How Large is the Potential of Brain Dead Donors and what Prevents Utilization? A Multicenter Retrospective Analysis at Seven University Hospitals in North Rhine-Westphalia.

Organ donation after brain death is constantly lower in Germany compared to other countries. Instead, representative surveys show a positive attitude towards donation. Why this does not translate into more donations remains questionable. We retrospectively analyzed all potential brain dead donors treated in the university hospitals of Aachen, Bielefeld, Bonn, Essen, Düsseldorf, Cologne and Münster between June 2020 and July 2021. 300 potential brain dead donors were identified. Donation was utilized in 69 cases (23%). Refused consent (n = 190), and failed utilization despite consent (n = 41) were reasons for a donation not realized. Consent was significantly higher in potential donors with a known attitude towards donation (n = 94) compared to a decision by family members (n = 195) (49% vs. 33%, p = 0.012). The potential donor´s age, status of interviewer, and the timing of the interview with decision-makers had no influence on consent rates, and it was comparable between hospitals. Refused consent was the predominant reason for a donation not utilized. Consent rate was lower than in surveys, only a known attitude towards donation had a significant positive influence. This indicates that survey results do not translate well into everyday clinical practice and promoting a previously documented decision on organ donation is important.

An Innovative Telemedical Network to Improve Infectious Disease Management in Critically Ill Patients and Outpatients (TELnet@NRW): Stepped-Wedge Cluster Randomized Controlled Trial.

BACKGROUND: Evidence-based infectious disease and intensive care management is more relevant than ever. Medical expertise in the two disciplines is often geographically limited to university institutions. In addition, the interconnection between inpatient and outpatient care is often insufficient (eg, no shared electronic health record and no digital transfer of patient findings). OBJECTIVE: This study aims to establish and evaluate a telemedical inpatient-outpatient network based on expert teleconsultations to increase treatment quality in intensive care medicine and infectious diseases. METHODS: We performed a multicenter, stepped-wedge cluster randomized trial (February 2017 to January 2020) to establish a telemedicine inpatient-outpatient network among university hospitals, hospitals, and outpatient physicians in North Rhine-Westphalia, Germany. Patients aged ≥18 years in the intensive care unit or consulting with a physician in the outpatient setting were eligible. We provided expert knowledge from intensivists and infectious disease specialists through advanced training courses and expert teleconsultations with 24/7/365 availability on demand respectively once per week to enhance treatment quality. The primary outcome was adherence to the 10 Choosing Wisely recommendations for infectious disease management. Guideline adherence was analyzed using binary logistic regression models. RESULTS: Overall, 159,424 patients (10,585 inpatients and 148,839 outpatients) from 17 hospitals and 103 outpatient physicians were included. There was a significant increase in guideline adherence in the management of Staphylococcus aureus infections (odds ratio [OR] 4.00, 95% CI 1.83-9.20; P<.001) and in sepsis management in critically ill patients (OR 6.82, 95% CI 1.27-56.61; P=.04). There was a statistically nonsignificant decrease in sepsis-related mortality from 29% (19/66) in the control group to 23.8% (50/210) in the intervention group. Furthermore, the extension of treatment with prophylactic antibiotics after surgery was significantly less likely (OR 9.37, 95% CI 1.52-111.47; P=.04). Patients treated by outpatient physicians, who were regularly participating in expert teleconsultations, were also more likely to be treated according to guideline recommendations regarding antibiotic therapy for uncomplicated upper respiratory tract infections (OR 1.34, 95% CI 1.16-1.56; P<.001) and asymptomatic bacteriuria (OR 9.31, 95% CI 3.79-25.94; P<.001). For the other recommendations, we found no significant effects, or we had too few observations to generate models. The key limitations of our study include selection effects due to the applied on-site triage of patients as well as the limited possibilities to control for secular effects. CONCLUSIONS: Telemedicine facilitates a direct round-the-clock interaction over broad distances between intensivists or infectious disease experts and physicians who care for patients in hospitals without ready access to these experts. Expert teleconsultations increase guideline adherence and treatment quality in infectious disease and intensive care management, creating added value for critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03137589; https://clinicaltrials.gov/ct2/show/NCT03137589.

[Perioperative management of the brain-dead organ donor : Anesthesia between ethics and evidence]. / Perioperatives Management der postmortalen Organspende : Anästhesie zwischen Ethik und Evidenz.

BACKGROUND: The number of organs donated after brain death in Germany is far lower than the demand. This underlines the importance of providing the brain-dead donor with optimal medical care throughout the donation process to decrease the risk of graft dysfunction. Several international guidelines and national recommendations guide the intensivists in organ-protective intensive care management of the brain-dead donor. OBJECTIVE: The anesthetist is a key member during organ retrieval procedures and plays a crucial role in physiological donor management; however, evidence-based recommendations for the perioperative anesthetic management, drug treatment strategies and target values are lacking. Anesthesia literature about donor management is scarce and predominantly composed of reviews of practice, with little exploration of the scientific foundations. The aim of this review is to guide the anesthetist in the organ-protective perioperative therapy. The pathophysiological changes in patients who progress to brain death are briefly summarized. The available evidence, guidelines and expert opinions regarding medical treatment strategies and therapeutic goals in organ-protective therapy are reviewed. The ethical and pathophysiological considerations regarding the performance of anesthesia during organ retrieval are discussed. METHODS: This review is based on a selective literature search in PubMed for publications regarding organ donation after brain death (keywords: "brain dead donor", "organ procurement", "organ protective therapy", "donor preconditioning", "perioperative donor management", "ethical considerations of brain dead donor"). International guidelines, national recommendations and expert opinions were given special consideration. RESULTS: Overall, the evidence for optimal perioperative organ-protective care of the brain-dead donor is limited. Most elements in the current recommendations and guidelines are based on pathophysiological reasoning, epidemiological observations or extrapolations from general organ-protective management strategies, and not on evidence from randomized controlled trials. National and international recommendations on treatment goals and drug therapy differ considerably in some aspects. The therapy concepts applied are very heterogeneous. Apart from medical challenges, the ethical circumstances are an additional burden for the entire treatment team. Whether anesthesia is reasonable during organ retrieval remains unclear. There is uncertainty about possible organ-protective effects of anesthetic drugs. Furthermore, ethical considerations raise the question of whether the determination of brain death and the use of anesthetic drugs during the procedure of organ retrieval are compatible with each other. CONCLUSION: Due to the lack of evidence, perioperative treatment should be guided by intensive care therapy strategies. The discussion about using anesthetic drugs during organ retrieval remains controversial. Pathophysiological considerations support the use of volatile anesthetics because of possible organ-protective effects. The use of neuromuscular blocking is justified to control any possible motor response resulting from spinal cord reflexes, whereas there is no evidence for a benefit from using opioids. Apart from that, it seems ethically problematic to anesthetise a brain-dead donor. Consequently, knowledge about the pathophysiological processes caused by brain death and about organ-protective therapy concepts are just as much a basic requirement as the consideration of ethical problems in organ donation after brain death. Only then are the caregivers able to do justice to both the organ recipient and the organ donor, as well as their relatives in this challenging situation.

A ten-year retrospective analysis of decompressive craniectomy or craniotomy after severe brain injury and its implications for donation after brain death.

Craniotomy or decompressive craniectomy are among the therapeutic options to prevent or treat secondary damage after severe brain injury. The choice of procedure depends, among other things, on the type and severity of the initial injury. It remains controversial whether both procedures influence the neurological outcome differently. Thus, estimating the risk of brain herniation and death and consequently potential organ donation remains difficult. All patients at the University Hospital Münster for whom an isolated craniotomy or decompressive craniectomy was performed as a treatment after severe brain injury between 2013 and 2022 were retrospectively included. Proportion of survivors and deceased were evaluated. Deceased were further analyzed regarding anticoagulants, comorbidities, type of brain injury, potential and utilized donation after brain death. 595 patients were identified, 296 patients survived, and 299 deceased. Proportion of decompressive craniectomy was higher than craniotomy in survivors (89% vs. 11%, p < 0.001). Brain death was diagnosed in 12 deceased and 10 donations were utilized. Utilized donations were comparable after both procedures (5% vs. 2%, p = 0.194). Preserved brain stem reflexes as a reason against donation did not differ between decompressive craniectomy or craniotomy (32% vs. 29%, p = 0.470). Patients with severe brain injury were more likely to survive after decompressive craniectomy than craniotomy. Among the deceased, potential and utilized donations did not differ between both procedures. This suggests that brain death can occur independent of the previous neurosurgical procedure and that organ donation should always be considered in end-of-life decisions for patients with a fatal prognosis.

Post-COVID-19 pandemic organ donation activities in Germany: a multicenter retrospective analysis.

Introduction: The COVID-19 pandemic had a negative impact on the number of solid organ transplantations. After a global decline of 16% in 2020, their numbers subsequently returned to pre-pandemic levels. In contrast, numbers in Germany remained almost constant in 2020 and 2021 but fell by 6.9% in 2022. The reasons for this divergent development are unknown. Methods: The number of deceased with a severe brain damage, potential and utilized donors after braindeath and the intensive care unit treatment capacity were retrospectively compared for the years 2022 and 2021 at five university hospitals in North Rhine-Westphalia, Germany. Reasons for a donation not utilized were reviewed. To enable a comparison of the results with the whole of Germany and the pre-pandemic period, numbers of potential and utilized donors were extracted from official organ donation activity reports of all harvesting hospitals in Germany for the years 2019-2022. Results: The numbers of deceased with a severe brain damage (-10%), potential (-9%), and utilized donors after braindeath (-44%), and intensive care unit treatment capacities (-7.2%) were significantly lower in 2022 than 2021. A COVID-19 infection was a rarer (-79%), but donor instability (+44%) a more frequent reason against donation in 2022, whereas preserved brain stem reflexes remained the most frequent reason in both years (54%). Overall numbers of potential and utilized donations in Germany were lower in 2022 than in the pre-pandemic period, but this was mainly due to lower numbers in hospitals of lower care. The number of potential donors in all university hospitals were higher in 2022 but utilized donations still lower than in 2019. Conclusion: The decrease in potential and utilized donations was a result of reduced intensive care unit treatment capacities and a lower conversion rate at the five university hospitals. A COVID-19 infection did not play a role in 2022. These results indicate that ICU treatment capacities must be restored to increase donations. The lower number of potential donors and the even lower conversion rate in 2022 throughout Germany show that restructuring the organ procurement process in Germany needs to be discussed to increase the number of donations.

[Organ donation after determination of brain death : Legal aspects and practical approach]. / Organspende nach irreversiblem Hirnfunktionsausfall : Rechtliche Aspekte und praktisches Vorgehen.

The prerequisites for post-mortem organ donation in Germany include the determination of irreversible loss of brain function, consent to organ donation, and the exclusion of medical contraindications. In addition, mainly because of the shortage of donor organs in Germany and the sometimes controversial social and media discussions on the topic of organ donation, all physicians involved in the donation process must be familiar with the relevant laws, guidelines, and procedural instructions. This applies especially to those who are to carry out the verification of irreversible brain death. Only then, can they act safely in this challenging situation and serve as competent consultants for all involved.

Risk factors associated with vasospasm after non-traumatic subarachnoid hemorrhage: a retrospective analysis of 456 patients.

BACKGROUND: The pathophysiology of vasospasm (VS) after non-traumatic subarachnoid hemorrhage is not completely understood. Several risk factors associated with VS were previously reported, partially with conflicting results. The aim of this study was to identify patients at increased risk for VS. METHODS: Retrospective analysis of data from all patients treated in our institutional intensive care unit (ICU) between 2010 and 2016 after non-traumatic subarachnoid hemorrhage. Possible contributing factors for VS studied were: age, sex, aneurysm-localization, treatment option, ICU-stay, ICU mortality, pre-existing condition, medication history, World Federation of Neurosurgical Societies (WFNS) grading system, modified Fisher scale. RESULTS: We obtained data from 456 patients. 184 were male and 272 female patients, respectively. Mean age was 57.7±13.9 and was not different between sexes. In 119 patients, VS was diagnosed after subarachnoid hemorrhage. Incidence of VS was not different between sexes (male: 22.3%, female: 28.7%, P=0.127). Patients with VS were significantly younger (mean age 52.2 vs. 59.7, P<0.001), meanwhile patients aged 36-40 yrs. had the highest incidence of VS. Most VS were found after rupture of middle cerebral artery-aneurysms. Higher incidence of VS was found after aneurysm clipping compared to coiling. VS developed more often in patients with more severe WFNS grade and Fisher scale. In multivariate analysis, age, previous drug abuse and history of anticoagulants were associated with the incidence of VS. CONCLUSIONS: Younger age, middle cerebral artery-aneurysms, aneurysm clipping, previous drug abuse and history of anticoagulants were associated with a higher incidence of VS after non-traumatic subarachnoid hemorrhage. No gender difference was found.

[Pain management after ambulatory surgery in Germany]. / Ambulante Schmerztherapie - Optimierung der Schmerztherapie nach ambulanten Operationen.

An increasing percentage of surgical procedures are performed in an ambulatory setting. However, a fairly high number of patients experience moderate to severe postoperative pain and pain is a common reason for unanticipated hospital admission. An adequate postoperative pain therapy in the ambulatory setting is therefore essential not only for ethical reasons or improvements in recovery but also for economic reasons but - in Germany - still remains inadequate. The following article deals with the problems that cause inadequat pain therapy after ambulatory surgery in Germany and introduces different therapeutic options, strategies and drugs relevant to optimize pain therapy after ambulatory surgery. Major aspects are education of the patient, the use of adequate non-opioid analgesics and implementation of regional analgesia techniques. Non-opioid analgesics are known to be effective to reduce opioid requirements and side effects; however, not all non-opioid analgesics are similar effective. Furthermore side effects and risks of these drugs need to be considered in individual patients. Benefits from regional anesthesia and analgesia techniques are well known after sugery. Experiences from other countries demonstrate improved analgesia, less side effects (e.g. sedation, insomnia) and increased patients satisfaction associated with continuous peripheral nerve blocks at home. In Germany, these techniques are not frequently used but need to be considered in the future to optimize postoperative pain management after ambulatory surgery.

Acute pain management in patients with fibromyalgia and other diffuse chronic pain syndromes.

PURPOSE OF REVIEW: Patients with fibromyalgia are at increased risk to experience increased and prolonged postoperative pain. In this review, we will provide an overview of pathophysiological characteristics of fibromyalgia relevant for enhanced pain processing after surgery. Furthermore, we will present some potential treatment options in the perioperative period based on specific symptoms of individual fibromyalgia patients to optimize their pain management after surgery. RECENT FINDINGS: Recent evidence points towards enhanced central nervous system sensitization and decreased descending inhibition in patients with fibromyalgia. Even in patients without fibromyalgia, these two mechanisms are seen as major contributors to the severity of acute and chronic pain states after surgery. Furthermore, other symptoms and comorbidities such as anxiety, depression and somatization disorder, frequently associated with fibromyalgia, are independently known to increase the risk of acute and prolonged pain after surgery. Therefore, an optimal treatment approach in the perioperative period should include substances and strategies targeting specific symptoms in fibromyalgia patients to prevent or specifically reduce acute and prolonged pain after surgery. Such multimodal pain management in fibromyalgia patients in the perioperative period should include nonopioid analgesics, gabapentinoids, antidepressants, N-methyl-D-asparate antagonists and use of regional techniques when appropriate. SUMMARY: The perioperative pain management of patients with fibromyalgia is challenging and should include symptom-based approaches to target enhanced central sensitization and decreased inhibition in these patients as well as their psychological syndromes aiming to decrease acute and prolonged pain after surgery.

Progesterone relates to enhanced incisional acute pain and pinprick hyperalgesia in the luteal phase of female volunteers.

The role of sex hormones on postsurgical pain perception is basically unclear. Here, we studied the role of endogenous gonadal hormones for pain and hyperalgesia in human volunteers after experimental incision. A 4-mm incision was made in the volar forearm of 15 female volunteers both in the follicular and the luteal phase (random block design). Somatosensory profiles were assessed at baseline and 1 to 72 hours after incision by quantitative sensory testing, compared between both cycle phases, and related to individual plasma levels of gonadal hormones. Sensory testing at baseline revealed significantly lower pain thresholds (25 vs 46 mN, P < 0.005) and increased pain ratings to pinprick (0.96 vs 0.47, P < 0.0001) in the luteal phase; similarly, 1 hour after incision, pain intensity to incision (38 vs 21/100, P < 0.005), pinprick hyperalgesia by rating (P < 0.05), and area of secondary hyperalgesia (P < 0.001) were enhanced in the luteal phase. Multiple regression analysis revealed that pinprick pain sensitivity at baseline was significantly predicted by progesterone (partial r = 0.67, P < 0.001), follicle-stimulating hormone (FSH) (partial r = 0.61, P < 0.005), and negatively by testosterone (partial r = -0.44, P < 0.05). Likewise, incision-induced pain and pinprick hyperalgesia (rating and area) were significantly predicted by progesterone (partial r = 0.70, r = 0.46, and r = 0.47, respectively; P < 0.05-0.0001) and in part by FSH; the contribution of estrogen, however, was fully occluded by progesterone for all measures. In conclusion, pinprick pain and incision-induced pain and mechanical hyperalgesia were greater in the luteal phase and predicted by progesterone, suggesting a major role for progesterone. Other hormones involved are testosterone (protective) and in part FSH.