Influence of Ketamine on Early Postoperative Cognitive Function After Orthopedic Surgery in Elderly Patients

Abstract

Background:Postoperative cognitive dysfunction (POCD) is a serious and frequent complication after surgery, especially in elderly patients. Ketamine is an N-methyl D-aspartic acid receptor antagonist with demonstrated neuroprotective effects. An intravenous bolus of a sub-anesthetic dose (0.5 mg/kg) of ketamine can reduce postoperative delirium (POD) and POCD after cardiac surgery. But, the influence of ketamine on early POCD after non-cardiac surgery is unclear.Objectives:The current study aimed to evaluate the influence of ketamine on early postoperative cognitive function after orthopedic surgery in elderly patients.Patients and Methods:Fifty six elderly patients (> 60-years-old), scheduled for elective orthopedic surgery during general anesthesia (duration of anesthesia > two hours) were enrolled. Patients received intravenous bolus, a total of 3 mL mixed with 0.9% normal saline and 0.5 mg/kg ketamine (K group) or 3 mL of 0.9% normal saline (N group). Three neurocognitive function tests (mini-mental status examination, trail-making test, digit substitution test), and c-reactive protein (CRP) concentration were determined before surgery and on postoperative day one (POD 1) and postoperative day six (POD 6).Results:The two groups had similar demographic characteristics except for the gender. Surgical and anesthetic data were not significantly different. A statistically significant difference was observed in comparison of trail-making test score. Trail-making test score increased more in the N group (52.5 points) than the K group (13 points) at POD 1 (P = 0.047) compared with baseline scores. There were no significant differences in the mini-mental status examination, digit substitution test and CRP concentration at POD 1 and POD 6 between the two groups. POCD (the two Z-scores in more than two tests or the combined Z-score was 1.96 or more) was present in one patient (4%) in the K group at POD 6 (P = 0.98).Conclusions:The incidence of POCD was not significantly influenced by a bolus dose of ketamine (0.5 mg/kg) after orthopedic surgery in elderly patients. There were no negative effects of ketamine on early POCD.

Patients prone for postoperative delirium

“…Recent randomized, prospective trials, however, could not confirm the effectiveness of haloperidol prophylaxis to reduce incidence or length of delirium [71][72][73]. Ketamine was reported to reduce the incidence of POD in a single-center prospective study in cardiac surgery, whereas no effect was found upon a single dose of 0.5 mg/kg ketamine in a study involving 56 elderly orthopedic patients under general anesthesia [74]. Though lower plasma GABA level had a significant independent association with POD [75], a perioperative course of gabapentin produced only a clinically insignificant improvement in analgesia, but was associated with a higher incidence of sedation [76].…”

Anesthesia and cognitive disorders: a systematic review of the clinical evidence

“…The influence of ketamine on early postoperative cognitive function after orthopedic surgery under GA was studied in a RCT that enrolled 56 (> 60 years old) patients [28]. GA was maintained with propofol, rocuronium, desflurane and remifentanil.…”

Intraoperative ketamine administration to prevent delirium or postoperative cognitive dysfunction: A systematic review and meta‐analysis

“…Of these, 12 were further excluded (not adequately controlled [n = 3], inadequate intervention [n = 3], no outcome of interest [n = 3], no general anaesthesia [n = 3]) . Seven reports comparing the administration of intraoperative ketamine with no intervention (no drug or placebo) were included . Data from 1 trial reported in 2 separate publications were merged under a unique identification (Hudetz 2009) .…”

“…All trials were performed in a major surgery setting except one conducted in a mixed setting (major and minor orthopaedic procedures) . Surgical settings and surgery duration varied across trials.…”