-12 scores over time.
Trajectory of chronic pain over time Participants will be followed at 6 month and 1- year following the date of surgery Chronic sternal pain will be assessed using the Numerical Pain Rating Scale (NPRS) at six and twelve months postoperatively assessed over the phone.
Trajectory of functional outcomes over time Participants will be followed at 1 month, 6 month and 1- year following the date of surgery Functional status (self care) will be assessed using the FuncAQ and FRAIL scale at one, six, and twelve months postoperatively assessed over the phone. A hierarchical linear regression model will be used to characterize the trajectory of FuncAQ and FRAIL scores over time.
Length of hospital stay Measured in days admitted in the hospital, an average of 6 days Defined by the number of days admitted in the hospital following the completion of surgery.
Trial Locations
- Locations (10)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of California Irvine
🇺🇸Irvine, California, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
Yale University/Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Albert Einstein College of Medicine- Montefiore
🇺🇸Bronx, New York, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States