Effect of Dexmedetomidine versus Ketamine on postoperative delirium and early cognitive dysfunction after off pump coronary artery bypass grafting: A prospective randomized study

Delirium is defined as a disturbance in attention, cognition, and/or awareness that develops over a short period, has a fluctuating course, and is accompanied by a change in cognition. Post-operative delirium (POD) can occur from 10 minutes after anesthesia to up to 7 days in the hospital or until discharge. In cardiac surgery patients, the incidence is between 26% and 52%. Postoperative cognitive dysfunction (POCD), characterized by impairment of attention, concentration, and memory with possible long-term implications, is a frequent neurological sequela following cardiac surgery. A retrospective study demonstrated that coronary artery bypass grafting (CABG) is the most common cause of POCD after a cardiac operation with an incidence of 37.6% in 7 days and 20.8% in the 3rd month of the postoperative period.

Dexmedetomidine a highly potent α2-agonist is used widely in critical care for control of delirium. Further, there is some evidence that ketamine which is a N-methyl-D-aspartic acid (NMDA) antagonist might also be an option to reduce the risk of POD and POCD in surgical patients.

Although several pharmacological agents have been studied individually, but these are not compared in terms of efficacy in reducing cognitive dysfunction after cardiac surgeries till date.

 Our primary objective is 1) To determine the difference in the CAM-ICU score among group D, group K, and group S, on 3rd postoperative day using CAM-ICU (Confusion Assessment Method) scoring for delirium in patients undergoing elective off-pump coronary artery bypass grafting. 2)To determine the changes in the neuropsychological test scores between group D, group K and group S, on 7th postoperative day using composite Z score of four neuropsychological tests in patients undergoing elective off-pump coronary artery bypass grafting. We will also compare the incidence of POD and POCD, hemodynamic stability, time of extubation, duration of ICU and hospital stay, in both the groups.

 Patients aged 45-85 years, of either sex belonging to American Society of Anesthesiologists physical status class I, II & III, posted for elective OPCAB surgery will be enrolled over a period of 18 months. Preoperative Mini-mental state examination (MMSE) will be used as a screening tool. Patients with MMSE<24 will be excluded. Baseline cognitive evaluation will be conducted using a battery of neuropsychological tests for comprehensive preoperative assessment of the cognitive status including memory, attention, language, executive function, and motor speed. These tests are Rey auditory verbal learning test ,Trail-making A and B test, Stroop color interference test, Letter Digit coding test. All the included patients will be randomized into three groups using computer generated random number through a software. Group D**:** Patients will receive continuous infusion of injection Dexmedetomidine @ 5ml/hr (0.5µg/kg/h), Group K**:**  Patients will receive continuous infusion of injection Ketamine @5ml/hr (0.3mg/kg/h) ,Group S: Patients will receive continuous infusion of normal saline @5ml/hr .The infusions will be started 10 minutes after the induction and after ensuring stable hemodynamic and will be continued till the end of surgery. The patients will be assessed on 3rd postoperative day for delirium and 7th day for cognitive dysfunction.

 Assessment of outcomes will be done as follows.1)Postoperative delirium will be assessed through Confusion Assessment Method (CAM-ICU) (Annexure 3) scoring on 3rd postoperative day; with scoring of 0-2: no delirium, 3-5: mild to moderate delirium, and 6-7: severe delirium. 2)Postoperative Cognitive Dysfunction will be assessed on 7th postoperative day through four neuropsychological tests (Rey auditory verbal test, Trail making A and B test, Stroop color word interference test, Letter digit coding test). Patient will be diagnosed with cognitive dysfunction if the composite Z score will be 1.96 or more, from the composite Z score one day before surgery or when the patient had two Z scores in individual tests at one week. Assessment of secondary outcomes will be done as follows. Intraoperative heart rate, mean arterial pressure and oxygen saturation will be noted .Duration of ICU stay (from the time of arrival to ICU till shifting to ward) and length of hospital stay (from the day of surgery till the discharge of patient from the hospital) will also be noted.