Severe Sepsis With Septic Shock, Severe Sepsis Without Septic Shock
Conditions
Keywords
sepsis, septic shock, ICU, long-term outcome, neurocognitive, inflammatory, MRI, EEG, brain imaging, serum biomarkers, CSF
Brief summary
The main goals of this study are to provide a cognitive, neurological, brain morphological, and serological profile of sepsis survivors in order to make long-term prognosis of recovery and estimate the need for rehabilitation measures in order to help patients reintegrate into normal daily life.
Detailed description
Comparison of cognitive function in severe septic/septic shock ICU patients with non-septic postoperative ICU patients and actively recruited healthy controls at several time points up to 12 months after leaving the ICU. Secondary aims: * Profiling specific cognitive deficits in sepsis survivors over time. * Identifying possible subclasses of long-term cognitive impairment according to facets of disease, therapy and ICU experience. * Investigating long-term brain morphological changes, with hippocampus as region of interest (ROI). * Determining values of Serum- and CSF-Biomarkers * Evaluation of diagnostic and prognostic value of non-routine biomarkers for systemic- and neuroinflammation in the acute phase and in the long-term * Investigate associations between brain morphological changes, cognitive changes, neurological status, psychiatric burden, disability level, employment status and health-related quality of life (HRQOL). * Investigating brain-activity changes in resting state electro-encephalogram (EEG)
Interventions
PROCEDUREBlood Sample
Blood Sample
BEHAVIORALNeurocognitive Assessment
Neurocognitive Assessment
OTHERResting State EEG
10-20 Minutes of Resting State EEG
PROCEDURELumbar Puncture
Lumbar Puncture
OTHERMRI
60 Minutes MRI
Sponsors
University Hospital, Bonn
German Center for Neurodegenerative Diseases (DZNE)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
sepsis/septic shock subjects will only be included in the study if they meet all of the following criteria: * Written informed consent of the subject. or legal representative patient at the Anesthesiological-Operative Intensive Care Unit of the University Hospital Bonn, the Department of Anesthesiology, Intensive Care and Pain Therapy of the Malteser Hospital, or the Department of Anesthesiology, Intensive Care Medicine and Pain Medicine of the Gemeinschaftskrankenhaus Bonn St. Petrus Hospital. At the Anesthesiological-Operative Intensive Care Unit of the University Hospital Bonn, only, or 1) documentation of presumed will via a relative or legal representative . together with 2) Documentation of verification by a doctor independent of the study that the patient's study participation is unobjectionable. Written informed consent of patient will be obtained at the earliest time possible. * Aged 25-80 years * Male or female * Admitted to the intensive care units of the Anesthesiological-Operative Intensive Care Unit of the University Hospital Bonn, from the Department of Anesthesiology, Intensive Care and Pain Therapy of the Malteser Hospital or from the Department of Anesthesiology, Intensive Care Medicine and Pain Medicine of the Gemeinschaftskrankenhaus Bonn St. Petrus Hospital. * Duration of ICU stay must be a minimum of 24 hours. In case of transfer to intermediate care or the observation ward before the 24 hour ICU period is complete, study parameters must be allowed to be assessed. * Fulfill the criteria of sepsis and/or septic shock patients according to theThird International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3, Singer et al, 2016). Postoperative ICU Patients will only be included in the study if they meet all of the following criteria: * Written informed consent of the subject. * Aged 25-80 years * Male or female * Admitted to the intensive care units of the Anesthesiological-Operative Intensive Care Unit of the University Hospital Bonn, which includes a surgical ICU, an anesthesiological ICU, and a cardio-surgical ICU * Duration of ICU stay must be a minimum of 24 hours. In case of transfer to intermediate care or the observation ward before the 24 hour ICU period is complete, study parameters must be allowed to be assessed. * Mini-Mental Status Examination (MMSE) Score of 25 or above Healthy Controls will only be included in the study if they meet all of the following criteria: * Written informed consent of the subject * Aged 25-80 years * Male or female
Exclusion criteria
Subjects presenting with any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Verbal Learning Memory Test Long Delayed Recall (Trial 7) | 6 months post ICU | Verbal Learning Memory Test Long Delayed Recall (Trial 7) at 6 months post ICU admission in sepsis/septic shock patients versus non-septic postoperative patients, and comparison to actively recruited healthy controls) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Verbal Learning Memory Test, German Version | For patient groups: 6 months; for Healthy Controls: Baseline | Verbal Learning and Memory: Verbal Learning Memory Test, German Version |
| Wechsler Memory Scale IV Visual Recall I and II | For patient groups: 6 months; for Healthy Controls: Baseline | Visual Memory: Wechsler Memory Scale IV Visual Recall I and II |
| Wechsler Memory Scale Digit-Span | For patient groups: 6 months; for Healthy Controls: Baseline | Working Memory: Wechsler Memory Scale Digit-Span |
| German Vocabulary Test | For patient groups: 6 months; for Healthy Controls: Baseline | Premorbid Verbal Ability: German Vocabulary Test Mehrfachwahl Wortschatztest B (MWT-B) |
| Symbol Digit Modalities Test | For patient groups: 6 months; for Healthy Controls: Baseline | Cognitive Speed |
| Trail Making Test A & B | For patient groups: 6 months; for Healthy Controls: Baseline | Simple and Divided Attention |
| Phonetic and Lexical Verbal Fluency | For patient groups: 6 months; for Healthy Controls: Baseline | Phonetic and Lexical Verbal Fluency |
| Patient Health Questionnaire Subtests Depression, Anxiety and Somatic Symptoms | For patient groups: 6 months; for Healthy Controls: Baseline | Depression and Anxiety Inventory |
| Post-Traumatic Stress Syndrome 10 | For patient groups: 6 months; for Healthy Controls: Baseline | Post-Traumatic Stress Screening |
| European Quality of Life 5 Dimensions-5 Levels | For patient groups: 6 months; for Healthy Controls: Baseline | Quality of Life |
| Functional Activities Questionnaire | For patient groups: 6 months; for Healthy Controls: Baseline | Activities of Daily Living |
| modified version of Rankin Scale Structured Interview (modified for ICU patients) | For patient groups: 6 months; for Healthy Controls: Baseline | Function Scale |
| Pittsburgh Sleep Quality Index | For patient groups: 6 months; for Healthy Controls: Baseline | Sleep Quality |
| Mini Mental Status Examination | For patient groups: (OP Probands 1-28 d before OP, 6 months; for Healthy Controls: Baseline | Cognitive Screening |
| Clinical Scales at ICU | For Patients during ICU Stay (Day 0, [Day 7 if still on ICU], Day of Release) | Therapeutic Intervention Scoring System-10, Total Score Simplified Acute Physiology Score, Sequential Organ Failure Assessment Confusion Assessment Method for the ICU |
| Neurological Examination | For patient groups: 6 months, 12 months; for Healthy Controls: Baseline and 6 months | Subscales Motor ability, Walking and Standing, Behavior, Praxis/Visual or Visuospatial, Speaking and Language, Autonomic Nervous System, Tone and Muscle Exam, Coordination and Movement |
| resting state electroencephalogram | For patient groups: 6 months, 12 months; for Healthy Controls: Baseline and 6 months | 10-20 system electroencephalogram (64 channels with additional electro-oculogram, electromyogram, electrocardiogram). The protocol includes 5 phases, each one minute long: 1) eyes open, relaxed state, fixation of a black dot at 2 m distance, 2) word generation using letter P with eyes closed, 3) mental arithmetic: continuous subtraction of 7 starting from 1,000 with eyes closed, 4) eyes closed, relaxed state, no task, 5) visualization of a previously memorized geometric figure with eyes closed. Data sampled at a rate of 256 Herz using an anti-aliasing low pass filter. Power spectra will be calculated for consecutive 4-second windows and calculated for each electrode contact. Absolute spectral power will be determined for the delta (0.5-4 Herz), theta (4-8 Herz), alpha (8-13 Herz), beta (13-20 Herz) and gamma (20-40 Herz) bands, which will be averaged across all windows. |
| MRI (3 Tesla) of brain with hippocampus as Region of Interest | For patient groups: 6 months, 12 months; for Healthy Controls: Baseline and 6 months | MRI (3 Tesla) of brain with hippocampus as Region of Interest. Protocol includes: three-dimensional, T1-weighted rapid gradient echo sequence, Resting State, Gradient Echo-Field-Map for Resting State, Inversion Recovery Echo Planar Imaging for Resting State, Spoiled Gradient Echo, Fluid Attenuated inversion Recovery, Susceptibility weighted imaging, Diffusion Tensor Imaging, Gradient Echo-Field-Map for Diffusion Tensor Imaging |
| Blood Sample | For Patient Groups 2-3 samples during ICU, 3-4 Months, 6 months, 12 Months | All blood samples shall be drawn, stored and analyzed according to the participant information in the laboratories of the Biomarker Dementia Working Group and the Central Laboratory. Blood sampling analysis will include leukocyte count, hemoglobin, hematocrit, erythrocytes, Mean Corpuscular Hemoglobin, Meam Corpuscular Volume, mean Corpuscular Hemoglobin Concentration, Thrombocytes, Glucose, Lactate, electrolytes Sodium, Potassium, Calcium, Cholesterine, Tumor necrosis Factor-alpha, Interleukin-1 alpha, Interleukin-1 beta, Interleukin-6, C-reactive protein, Neuron Specific Enolase, Procalcitonin, S-100 Protein, as well as DNA and serum biorepository for further scientific analysis. |
| Lumbar Puncture (voluntary) | For Patients: (while at ICU, if clinically indicated as part of clinical routine and only if patient directly gives informed consent), 12 months; For Healthy Controls: Baseline and 6 months | Cerebrospinal fluid (CSF) routine parameters will be analyzed by the Central Laboratory. Results will then be provided to the investigator. For determination of τ, phospho-τ, β-amyloid 1 40 and β-amyloid 1 42, 5 ml of cerebral-spinal-fluid will be analyzed at the laboratories of the German Center for Neurodegenerative Diseases (DZNE), Biomarker Dementia Working Group, Sigmund-Freud-Str. 25, 53105 Bonn |
Countries
Germany
Contacts
Primary ContactCatherine N. Widmann, M.A.
Backup ContactMichael T. Heneka, MD
Outcome results
None listed