Rate of Postoperative Delirium and Postoperative Cognitive Dysfunction After Spinal Anesthesia

• ClinicalTrials.gov Identifier: NCT03715244
• Recruitment Status: Active, not recruiting
• First Posted: October 23, 2018
• Last Update Posted: August 9, 2021
• Sponsor: Charite University, Berlin, Germany
• Information provided by (Responsible Party): Claudia Spies, Charite University, Berlin, Germany

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Delirium	Procedure: Spinal anesthesia with short-acting local anesthetics; Procedure: General anesthesia (current standard)

Detailed Description:

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

Study Design

• Study Type: Observational
• Actual Enrollment: 237 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: 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
• Actual Study Start Date: March 12, 2019
• Estimated Primary Completion Date: November 30, 2021
• Estimated Study Completion Date: December 30, 2021

Groups and Cohorts

Group/Cohort	Intervention/treatment
Study group 1; n=220 patients for routine data of spinal anesthesia with short-acting local anesthetics	Procedure: Spinal anesthesia with short-acting local anesthetics; Spinal anesthesia in patients with duration of surgery < 90 minutes
Study group 2; n= 220 patients for routine data of general anesthesia (current standard)	Procedure: General anesthesia (current standard); General anesthesia in patients with duration of surgery < 90 minutes
No intervention: Control group postoperative cognitive deficit; 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.

Outcome Measures

Primary Outcome Measures :

1. Rate of postoperative delirium [ Time Frame: Up to five postoperative days ]
   Postoperative delirium 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) and/or 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).

Secondary Outcome Measures :

1. Perioperative cognitive disturbances [ Time Frame: Up to 1 year ]
   Cognitive disorders are evaluated according to DSM-V (formal cognitive testing, subjective memory sensing and instrumental activities of daily living, ).
2. MONTREAL COGNITIVE ASSESSMENT (MOCA) [ Time Frame: Up to 1 year ]
   Test performance of the MONTREAL COGNITIVE ASSESSMENT (MOCA) for screening of dementia
3. Formal cognitive testing [ Time Frame: Up to 1 year ]
   Perioperative changes of damain specific test performance in formal cognitive testing
4. Postoperative cognitive dysfunction (POCD) [ Time Frame: Up to 1 year ]
   Postoperative cognitive dysfunction (POCD) is measured by computerized Cambridge Neuropsychological Test Automated Battery - CANTAB connect and paper pencil testing and subjective memory sensing.
5. Duration of delirium [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 7 days ] ]
   Diagnostic and Statistical Manual of Mental Disorders (DSM-V) Nursing Delirium Screening Scale (Nu-DESC) Intensive Care Delirium Screening Checklist (ICDSC) Delirium Detection Scale (DDS) Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) Confusion Assessment Method (CAM) Chart Review
6. Severity of delirium [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 7 days ] ]
   Diagnostic and Statistical Manual of Mental Disorders (DSM-V) Nursing Delirium Screening Scale (Nu-DESC) Intensive Care Delirium Screening Checklist (ICDSC) Delirium Detection Scale (DDS) Confusion Assessment Method (CAM) Chart Review
7. Time to mobilization [ Time Frame: Up to five postoperative days ]
8. Time to first oral nutritional intake [ Time Frame: Up to five postoperative days ]
9. Time until leaving the recovery room [ Time Frame: Up to leaving the recovery room ]
   Fulfillment of discharge criteria from the recovery room
10. Time until leaving hospital [ Time Frame: Up to five postoperative days ]
    Fulfillment of discharge criteria from hospital after study procedure
11. Organ complications according to Clavien [ Time Frame: Up to five postoperative days ]
12. Autonomy Preference Index (API) [ Time Frame: Up to five postoperative days ]
13. Perceived involvement in care scales (PICS) [ Time Frame: Up to five postoperative days ]
14. Total treatment outcome in terms of quality of life of patients [ Time Frame: Up to 1 year ]
    EQ-5D
15. Total treatment outcome in terms of functional autonomy of patients [ Time Frame: Up to 1 year ]
    Activities of Daily Living (ADLs) or Instrumental Activities of Daily Living (IADLs)
16. Intraoperative Neuromonitoring [ Time Frame: Up to the end of surgical procedure ]
17. Cerobrospinal fluid parameter [ Time Frame: Until the end of surgery ]
    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
18. Apolipoprotein E [ Time Frame: Until the end of surgery ]
    Blood marker Apolipoprotein E for measuring dementia
19. Multiplex Gene Expression Analysis (Whole Blood) [ Time Frame: Until first postoperative day ]
20. Antibodies [ Time Frame: Until first postoperative day ]
    Antibody from serum (anti-beta2-adrenergic receptor, anti-muscarinic acetylcholine receptor (M3 / M4), anti-serotonin receptor, anti-dopamine receptor)
21. Pro and anti-inflammatory markers [ Time Frame: Until first postoperative day ]
    IL-8 from whole blood and IL-6, IL-8 and TGF
22. Immune cells [ Time Frame: Until first postoperative day ]
    Immune cells from citrate blood
23. Autophagy of platelets [ Time Frame: Until first postoperative day ]
    Autophagy of platelets from citrate blood
24. Intracellular pH [ Time Frame: Until first postoperative day ]
    Intracellular pH from citrate blood
25. Cholinesterases [ Time Frame: Until the third postoperative day ]
26. Anxiety [ Time Frame: Up to 1 year ]
    Anxiety is measured by Generalized Anxiety Disorder 7 (GAD-7) and Patient Health Questionnaire 9 (PHQ-9)
27. Anxiety [ Time Frame: Up to 1 year ]
    Anxiety is measured by Amsterdam Preoperative Anxiety and Information Scale (APAIS) and Faces Anxiety Scale (FAS)
28. Patient records from Memory clinic [ Time Frame: Up to 1 year ]
    Results from memory consultation session are evaluated
29. Obstructive Sleep Apnea (OSAS) [ Time Frame: Up to 1 year ]
    Obstructive Sleep Apnea (OSAS) is measured by the STOP-Bang Questionnaire.
30. Fatigue [ Time Frame: Up to 1 year ]
    Fatigue is monitored by Acute Fatigue Score
31. Sleep behavior [ Time Frame: Up to 1 year ]
    Sleep behaviour is measured by Insomnia Severity Index (ISI) and 2 items from the Pittsburgh Sleep Quality Index (PSQI): "How would you describe the overall quality of your sleep during the last 6 months" (modified Item 6) and how often do you have sleep aids during the last four weeks taken; Which sleeping aid you have taken (Item 7); at baseline, 3 months, 1 year
32. Sleep behavior [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 7 days ] ]
    Sleep behaviour is measured by intraclinical course (immediate perioperative: Richards Campbell Sleep Questionnaire)
33. Frailty [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 7 days ]
    Frailty is measured with a modified frailty score according to Fried´s frailty phenotype assessment
34. Stress [ Time Frame: Up to 1 year ]
    Stress is monitored by Perceived Stress Questionnaire 20 (PSQ20) and Disstressthermometer without areas
35. Dose of concomitant medication [ Time Frame: Up to 5 postoperative days ]
    The types of medications used in the management of pain, agitation, and delirium on that day are documented.
36. Duration of concomitant medication [ Time Frame: Up to 5 postoperative days ]
    The types of medications used in the management of pain, agitation, and delirium on that day are documented.
37. Time of mechanical ventilation [ Time Frame: Participants will be followed for the duration of intensive care unit stay, an expected average of 1 day] ]
38. Intensive care unit stay [ Time Frame: Participants will be followed for the duration of intensive care unit stay, an expected average of 1 day] ]
39. Number of stationary recoveries [ Time Frame: Up to 1 year ]
40. Visits to doctors and outpatient treatments [ Time Frame: Up to 1 year ]
41. Number of additional operations [ Time Frame: Up to 1 year ]
42. Mortality [ Time Frame: Up to 1 year ]

Biospecimen Retention:   Samples With DNA

Apolipoprotein-E-4, ncounter Neuroinflammation and micro RNA Panel from Multiplex-Genexpressionsanalyses

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Probability Sample

Study Population

Surgical patients at Campus Virchow - Klinikum and Campus Charité Mitte (Charité - Universitätsmedizin Berlin) with short, elective procedure (<90 minutes), feasible in spinal anesthesia

Criteria

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

Contacts and Locations

Locations

Germany

Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité - Universitätsmedizin Berlin

Berlin, Germany, 10117

Sponsors and Collaborators

Charite University, Berlin, Germany

Investigators

• Study Director: Claudia Spies, MD, Prof.; Charite University, Berlin, Germany

More Information

Publications:

Aldecoa C, Bettelli G, Bilotta F, Sanders RD, Audisio R, Borozdina A, Cherubini A, Jones C, Kehlet H, MacLullich A, Radtke F, Riese F, Slooter AJ, Veyckemans F, Kramer S, Neuner B, Weiss B, Spies CD. European Society of Anaesthesiology evidence-based and consensus-based guideline on postoperative delirium. Eur J Anaesthesiol. 2017 Apr;34(4):192-214. doi: 10.1097/EJA.0000000000000594. Review. Erratum in: Eur J Anaesthesiol. 2018 Sep;35(9):718-719.

• Responsible Party: Claudia Spies, Head of the Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité - University Medicine Berlin, Charite University, Berlin, Germany
• ClinicalTrials.gov Identifier: NCT03715244
• Other Study ID Numbers: PODSPA
• First Posted: October 23, 2018
• Last Update Posted: August 9, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Delirium; Postoperative Cognitive Complications; Cognitive Dysfunction; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Postoperative Complications; Pathologic Processes; Anesthetics; Anesthetics, Local; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents