Rate of Postoperative Delirium and Postoperative Cognitive Dysfunction After Spinal Anesthesia

Study Overview
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Brief Summary
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The aim of this investigation is to compare the standard of general anesthesia used in these patients with these short-acting local anesthetics (Chloroprocain (Ampres®) and Prilocain (Takipril®)) for spinal anesthesia as well as to report the patient centered outcome of postoperative delirium and neurocognitive disorder. In accordance to current evidence regarding the occurrence of postoperative delirium and postoperative cognitive deficit, patients are to be screened daily for delirium up to the fifth postoperative day if in hospital, or till the first postoperative day after ambulatory surgery and for neurocognitive disorder 1 year following the surgery. To detect delirium the Nu-DESC (Nursing Delirium Screening Scale) will be used as a validated scoring systems to ensure the highest sensitivity in delirium identification. CANTAB battery will be used for assessment of neurocognitive disorder. This is a neuropsychological testing (computer-based (I-Pad) [Cambridge Neuropsychological Test Automated Battery - CANTAB connect and parameters from the item list], as well as the subjective / by proxy Assessment of Cognitive Limitations. It is essential to perform the appropriate cognitive performance tests not only on operative patients but also on a non-surgical cohort, using currently established models of calculation in postoperative cognitive deficits and a control group generated from non-surgical patients.

Detailed Description
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A conventional spinal anesthesia with long-acting drugs (such as bupivacaine) can lead to delays in postoperative recovery, mobilization, delays in discharge from recovery room and in ambulatory surgery. Short-acting local anesthetics (Chloroprocain (Ampres®) and Prilocain (Takipril®)) might be beneficial in short duration surgery under spinal anesthesia and could improve patients' acceptance for neuroaxial anesthesia as it might improve early recovery and early mobilization. Time to first oral nutritional intake/postoperative nausea and vomiting (PONV), time to discharge from post-anesthesia recovery unit and time to discharge home after ambulatory operation might be reduced and might reduce incidence of postoperative delirium and neurocognitive disorder after peripheral surgery. It is planned to retrospectively examine a group of surgical patients for the purpose of a comparative descriptive collective. This comparison collective is required for various questions, in particular influencing factors with regard to the postoperative outcomes delirium, neurocognitive disorder and mortality. Only the routine data is used and no additional surveys are performed on these patients. Inclusion criteria such as the study cohort and additionally the inclusion criterion: Spinal anesthesia with another local anesthetic

Official Title
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Rate of Postoperative Delirium and Postoperative Cognitive Dysfunction After Spinal Anesthesia With Short-acting Local Anesthetics Compared to General Anesthesia After a Shared Decision Making Process

Conditions
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Delirium

Intervention / Treatment
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* Procedure: Spinal anesthesia with short-acting local anesthetics
* Procedure: General anesthesia (current standard)


Participation Criteria
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Eligibility Criteria
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Study group 1 and 2 Inclusion Criteria: Surgical patients at Campus Virchow - Klinikum and Campus Charité Mitte (Charité - Universitätsmedizin Berlin) Short, elective procedure (<90 minutes), feasible in spinal anesthesia American Society of Anesthesiologists (ASA-Score I to III) Age ≥ 18 years Informed consent process Exclusion Criteria: Non-consenting patients Lack of consent to participate in the study or to store, process and disseminate pseudonymised study data Allergy or contraindications to local anesthetics Contraindications to spinal anesthesia Coagulopathy or therapy with anticoagulants Higher grade aortic stenosis Anomaly of the spinal cord Pre-existing neurological deficit Pre-existing neurological disease that severely limits the performance of neurocognitive testing Hearing and / or visual disturbances (such as color blindness) or relevant language barrier severely limiting the performance of neurocognitive testing Spinal anesthesia with another local anesthetic Sole peripheral local anesthesia Participation in another prospective intervention study Emergency operation Pregnancy and breast feeding period POCD Control group: Inclusion criteria: Male and female patients ages 18-100 years, also controls from the POCD registry (EA1/104/16) Healthy volunteers (ASA I) / ASA II + III patients who are not scheduled for surgery next year Ability to consent to oral and written information Patient education and written consent Exclusion criteria: Operation in the last six months before inclusion in this study Lack of consent for the pseudonymised disease data to be stored and shared in this clinical trial Lack of readiness to participate in the follow-up examinations and contact to make an appointment Patients with a neuropsychiatric condition that limits the performance of neurocognitive testing Patients with hearing and / or vision disorders or relevant language barriers that limit the performance of neuro-cognitive testing Simultaneous participation in a prospective clinical intervention study

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study group 1<br>n=220 patients for routine data of spinal anesthesia with short-acting local anesthetics | Procedure: Spinal anesthesia with short-acting local anesthetics<br>* Spinal anesthesia in patients with duration of surgery < 90 minutes<br>|
| Study group 2<br>n= 220 patients for routine data of general anesthesia (current standard) | Procedure: General anesthesia (current standard)<br>* General anesthesia in patients with duration of surgery < 90 minutes<br>|
| No intervention: Control group postoperative cognitive deficit<br>n= 90 control subjects aged 18 years or older (without surgery) with a similar health status and age as the study group patients (similar distribution in the American Society of Anaesthesiologists physical status classification and relevant co-morbidities, e.g. diabetes, coronary artery disease, hypertension and hyperlipidemia). The patients are analyzed to correct for learning effects of the cognitive assessment testings in the study groups. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of postoperative delirium | Postoperative delirum rate, defined according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and/or as ≥ 2 cumulative points in the nursing Delirium Screening Scale (Nu-DESC) and/or a positive Confusion Assessment Method (CAM) Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score and/or patient chart review that shows descriptions of delirium. The basis is the elevation of the sedation depth with the Richmond Agitation Sedation Scale (RASS). | Up to five postoperative days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perioperative cognitive disturbances | Cognitive disorders are evaluated according to DSM-V (formal cognitive testing, subjective memory sensing and instrumental activities of daily living, ). | Up to 1 year | 
| MONTREAL COGNITIVE ASSESSMENT (MOCA) | Test performance of the MONTREAL COGNITIVE ASSESSMENT (MOCA) for screening of dementia | Up to 1 year | 
| Formal cognitive testing | Perioperative changes of damain specific test performance in formal cognitive testing | Up to 1 year | 
| Postoperative cognitive dysfunction (POCD) | Postoperative cognitive dysfunction (POCD) is measured by computerized Cambridge Neuropsychological Test Automated Battery - CANTAB connect and paper pencil testing and subjective memory sensing. | Up to 1 year | 
| Duration of delirium | Diagnostic and Statistical Manual of Mental Disorders (DSM-V) Nursing Delirium Screening Scale (Nu-DESC) Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) Confusion Assessment Method (CAM) Chart Review | Participants will be followed for the duration of hospital stay, an expected average of 7 days ] | 
| Severity of delirium | Diagnostic and Statistical Manual of Mental Disorders (DSM-V) Nursing Delirium Screening Scale (Nu-DESC), Confusion Assessment Method (CAM) and or Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), Chart Review | Participants will be followed for the duration of hospital stay, an expected average of 7 days ] | 
| Time to mobilization |  | Up to five postoperative days | 
| Time to first oral nutritional intake |  | Up to five postoperative days | 
| Time until leaving the recovery room | Fulfillment of discharge criteria from the recovery room | Up to leaving the recovery room | 
| Time until leaving hospital | Fulfillment of discharge criteria from hospital after study procedure | Up to five postoperative days | 
| Organ complications according to Clavien |  | Up to five postoperative days | 
| Autonomy Preference Index (API) |  | Up to five postoperative days | 
| Questionnaire for shared decision making (PEF-FB-9) | Results from PEF-FB-9 are evaluated | Up to five postoperative days | 
| Total treatment outcome in terms of quality of life of patients | EQ-5D | Up to 1 year | 
| Total treatment outcome in terms of functional autonomy of patients | Activities of Daily Living (ADLs) or Instrumental Activities of Daily Living (IADLs) | Up to 1 year | 
| Intraoperative Neuromonitoring |  | Up to the end of surgical procedure | 
| Cerobrospinal fluid parameter | Beta-Amyloid 1-40, beta-Amyloid 1-42, beta-Amyloid Ratio (42/40*10), phospho-TAU, Protein 14-3-3, PRPSc, TAU (Gesamt-Tau) from cerobrospinal fluid for measuring dementia | Until the end of surgery | 
| Apolipoprotein E | Blood marker Apolipoprotein E for measuring dementia | Until the end of surgery | 
| Multiplex Gene Expression Analysis (Whole Blood) |  | Until first postoperative day | 
| Antibodies | Antibody from serum (anti-beta2-adrenergic receptor, anti-muscarinic acetylcholine receptor (M3 / M4), anti-serotonin receptor, anti-dopamine receptor) | Until first postoperative day | 
| Pro and anti-inflammatory markers | IL-8 from whole blood and IL-6, IL-8 and TGF | Until first postoperative day | 
| Immune cells | Immune cells from citrate blood | Until first postoperative day | 
| Autophagy of platelets | Autophagy of platelets from citrate blood | Until first postoperative day | 
| Intracellular pH | Intracellular pH from citrate blood | Until first postoperative day | 
| Cholinesterases |  | Until the third postoperative day | 
| Anxiety 1 | Anxiety 1 is measured by Generalized Anxiety Disorder 7 (GAD-7) and Patient Health Questionnaire 9 (PHQ-9) | Up to 1 year | 
| Anxiety 2 | Anxiety 2 is measured by Amsterdam Preoperative Anxiety and Information Scale (APAIS) and Faces Anxiety Scale (FAS) | Up to 1 year | 
| Subsequent surgery | Results from subsequent surgery are evaluated | Up to 1 year | 
| Obstructive Sleep Apnea (OSAS) | Obstructive Sleep Apnea (OSAS) is measured by the STOP-Bang Questionnaire. | Up to 1 year | 
| Fatigue | Fatigue is monitored by Acute Fatigue Score | Up to 1 year | 
| Sleep behavior | Sleep behaviour is measured by Insomnia Severity Index (ISI) at baseline, 3 months, 1 year | Up to 1 year | 
| Sleep behavior | Sleep behaviour is measured by intraclinical course (immediate perioperative: Richards Campbell Sleep Questionnaire) | Participants will be followed for the duration of hospital stay, an expected average of 7 days ] | 
| Frailty | Frailty is measured with a modified frailty score according to Fried´s frailty phenotype assessment | Participants will be measured at the beginning of the investigation. | 
| Stress | Stress is monitored by Perceived Stress Questionnaire 20 (PSQ20) and Disstressthermometer without areas | Up to 1 year | 
| Dose of concomitant medication | The types of medications used in the management of pain, agitation, and delirium on that day are documented. | Up to 5 postoperative days | 
| Duration of concomitant medication | The types of medications used in the management of pain, agitation, and delirium on that day are documented. | Up to 5 postoperative days | 
| Time of mechanical ventilation |  | Participants will be followed for the duration of intensive care unit stay, an expected average of 1 day] | 
| Intensive care unit stay |  | Participants will be followed for the duration of intensive care unit stay, an expected average of 1 day] | 
| Number of stationary recoveries |  | Up to 1 year | 
| Visits to doctors and outpatient treatments |  | Up to 1 year | 
| Number of additional operations |  | Up to 1 year | 
| Mortality |  | Up to 1 year |