Baden Prevention and Reduction of Incidence of Postoperative Delirium Trial

Study Overview
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Brief Summary
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The purpose of this study is to find out whether postoperative delirium can be more properly prevented by the combination of determined preventive agents in past studies. Further on the investigators measure pre- and postoperative cortisol, neuron specific enolase (NSE) and S-100beta levels.

Detailed Description
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The postoperative delirium remains a challenge for medical stuff concerning detection, therapy and avoidance of consequences. Over the years numerous risk factors were detected which emphasizes the importance of its prevention. Within these studies some possibilities, but no strictly defined rules of action for pharmacological or neuropsychological prevention are described. This is why in this randomized, double-blinded, placebo-controlled study, the investigators want to compare two agents that were found to prevent postoperative delirium to a certain level, even in combination: the investigators arrange the patients within four study groups, one receiving Haloperidol, one Ketamine, one both and one placebo. The patients receive the study drug only once right before induction of anesthesia. After the day of recruitment there is the day of operation and a follow-up of three days (5 days of observation in total, where the investigators will test cognitive function with Mini Mental Status Examination (MMSE), Delirium Observation Scale (DOS), Nursing Delirium Screening Scale (Nu-DESC) or Intensive Care Delirium Screening Checklist (ICDSC). Additionally the investigators will measure and compare pre- and postoperative Cortisol, NSE and S-100beta levels.

Official Title
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Baden PRIDe Trial - Baden Prevention and Reduction of Incidence of Postoperative Delirium Trial

Conditions
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Postoperative Delirium

Intervention / Treatment
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* Drug: Haloperidol
* Drug: Ketamine
* Drug: Haloperidol + Ketamine
* Drug: Saline solution (NaCl 0.9%)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 65 years and older Signed agreement Exclusion Criteria: Delirium at admittance or MMSE score <24 points High risk for postoperative ICU treatment Haloperidol or Ketamine intolerance Risk of lack of cooperation Drug an alcohol abuse Dementia QT interval (QTc) prolongation (at least 460ms in men, at least 470ms women) or drugs influencing QT interval, such as class Ia and III antiarrhythmics, Gatifloxacin, Moxifloxacin, Pentamidin, Cotrimoxazol, Tacrolimus, Dolasetron Parkinson's disease Intake of dopaminergic drugs (Levodopa, dopamine agonists) Parkinsonism Epilepsy Unable to be interviewed (severe Dementia, speaking disorders, intubation, respiratory isolation, aphasia, coma, terminal illness) Delay of operation of more than 72 hours past hospital admittance Body weight >100kg

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Haloperidol<br>Haloperidol 0.005mg/kg at induction of anesthesia | Drug: Haloperidol<br>* Haloperidol 0.005mg/kg at induction of anesthesia<br>|
| Active Comparator: Ketamine<br>Ketamine 1mg/kg at induction of anesthesia | Drug: Ketamine<br>* Ketamine 1mg/kg at induction of anesthesia to test its power to prevent postoperative delirium<br>|
| Active Comparator: Haloperidol + Ketamine<br>Combination of Haloperidol + Ketamine in same dosage at induction of anesthesia | Drug: Haloperidol + Ketamine<br>* Haloperidol 0.005mg/kg + Ketamine 1mg/kg at induction of anesthesia to test their power to prevent postoperative delirium if given together<br>|
| Placebo Comparator: Saline solution (NaCl 0.9%)<br>Placebo | Drug: Saline solution (NaCl 0.9%)<br>* Placebo being used in one of the four groups<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences among study groups - Significant drop in MMSE of two points in one of the three postoperative follow-up days | Significant drop in MMSE of two points in one of the three postoperative follow-up days (ICU patients excluded) | 5 day follow-up (preoperative, day of surgery, postoperative days 1-3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of incidence of postoperative delirium based on cognitive testing and lab parameters | Drop of one point in Nursing Delirium Screening Scale (Nu-DESC) compared pre- and postoperatively, comparison of levels of NSE, S-100beta and Cortisol (significantly elevated postoperatively?) | 5 day follow-up (preoperative, day of surgery, postoperative days 1-3) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSE, Postoperative delirium, Cortisol, S-100beta, MMSE, Nu-DESC, ICDSC, DOS, Haloperidol, Ketamine, Combination of Haloperidol and Ketamine, Placebo, Prevention of