Approaching the Families of Potential Deceased Organ Donors: An Overview of Regulations and Practices in Council of Europe Member States.

The primary aim of this study was to describe regulations and practices concerning the family approach to discuss donation, specifically after the neurological determination of death, one of the most challenging steps in the donation pathway. A secondary objective was to assess the impact of legislation on consent rates for organ donation. The Council of Europe surveyed 39 member states about national regulations, practices, and consent rates; 34 replied. Opt-out legislation is present in 19, opt-in in 9 and a mixed system in six countries. An opt-out register is kept by 24 countries and an opt-in register by 18 countries, some keeping both. The mean consent rate was 81.2% of all family approaches. Most countries regulate how death using neurological criteria is confirmed (85.3%), while regulation of other aspects of the deceased donation pathway varies: the timing of informing the family about brain death (47.1%) and organ donation (58.8%), the profile of professional who discusses both topics with the family (52.9% and 64.7%, respectively) and the withdrawal of treatment after brain death (47.1%). We also noted a mismatch between what regulations state and what is done in practice in most countries. We suggest possible reasons for this disparity.

Organ donor screening for carbapenem-resistant gram-negative bacteria in Italian intensive care units: the DRIn study.

The 759 cases of brain death declaration (BDD [Italian law, 6 hours of observation time]) that occurred in 190 Italian intensive care units (ICUs) between May and September 2012 were studied to quantify carbapenem-resistant gram-negative bacteria (CR-GN) isolated in organ donors, to evaluate adherence to national screening guidelines, and to identify risk factors for CR-GN isolation. Mandatory blood, bronchoalveolar lavage, and urine cultures were performed on the BDD day in 99% of used donors. Because results were rarely made available before transplant, >20% of transplants were performed before obtaining any microbiological information, and organs from 15 of 22 CR-GN cases were used. Two (lung-liver) of the 37 recipients died, likely because of donor-derived early CR-GN sepsis. ICU stay >3 days (odds ratio [OR] = 7.49, P = .004), fever (OR = 3.11, P = .04), age <60 years (OR = 2.80, P = .06), and positive ICU epidemiology (OR = 8.77, P = .07) were associated with CR-GN isolation. An association between single ICU and risk of CR-GN was observed, as a result of differences across ICUs (ICC = 29%; 95% confidence interval [CI] 6.5%-72%) probably related to inadequate practices of infection control. Continuous education aimed at implementing priority actions, including stewardship programs for a rational use of antimicrobials, is a priority in healthcare systems and transplant networks. Improved awareness among ICU personnel regarding the importance of early CR-GN detection and timely alert systems might facilitate decisions regarding organ suitability and eventually save recipient lives.

Donation after circulatory death today: an updated overview of the European landscape.

Donation after circulatory death (DCD) has become an accepted practice in many countries and remains a focus of intense interest in the transplant community. The present study is aimed at providing a description of the current situation of DCD in European countries. Specific questionnaires were developed to compile information on DCD practices, activities and post-transplant outcomes. Thirty-five countries completed the survey. DCD is practiced in 18 countries: eight have both controlled DCD (cDCD) and uncontrolled DCD (uDCD) programs, 4 only cDCD and 6 only uDCD. All these countries have legally binding and/or nonbinding texts to regulate the practice of DCD. The no-touch period ranges from 5 to 30 min. There are variations in ante and post mortem interventions used for the practice of cDCD. During 2008-2016, the highest DCD activity was described in the United Kingdom, Spain, Russia, the Netherlands, Belgium and France. Data on post-transplant outcomes of patients who receive DCD donor kidneys show better results with grafts obtained from cDCD versus uDCD donors. In conclusion, DCD is becoming increasingly accepted and performed in Europe, importantly contributing to the number of organs available and providing acceptable post-transplantation outcomes.

Infections in liver and lung transplant recipients: a national prospective cohort.

Infections are a major complication of solid organ transplants (SOTs). This study aimed to describe recipients' characteristics, and the frequency and etiology of infections and transplant outcome in liver and lung SOTs, and to investigate exposures associated to infection and death in liver transplant recipients. The study population included recipients of SOTs performed in Italy during a 1-year period in ten Italian lung transplant units and eight liver transplant units. Data on comorbidities, infections, retransplantation, and death were prospectively collected using a web-based system, with a 6-month follow-up. The cumulative incidence of infection was 31.7% and 47.8% in liver and lung transplants, respectively, with most infections occurring within the first month after transplantation. Gram-negatives, which were primarily multidrug-resistant, were the most frequent cause of infection. Death rates were 0.42 per 1000 recipient-days in liver transplants and 1.41 per 1000 recipient-days in lung transplants. Infection after SOT in adult liver recipients is associated to an increased risk of death (OR = 13.25; p-value < 0.001). Given the frequency of infection caused by multidrug-resistant microorganisms in SOT recipients in Italy and the heavy impact of infections on the transplant outcome, the reinforcement of surveillance and control activities to prevent the transmission of multidrug-resistant microorganisms in SOT recipients represents a priority. The implementation of the study protocol in liver and lung transplant units and the sharing of results have increased the awareness about the threat due to antimicrobial resistance in the country.

Liver transplant recipients and prioritization of anti-HCV therapy: an Italian cohort analysis.

BACKGROUND AND AIMS: In patients with hepatitis C virus (HCV), recurrence of infection after liver transplant (LT) is universal and associated with worst survival. We present the results of an Italian cohort to compare the 3-year outcome of HCV-Ab-positive and HCV-Ab-negative LT recipients and to assess the potential interaction between HCV-Ab sero-status and other risk factors for LT failure. METHODS: The study is a multicentre cohort including a sample of liver transplant centres. Participant's information was collected at the local level. The best functional form of variables was decided according to the objective methods based on information theory. Association between transplant failure and potential risk factors was assessed in univariate and multivariate Poisson regression model with random intercept. RESULTS: Between June 2007 and May 2009, 1164 LT recipients were enrolled in 16 Italian transplant centres, of them 275 (23.63%) experienced LT failure. Incidence rates of LT failure was 0.32 and 0.23 per 1000 person-days in HCV-Ab-positive and HCV-Ab-negative recipients respectively (P = 0.003). Inferential models according to Akaike information criterion indicated that donor-recipient age difference and donor-recipient sex matching were more informative to predict LT failure than the age and the sex as separate variables. Multivariate analysis provided evidence that HCV-Ab sero-status, time after LT, donor-recipient age difference, donor-recipient sex matching and recipient's MELD score were significantly associated with LT failure. Moreover, the effect of HCV-Ab sero-status on LT failure was modified by the simultaneous action of time after LT and donor-recipient age difference. No interaction was found between recipient's HCV-Ab sero-status and either recipient's MELD or donor-recipient sex matching. CONCLUSION: In view of the imminent introduction of new anti-HCV therapies, our study provides information to assess which LT recipients should be prioritized for receiving these highly effective, but expensive, new treatments. This is particularly relevant for those clinical settings where healthcare prioritization is endorsed by national authorities.

Medium-term outcome of recipients of marginal donor hearts selected with new stress-echocardiographic techniques over standard criteria.

BACKGROUND: Heart transplantation is limited by severe donor organ shortage. Regardless of the changes made in the acceptance of marginal donors, any such mechanism cannot be considered successful unless recipient graft survival rates remain acceptable. A stress echo-driven selection of donors has proven successful in older donors with normal left ventricular resting function and in standard donors with reversible resting left ventricular dysfunction acutely improving during stress, or slowly improving (over hours) during intensive hormonal treatment. Aim of this study is to assess the medium-term outcome of recipients of marginal donor hearts selected with new echocardiographic techniques over standard criteria. METHODS AND RESULTS: We enrolled 43 recipients of marginal donor hearts: age > 55 years, or < 55 years but with concomitant risk factors, n = 32; acutely improving during stress, n = 3; or slowly improving during hormonal treatment, n = 8. At follow-up (median, 30 months; interquartile range, 21-52 months), 37 of the recipients were still alive. One-year survival was 93%. CONCLUSION: The strict use of new stress-echocardiographic techniques over standard criteria of marginal donor management, together with comprehensive monitoring of the donor, has the potential to substantially increase the number of donor hearts without adverse effects on recipient medium-term outcome.

Reinforcing Global Oversight of Organ Transplantation: Activity and Outcome Monitoring Through the Development of Registries.

Establishing transparency and oversight of organ transplantation by regulatory agencies is of paramount importance to assure ethical, legal, and clinically robust transplantation practices. Registries reporting activity and outcome data of the donor and recipient, including donor source (living or deceased), must be developed for each transplant and should be a mandatory requirement to achieve accreditation to perform transplant surgeries. Collected data for the living organ donor must include the nationality, the nature of their relationship with the recipient, and the complications encountered by living donors that result in prolonged morbidity or mortality. Long-term patient and graft survival must be reported for the recipient with the underlying reasons for mortality or graft loss. To retain the authorization to perform organ transplantation, a facility must ensure that it reports this required information regarding every organ transplant.

Developing and Expanding Deceased Organ Donation to its Maximum Therapeutic Potential: An Actionable Global Challenge From the 2023 Santander Summit.

On November 9 and 10, 2023, the Organización Nacional de Trasplantes (ONT), under the Spanish Presidency of the Council of the European Union, convened in Santander a Global Summit entitled "Towards Global Convergence in Transplantation: Sufficiency, Transparency and Oversight." This article summarizes two distinct but related challenges elaborated at the Santander Summit by Working Group 2 that must be overcome if we are to develop and expand deceased donation worldwide and achieve the goal of self-sufficiency in organ donation and transplantation. Challenge 1: the need for a unified concept of death based on the permanent cessation of brain function. Working group 2 proposed that challenge 1 requires the global community to work toward a uniform, worldwide definition of human death, conceptually unifying circulatory and neurological criteria of death around the cessation of brain function and accepting that permanent cessation of brain function is a valid criterion to determine death. Challenge 2: reducing disparities in deceased donation and increasing organ utilization through donation after the circulatory determination of death (DCDD). Working group 2 proposed that challenge 2 requires the global community to work toward increasing organ utilization through DCDD, expanding DCDD through in situ normothermic regional perfusion, and expanding DCDD through ex situ machine organ perfusion technology. Recommendations for implementation are described.

Life beyond life: Perceptions of post-mortem organ donation and consent to donate-A focus group study in Italy.

OBJECTIVES: Many factors such as personal and cultural beliefs, misinformation, fear of death and inadequate will registering procedures can influence post-mortem organ donation. The present study aimed to explore the perceptions, beliefs and information around post-mortem donation and will expression in different groups of the Italian population, to orient future interventions and raise awareness. DESIGN: Qualitative research with focus groups. METHODS: A total of 38 focus groups involving 353 participants including the general population (young adults: 18-39, mature adults: 40-70), local and hospital health professionals, critical area health professionals (emergency room and intensive care), registry office employees and opinion leaders, were conducted in six regions from different parts of Italy between June and November 2021. Thematic analysis was conducted with the use of Atlas.ti9. RESULTS: Five overarching themes were identified: dilemmas regarding donation, resistance to donation, facilitators of donation, difficulties in terms of will expression and proposals to encourage will expression. Possible facilitators were having personal and professional experiences with organ donation, feeling useful for society, having reliable information and trust in the health care system. Potential barriers to donation were doubts and fears about brain death, bodily integrity concerns, religious beliefs, misinformation and distrust in the health care system. CONCLUSIONS: These results highlighted the significance of a bottom-up perspective with regard to identifying the personal perceptions and beliefs with regard to donation, underlining the urgency of creating tailored interventions to sensitize different groups of the population in terms of promoting an informed choice and a culture of donation.

Pharmacokinetics of colistin in cerebrospinal fluid after intraventricular administration of colistin methanesulfonate.

Intraventricular colistin, administered as colistin methanesulfonate (CMS), is the last resource for the treatment of central nervous system infections caused by panresistant Gram-negative bacteria. The doses and daily regimens vary considerably and are empirically chosen; the cerebrospinal fluid (CSF) pharmacokinetics of colistin after intraventricular administration of CMS has never been characterized. Nine patients (aged 18 to 73 years) were treated with intraventricular CMS (daily doses of 2.61 to 10.44 mg). Colistin concentrations were measured using a selective high-performance liquid chromatography (HPLC) assay. The population pharmacokinetics analysis was performed with the P-Pharm program. The pharmacokinetics of colistin could be best described by the one-compartment model. The estimated values (means ± standard deviations) of apparent CSF total clearance (CL/Fm, where Fm is the unknown fraction of CMS converted to colistin) and terminal half-life (t(1/2λ)) were 0.033 ± 0.014 liter/h and 7.8 ± 3.2 h, respectively, and the average time to the peak concentration was 3.7 ± 0.9 h. A positive correlation between CL/Fm and the amount of CSF drained (range 40 to 300 ml) was observed. When CMS was administered at doses of ≥5.22 mg/day, measured CSF concentrations of colistin were continuously above the MIC of 2 µg/ml, and measured values of trough concentration (C(trough)) ranged between 2.0 and 9.7 µg/ml. Microbiological cure was observed in 8/9 patients. Intraventricular administration of CMS at doses of ≥5.22 mg per day was appropriate in our patients, but since external CSF efflux is variable and can influence the clearance of colistin and its concentrations in CSF, the daily dose of 10 mg suggested by the Infectious Diseases Society of America may be more prudent.

Wait, treat and see: echocardiographic monitoring of brain-dead potential donors with stunned heart.

BACKGROUND: Heart transplantation is limited by a severe donor organ shortage. Potential donors with brain death (BD) and left ventricular dysfunction due to neurogenic stunning are currently excluded from donation--although such abnormalities can be reversible with aggressive treatment including Hormonal Treatment (HT) and deferred organ retrieval. AIM: To assess the recovery of left ventricular dysfunction in potential brain-dead donors with hemodynamic instability treated by aggressive treatment and HT. METHODS: In a single-center, observational study design, we evaluated 15 consecutive brain-dead potential donors (DBD) (8 males, age = 48 ± 15 years) with hemodynamic instability. All underwent standard hemodynamic monitoring and transthoracic 2-dimensional echo (2-DE) with assessment of Ejection Fraction (EF). Measurements were obtained before BD and after BD within 6 h, at 24 h and within 48 h. HT (with insulin, methylprednisolone, vasopressin and T3) was started as soon as possible to treat hemodynamic instability and avoid administration of norepinephrine (NE). Eligible potential heart donors underwent coronary angiography. RESULTS: After HT, we observed a normalization of hemodynamic conditions with improvement of mean arterial pressure (pre = 68 ± 8 mmHg vs post = 83 ± 13 mmHg, p < .01), cardiac index (pre = 2.4 ± 0.6 L/min/m2 vs post 3.7 ± 1.2 L/min/m2, p < .05), EF (pre = 48 ± 15 vs post = 59 ± 3%, p < .01) without administration of norepinephrine (NE) in 67% of cases. Five potential donors were excluded from donation (opposition, n = 3, tubercolosis n = 1, malignancy n = 1). At pre-harvesting angiography, coronary artery stenosis was present in 2 of the 10 consented donors. Eight hearts were uneventfully transplanted. No early graft failure occurred and all eight recipients were alive at 6-month follow-up. CONCLUSION: In BD donors, intensive treatment including HT is associated with improvement of regional and global LV function and reverse remodeling detectable by transthoracic 2DE. Donor hearts with recovered LV function may be eligible for uneventful heart transplant. The wait (in brain death), treat (with HT) and see (with 2D echo) strategy can help rescue organs suitable for heart donation.

Management of donation after brain death (DBD) in the ICU: the potential donor is identified, what's next?

The success of any donation process requires that potential brain-dead donors (PBDD) are detected and referred early to professionals responsible for their evaluation and conversion to actual donors. The intensivist plays a crucial role in organ donation. However, identification and referral of PBDDs may be suboptimal in the critical care environment. Factors influencing lower rates of detection and referral include the lack of specific training and the need to provide concomitant urgent care to other critically ill patients. Excellent communication between the ICU staff and the procurement organization is necessary to ensure the optimization of both the number and quality of organs transplanted. The organ donation process has been improved over the last two decades with the involvement and commitment of many healthcare professionals. Clinical protocols have been developed and implemented to better organize the multidisciplinary approach to organ donation. In this manuscript, we aim to highlight the main steps of organ donation, taking into account the following: early identification and evaluation of the PBDD with the use of checklists; donor management, including clinical maintenance of the PBDD with high-quality intensive care to prevent graft failure in recipients and strategies for optimizing donated organs by simplified care standards, clinical guidelines and alert tools; the key role of the intensivist in the donation process with the interaction between ICU professionals and transplant coordinators, nurse protocol managers, and communication skills training; and a final remark on the importance of the development of research with further insight into brain death pathophysiology and reversible organ damage.

"Why can't I give you my organs after my heart has stopped beating?" An overview of the main clinical, organisational, ethical and legal issues concerning organ donation after circulatory death in Italy.

Donation after circulatory death (DCD) is a valuable option for the procurement of functioning organs for transplantation. Clinical results are promising and public acceptance is quite good in most western countries. Yet, although DCD is widespread in Europe, several problems still persist in Italy as well as in some other countries. This paper aims to describe the main clinical, organisational, ethical and legal issues at stake, bearing in mind the particular situation created by Italian legislation. Currently, as regards DCD, Italy is somewhat different from other countries. Therefore, every effort should be made for the safe and effective implementation of DCD programs: uncontrolled DCD programs should be promoted and encouraged, within the framework of shared and authoritative rules. At the same time, we need to tackle the question of controlled DCD, promoting debate among all involved subjects regarding the fundamental issues of end-of-life care within protocols that best integrate the highest standard of care for the dying and the legitimate interests of those awaiting a life-saving organ.

Incidence of carbapenem-resistant gram negatives in Italian transplant recipients: a nationwide surveillance study.

BACKGROUND: Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients. METHODS AND FINDINGS: Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients' mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively). Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days). Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%). Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s) positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days) during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not. CONCLUSION: The isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant and in those receiving either heart or lung transplants. Carbapenem-resistant gram negative isolates are associated with significant mortality.

Eligibility criteria and psychological profiles in patient candidates for awake craniotomy: a pilot study.

BACKGROUND: Although generally well tolerated, awake craniotomy is burdened by non-negligible failure rates. The aim of this pilot study was to verify the feasibility of a wider research scope to define objective criteria for patient exclusion and the risk of intraoperative mapping failures. METHODS: Twenty-one patients with brain tumors were subjected to a procedure in 3 steps: neuropsychological criteria for both cognition and language; psychological questionnaires for anxiety, attitude to pain and depression, and psychophysiological monitoring for the candidate's capacity for self-control; and an intraoperative interview for the patient's perception during awake procedure. Outcome measures were as follows: (1) patient compliance, defined as patient response to the intraoperative procedure and measured by psychological scale scores for fear and pain, and (2) failure, defined as the impossibility to complete brain mapping (minor) or conversion to general anesthesia (major). Data analysis included the description of preoperative and intraoperative assessments and their evaluation (Spearman ρ test), and the prognostic factors for intraoperative compliance and procedure failure (Mann-Whitney test). RESULTS: Three patients were considered ineligible after the first step. In the remaining 18, the responses of 10 patients fell within the normal range and 8 showed some degree of impairment on at least 1 preoperative evaluation, but not enough to be excluded from awake surgery. The data analysis also showed that fear of pain correlated with pain felt during the operation and preoperatively with depression and psychophysiological changes, the latter of which was associated with fear felt during craniotomy. Minor failures occurred in 2 patients. CONCLUSIONS: From these preliminary results, we observed that warning signs for minor failure were fear of pain and anxiety, as revealed by psychological questionnaire responses, and the incapability of self-control at psychophysiological monitoring. This assessment may serve to fit mapping modality to the single patient and to avoid complications.