Strengths and limitations of the study
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The trial tests the preventative properties of ketamine and haloperidol, which can be demonstrated in a broad field of surgical procedures.
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No adverse events are to be expected from the administration of the trial medication as a weight-dependent single dose following careful consideration of exclusion criteria.
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Evidence from previous studies suggests a considerable benefit for prevention of delirium along with increased comfort and safety for patients involved in the study.
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The Baden PRIDe Trial will primarily recruit patients from two Swiss anaesthesiology departments to achieve the calculated sample size within the foreseen time period.
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The study is limited by the heterogeneous risk constellation of our patients considering the risk factors for delirium that have been gathered to date.
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These variable conditions will not be addressed by the evaluation of a score to assess patient comorbidity (e.g., Simplified Acute Physiology Score II).
Background
Methods
Study setting
Eligibility criteria
Inclusion criteria
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Adult patients age 65 years or older
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Scheduled for surgery within the following fields:
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○ Visceral
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○ Orthopaedic
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○ Vascular
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○ Gynaecological
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○ Cardiac
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○ Thoracic
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Receive general or combined anaesthesia for their surgery
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Signed informed consent agreement
Exclusion criteria
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Delirium upon hospital admission or during the course of the hospital stay or Mini Mental State Examination (MMSE) score < 24 points or a Delirium Observation Screening Scale (DOS) score ≥ 3 points
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Dementia
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High risk of postoperative treatment in the intensive care unit (ICU) (standard procedure excluded)
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Known haloperidol or ketamine intolerance
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Lack of cooperation or lack of communication possibilities
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○ Speech disorders
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○ Isolation
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○ Aphasia
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○ Coma
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○ Terminal illness
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○ Drug or alcohol abuse
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QT interval (QTc) prolongation (≥ 460 ms in men, ≥ 470 ms in women) or drugs influencing QT interval (see Appendix)
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Parkinson’s disease
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Parkinsonism
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Intake of dopaminergic drugs (levodopa, dopamine agonists)
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Epilepsy
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Delay of surgery for > 72 h after set indication for surgery
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Body weight > 100 kg
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Patient is unable to read German
Interventions
Treatment arms | Assigned interventions |
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Active comparator: haloperidol | Haloperidol 0.005 mg/kg body weight at induction of anaesthesia |
Active comparator: ketamine | Ketamine 1 mg/kg body weight at induction of anaesthesia |
Active comparators: haloperidol + ketamine in combination | Haloperidol 0.005 mg/kg body weight + ketamine 1 mg/kg body weight at induction of anaesthesia |
Placebo comparator | Normal saline (NaCl 0.9%) |
Haloperidol: 5 μg/kg body weight diluted in NaCl 0.9%, haloperidol 5 mg/ml concentrate | |||||
Weight (kg) | Haloperidol (mg) | NaCl (ml) | Weight (kg) | Haloperidol (mg) | NaCl (ml) |
40–50 | 0.5 | 19.5 | 71–80 | 0.8 | 19.2 |
51–60 | 0.6 | 19.4 | 81–90 | 0.9 | 19.1 |
61–70 | 0.7 | 19.3 | 91–100 | 1.0 | 19.0 |
Ketamine: 1 mg/kg body weight diluted in NaCl 0.9%, ketamine 50 mg/ml concentrate | |||||
Weight (kg) | Ketamine (mg) | NaCl (ml) | Weight (kg) | Ketamine (mg) | NaCl (ml) |
40–50 | 50 | 19.0 | 71–80 | 80 | 18.4 |
51–60 | 60 | 18.8 | 81–90 | 90 | 18.2 |
61–70 | 70 | 18.6 | 91–100 | 100 | 18.0 |
Outcomes
Primary outcome measure
Secondary outcome measures
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A 1-point drop in Nu-DESC score on 1 of the 3 postoperative days
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Significant elevation of study-specific laboratory values after surgery:
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○ Elevation of NSE above 16.3 μg/l (normal value)
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○ Elevation of S-100β above 0.1 μg/l (normal value) or doubling of the preoperative value
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○ Elevation of cortisol level above 638 nmol/l (upper limit of normal range)
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