Uncontrolled Donation after Circulatory Death: European practices and recommendations for the development and optimization of an effective programme.

Shortage of organs has made a global interest for donation after circulatory death (DCD) to re-emerge. While controlled DCD (cDCD) has been progressively increasing, uncontrolled DCD (uDCD) has only been developed in a few settings.1 This activity is quantitatively important in France and Spain, although it has also been reported in other European countries, as Austria, Belgium, Italy, the Netherlands, and recently in Russia.2,3 uDCD protocols have allowed the transplantation of a significant number of kidneys, livers and lungs at these countries.3 Excellent graft survival has been reported in kidney transplantation from uDCD, in spite of an increased incidence of delayed graft function (DGF).4,5,6,7,8,9,10,11,12,13,14,1516 Albeit promising, results with liver transplants obtained in uDCD protocols do not consistently provide similar outcomes compared with livers from donors after brain death (DBD), mainly due to a higher incidence of primary graft dysfunction and non-function and biliary complications.17,18,19,20,21,22 Lung transplantation is still facing limited experience, but preliminary results are encouraging.pre-print938 K

비침습적 뇌파 신호를 이용한 응급환자의 생체반응 모니터링 기법

학위논문 (박사) -- 서울대학교 대학원 : 공과대학 협동과정 바이오엔지니어링전공, 2021. 2. 김희찬.뇌파는 대뇌피질이나 두피의 전극을 통해서 뇌의 전기적 신호를 기록한 것을 의미한다. 뇌 기능 관찰을 위한 진단도구로써 뇌파는 뇌전증이나 치매 진단 등의 목적으로 활용되고 있다. 본 논문에서는 비침습적 뇌파를 이용하여 응급환자의 주요 생리학적 지표를 모니터링하는 기술을 개발하였다. 처음 두 연구에서 심폐소생술의 효과를 평가하기 위한 심정지 돼지실험모델을 고안하였다. 현재의 심폐소생술 지침은 체순환 평가를 위해 기도삽관을 통한 호기말 이산화탄소 분압의 측정을 권고한다. 하지만, 정확한 기도삽관이 특히 병원 밖 상황에서 어려울 수 있다. 따라서, 간편히 측정할 수 있고 소생 환자의 신경학적 예후를 진단하는데 사용되는 뇌파를 이용한 예측 기술이 심폐소생술 품질평가지표의 대안으로 제안되었다. 첫 번째 실험에서는 고품질과 저품질 기본심폐소생술을 10회 반복하면서 측정된 뇌파를 분석하였다. 심폐소생술의 품질에 따른 뇌파의 변화를 이용하여 체순환 평가를 위한 EEG-based Brain Resuscitation Index (EBRI) 모델을 도출하였다. EBRI 모델에서 획득한 호기말 이산화탄소 분압 예측치는 실제 값과 양의 상관관계를 보이며, 병원 밖 상황에서의 활용 가능성을 보였다. 두 번째 실험에서는 두 가지 심폐소생술(기본심폐소생술, 전문심폐소생술)이 수행되었다. 제세동 직전에 수집된 뇌파는 심폐소생술 도중 경동맥혈류의 회복률과 함께 분석되었다. 심폐소생술 도중 경동맥혈류의 회복률을 반영하는 뇌파 변수를 규명한 후, 이를 이용하여 높은 회복률(30% 이상)과 낮은 회복률(30% 미만)을 구분하는 기계학습 기반 이진분류모델을 도출하였다. 서포트 벡터 머신 기반의 예측모델이 0.853의 정확도와 0.909의 곡선하면적을 보이며 가장 우수한 성능을 보였다. 이러한 예측모델은 심정지 환자의 뇌 소생을 향상시켜 빠른 뇌 기능 회복을 가능하게 할 것으로 기대된다. 세 번째 연구에서 비침습적 뇌파를 이용하여 두개내압을 예측하는 모델을 개발하기 위한 외상성 뇌손상 돼지실험모델이 고안되었다. 외상성 뇌손상은 물리적 충격에 의해 정상적인 뇌 기능이 중단된 상태를 의미하며, 이 때의 두개내압 상승과 관류저하가 뇌파에 영향을 끼칠 수 있다. 따라서, 우리는 뇌파 기반 두개내압 예측모델을 개발하였다. 폴리카테터로 실험동물의 두개내압을 변경하면서 뇌파를 획득하였다. 두개내압의 정상구간(25 mmHg 미만)과 위험구간(25 mmHg 이상)을 유의미하게 구분하는 뇌파 변수를 규명한 후 기계학습 기반 이진분류모델을 도출하였다. 다층 퍼셉트론 기반의 예측모델이 0.686의 정확도와 0.754의 곡선하면적을 보이며 가장 우수한 성능을 보였다. 또다른 비침습 데이터인 심박수 정보와 함께 사용하였을 때 정확도와 곡선하면적은 각각 0.760과 0.834로 향상되었다. 제안된 예측모델은 응급상황에서 비침습적으로 두개내압을 관찰하여 정상 수준의 두개내압을 유지하는데 도움을 줄 것으로 기대된다. 본 논문은 응급환자의 주요 생리학적 지표를 비침습적 뇌파를 이용하여 관찰하는 예측모델을 제안하고 성능을 검증하였다. 본 연구에서는 뇌파를 이용하여 즉각적인 호기말 이산화탄소 분압, 경동맥혈류, 두개내압을 추정하기 위한 예측모델을 수립하였다. 하지만, 뇌파 데이터는 장기간의 신경학적, 기능적 회복과 함께 평가되어야 한다. 본 논문에서 개발한 예측모델의 성능과 적용 가능성은 향후 다양한 임상연구를 통해 cerebral performance category와 modified Rankin scale 등의 신경학적 평가지표와 함께 분석, 개선되어야 할 것이다.Electroencephalogram (EEG) is a recording of the electrical activity of the brain, measured using electrodes attached to the cerebrum cortex or the scalp. As a diagnostic tool for brain disorders, EEG has been widely used for clinical purposes such as epilepsy- and dementia diagnosis. This study develops an EEG-based noninvasive critical care monitoring method for emergency patients. In the first two studies, ventricular fibrillation swine models were designed to develop EEG-based monitoring methods for evaluating the effectiveness of cardiopulmonary resuscitation (CPR). The CPR guidelines recommend measuring end-tidal carbon dioxide (ETCO2) via endotracheal intubation to assess systemic circulation. However, accurate insertion of the endotracheal tube might be difficult in an out-of-hospital setting (OOHS). Therefore, an easily measurable EEG, which has been used to predict resuscitated patients neurologic prognosis, was suggested as a surrogate indicator for CPR feedback. In the first experimental setup, the high- and low quality CPRs were altered 10 times repeatedly, and the EEG parameters were analyzed. Linear regression of an EEG-based brain resuscitation index (EBRI) was used to estimate ETCO2 levels as a novel feedback indicator of systemic circulation during CPR. A positive correlation was found between the EBRI and the real ETCO2, which indicates the feasibility of EBRI in OOHSs. In the second experimental setup, two types of CPR mode were performed: basic life support and advanced cardiovascular life support. EEG signals that were measured between chest compressions and defibrillation shocks were analyzed to monitor the cerebral circulation with respect to the recovery of carotid blood flow (CaBF) during CPR. Significant EEG parameters were identified to represent the CaBF recovery, and machine learning (ML)-based classification models were established to differentiate between the higher (≥ 30%) and lower (< 30%) CaBF recovery. The prediction model based on the support vector machine (SVM) showed the best performance, with an accuracy of 0.853 and an area under the curve (AUC) of 0.909. The proposed models are expected to guide better cerebral resuscitation and enable early recovery of brain function. In the third study, a swine model of traumatic brain injury (TBI) was designed to develop an EEG-based prediction model of an elevated intracranial pressure (ICP). TBI is defined as the disruption of normal brain function due to physical impact. This can increase ICP, and the resulting hypoperfusion can affect the cerebral electrical activity. Thus, we developed EEG-based prediction models to monitor ICP levels. During the experiments, EEG was measured while the ICP was adjusted with the Foley balloon catheter. Significant EEG parameters were determined to differentiate between the normal (< 25 mmHg) and dangerous (≥ 25 mmHg) ICP levels and ML-based binary classifiers were established to distinguish between these two groups. The multilayer perceptron model showed the best performance with an accuracy of 0.686 and an AUC of 0.754, which were improved to 0.760 and 0.834, respectively, when a noninvasive heart rate was also used as an input. The proposed prediction models are expected to instantly treat an elevated ICP (≥ 25 mmHg) in emergency settings. This study presents a new EEG-based noninvasive monitoring method of the physiologic parameters of emergency patients, especially in an OOHS, and evaluates the performance of the proposed models. In this study, EEG was analyzed to predict immediate ETCO2, CaBF, and ICP. The prediction models demonstrate that a noninvasive EEG can yield clinically important predictive outcomes. Eventually, the EEG parameters should be investigated with regard to the long-term neurological and functional outcomes. Further clinical trials are warranted to improve and evaluate the feasibility of the proposed method with respect to the neurological evaluation scores, such as the cerebral performance category and modified Rankin scale.Abstract i Contents iv List of Tables viii List of Figures x List of Abbreviations xii Chapter 1 General Introduction 1 1.1 Electroencephalogram 1 1.2 Clinical use of spontaneous EEG 5 1.3 EEG and cerebral hemodynamics 7 1.4 EEG use in emergency settings 9 1.5 Noninvasive CPR assessment 10 1.6 Noninvasive traumatic brain injury assessment 16 1.7 Thesis objectives 21 Chapter 2 EEG-based Brain Resuscitation Index for Monitoring Systemic Circulation During CPR 23 2.1 Introduction 23 2.2 Methods 25 2.2.1 Ethical statement 25 2.2.2 Study design and setting 25 2.2.3 Experimental animals and housing 27 2.2.4 Surgical preparation and hemodynamic measurements 27 2.2.5 EEG measurement 29 2.2.6 Data analysis 32 2.2.7 EBRI calculation 33 2.2.8 Delta-EBRI calculation 34 2.3 Results 36 2.3.1 Hemodynamic parameters 36 2.3.2 Changes in EEG parameters 37 2.3.3 EBRI calculation 39 2.3.4 Delta-EBRI calculation 41 2.4 Discussion 42 2.4.1 Accomplishment 42 2.4.2 Limitations 45 2.5 Conclusion 46 Chapter 3 EEG-based Prediction Model of the Recovery of Carotid Blood Flow for Monitoring Cerebral Circulation During CPR 47 3.1 Introduction 47 3.2 Methods 50 3.2.1 Ethical statement 50 3.2.2 Study design and setting 50 3.2.3 Experimental animals and housing 52 3.2.4 Surgical preparation and hemodynamic measurements 54 3.2.5 EEG measurement 55 3.2.6 Data processing 57 3.2.7 Data analysis 58 3.2.8 Development of machine-learning based prediction model 59 3.3 Results 63 3.3.1 Results of CPR process 63 3.3.2 EEG changes with the recovery of CaBF 66 3.3.3 Changes in EEG parameters depending on four CaBF groups 68 3.3.4 Changes in EEG parameters depending on two CaBF groups 69 3.3.5 EEG parameters for prediction models 70 3.3.6 Performances of prediction models 73 3.4 Discussion 76 3.4.1 Accomplishment 76 3.4.2 Limitations 78 3.5 Conclusion 80 Chapter 4 EEG-based Prediction Model of an Increased Intra-Cranial Pressure for TBI patients 81 4.1 Introduction 81 4.2 Methods 83 4.2.1 Ethical statement 83 4.2.2 Study design and setting 83 4.2.3 Experimental animals and housing 85 4.2.4 Surgical preparation and hemodynamic measurements 86 4.2.5 EEG measurement 88 4.2.6 Data processing 90 4.2.7 Data analysis 90 4.2.8 Development of machine-learning based prediction model 91 4.3 Results 92 4.3.1 Hemodynamic changes during brain injury phase 92 4.3.2 EEG changes with an increase of ICP 93 4.3.3 EEG parameters for prediction models 94 4.3.4 Performances for prediction models 95 4.4 Discussion 100 4.4.1 Accomplishment 100 4.4.2 Limitations 104 4.5 Conclusion 104 Chapter 5 Summary and Future works 105 5.1 Thesis summary and contributions 105 5.2 Future direction 108 Bibilography 113 Abstract in Korean 135Docto

2023 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces

The International Liaison Committee on Resuscitation engages in a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation and first aid science. Draft Consensus on Science With Treatment Recommendations are posted online throughout the year, and this annual summary provides more concise versions of the final Consensus on Science With Treatment Recommendations from all task forces for the year. Topics addressed by systematic reviews this year include resuscitation of cardiac arrest from drowning, extracorporeal cardiopulmonary resuscitation for adults and children, calcium during cardiac arrest, double sequential defibrillation, neuroprognostication after cardiac arrest for adults and children, maintaining normal temperature after preterm birth, heart rate monitoring methods for diagnostics in neonates, detection of exhaled carbon dioxide in neonates, family presence during resuscitation of adults, and a stepwise approach to resuscitation skills training. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research. Additional topics are addressed with scoping reviews and evidence updates

2023 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces

The International Liaison Committee on Resuscitation engages in a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation and first aid science. Draft Consensus on Science With Treatment Recommendations are posted online throughout the year, and this annual summary provides more concise versions of the final Consensus on Science With Treatment Recommendations from all task forces for the year. Topics addressed by systematic reviews this year include resuscitation of cardiac arrest from drowning, extracorporeal cardiopulmonary resuscitation for adults and children, calcium during cardiac arrest, double sequential defibrillation, neuroprognostication after cardiac arrest for adults and children, maintaining normal temperature after preterm birth, heart rate monitoring methods for diagnostics in neonates, detection of exhaled carbon dioxide in neonates, family presence during resuscitation of adults, and a stepwise approach to resuscitation skills training. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research. Additional topics are addressed with scoping reviews and evidence updates

PhD

dissertationThe physiological consequences of major thermal injury center around profound, life-threatening shock occurring in conjunction with the burn and consisting of two pathological syndromes: hypovolemic and cellular shock. Intravascular hypovolemia following major thermal injury results from increased capillary permeability with subsequent loss of intravascular fluid into the interstitium. The purpose of this study was to evaluate the effect of a therapeutic regime involving the removal of the circulating factors by performing plasma exchange. Fourteen adult patients with burns of 40% total body surface area (TBSA) served as subjects. Seven were randomly assigned to the control group which received standard burn shock resuscitation. Seven were randomly assigned to the treatment group which received the same resuscitation in combination with plasma exchange. The study period was the first 48 hours postburn with the plasma exchange procedures performed as soon as was clinically feasible. A total of 937 measurements of physiological variables were made on each patient. These included vital signs, cardiopulmonary parameters, respiratory status, and serum content analysis measured upon admission and every 4 hours thereafter during the study period. Hourly fluid intake and output records were compiled. Data were analyzed for statistical significance. The findings were as follows: the sample was unevenly distributed, with the treatment group more critically ill than the control on the basis of the variable or percent TBSA full-thickness injury (p < .01) and the incidence of documented inhalation injury. No significant difference was found between the groups on the variable of fluid requirement, either in subjects with or without associated inhalation injury. Plasma exchange significantly decreased platelet count (p < .05) in the treatment group when compared with the control but did not alter other serum chemistry values. The coagulopathy reported to occur in burn patients was not observed in this group of 14 subjects. The plasma exchange group was in significantly (p < .05) more normal base excess balance at both postburn hour 16 and 24 than the control. There was no evidence that plasma exchange performed during burn shock for the purpose of removing circulating factors was harmful in any way to the treatment subjects

Cardiac arrest and therapeutic hypothermia: Prognosis and outcome

Abstract Therapeutic hypothermia (TH) is the only treatment available to reduce neurological sequels for unconscious patients following cardiac arrest (CA). TH requires sedation and muscular relaxation, obscuring the clinical neurological examination for estimation of prognosis, and clinical decision making. Continuous amplitude-integrated EEG (aEEG) has been used to predict outcome in neonates suffering from asphyxia. In adults following CA and TH, the novel observation was made that a continuous aEEG-pattern prior to or at normothermia strongly correlated to return of consciousness, while other patterns strongly correlated to continued coma. A status epilepticus aEEG-pattern carried a poor, but not desolate prognosis. Biochemical neuronal-markers (neuron-specific enolase (NSE) and S-100B) have previously been assessed in non-TH CA patients. In TH, an NSE level of 28 μg/l 48h after CA, or an increase of more than 2 μg/l between 24 and 48h were strongly associated to a poor outcome. Five days after the CA, one third of the patients remained in coma. They either had multimodal signs of extensive brain damage (high NSE levels, ischemic changes on MRI or neurophysiological evidence of advanced brain damage (bilateral lack of SSEP)), or showed sustained unconsciousness and a status epilepticus aEEG-pattern. Unconscious patients without these signs of brain injury eventually regained consciousness. Approximately 50% of hypothermia treated patients regained consciousness. Ninety-eight percent of surviving patients had an independent lifestyle six months after the CA. The dominant cognitive problem was a disturbed memory function. Taken together, aEEG appears superior in early neurological prognostication in these patients

Updates Regarding Prediction and Prevention of Sudden Cardiac Death

Sudden cardiac death (SCD) remains a major public health problem globally, especially in the United States causing more than 300,000 deaths annually. SCD from cardiac arrest is the most common cause of death worldwide, accounting for >50% of all deaths from cardiovascular diseases (CVDs) and it is characterized by unexpected collapse due to an underlying cardiovascular cause. The condition usually results from an electrical disturbance in the heart that disrupts its pumping action, stopping blood flow to the body. When the heart stops, the lack of oxygenated blood can causes death or permanent brain damage within minutes. Time is extremely critical when someone or a clinician is helping an unconscious person who is not breathing. SCD represents a major challenge for the clinician because most episodes occur in individuals without previously known cardiac disease. Hence, an early prediction of individuals at risk of SCD is the holly-grail of all physicians. Because most individuals experiencing SCD currently are not identifiable as being at high risk, community-based public access to defibrillation programs is essential to save lives and more so to improve neurological and functional outcomes for cardiac arrest victims. In order to prevent SCD, it is imperative to impose an aggressive management of cardiovascular risk factors, including performing exercise regularly, educating patients about the dangers of CVDs, promoting a healthy diet, restricting consumption of sugar, saturated fat, salt and smoking cessation to promote a heart healthy behavior to all, young children in particular. Finally, a preclinical prediction of patients at risk of SCD and early detection of the disease is crucial for early intervention and definitely will reduce the incidence of sudden cardiac death dramatically

2023 International consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations: summary from the basic life support; advanced life support; pediatric life support; neonatal life support; education, implementation, and teams; and first aid task forces

The International Liaison Committee on Resuscitation engages in a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation and first aid science. Draft Consensus on Science With Treatment Recommendations are posted online throughout the year, and this annual summary provides more concise versions of the final Consensus on Science With Treatment Recommendations from all task forces for the year. Topics addressed by systematic reviews this year include resuscitation of cardiac arrest from drowning, extracorporeal cardiopulmonary resuscitation for adults and children, calcium during cardiac arrest, double sequential defibrillation, neuroprognostication after cardiac arrest for adults and children, maintaining normal temperature after preterm birth, heart rate monitoring methods for diagnostics in neonates, detection of exhaled carbon dioxide in neonates, family presence during resuscitation of adults, and a stepwise approach to resuscitation skills training. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research. Additional topics are addressed with scoping reviews and evidence updates

Diagnosis of brain death

Brain death (BD) should be understood as the ultimate clinical expression of a brain catastrophe characterized by a complete and irreversible neurological stoppage, recognized by irreversible coma, absent brainstem reflexes, and apnea. The most common pattern is manifested by an elevation of intracranial pressure to a point beyond the mean arterial pressure, and hence cerebral perfusion pressure falls and, as a result, no net cerebral blood flow is present, in due course leading to permanent cytotoxic injury of the intracranial neuronal tissue. A second mechanism is an intrinsic injury affecting the nervous tissue at a cellular level which, if extensive and unremitting, can also lead to BD. We review here the methodology of diagnosing death, based on finding any of the signs of death. The irreversible loss of cardio-circulatory and respiratory functions can cause death only when ischemia and anoxia are prolonged enough to produce an irreversible destruction of the brain. The sign of such loss of brain functions, that is to say BD diagnosis, is fully reviewed