The Prevention of Delirium and Complications Associated With Surgical Treatments Multi Center Clinical Trial

Condition(s) targeted: Delirium

Intervention: Ketamine (0.5 mg/kg) (Drug); Normal Saline (placebo) (Drug); Ketamine (1 mg/kg) (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Washington University School of Medicine

Official(s) and/or principal investigator(s):
George A Mashour, MD PhD, Principal Investigator, Affiliation: University of Michigan
Daniel A Emmert, MD PhD, Study Director, Affiliation: Washington University School of Medicine
Kane Pryor, MBBS, Study Director, Affiliation: Cornell
Eric Jacobsohn, MB ChB, Study Director, Affiliation: University of Manitoba
Judith Hudetz, PhD, Study Director, Affiliation: Medical College of Wisconsin
Hilary P Grocott, MD, Study Chair, Affiliation: University of Manitoba
Michael S Avidan, MBBCh, Principal Investigator, Affiliation: Washington University School of Medicine
Sharon Inouye, Study Director, Affiliation: Harvard Medical School
Robert Veselis, Study Director, Affiliation: Memorial Sloan Kettering Medical Center
Jayant Aveek, Study Director, Affiliation: Postgraduate Institute of Medical Education and Research
Heiko Kaiser, Study Director, Affiliation: University of Bern
Stephen Choi, Study Chair, Affiliation: University of Toronto
Ryan Pong, Study Chair, Affiliation: Virginia Mason Medical Center
Gyujeong Noh, Study Director, Affiliation: Asan Medical Center

Delirium is a medical term or condition that includes a temporary inability to focus attention and to think clearly. Delirium occurs commonly (10% to 70%) in patients older than 60 undergoing large surgeries. The purpose of this study is to test rigorously whether a drug called ketamine can decrease the chance that patients will experience delirium after their surgery. The investigators are also testing whether ketamine decreases postoperative pain, postoperative opioid consumption, postoperative nausea and vomiting, ICU and hospital length of stay, and adverse outcomes (e. g. hallucinations and nightmares).

Official title: The Prevention of Delirium and Complications Associated With Surgical Treatments Multi Center Clinical Trial

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome: Delirium

Secondary outcome:

Acute pain

Postoperative opioid consumption

Postoperative nausea and vomiting

ICU and/or hospital length of stay

Adverse outcomes (e.g. hallucinations and nightmares)

Detailed description: Postoperative delirium is one of the most common complications of major surgery, affecting between 10% and 70% of all elderly surgical patients. Delirium manifests as poor attention and inability to think logically, and is associated with longer intensive care unit and hospital stay, long lasting cognitive deterioration, and increased mortality rate. Studies have shown that a low sub-anesthetic dose of ketamine, an anesthetic drug, has the potential to decrease several postoperative complications, including delirium, pain, opioid consumption, and nausea and vomiting. Low dose ketamine would be particularly appealing as a drug to prevent delirium and other postoperative complications, as it is inexpensive and extremely safe. However, these proposed benefits of ketamine in the perioperative setting have not yet been tested in a large clinical trial. The investigators are therefore proposing a pragmatic, exploratory clinical trial to support or refute the contention that low dose ketamine decreases the incidence of postoperative delirium, with the possibility of conducting a larger randomized clinical trial pending the results of this study. At the time of enrollment, patients will undergo the same delirium and pain evaluation that will be used postoperatively. Additionally patients will be screened for functional dependence using the Barthel Index of Activities of Daily Living, for depression using the Geriatric Depression

Scale - Short Form, and for obstructive sleep apnea using the STOP-Bang criteria. They will

also be asked about any falls they have experienced in the six months prior to surgery. Comorbid conditions, including the components of the Charlson Comorbidity Index, will be obtained by reviewing the patients' medical records. Any available preoperative lab results, including electrolytes and blood counts, will also be recorded. Patients will be randomized to receive low dose ketamine or placebo following induction of anesthesia and prior to surgical incision. Blinded observers will assess delirium on the afternoon/evening of postoperative day 0 (if feasible) and twice daily (morning and afternoon/evening with at least six hours between assessments) on postoperative days 1-3 using the Confusion Assessment Method or the Confusion Assessment Method for Intensive Care Unit. Acute pain will be assessed via the observer-based Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) with subsequent administration of the patient-reported Visual Analog Scale from postoperative days 0-3. Postoperative opioid consumption will be assessed from the patients' medical charts for postoperative days 0-3. Postoperative nausea and vomiting will be assessed via a patient-reported section of the Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) for postoperative days 0-3. ICU and/or hospital length of stay will be assessed from the patients' medical charts. Adverse outcomes (e. g. hallucinations and nightmares) will be assessed via the Confusion Assessment Method or the Confusion Assessment Method for Intensive Care Unit for postoperative days 0-3.

Minimum age: 60 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients 60 and older

- Competent to provide informed consent

- Undergoing major surgery (e. g., open cardiac surgery, open or thoracoscopic thoracic

surgery, abdominal surgery, open urological surgery, open gynecological surgery, major orthopedic surgery, major vascular surgery including endovascular procedures, major ear, nose and throat surgery). Exclusion Criteria:

- Patients with an allergy to ketamine

- Those in whom a significant elevation of blood pressure would constitute a serious

hazard (e. g., pheochromocytoma, aortic dissection)

- Unable to provide informed consent

- Patients with drug misuse history (e. g., ketamine, cocaine, heroin, amphetamine,

methamphetamine, MDMA, phencyclidine, lysergic acid, mescaline, psilocybin)

- Patients taking anti-psychotic medications (e. g., chlorpromazine, clozapine,

olanzapine, risperidone, haloperidol, quetiapine, risperidone, paliperidone, amisulpride, sertindole)

- Patients with a weight outside the range 50 kg - 200 kg (110 lbs - 440 lbs)

Washington University School of Medicine, St. Louis, Missouri 63110, United States; Recruiting
Michael Avidan, MD, Phone: 314-747-4155, Email: avidanm@anest.wustl.edu
Michael Avidan, MD, Principal Investigator

Starting date: February 2014
Last updated: February 12, 2015