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There is international variability in the determination of death. Death in donation after circulatory death (DCD) can be defined by the permanent cessation of brain circulation. Post‐mortem interventions that restore brain perfusion should be prohibited as they invalidate the diagnosis of death. Retrieval teams should develop protocols that ensure the continued absence of brain perfusion during DCD organ recovery. In situ normothermic regional perfusion (NRP) or restarting the heart in the donor's body may interrupt the permanent cessation of brain perfusion because, theoretically, collateral circulations may restore it. We propose refinements to current protocols to monitor and exclude brain reperfusion during in situ NRP. In abdominal NRP, complete occlusion of the descending aorta prevents brain perfusion in most cases. Inserting a cannula in the ascending aorta identifies inadequate occlusion of the descending aorta or any collateral flow and diverts flow away from the brain. In thoracoabdominal NRP opening the aortic arch vessels to atmosphere allows collateral flow to be diverted away from the brain, maintaining the permanence standard for death and respecting the dead donor rule. We propose that these hypotheses are correct when using techniques that simultaneously occlude the descending aorta and open the aortic arch vessels to atmosphere., The authors present techniques to prevent the restoration of brain perfusion during in situ normothermic regional perfusion by ensuring the diversion of any possible collateral supply.

Good practice statements (GPSs) have been proposed by the GRADE working group as a way of avoiding the inappropriate characterization of evidence as low quality in support of strong recommendations justified by indirect evidence. This commentary examines how the GPS methodology was applied to the development of a recent guideline for pediatric deceased donation after circulatory determined death. This guideline was informed by a broad body of indirect literature and addressed a variety of social, legal, and ethical questions in addition to several implementation issues. While the resulting document contained a vast majority of GPS (63 as opposed to seven actionable GRADEd recommendations), we maintain that this application was appropriate to develop recommendations within the GRADE framework. This commentary explores how GPS may be applied in this context and explores whether a new classification of recommendations focused on these types of issues may be appropriate.

Out-of-hospital cardiac arrest (OHCA) affects 134 per 100,000 citizens annually. Extracorporeal cardiopulmonary resuscitation (ECPR), providing mechanical circulatory support, may improve the likelihood of survival among those with refractory OHCA. Compared with in-hospital ECPR candidates, those in the out-of-hospital setting tend to be sudden unexpected arrests in younger and healthier patients. The aims of this review were to summarize, and identify the limitations of, the evidence evaluating ECPR for OHCA, and to provide an approach for ECPR program application. Although there are many descriptions of ECPR-treated cohorts, we identified a paucity of robust data showing ECPR effectiveness compared with conventional resuscitation. However, it is highly likely that ECPR, provided after a prolonged attempt with conventional resuscitation, does benefit select patient populations compared with conventional resuscitation alone. Although reliable data showing the optimal patient selection criteria for ECPR are lacking, most implementations sought young previously healthy patients with rapid high-quality cardiopulmonary resuscitation. Carefully planned development of ECPR programs, in high-performing emergency medical systems at experienced extracorporeal membrane oxygenation centres, may be reasonable as part of systematic efforts to determine ECPR effectiveness and globally improve care. Protocol evaluation requires regional-level assessment, examining the incremental benefit of survival compared with standard care, while accounting for resource utilization.

Aim Extracorporeal resuscitation during cardiopulmonary resuscitation (ECPR) deploys rapid cardiopulmonary bypass to sustain oxygenated circulation until the return of spontaneous circulation (ROSC). The purpose of this systematic review is to address the defining elements and outcomes (quality survival and organ donation) of currently active protocols for ECPR in refractory out-of-hospital cardiac arrest (OHCA) of cardiac origin in adult patients. The results may inform policy and practices for ECPR and help clarify the corrresponding intersection with deceased organ donation. Methods We searched Medline, Embase, Cochrane and seven other electronic databases from 2005 to 2015, with no language restrictions. Internal validity and the quality of the studies reporting outcomes and guidelines were assessed. The review was included in the international prospective register of systematic reviews (Prospero, CRD42014015259). Results One guideline and 20 outcome studies were analyzed. Half of the studies were prospective observational studies assessed to be of fair to good methodological quality. The remainder were retrospective cohorts, case series, and case studies. Ages ranged from 16 to 75 years and initial shockable cardiac rhythms, witnessed events, and a reversible primary cause of cardiac arrest were considered favorable prognostic factors. CPR duration and time to hospital cannulation varied considerably. Coronary revascularization, hemodynamic interventions and targeted temperature management neuroprotection were variable. A total of 833 patients receiving this ECPR approach had an overall reported survival rate of 22%, including 13% with good neurological recovery. Additionally, 88 potential and 17 actual deceased organ donors were identified among the non-survivor population in 8 out of 20 included studies. Study heterogeneity precluded a meta-analysis preventing any meaningful comparison between protocols, interventions and outcomes. Conclusions ECPR is feasible for refractory OHCA of cardiac origin in adult patients. It may enable neurologically good survival in selected patients, who practically have no other alternative in order to save their lives with quality of life, and contribute to organ donation in those who die. Large, prospective studies are required to clarify patient selection, modifiable outcome variables, risk-benefit and cost-effectiveness.

There is growing medical consensus in a unifying concept of human death. All human death involves the irreversible loss of the capacity for consciousness, combined with the irreversible loss of the capacity to breathe. Death then is a result of the irreversible loss of these functions in the brain. This paper outlines three sets of criteria to diagnose human death. Each set of criteria clearly establishes the irreversible loss of the capacity for consciousness, combined with the irreversible loss of the capacity to breathe. The most appropriate set of criteria to use is determined by the circumstances in which the medical practitioner is called upon to diagnose death. The three criteria sets are somatic (features visible on external inspection of the corpse), circulatory (after cardiorespiratory arrest), and neurological (in patients in coma on mechanical ventilation); and represent a diagnostic standard in which the medical profession and the public can have complete confidence. This review unites authors from Australia, Canada, and the UK and examines the medical criteria that we should use in 2012 to diagnose human death.

Summary Background Endotoxin is a primary trigger of the inflammatory processes that lead to shock, multiorgan failure, and purpura fulminans in meningococcal sepsis. Bactericidal/permeability-increasing protein (BPI) is a natural protein, stored within the neutrophil granules, that binds to and neutralises the effects of endotoxin in vitro, in laboratory animals, and in humans. To establish whether a recombinant 21-kDa modified fragment of human BPI (rBPI 21 ), containing the active antimicrobial and endotoxin-neutralising moiety, would decrease death and long-term disability from meningococcal sepsis, we did a randomised, double-blind, placebo-controlled trial of rBPI21 in children with severe meningococcal sepsis. Methods We enrolled children (2 weeks to 18 years of age) presenting to 22 centres in the UK and the USA with a clinical picture suggestive of meningococcal sepsis, and with evidence of severe disease. Children were randomly assigned rBPI 21 (2 mg/kg over 30 min followed by 2 mg/kg over 24 h) or placebo (0·2 mg/mL human albumin solution) in addition to conventional medical therapy. Primary outcome variables were mortality, amputations, and change in paediatric overall performance category (POPC) from before illness to day 60. Analysis was by intention to treat. Findings Of 1287 patients screened, 892 were excluded, including 57 patients who died or who met criteria for imminent death before receiving the study drug. 190 patients received rBPI21, and 203 placebo. 34 (8·7%) of 393 patients died during the study: 14 (7·4%) in the rBPI21 group and 20 (9·9%) in the placebo group (odds ratio 1·31 [95% Cl 0·62–2·74], p=0·48). Compared with patients randomised to placebo, fewer patients treated with rBPI21 had multiple severe amputations (six of 190 [3·2%] vs 15 of 203 [7·4%], odds ratio 2·47 [0·94–6·51], p=0·067), and more had a functional outcome similar to that before illness (as measured by the POPC scale) at day 60 (136 of 176 [77·3%] vs 126 of 190 [66·3%], p=0·019). Interpretation Because most deaths occurred in the interval between identification of patients and study drug administration, the mortality rate in the placebo group was substantially lower than predicted. The trial was therefore underpowered to detect significant differences in mortality. However, patients receiving rBPI21 had a trend towards improved outcome in all primary outcome variables. Given the excellent severity match between placebo and rBPI21 groups at study entry, the results overall indicate that rBPI21 is beneficial in decreasing complications of meningococcal disease.

Study objective: Sudden death from obstructive hydrocephalus related to intracranial neoplasms has rarely been reported in the pediatric literature. We sought to review the presenting signs and symptoms of acute hydrocephalus resulting from intracranial mass lesions to guide clinicians in the early identification of these potentially reversible lesions. Methods: All cases of sudden unexpected death attributable to obstructive hydrocephalus that occurred from 1990 through 1994 at the Hospital for Sick Children, Toronto, were retrospectively reviewed. Results: During the study period, seven children, ages 10 months to 15 years, died unexpectedly with acute obstructive hydrocephalus. Six children were apparently normal, and none had any known neurologic disease. All patients had a previously undiagnosed intracranial tumor located at a critical site for CSF flow: colloid cyst (n=2), astrocytoma (n=2), ependymoma (n=2), suspected lymphoma (n=1). Presenting features included vomiting in all cases, vomiting for longer than 2 weeks in three, headache in four, and lethargy in three. Five patients were misdiagnosed with viral illnesses, including three with presumed gastroenteritis who received intravenous rehydration therapy. Focal gastrointestinal signs were absent. Conclusion: This case series highlights a life-threatening but misleading presentation of intracranial tumors. The diagnosis of gastroenteritis should be made cautiously when headache and vomiting occur in the absence of focal intestinal complaints. A history of vomiting exceeding a few days' duration warrants further investigation. Persistent lethargy should be considered a neurologic rather than a nonspecific clinical sign. Heightened awareness of this neurosurgical emergency may lead to swift intervention and potential reversibility with diversion of CSF. [Shemie S, Jay V, Rutka J, Armstrong D: Acute obstructive hydrocephalus and sudden death in children. Ann Emerg Med April 1997; 29:524-528.]