Cynthia J. Gries

The circulatory-respiratory determination of death in organ donation

Objective:Death statutes permit physicians to declare death on the basis of irreversible cessation of circulatory–respiratory or brain functions. The growing practice of organ donation after circulatory determination of death now requires physicians to exercise greater specificity in circulatory–respiratory death determination. We studied circulatory–respiratory death determination to clarify its concept, practice, and application to innovative circulatory determination of death protocols. Results:It is ethically and legally appropriate to procure organs when permanent cessation (will not return) of circulation and respiration has occurred but before irreversible cessation (cannot return) has occurred because permanent cessation: 1) is an established medical practice standard for determining death; 2) is the meaning of “irreversible” in the Uniform Determination of Death Act; and 3) does not violate the “Dead Donor Rule.” Conclusions:The use of unmodified extracorporeal membrane oxygenation in the circulatory determination of death donor after death is declared should be abandoned because, by restoring brain circulation, it retroactively negates the previous death determination. Modifications of extracorporeal membrane oxygenation that avoid this problem by excluding brain circulation are contrived, invasive, and, if used, should require consent of surrogates. Heart donation in circulatory determination of death is acceptable if proper standards are followed to declare donor death after establishing the permanent cessation of circulation. Pending additional data on “auto-resuscitation,” we recommend that all circulatory determination of death programs should utilize the prevailing standard of 2 to 5 mins of demonstrated mechanical asystole before declaring death.

Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement

This document was developed through the collaborative efforts of the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations. Under the auspices of these societies, a multidisciplinary, multi-institutional task force was convened, incorporating expertise in critical care medicine, organ donor management, and transplantation. Members of the task force were divided into 13 subcommittees, each focused on one of the following general or organ-specific areas: death determination using neurologic criteria, donation after circulatory death determination, authorization process, general contraindications to donation, hemodynamic management, endocrine dysfunction and hormone replacement therapy, pediatric donor management, cardiac donation, lung donation, liver donation, kidney donation, small bowel donation, and pancreas donation. Subcommittees were charged with generating a series of management-related questions related to their topic. For each question, subcommittees provided a summary of relevant literature and specific recommendations. The specific recommendations were approved by all members of the task force and then assembled into a complete document. Because the available literature was overwhelmingly comprised of observational studies and case series, representing low-quality evidence, a decision was made that the document would assume the form of a consensus statement rather than a formally graded guideline. The goal of this document is to provide critical care practitioners with essential information and practical recommendations related to management of the potential organ donor, based on the available literature and expert consensus.

Spiritual care of families in the intensive care unit

Objectives:There is growing recognition of the importance of spiritual care as a quality domain for critically ill patients and their families, but there is a paucity of research to guide quality improvement in this area. Our goals were to: 1) determine whether intensive care unit (ICU) family members who rate an item about their spiritual care are different from family members who skip the item or rate the item as “not applicable” and 2) identify potential determinants of higher family satisfaction with spiritual care in the ICU. Design:Cross-sectional study, using data from a cluster randomized trial aimed at improving end-of-life care in the ICU. Setting:ICUs in ten Seattle-area hospitals. Subjects:A total of 356 family members of patients dying during an ICU stay or within 24 hrs of ICU discharge. Intervention:None. Measurements and Main Results:Family members were surveyed about spiritual care in the ICU. Chart abstractors obtained clinical variables including end-of-life care processes and family conference data. The 259 of 356 family members (73%) who rated their spiritual care were slightly younger than family members who did not rate this aspect of care (p = .001). Multiple regression revealed family members were more satisfied with spiritual care if a pastor or spiritual advisor was involved in the last 24 hrs of the patients life (p = .007). In addition, there was a strong association between satisfaction with spiritual care and satisfaction with the total ICU experience (p < .001). Ratings of spiritual care were not associated with any other demographic or clinical variables. Conclusions:These findings suggest that for patients dying in the ICU, clinicians should assess each familys spiritual needs and consult a spiritual advisor if desired by the family. Further research is needed to develop a comprehensive approach to ICU care that meets not only physical and psychosocial but also spiritual needs of patients and their families.

Solid-organ transplantation in older adults: Current status and future research

An increasing number of patients older than 65 years are referred for and have access to organ transplantation, and an increasing number of older adults are donating organs. Although short‐term outcomes are similar in older versus younger transplant recipients, older donor or recipient age is associated with inferior long‐term outcomes. However, age is often a proxy for other factors that might predict poor outcomes more strongly and better identify patients at risk for adverse events. Approaches to transplantation in older adults vary across programs, but despite recent gains in access and the increased use of marginal organs, older patients remain less likely than other groups to receive a transplant, and those who do are highly selected. Moreover, few studies have addressed geriatric issues in transplant patient selection or management, or the implications on health span and disability when patients age to late life with a transplanted organ. This paper summarizes a recent trans‐disciplinary workshop held by ASP, in collaboration with NHLBI, NIA, NIAID, NIDDK and AGS, to address issues related to kidney, liver, lung, or heart transplantation in older adults and to propose a research agenda in these areas.

An Official American Thoracic Society/International Society for Heart and Lung Transplantation/Society of Critical Care Medicine/Association of Organ and Procurement Organizations/United Network of Organ Sharing Statement: Ethical and Policy Considerations in Organ Donation after Circulatory Determination of Death

RATIONALE Donation after circulatory determination of death (DCDD) has the potential to increase the number of organs available for transplantation. Because consent and management of potential donors must occur before death, DCDD raises unique ethical and policy issues. OBJECTIVES To develop an ethics and health policy statement on adult and pediatric DCDD relevant to critical care and transplantation stakeholders. METHODS A multidisciplinary panel of stakeholders was convened to develop an ethics and health policy statement. The panel consisted of representatives from the American Thoracic Society, Society of Critical Care Medicine, International Society for Heart and Lung Transplantation, Association of Organ Procurement Organizations, and the United Network of Organ Sharing. The panel reviewed the literature, discussed important ethics and health policy considerations, and developed a guiding framework for decision making by stakeholders. RESULTS A framework to guide ethics and health policy statement was established, which addressed the consent process, pre- and post mortem interventions, the determination of death, provisions of end-of-life care, and pediatric DCDD. CONCLUSIONS The information presented in this Statement is based on the current evidence, experience, and clinical rationale. New clinical research and the development and dissemination of new technologies will eventually necessitate an update of this Statement.

De novo donor-specific HLA antibodies are associated with early and high-grade bronchiolitis obliterans syndrome and death after lung transplantation

BACKGROUND The development of human leukocyte antigen (HLA) antibody responses has been associated with worse clinical outcomes, such as bronchiolitis obliterans syndrome (BOS) and death, in lung transplant recipients (LTRs). However, the role of donor-specific HLA antibody (DSA) responses as a risk factor for poor outcomes remains controversial. METHODS We prospectively screened 445 LTRs for DSA at our institution at the time of surveillance bronchoscopies for the first 2 years after transplantation between 2003 and 2008, and evaluated clinical outcomes. For this purpose, we used the combination of panel-reactive antibodies (PRA) by enzyme-linked immunosorbent assay (ELISA) and the Luminex single-antigen bead (SAB) assay (One Lambda, Canoga Park, CA). RESULTS We detected de novo DSA (dnDSA) in 58 of 445 (13%) LTRs in our cohort. Freedom from BOS was significantly reduced in LTRs with dnDSA versus those without dnDSA (p < 0.001). Using a Cox proportional hazards model, the development of dnDSA was associated with a significantly increased hazard ratio (HR = 6.59 [4.53 to 9.59]; p < 0.001) for BOS and high-grade BOS (Stage ≥ 2) (HR = 5.76 [3.48 to 9.52]; p < 0.001). Freedom from death was significantly reduced in LTRs with dnDSA (p < 0.001), including mortality attributable to BOS (HR = 9.86 [4.91 to 19.78]; p < 0.001). CONCLUSIONS Taken together, our findings provide evidence that dnDSA is associated with accelerated BOS kinetics and severity, as well as death due to BOS after lung transplantation. In addition, these data support regular monitoring for the development of dnDSA in LTRs and underscore the need for novel strategies to mitigate the increased risk of poor outcomes associated with dnDSA.

Frailty Phenotypes, Disability, and Outcomes in Adult Candidates for Lung Transplantation

RATIONALE Frailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation. OBJECTIVES To examine the construct and predictive validity of frailty phenotypes in lung transplant candidates. METHODS In a multicenter prospective cohort, we measured frailty with the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB). We evaluated construct validity through comparisons with conceptually related factors. In a nested case-control study of frail and nonfrail subjects, we measured serum IL-6, tumor necrosis factor receptor 1, insulin-like growth factor I, and leptin. We estimated the association between frailty and disability using the Lung Transplant Valued Life Activities disability scale. We estimated the association between frailty and risk of delisting or death before transplant using multivariate logistic and Cox models, respectively. MEASUREMENTS AND MAIN RESULTS Of 395 subjects, 354 completed FFP assessments and 262 completed SPPB assessments; 28% were frail by FFP (95% confidence interval [CI], 24-33%) and 10% based on the SPPB (95% CI, 7-14%). By either measure, frailty correlated more strongly with exercise capacity and grip strength than with lung function. Frail subjects tended to have higher plasma IL-6 and tumor necrosis factor receptor 1 and lower insulin-like growth factor I and leptin. Frailty by either measure was associated with greater disability. After adjusting for age, sex, diagnosis, and transplant center, both FFP and SPPB were associated with increased risk of delisting or death before lung transplant. For every 1-point worsening in score, hazard ratios were 1.30 (95% CI, 1.01-1.67) for FFP and 1.53 (95% CI, 1.19-1.59) for SPPB. CONCLUSIONS Frailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death.

Development of a predictive model for long-term survival after lung transplantation and implications for the lung allocation score

BACKGROUND Improving long-term survival after lung transplantation can be facilitated by identifying patient characteristics that are predictors of positive long-term outcomes. Validated survival modeling is important for guiding clinical decision-making, case-mix adjustment in comparative effectiveness research and refinement of the lung allocation system (LAS). METHODS We used the registry of the International Society for Heart and Lung Transplantation (ISHLT) to develop and validate a predictive model of 5-year survival after lung transplantation. A total of 18,072 eligible cases were randomly split into development and validation datasets. Pre-transplant recipient variables considered included age, gender, diagnosis, body mass index, serum creatinine, hemodynamic variables, pulmonary function variables, viral status and comorbidities. Predictors were considered in a stepwise approach with the Akaike Information Criteria (AIC). Time-dependent receiver operator characteristic (ROC) curves assessed predictive ability. A 1-year conditional model and three models for disease subgroups were considered. ROC methods were used to characterize the predictive potential of the LAS post-transplant model at 1 and 5 years. RESULTS The baseline model included age, diagnosis, creatinine, bilirubin, oxygen requirement, cardiac output, Epstein-Barr virus status, transfusion history and diabetes history. Prediction of long-term survival was poor (area under the curve [AUC] = 0.582). Neither the 1-year conditional model (AUC = 0.573) nor models designed for separate diseases (AUC = 0.553 to 0.591) improved survival prediction. The predictive ability of the LAS post-transplant parameters was similar to that of our model (1-year AUC = 0.580 and 5-year AUC = 0.566). CONCLUSIONS Models developed from pre-transplant characteristics poorly predict long-term survival. Models for separate diseases and 1-year conditional models did not improve prediction. Better databases and approaches to predict survival are needed to improve lung allocation.

Circulatory Death Determination in Uncontrolled Organ Donors: A Panel Viewpoint

One barrier for implementing programs of uncontrolled organ donation after the circulatory determination of death is the lack of consensus on the precise moment of death. Our panel was convened to study this question after we performed a similar analysis on the moment of death in controlled organ donation after the circulatory determination of death. We concluded that death could be determined by showing the permanent or irreversible cessation of circulation and respiration. Circulatory irreversibility may be presumed when optimal cardiopulmonary resuscitation efforts have failed to restore circulation and at least a 7-minute period has elapsed thereafter during which autoresuscitation to restored circulation could occur. We advise against the use of postmortem organ support technologies that reestablish circulation of warm oxygenated blood because of their risk of retroactively invalidating the required conditions on which death was declared.

Lung transplantation in patients with prior cardiothoracic surgical procedures.

The full spectrum of prior cardiothoracic procedures in lung transplant candidates and the impact of prior procedures on outcomes after lung transplantation (LTx) remain unknown, though the impact is considered to be large. Patients transplanted at our institution from 2004 to 2009 were identified (n = 554) and divided into two groups: patients who had undergone cardiothoracic surgical (CTS) procedures prior to LTx (n = 238) and patients who had not (non‐CTS: n = 316). Our primary endpoint was survival. Secondary endpoints included allograft function and the incidence of major complications including reexploration due to bleeding, prolonged ventilation, renal insufficiency and primary graft dysfunction. Long‐term survival was not significantly different between the groups whereas postoperative bleeding, nerve injury, respiratory and renal complications were higher in the CTS group. Posttransplant peak FEV1 was lower in the CTS group (73.4% vs. 86.9%, p < 0.05). In multivariate analysis, performance of a chemical pleurodesis procedure and prolonged cardiopulmonary bypass were significantly associated with mortality (OR, 1.7; CI, 1.5–2.0; p < 0.005). Our results suggest that patients with LTx and prior CTS remain technically challenging and experience worse outcomes than patients without prior CTS. A surgical strategy to minimize cardiopulmonary bypass time is critical for these challenging LTx patients.