The Impact of Ketamine on Postoperative Cognitive Dysfunction, Delirium, and Renal Dysfunction

The Impact of Ketamine on Postoperative Cognitive Dysfunction, Delirium, and Renal Dysfunction in Patients 75 Years of Age or Older and Undergoing Cardiac Surgery

Ketamine is a commonly used anesthetic medication which is used for induction of anesthesia as well as as an analgesic. It has been shown to have anti-inflammatory properties which may decrease post-operative complications following cardiac surgery with cardiopulmonary bypass that are thought to associated with inflammation. Some studies have shown that ketamine does decrease these complications when compared with anesthetics that are not commonly used in our cardiac anesthesiology practice. Propofol is another commonly used anesthetic medication which is used for induction of anesthesia. Ketamine has not been compared with propofol for potential to reduce post-operative complications associated with the inflammatory process. This study aims to see if ketamine will reduce the incidence of cognitive dysfunction, delirium, and renal dysfunction in comparison with propofol. In addition, the hemodynamic impact of ketamine compared propofol will be investigated.

Study Overview

• Status: Completed
• Conditions: Delirium; Acute Kidney Injury; Cognitive Disorders
• Intervention / Treatment: Drug: Ketamine; Drug: Propofol

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Scheduled to undergo cardiac surgery.

Inclusion criteria:

• age greater than or equal to 75 years presenting for cardiac surgery at the Mayo Clinic in Rochester, Minnesota;
• schedule to undergo complex cardiac surgery. Complex cardiac surgery will be defined as surgery involving more than one heart valve, redo-sternotomy procedures, or combined valvular and CABG procedures.

Exclusion criteria will include:

• left or right ventricular assist device implantation or explantation,
• procedures not requiring cardiopulmonary bypass,
• active infection or sepsis, severe hepatic disease or ascites,
• pre-operative renal dysfunction including a baseline creatinine equal to or greater than 1.5 mg/dL or requiring dialysis,
• immunosuppressive medication use (including steroid use),
• immunodeficiency syndrome,
• known neurologic or psychiatric disorder, or
• use of drugs for psychosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ketamine; Ketamine induction	Drug: Ketamine; Ketamine used for induction; Other Names: Ketalar
Active Comparator: Propofol; Propofol induction	Drug: Propofol; Propofol for induction; Other Names: Diprivan; Propoven

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Postoperative Cognitive Dysfunction	Pre and postoperative cognitive studies will be performed to assess change in cognitive function. Postoperative cognitive dysfunction (POCD) was defined a-priori as a decline of decline of >1 standard deviation (i.e. z-score decline of > 1) on at least 2 neurocognitive tests. The neurocognitive tests utilized include Trail making Test A, Trail making Test B, Hopkins Verbal Learning Test-Revised Learning trials, Hopkins Verbal Learning Test-Revised Delayed Recall, Digit Span, Controlled Oral Word Association Test, Stroop color/word test, and the Mini Mental Status Examination.	Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Acute Kidney Injury	AKI was defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria including an increase in serum creatinine ≥0.3 mg/dL within 48 hours, an increase in serum creatinine to ≥1.5 times baseline within 7 days, and urine output < 0.5 mL/kg/hr for 6 hours.	Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first.
Number of Patients Who Develop Postoperative Delirium	Delirium was defined as a positive CAM (Confusion assessment method) score. CAM score was recorded every 12 hours postoperatively as per routine. The CAM consists of 4 features: 1-Onset, 2-Inattention, 3-Disorganized thinking, and 4-altered level of consciousness. The diagnosis of delirium by CAM is based on the presence of features 1 and 2, and either 3 or 4. The score is either positive or negative. Positive means the patient has delirium and negative indicates the patient is not delirious.	Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first.

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Erica Wittwer, MD, PhD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: September 16, 2015
• First Submitted That Met QC Criteria: September 17, 2015
• First Posted (Estimate): September 18, 2015

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: January 24, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Kidney Diseases; Urologic Diseases; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Renal Insufficiency; Cognitive Dysfunction; Postoperative Cognitive Complications; Acute Kidney Injury; Cognition Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Hypnotics and Sedatives; Ketamine; Propofol
• Other Study ID Numbers: 14-007148

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No