[FG] Sutter Raoul Christian

Research Project  | 3 Project Members

Assessment of the pupils regarding symmetry and reactivity to light are important parts of the neurological evaluation of critically ill patients treated in intensive care units. Thereby, anisocoria can be found in up to 60% of patients with acute neurologic injuries(2). Furthermore, anisocoria or pupillary areflexia can be signs of increasing intracranial hypertension with brain herniation, ischemia in traumatic brain injury, cerebrovascular accidents, intoxication with psychotropic and neurotropic drugs including anticholinergic, opioids, and cannabinoids. While anisocoria or impaired pupillary reactivity may result from such devastating cerebral injuries, they can also be caused by more benign and potentially reversible scenarios, such as pharmacological effects (e.g. agents such as ipatroprium bromide) or as part of the Horner’s syndrome following jugular central venous cannulation. Despite these well-known underlying pathomechanisms of pupillary anomalias, data on the prevalence and associated clinical consequences of anisocoria in non-selected general ICU populations is scarce. Due to the lack of data on the prognostic implications of anisocoria or changes in pupillary reactivity for non-neurological ICU patients, the new onset of any pupillary abnormality necessitates a rapid and thorough evaluation usually including clinical neurological examination and the performance of neuroimaging, such as a cerebral computed tomography (CT) or magnetic resonance imaging (MRI). Considering the the variety of more benign and reversible causes of pupillary abnormalities, alongside the potential for missed underlying pathomechanisms with severe clinical implications, it is highly probable that a significant number of unremarkable CT or MRI scans are conducted to investigate acute pupillary abnormalities. This practice may expose patients to unnecessary risks and contribute to increased healthcare costs. While quantitative pupillometry with dynamic pupil assessments after light has shown some promise to distinguish between clinically relevant anisocoria and benign variations, further validation is still lacking. Unfortunately, studies elucidating to what extent a cerebral CT or MRI detects clinically relevant findings in specific patient groups with particular clinical contexts, and in which clinical scenarios CTs are likely to provide no clinical relevance beyond exposing the patient to radiation are still pending.

This retrospective single-center cohort study has four primary objectives. 

-   First, it aims to determine the prevalence of acute "new onset" pupillary abnormalities (anisocoria and/or impaired light-reactive pupillary response) in adult ICU patients. 

-   Second, it seeks to assess the clinical impact of these abnormalities, particularly in terms of the frequency of diagnostic tests ordered, such as neuroimaging (i.e., head CT or MRI scans, and ophthalmologic and neurologic consultations. 

-   Third, the study aims to identify specific clinical contexts in which significant pathological findings lead to treatment modifications, as well as those scenarios where no clinically relevant findings are detected.

-   Finally, it evaluates the prognostic implications of these pupillary abnormalities on patient outcomes.

Research Project  | 4 Project Members

Brain death is the irreversible loss of brain function necessary to sustain life. Its diagnosis is based on the absence of brainstem reflexes, unresponsiveness to endo- or exogenous stimuli, apnea, and the exclusion of factors confounding the clinical presentation(4). While other organ functions may be preserved, the identification of brain death raises the question of whether viable organs can and should be transplanted to save the lives of critically ill patients in need of organ support.

 

With advancements in critical care techniques enabling the maintenance of organ function beyond brain death, as well as the intricate legal and regulatory frameworks surrounding organ donation, healthcare professionals in intensive care units are increasingly faced with complex clinical scenarios, considerations, and challenges related to the concept and diagnosis of brain death and ethical and legal aspects associated with organ donation. Studies investigating the individual conceptual understanding of brain death and organ donation of health care professionals on Intensive Care Units (ICUs) as well as their experiences and opinions related to these topics, are scarce(5-8).

 

The study aims to gather information regarding the individual perceptions, opinions, beliefs, and conceptual understanding of healthcare professionals working in the intensive care units at the University Hospital Basel and to determine associations of individual beliefs, personal, educational, and professional experiences with individual perceptions, opinions, and conceptual understanding regarding brain death and organ donation. 

To achieve the study objectives, we will employ a questionnaire-based survey administered to the consenting/participating nurses and physicians. The questionnaire will address various aspects related to personal background, religious affiliation, beliefs about life after death, the conceptual understanding of brain death and organ donation, as well as experiences and opinions related to these topics.

Participating in this study will create no additional risk or burden for patients and is therefore classified under category A according to HRO Art. 7.(1)

Hypothesis and primary objective

The primary objective of this study is to gather insights into the individual perceptions, opinions, beliefs, and conceptual understanding regarding brain death and organ donation of healthcare professionals working in the ICU at the University Hospital Basel in Switzerland. 

The following hypotheses will be tested: Individual perceptions, opinions, beliefs, and conceptual understanding regarding brain death and organ donation vary between the different professions and in dependence of specific aspects regarding personal, educational and professional experiences.

Primary and secondary endpoints

The primary endpoints of this study will be information on individual perceptions, opinions, beliefs, and conceptual understanding of healthcare professionals in the ICU regarding brain death and organ donation and the identification ofinterprofessional variations.

The secondary endpoints will be associations of specific demographics, beliefs, personal, educational, social and professional experiences with individual perceptions, opinions, and conceptual understanding regarding brain death and organ donation.

References

1.         Council TSF. Ordinance on Human Research with the Exception of Clinical Trials (HRO)2013.

2.         Council TSF. Ordinance on Clinical Trials in Human Research (HRA)2013.

3.         World Medical A. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. Jama. 2013;310(20):2191-4.

4.         Wijdicks EF. The diagnosis of brain death. N Engl J Med. 2001;344(16):1215-21.

5.         Ferhatoglu SY, Ferhatoglu MF, Gurkan A. Approach of the Clinicians Practicing in Intensive Care Units to Brain Death Diagnosis and Training Expectations in Turkey: A Web-Based Survey. Transplant Proc. 2020;52(10):2916-22.

6.         Al-Mousawi M, Abdul-Razzak M, Samhan M. Attitude of ICU staff in Kuwait regarding organ donation and brain death. Transplant Proc. 2001;33(5):2634-5.

7.         Ong JS, James Foong W, Oo WL, Vallapil MK, Hossain MM, Hossain H, et al. Does knowledge and attitude of healthcare professionals working in critical care areas affect their willingness to offer the option of organ donation? results of a tertiary hospital survey. Med J Malaysia. 2022;77(3):347-56.

8.         Camut S, Baumann A, Dubois V, Ducrocq X, Audibert G. Non-therapeutic intensive care for organ donation: A healthcare professionals' opinion survey. Nurs Ethics. 2016;23(2):191-202.

Research Project  | 3 Project Members

Brief Summary

The aim of the study is to verify the reliability of the current purely clinical examination of the pupils (without the support of a pupillometer) in the context of clinically suspected brain death, compared to the results of a non-invasive, automated, and highly precise monocular pupillometric examination.

Detailed Description

This prospective quality control study will evaluate the reliability of the clinical exam regarding pupils' reaction to light (as performed by two board certified physicians in Neurology and/or Intensive Care Medicine) as recommended by the SAMW guidelines for brain death diagnosis (SAMW-guidelines) when compared to the results of a noninvasive automated and highly-precise pupillometry in adult patients with clinically suspected brain death. Automated pupillometric measurements will be performed by the PI (RS), or the co-investigator (Dr. Pascale Grzonka) using the NeurOptics® NPi®-200 pupillometer system immediately before and after the standardized diagnostic workup for suspected brain death. In addition, demographics, clinical characteristics , treatment and laboratory data from the patients examined will be anonymously collected.

Research Project  | 4 Project Members

Brief Summary

In the trial the effectiveness of pre-briefing physicians with the current guideline on Status epilepticus (SE) treatment or a consolidated "one page" guideline regarding quality enhancement of the physician's clinical performances is investigated.

Detailed Description

Status epilepticus (SE) is a life-threatening neurological emergency defined as a state of continuous seizure or multiple seizures without full recovery of sensory, motor and/or cognitive function for at least 30 minutes. To achieve high quality management of SE, the American Epilepsy Society published an evidence-based guideline for the treatment of SE, which serves as reference for most national guidelines, but analyses regarding practicability, strict adherence, correct translation into clinical practice, and identification of recommended treatment steps at risk of being modified or missed are lacking. Simulator-based studies offer a platform for the design of standardized clinical scenarios that enable detailed investigations regarding the effect of the implementation and practicability of treatment guidelines.

This randomized controlled intervention study performed at the simulation center of the medical intensive care units (ICUs) at the University Hospital Basel is to investigate the effectiveness of pre-briefing physicians with both the current guideline on Status epilepticus (SE) treatment or a consolidated "one page" guideline regarding quality enhancement of the physicians' clinical performances..

Physicians from different medical specialties and with different duration of clinical experience will be enrolled. Participants will be randomly assigned to one of the following three pre-briefing groups: (1) no pre-briefing prior to the simulation training; (2) pre-briefing with the current SE treatment guidelines; (3) pre-briefing with the consolidated "one page" SE treatment guideline.

Research Project  | 3 Project Members

An ongoing study on aspects of advance directives of critically ill adult patients treated in the intensive care units. A collaboration between the Intensive Care Unit of Basel (PI of Basel: Prof. Dr. Raoul Sutter) and the Intensive Care Unit of Aarau (Co Investigator of Aarau: PD Dr. Luca Cioccari).

Research Project  | 4 Project Members

Ongoing two center study on different aspects regarding neurocritically ill adult patients with status epilepticus in collaboration between the Intensive Care Unit of Basel (PI of Basel: Prof. Dr. Raoul Sutter) and the Neurointensive Care Unit of Geneva (Co Investigator of Geneva: Dr. Pia De Stefano).

Research Project  | 1 Project Members

The role of IMMUNITY AND INFLAMMATION IN EPILEPSY, the MECHANISTIC INSIGHTS and THERAPEUTIC PERSPECTIVES comprise one of the emerging hot topics in the epilepsy area both among basic scientists and clinicians. We feel that a first international brainstorm meeting of world leaders in inflammatory and immunological aspects of epileptology would be a strong initiative to collect and exchange the yet available data and to boost clinical and basic research in an area where an outstanding number of innovative treatments are on the horizon.

Research Project  | 10 Project Members

Objective: To establish a numerical model for better characterization and prediction of the course of the two most prevalent chronic neurological disorders with high impact on quality of life in young and elderly human beings, respectively: Multiple Sclerosis (MS) and Alzheimer's disease (AD). The numerical model will contain clinical, neuropsychological, genetic, imaging and neurophysiological data. Background: Although diagnosis of MS has greatly improved over the last decade, reliable prediction of the disease course (prognosis) is still not satisfying. In AD and other dementia types diagnosis is more difficult early in the disorder and depends in part on the course of symptoms. In both disease groups, clinical examination is still the main tool to assess the course of disease and the grade of impairment. Neurophysiological measurements like electroencephalography (EEG) at rest and during visual and sensory stimulation (evoked potentials, EP) represent parameters of impulse propagation in the central nervous system. These measures are likely to be abnormal early in the course of MS and AD. Therefore, they may add important information on the prognosis in MS and AD, and on the differential diagnosis of dementias. Recent technical developments allow the recording of EEG and EP with high resolution (256 channels) resulting in precise identification and localization of pathological changes. Genetic testing is likely to further improve the prediction of the disease course. Methods: In the MS subproject one hundred patients and fifty age-matched healthy controls will be examined three times at yearly intervals. Clinical and neuropsychological examination will be complemented by high-resolution EEG and EP, genetic testing and brain imaging by magnetic resonance tomography. In the AD subproject, forty patients with dementia will be compared to forty age matched healthy controls in regard to their cognitive performance, genetic profile and results of high resolution EEG and EP. All results of the different tests will be analyzed with a statistical model, which summarizes all data of an individual to a score to predict the clinical course in MS and AD. Significance: Reliable markers of disease progression and prognosis would allow to conduct clinical trials with a smaller number of patients or in less time, thus reaching clinically meaningful results more efficiently. This is especially important in MS and AD, where innovative treatment options are entering the phase of clinical testing in coming years. Moreover, improved prediction of the course of MS and AD may be useful even in individual patients for counselling and treatment decisions.

Research Project  | 2 Project Members

Recent developments in neurophysiological methods allow more precise electric source imaging and quantitation of brain connectivity. The former permits localization of brain activity with a temporal resolution of milliseconds, the latter characterization of the network configuration of the brain. Using high-resolution recordings, evoked potentials (EP) cannot only be analyzed in regard to their latency and amplitude, but also in regard to their spatial extent, which may conveys important clinical information. Furthermore, application of source localization algorithms allows automatic analysis of EP, making measurements operator independent and probably more sensitive to change. Measures of brain connectivity are based on analysis of the electro-encephalogram (EEG) at rest. High-resolution recordings allow estimating quasi reference-independent potentials and applying methods to account for volume conduction. Connectivity measures are derived from the statistical interdependency between two electrodes, which is assumed to represent connection of the underlying brain activity. As neural synchrony probably is an electrophysiological correlate of cognitive function, brain states with cognitive impairment may be characterized by altered connectivity measures. Furthermore, global measures of the configuration of the networks of the brain can be derived from connectivity analysis, which have been shown to be abnormal in case of cognitive impairment. High-resolution EEG and high-resolution EP recordings are the core methods of the research projects described below. The main project is a SNSF-sponsored project in the Special Program University Medicine (SPUM, SNSF 33CM30-124115), which is collaborative work between the Universities of Basel, Berne and Geneva. It is a longitudinal study over three years entitled: Improved prediction and monitoring of CNS disorders with advanced neurophysiological and genetic assessment. Based on previous work, high resolution EP are evaluated in Multiple Sclerosis (MS), and high resolution EEG measures in both, MS and Alzheimer s disease (AD) in regard to their value as prognostic and surrogate markers. In view of the only weak correlation of existing markers, more sensitive tools are needed to better assess new treatment options in these two disabling disorders. As neurophysiological measures directly assess function in a quantitative and reliable way, they are good candidates to meet the requirements of valid, sensitive surrogate markers. A second project on Parkinson s disease in patients undergoing deep brain stimulation evaluates the prognostic value of high-resolution EEG in regard to the cognitive outcome after surgery, a still only marginally studied aspect but with considerable impact on patients. A planned project is to correlate of the amplitude and spatial extent of the high resolution visual EP in MS patients to the measurement of the thickness of the retinal nerve fiber layer, a direct marker of axonal loss. A further project will evaluate measures from high resolution EEG and event-related desynchronisation as diagnostic markers in patients with HIV and cognitive symptoms. 19.05.2009 11:50:20 Page - 7 - As high-resolution EEG is a non-invasive tool, posing only minor inconveniences to patients it is well suitable to be employed in a clinical context. Furthermore, acquisition and maintenance of the equipment is cheap in comparison to other modalities. These facts make high resolution EEG an effective and efficient tool to advance clinical research and consequently, patient care.

Research Project  | 3 Project Members

Recent developments in neurophysiological methods allow more precise electric source imaging and quantitation of brain connectivity. The former permits localization of brain activity with a temporal resolution of milliseconds, the latter characterization of the network configuration of the brain. Using high-resolution recordings, evoked potentials (EP) cannot only be analyzed in regard to their latency and amplitude, but also in regard to their spatial extent, which may conveys important clinical information. Furthermore, application of source localization algorithms allows automatic analysis of EP, making measurements operator independent and probably more sensitive to change. Measures of brain connectivity are based on analysis of the electro-encephalogram (EEG) at rest. High-resolution recordings allow estimating quasi reference-independent potentials and applying methods to account for volume conduction. Connectivity measures are derived from the statistical interdependency between two electrodes, which is assumed to represent connection of the underlying brain activity. As neural synchrony probably is an electrophysiological correlate of cognitive function, brain states with cognitive impairment may be characterized by altered connectivity measures. Furthermore, global measures of the configuration of the networks of the brain can be derived from connectivity analysis, which have been shown to be abnormal in case of cognitive impairment. High-resolution EEG and high-resolution EP recordings are the core methods of the research projects described below. The main project is a SNSF-sponsored project in the Special Program University Medicine (SPUM, SNSF 33CM30-124115), which is collaborative work between the Universities of Basel, Berne and Geneva. It is a longitudinal study over three years entitled: Improved prediction and monitoring of CNS disorders with advanced neurophysiological and genetic assessment. Based on previous work, high resolution EP are evaluated in Multiple Sclerosis (MS), and high resolution EEG measures in both, MS and Alzheimer s disease (AD) in regard to their value as prognostic and surrogate markers. In view of the only weak correlation of existing markers, more sensitive tools are needed to better assess new treatment options in these two disabling disorders. As neurophysiological measures directly assess function in a quantitative and reliable way, they are good candidates to meet the requirements of valid, sensitive surrogate markers. A second project on Parkinson s disease in patients undergoing deep brain stimulation evaluates the prognostic value of high-resolution EEG in regard to the cognitive outcome after surgery, a still only marginally studied aspect but with considerable impact on patients. A planned project is to correlate of the amplitude and spatial extent of the high resolution visual EP in MS patients to the measurement of the thickness of the retinal nerve fiber layer, a direct marker of axonal loss. A further project will evaluate measures from high resolution EEG and event-related desynchronisation as diagnostic markers in patients with HIV and cognitive symptoms. 19.05.2009 11:50:20 Page - 7 - As high-resolution EEG is a non-invasive tool, posing only minor inconveniences to patients it is well suitable to be employed in a clinical context. Furthermore, acquisition and maintenance of the equipment is cheap in comparison to other modalities. These facts make high resolution EEG an effective and efficient tool to advance clinical research and consequently, patient care.