Laura Hornby

A systematic review of autoresuscitation after cardiac arrest

Objective:There is a lack of consensus on how long circulation must cease for death to be determined after cardiac arrest. The lack of scientific evidence concerning autoresuscitation influences the practice of organ donation after cardiac death. We conducted a systematic review to summarize the evidence on the timing of autoresuscitation. Data Sources:Electronic databases were searched from date of first issue of each journal until July 2008. Study Selection:Any original study reporting autoresuscitation, as defined by the unassisted return of spontaneous circulation after cardiac arrest, was considered eligible. Reports of electrocardiogram activity without signs of return of circulation were excluded. Data Extraction:For each study case, we extracted patient characteristics, duration of cardiopulmonary resuscitation, terminal heart rhythms, time to unassisted return of spontaneous circulation, monitoring, and outcomes. Data Synthesis:A total of 1265 citations were identified and, of these, 27 articles describing 32 cases of autoresuscitation were included (n = 32; age, 27–94 yrs). The studies came from 16 different countries and were considered of very-low quality (case reports or letters to the editor). All 32 cases reported autoresuscitation after failed cardiopulmonary resuscitation, with times ranging from a few seconds to 33 mins; however, continuity of observation and methods of monitoring were highly inconsistent. For the eight studies reporting continuous electrocardiogram monitoring and exact times, autoresuscitation did not occur beyond 7 mins after failed cardiopulmonary resuscitation. No cases of autoresuscitation in the absence of cardiopulmonary resuscitation were reported. Conclusions:These findings suggest that the provision of cardiopulmonary resuscitation may influence autoresuscitation. In the absence of cardiopulmonary resuscitation, as may apply to controlled organ donation after cardiac death after withdrawal of life-sustaining therapies, autoresuscitation has not been reported. The provision of cardiopulmonary resuscitation, as may apply to uncontrolled organ donation after cardiac death, may influence observation time. However, existing evidence is limited and is consequently insufficient to support or refute the recommended waiting period to determine death after a cardiac arrest, strongly supporting the need for prospective studies in dying patients.

International guideline development for the determination of death.

Introduction and MethodsThis report summarizes the results of the first phase in the development of international guidelines for death determination, focusing on the biology of death and the dying process, developed by an invitational forum of international content experts and representatives of a number of professional societies.Results and ConclusionsPrecise terminology was developed in order to improve clarity in death discussion and debate. Critical events in the physiological sequences leading to cessation of neurological and/or circulatory function were constructed. It was agreed that death determination is primarily clinical and recommendations for preconditions, confounding factors, minimum clinical standards and additional testing were made. A single operational definition of human death was developed: ‘the permanent loss of capacity for consciousness and all brainstem functions, as a consequence of permanent cessation of circulation or catastrophic brain injury’. In order to complete the project, in the next phase, a broader group of international stakeholders will develop clinical practice guidelines, based on comprehensive reviews and grading of the existing evidence.

Precision and reliability of strength (Jamar vs. Biodex handgrip) and body composition (dual-energy X-ray absorptiometry vs. bioimpedance analysis) measurements in advanced cancer patients.

Important deteriorations in body composition and strength occur and need to be accurately measured in advanced cancer patients (ACPs). The aim of this study was to establish the relationship between a single-frequency bioimpedance analyzer (BIA) and the dual-energy X-ray absorptiometer (DXA), as well as the Jamar handgrip dynometer and the Biodex handgrip attachment, and to determine the precision of each of these instruments in ACPs. Eighty-one ACPs with non-small-cell lung cancer and gastrointestinal cancer were recruited from the McGill University Health Centre (Montreal, Que.). Consecutive paired measurements, with repositioning between measurements, were obtained for total-body DXA, BIA, Biodex handgrip, and BIA plus Jamar handgrip. The total-body percent coefficient of variation (%CV) for the BIA and DXA were 1.34 and 1.56 for fat mass (FM), respectively, and 0.42 and 0.72 for fat free mass (FFM), respectively. The %CV for the Jamar and Biodex handgrips were 6.3 and 16.7, respectively. Bland-Altman plots were used to characterize the limits of agreement between DXA and BIA for FM (4.60 +/- 7.80 (-3.19 to 12.39) kg) and FFM (-1.87 +/- 7.16 (-9.03 to 5.29) kg). Both DXA and BIA demonstrate good short-term precision in ACPs. However, given its poor accuracy, it remains to be determined if BIA can be used to monitor ACPs for changes in total-body tissue composition as a function of time, whether for observation or response to treatment. Furthermore, because of wide limits of agreement, the DXA and BIA cannot be used interchangeably in research or clinical settings. The Jamar handgrip dynamometer shows more consistency than the Biodex handgrip attachment in ACPs, and should therefore be the preferred measure of changes in strength over time.

Male hypogonadism associated with advanced cancer: a systematic review

Male hypogonadism is commonly diagnosed on the basis of subphysiological concentrations of androgen hormones, and is associated with many symptoms present in advanced cancer. Androgen deficiency might be an important cause of muscle wasting in both cancer cachexia and sarcopenia. We did a systematic review of the clinical association of male hypogonadism in advanced cancer. We searched PubMed, Medline, and Embase for publications on the relation between male hypogonadism and functional status, nutritional status, body composition, symptoms, and quality of life in patients with advanced cancer. Of 381 publications identified, six original articles were included. We found no definitive association between nutritional, functional, or quality-of-life characteristics and male hypogonadism. Possible associations between male hypogonadism and weight loss, low albumin, low-body cell mass index, low-peripheral fat and muscle mass, higher inflammation, higher pain, higher opioid consumption, worse scores for anxiety, depression, and emotional and functional well-being need to be confirmed by better designed studies. There is no clear epidemiological data to indicate whether male hypogonadism is independently associated with clinical and biological sequelae of cancer cachexia, such as higher inflammation, fatigue, and body wasting. Standardised kits sensitive to low concentrations of free-testosterone or bioavailable testosterone are needed to diagnose androgen deficiency in women. A clearer epidemiology of androgen deficiencies in advanced cancer will help determine which patients should receive testosterone-replacement therapy for alleviating cancer cachexia symptoms and improving quality of life.

Vital signs after cardiac arrest following withdrawal of life-sustaining therapy: a multicenter prospective observational study.

Objective: Controversies regarding the process and timing of the determination of death for controlled organ donation after circulatory death persist. This study assessed the feasibility of conducting a prospective, observational study of continuous monitoring of vital signs for 30 minutes after the clinical determination of death in five Canadian ICUs. Waveform data were analyzed. Design: Prospective observational cohort study. Setting: One pediatric and four adult Canadian ICUs. Patients: One month of age or older, admitted to the ICU, and for whom a consensual decision to withdraw life-sustaining therapies had been made, with an anticipation of imminent death. Interventions: None. Measurements and Main Results: Invasive arterial blood pressure, electrocardiogram, and oxygen saturation plethysmography activity were recorded and reviewed for 30 minutes after declaration of death. Feasibility was assessed (recruitment, consent rate, protocol compliance, and staff satisfaction). Of 188 subjects screened over 16 months, 41 subjects were enrolled (87% consent rate). Data collection was complete for 30 subjects (73% protocol compliance). In four subjects, arterial blood pressure resumed following cessation of activity. The longest period of cessation of arterial blood pressure before resumption was 89 seconds. The duration of resumed activity ranged from 1 to 172 seconds. No cases of sustained resumption of arterial blood pressure activity were recorded, and no instances of clinical autoresuscitation were reported. In nearly all patients (27 of 30), electrocardiogram activity continued after the disappearance of arterial blood pressure. Conclusions: This is the first observational study to prospectively collect waveform data for 30 minutes after the declaration of death. A future larger study may support initial data suggesting that circulatory function does not resume after more than 89 seconds of absence. Furthermore, persistence of cardiac electrical activity with the documented absence of circulation may not be relevant to declaration of death.

Relationship Between Angiotensin-Converting Enzyme Gene Polymorphism and Body Composition, Functional Performance, and Blood Biomarkers in Advanced Cancer Patients

Purpose: Nutritional and functional outcome measures have been shown to vary in patients with chronic diseases according to the polymorphic alleles of angiotensin-converting enzyme (ACE), but little is known about the associations between ACE gene polymorphism (ACEGP) and the components of body composition, strength, and selected blood markers in advanced cancer patients (ACP). Experimental Design: Data were collected from an inception cohort of 172 newly diagnosed ACP with gastrointestinal and non–small cell lung cancer. ACEGP status was defined by the presence of one of the following three combinations of alleles: insertion/insertion, insertion/deletion, and deletion/deletion. Body composition measurements using Dual-energy X-ray Absorptiometry comprised of the following: total fat mass, percent body fat, lean body mass, and appendicular lean mass. Body mass index; handgrip force by Jamar dynamometry; subjective recording of nutrition and performance status as per patient-generated subjective global assessment; cell blood count and differential, serum albumin, ACE, and C-reactive protein were also recorded. Results: Multiple regression analysis, controlling for gender, age, diagnosis, treatments (radio/chemo), survival, and medication use (ACE inhibitors, anti-inflammatories, statins) revealed the following significant (P ≤ 0.05) relationships in the insertion/deletion compared with insertion/insertion group: higher hemoglobin (Hb; β, 6.39 g/dl; 95% confidence interval, 0.01-12.78), lower total fat mass (−5.78 kg; −11.62 to 0.07), percent body fat (−6.04%; −12.20 to 0.12), and lean body mass (−3.26 kg; −6.78 to 0.26). When comparing the DD to the II group, higher serum ACE (9.10; 1.96-16.25), Hb (6.25 g/dl; −0.63 to 13.12), and handgrip force by Jamar (6.85 lbs; 0.78-12.93) were found. Conclusion: Of the variables studied, ACEGP seems to be primarily associated with differences in body composition, Hb, and muscle strength in ACP. Further data are needed to determine the clinical effect of ACEGP in cancer cachexia.

Survey of determination of death after cardiac arrest by intensive care physicians.

Objective: The controversy regarding death determination in the context of organ donation after cardiocirculatory death requires investigation. We sought to describe the manner in which Canadian adult and pediatric intensive care physicians report death determination after cardiac arrest. Design: Pilot-tested paper survey. Setting: Mail out between June and November 2009. Subjects: Canadian adult and pediatric intensive care physicians. Intervention: Paper-based survey. Main Results: Forty-nine percent of 501 Canadian intensive care physicians responded. Eighty-five percent practiced in tertiary care, university-affiliated centers, and 26% were from pediatric centers. Physicians had a median of 10 yrs (range 0–35) experience. Physicians reported that they performed determination of death after cardiac arrest a median of seven (range 0–60) times per year. Of 11 tests or procedures used, the absence of heart sounds by auscultation, palpable pulse, and breath sounds were the most common, although there was high variability in practice. No diagnostic test/procedure was uniformly performed or omitted. Sixty-five percent of respondents believed autoresuscitation exists and 37% of physicians reported to have seen a possible case during their career. Forty-eight percent had formal training for determining death after cardiac arrest and 22% used guidelines. The majority of respondents agreed that standardized methods for determination of death after cardiac arrest are required in general (69%) and specifically for donation after cardiocirculatory death (91%). Conclusions: Intensive care physicians in Canada report: 1) variability in the practice of determining death after cardiac arrest; 2) the existence of autoresuscitation; and 3) a need for standardization of practice. The results of this survey support the need to develop more robust education, guidelines, and standards for the determination of death after cardiac arrest, in general, as well as within the context of donation after cardiocirculatory death.

Pediatric Donation After Circulatory Determination of Death: A Scoping Review*

Objective: Although pediatric donation after circulatory determination of death is increasing in frequency, there are no national or international donation after circulatory determination of death guidelines specific to pediatrics. This scoping review was performed to map the pediatric donation after circulatory determination of death literature, identify pediatric donation after circulatory determination of death knowledge gaps, and inform the development of national or regional pediatric donation after circulatory determination of death guidelines. Data Sources: Terms related to pediatric donation after circulatory determination of death were searched in Embase and MEDLINE, as well as the non-MEDLINE sources in PubMed from 1980 to May 2014. Study Selection: Seven thousand five hundred ninety-seven references were discovered and 85 retained for analysis. All references addressing pediatric donation after circulatory determination of death were considered. Exclusion criteria were articles that did not address pediatric patients, animal or laboratory studies, surgical techniques, and local pediatric donation after circulatory determination of death protocols. Narrative reviews and opinion articles were the most frequently discovered reference (25/85) and the few discovered studies were observational or qualitative and almost exclusively retrospective. Data Extraction Retained references were divided into themes and analyzed using qualitative methodology. Data Synthesis: The main discovered themes were 1) studies estimating the number of potential pediatric donation after circulatory determination of death donors and their impact on donation; 2) ethical issues in pediatric donation after circulatory determination of death; 3) physiology of the dying process after withdrawal of life-sustaining therapy; 4) cardiac pediatric donation after circulatory determination of death; and 5) neonatal pediatric donation after circulatory determination of death. Donor estimates suggest that pediatric donation after circulatory determination of death will remain an event less common than brain death, albeit with the potential to substantially expand the existing organ donation pool. Limited data suggest outcomes comparable with organs donated after neurologic determination of death. Although there is continued debate around ethical aspects of pediatric donation after circulatory determination of death, all pediatric donation after circulatory determination of death publications from professional societies contend that pediatric donation after circulatory determination of death can be practiced ethically. Conclusions: This review provides a comprehensive overview of the published literature related to pediatric donation after circulatory determination of death. In addition to informing the development of pediatric-specific guidelines, this review serves to highlight several important knowledge gaps in this topic.

Canadian Guidelines for Controlled Pediatric Donation After Circulatory Determination of Death—summary Report*

Objectives: Create trustworthy, rigorous, national clinical practice guidelines for the practice of pediatric donation after circulatory determination of death in Canada. Methods: We followed a process of clinical practice guideline development based on World Health Organization and Canadian Medical Association methods. This included application of Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions requiring recommendations were generated based on 1) 2006 Canadian donation after circulatory determination of death guidelines (not pediatric specific), 2) a multidisciplinary symposium of national and international pediatric donation after circulatory determination of death leaders, and 3) a scoping review of the pediatric donation after circulatory determination of death literature. Input from these sources drove drafting of actionable questions and Good Practice Statements, as defined by the Grading of Recommendations Assessment, Development, and Evaluation group. We performed additional literature reviews for all actionable questions. Evidence was assessed for quality using Grading of Recommendations Assessment, Development, and Evaluation and then formulated into evidence profiles that informed recommendations through the evidence-to-decision framework. Recommendations were revised through consensus among members of seven topic-specific working groups and finalized during meetings of working group leads and the planning committee. External review was provided by pediatric, critical care, and critical care nursing professional societies and patient partners. Results: We generated 63 Good Practice Statements and seven Grading of Recommendations Assessment, Development, and Evaluation recommendations covering 1) ethics, consent, and withdrawal of life-sustaining therapy, 2) eligibility, 3) withdrawal of life-sustaining therapy practices, 4) ante and postmortem interventions, 5) death determination, 6) neonatal pediatric donation after circulatory determination of death, 7) cardiac and innovative pediatric donation after circulatory determination of death, and 8) implementation. For brevity, 48 Good Practice Statement and truncated justification are included in this summary report. The remaining recommendations, detailed methodology, full Grading of Recommendations Assessment, Development, and Evaluation tables, and expanded justifications are available in the full text report. Conclusions: This process showed that rigorous, transparent clinical practice guideline development is possible in the domain of pediatric deceased donation. Application of these recommendations will increase access to pediatric donation after circulatory determination of death across Canada and may serve as a model for future clinical practice guideline development in deceased donation.

Metabolic, nutritional and inflammatory characteristics in elderly women with advanced cancer

OBJECTIVE Few studies have focused on the metabolic profiling of patients with advanced cancer and the relationship with nutritional and inflammatory characteristics, which have important diagnostic, treatment and prognostic implications, particularly in the elderly. Our objective was to determine differences in energy expenditure during rest and activity, body composition, nutrition, and inflammatory markers between healthy elderly females and those with advanced cancer. MATERIALS AND METHODS Twenty elderly (74.8±6.7years) females (9 with solid malignancies, 11 healthy) were evaluated for energy expenditure using indirect calorimetry at rest and throughout a 6-min walk test (6MWT). Body composition (dual-energy x-ray absorptiometry); nutritional intake (3-day 24-h food recall); and markers of nutrition and inflammation (complete blood count, albumin and C-reactive protein) were also measured. RESULTS Compared to healthy controls, patients with cancer had similar energy expenditures, but significantly lower (p<0.05) respiratory quotients at rest. During the 6MWT, the group with cancer walked shorter distances at slower speeds (p<0.001), consumed less oxygen (p<0.05), and trended toward an increased oxygen cost while walking. The patients with cancer ingested fewer calories and presented with higher levels of inflammatory markers (p<0.05). No differences in body composition were observed. CONCLUSION Early signs of cachexia (i.e. reduced caloric intake, inflammation and greater fat metabolism) may be present in older patients with cancer, along with poorer levels of functional capacity, compared to healthy controls. Timely recognition of these signs may allow therapeutic interventions to better prevent or delay nutritional and functional demise in elderly patients with cancer.