Impact of Esketamine on Delayed Neurocognitive Recovery in Older Patients
Trial statusNot yet recruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age65-90
SponsorPeking University First Hospital
About this trial
Esketamine is frequently used during the perioperative period for supplemental analgesia. Small sample size trials showed that subanesthetic dose esketamine may decrease postoperative neurocognitive complications. However, conflicting results exist and optimal dose of esketamine remains to be determined. This dose-exploring pilot trial is designed to evaluate the safety and efficacy of three different perioperative esketamine dosing regimens in older patients undergoing major non-cardiac surgery. The primary purpose is to explore the optimal dosing strategy that produce maximal neurocognitive benefits with minimal adverse neuropsychiatric symptoms.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Aged >=65 but <= 90 years;
Scheduled to undergo non-cardiac surgery with an expected duration of >= 2 hours under general anesthesia;
Requiring patient-controlled intravenous analgesia (PCIA) after surgery.
Disqualifiers
Unable to communicate preoperatively due to visual or auditory impairment, language barrier, or severe dementia;
Comorbid with schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis;
Traumatic brain injury or neurosurgery;
Severe hepatic dysfunction (Child-Pugh Class C), severe renal dysfunction (receiving dialysis preoperatively), or American Society of Anesthesiologists physical status classification >= Ⅳ;
Trial design
Design model
Parallel
Treatments tested in this trial
Esketamine 1
DrugDuring anesthesia, a loading dose esketamine (0.5 mg/ml) 0.4 ml/kg will be infused over 30 minutes (0.1 mg/kg) after anesthesia induction, followed by a continuous infusion at 0.1 ml/kg/h (0.05 mg/kg/h) until 1 hour before the expected end of surgery. After surgery, patient-controlled intravenous analgesia will be established with esketamine (0.25 mg/ml) and sufentanil (1 ug/ml), programmed to deliver 2-ml bolus (0.5 mg esketamine) with a 8-10-minute lock-out time and a 1-ml/h (0.25 mg/h esketamine) background infusion, and used for up to 48 hours.
Esketamine 2
DrugDuring anesthesia, a loading dose esketamine (1.0 mg/ml) 0.4 ml/kg will be infused over 30 minutes (0.2 mg/kg) after anesthesia induction, followed by a continuous infusion at 0.1 ml/kg/h (0.1 mg/kg/h) until 1 hour before the expected end of surgery. After surgery, patient-controlled intravenous analgesia will be established with esketamine (0.5 mg/ml) and sufentanil (1 ug/ml), programmed to deliver 2-ml bolus (1 mg esketamine) with a 8-10-minute lock-out time and a 1-ml/h (0.5 mg/h esketamine) background infusion, and used for up to 48 hours.
Esketamine 3
DrugDuring anesthesia, a loading dose esketamine (1.5 mg/ml) 0.4 ml/kg will be infused over 30 minutes (0.3 mg/kg) after anesthesia induction, followed by a continuous infusion at 0.1 ml/kg/h (0.15 mg/kg/h) until 1 hour before the expected end of surgery. After surgery, patient-controlled intravenous analgesia will be established with esketamine (0.75 mg/ml) and sufentanil (1 ug/ml), programmed to deliver 2-ml bolus (1.5 mg esketamine) with a 8-10-minute lock-out time and a 1-ml/h (0.75 mg/h esketamine) background infusion, and used for up to 48 hours.
Normal saline
DrugDuring anesthesia, a loading dose placebo (normal saline) 0.4 ml/kg will be infused over 30 minutes after anesthesia induction, followed by a continuous infusion at 0.1 ml/kg/h until 1 hour before the expected end of surgery. After surgery, patient-controlled intravenous analgesia will be established with sufentanil (1 ug/ml), programmed to deliver 2-ml bolus with a 8-10-minute lock-out time and a 1-ml/h background infusion, and used for up to 48 hours.
Treatment groups
120 Participants
are divided into 4 treatment groupsGroup A: Esketamine dose 1Experimental treatment 1 intervention
Group B: Esketamine dose 2Experimental treatment 1 intervention
Group C: Esketamine dose 3Experimental treatment 1 intervention
Group D: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Incidence of dissociative symptoms
Dissociative symptoms will be assessed at 30 minutes after extubation and then twice daily (8:00-10:00, 18:00-20:00) during the first 4 days after surgery, using the 6-item Clinician Administered Dissociative State Scale (CADSS-6; scores range frrom 0 to 24 with higher scores indicating more severe dissociative symptoms; a score \>=3 indicates presence of dissociative symptoms).
Time frame
Up to 4 days after surgerySecondary outcomes
1
Incidence of emergence delirium
Emergence delirium will be assessed at 30 minutes after extubation, during stay in the postanesthesia care unit, using the Confusion Assessment Methods for the Intensive Care Unit (CAM-ICU).
Time frame
At 30 minutes after extubation2
Incidence of postoperative delirium
Postoperative delirium will be assessed twice daily (8:00-10:00, 18:00-20:00) during the first 4 days after surgery, using the 3-Minute Diagnostic Interview for the Confusion Assessment Method (3D-CAM) for non-intubated patients or the Confusion Assessment Methods for the Intensive Care Unit (CAM-ICU) for intubated patients.
Time frame
Up to 4 days after surgery3
Incidence of delayed neurocognitive recovery
Cognitive function will be assessed with the Montreal Cognitive Assessment (MoCA; scores range from 0 to 30, with higher scores indicating better function) at baseline and on the 5th day/before hospital discharge after surgery. Delayed neurocognitive recovery is defined as \|Z\| score of MoCA decline \>=1.96. Z score = (MoCA change of patients - MoCA change of normal control)/standard deviation of MoCA change of normal control.
Time frame
Up to 5 days after surgeryOther outcomes
1
Area under curve of dissociative symptom severity at various timepoints after surgery
Dissociative symptoms will be assessed at 30 minutes after extubation and then twice daily (8:00-10:00, 18:00-20:00) during the first 4 days after surgery, using the 6-item Clinician Administered Dissociative State Scale (CADSS-6; scores range from 0 to 24 with higher scores indicating more severe dissociative symptoms; a score \>=3 indicates presence of dissociative symptoms).
Time frame
Up to 4 days after surgery2
Area under curve of pain intensity at various timeoints after surgery
Pain intensity will be assessed at 30 minutes after extubation and then twice daily (8:00-10:00, 18:00-20:00) during the first 4 days after surgery, using the Numeric Rating Scale (NRS; scores range from 0 to 10 with 0=no pain at all and 10=the worst pain).
Time frame
Up to 4 days after surgery3
Scores of subjective sleep quality after surgery
Subjective sleep quality will be assessed once daily (8:00-10:00) during the first 4 days after surgery, using the Numeric Rating Scale (NRS; scores range from 0 to 10 with 0=the best sleep quality and 10=the worst sleep quality).
Time frame
Up to 4 days after surgery4
Severity of anxiety after surgery
Severity of anxiety will be assessed on the 5th day or before hospital discharge after surgery, using the Generalized Anxiety Disorde-7 (GAD-7; scores range from 0 to 21 with higher scores indicating more severe anxiety).
Time frame
Up to 5 days after surgerySponsors and contacts
Click on the lead sponsor to view all of their trials.
Peking University First Hospital
Lead sponsor
Tianjin Medical University General Hospital
Collaborator
Source ClinicalTrials.gov
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