RESUMO
OBJECTIVE: The objective of this review was to perform a rapid evidence summary to determine the prevalence of subaneurysmal aortic aneurysms, growth rates, and risk factors that modulate growth in average-risk men aged 65 years and older. Secondary objectives were to evaluate benefits and harms of lifelong ultrasound (US) surveillance and treatment outcomes for any large aneurysms that develop in the screened population. METHODS: We searched multiple databases (eg, Ovid MEDLINE, Embase Classic and Embase, and the Cochrane Library) on February 16, 2016. Using a liberal accelerated method, two reviewers screened titles and abstracts for relevance and subsequently screened full-text studies. General study characteristics (eg, country, study design, number of participants) and data (eg, number of men with subaneurysmal aortas, quality of life [QoL], mortality) were extracted. One reviewer performed data extraction and risk of bias assessments, and a second reviewer verified 100% of studies. Any disagreements were resolved by consensus. RESULTS: The search identified 37 relevant studies ranging in size from 3 to 52,690 participants. Prevalence of subaneurysmal aortas ranged from 1.14% to 8.53%, and 55% to 88% of these men progressed to a 3.0-cm aneurysm by 5 years of follow-up. Risk factors for growth included the infrarenal aortic diameter at age 65 years, having a subaneurysmal aorta at age 65 years, and current smoking. The 36-Item Short Form Health Survey was the most commonly used tool to measure QoL, and QoL was typically lower in people with abdominal aortic aneurysm. Anxiety and depression levels did not differ significantly between comparison groups in any studies. Four studies reported on the number of men whose aorta was subaneurysmal on initial US who went on to surgery. Overall, 10% (57/547) of men initially measuring in the subaneurysmal range progressed to abdominal aortic aneurysm >5.4 cm and received elective surgery; 1% (6/547) received emergency surgery because of a ruptured aorta. Among those who did, mortality rates were much lower for elective (9.5%) vs emergency surgery (50%). Risk of bias was usually low for studies measuring prevalence and moderate and high for studies measuring psychological harms of screening and harms and benefits of surgery. Overall, using the Grading of Recommendations Assessment, Development, and Evaluation framework as guidance, the quality of the evidence was generally very low. CONCLUSIONS: Because of the limited evidence and the low quality of the existing evidence, it is not possible to determine confidently whether men with abdominal aortas measuring 2.5 to 2.9 cm should be observed in a lifelong US surveillance program.
Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Ultrassonografia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/epidemiologia , Aneurisma da Aorta Abdominal/mortalidade , Aneurisma da Aorta Abdominal/terapia , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Ultrassonografia/efeitos adversosAssuntos
Animais de Laboratório , Pesquisa Biomédica/estatística & dados numéricos , Países Desenvolvidos/estatística & dados numéricos , Países em Desenvolvimento/estatística & dados numéricos , Publicações Periódicas como Assunto/ética , Editoração/ética , Pesquisadores/estatística & dados numéricos , Animais , Autoria , Aprendizagem da Esquiva , Pesquisa Biomédica/normas , Ensaios Clínicos como Assunto/estatística & dados numéricos , Países Desenvolvidos/economia , Países em Desenvolvimento/economia , Guias como Assunto , Humanos , Internacionalidade , National Institutes of Health (U.S.)/economia , Publicação de Acesso Aberto/economia , Publicação de Acesso Aberto/estatística & dados numéricos , Publicação de Acesso Aberto/provisão & distribuição , Publicações Periódicas como Assunto/normas , Editoração/normas , Editoração/provisão & distribuição , Pesquisadores/educação , Pesquisadores/ética , Pesquisadores/normas , Apoio à Pesquisa como Assunto/normas , Apoio à Pesquisa como Assunto/estatística & dados numéricos , Literatura de Revisão como Assunto , Estados UnidosRESUMO
BACKGROUND: The timing of the circulatory determination of death for organ donation presents a medical and ethical challenge. Concerns have been raised about the timing of electrocerebral inactivity in relation to the cessation of circulatory function in organ donation after cardio-circulatory death. Nonprocessed electroencephalographic (EEG) measures have not been characterized and may provide insight into neurological function during this process. METHODS: We assessed electrocortical data in relation to cardiac function after withdrawal of life-sustaining therapy and in the postmortem period after cardiac arrest for four patients in a Canadian intensive care unit. Subhairline EEG and cardio-circulatory monitoring including electrocardiogram, arterial blood pressure (ABP), and oxygen saturation were captured. RESULTS: Electrocerebral inactivity preceded the cessation of the cardiac rhythm and ABP in three patients. In one patient, single delta wave bursts persisted following the cessation of both the cardiac rhythm and ABP. There was a significant difference in EEG amplitude between the 30-minute period before and the 5-minute period following ABP cessation for the group, but we did not observe any well-defined EEG states following the early cardiac arrest period. CONCLUSIONS: In a case series of four patients, EEG inactivity preceded electrocardiogram and ABP inactivity during the dying process in three patients. Further study of the electroencephalogram during the withdrawal of life sustaining therapies will add clarity to medical, ethical, and legal concerns for donation after circulatory determined death.
Assuntos
Pressão Sanguínea/fisiologia , Morte , Eletroencefalografia/métodos , Parada Cardíaca/fisiopatologia , Idoso , Ondas Encefálicas/fisiologia , Canadá , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Suspensão de TratamentoRESUMO
Studying patients during the end of life is important, as it has the potential to lead to improvements in care for the dying. For patients who die after a controlled withdrawal of life-sustaining therapies in the intensive care unit, information about the natural history of death and the process of removing life support has additionally led to advances in practice for deceased organ donation. However, this unique population of severely critically ill and imminently dying patients has been difficult to study, largely due to assumptions made by research teams and ethics boards alike about the logistical difficulties of obtaining consent and completing research procedures before or during the process of withdrawal of life-sustaining therapies. In this paper, we describe the ethics substudy of the first prospective observational research study in Canada to obtain consent and collect clinical data on patients during the process of withdrawal of life-sustaining therapies in the intensive care unit. We describe in detail the process of protocol development, review by five institutional research ethics boards and bedside staff satisfaction with the study. We conclude that prospective research on a critically ill and imminently dying population is feasible and can be conducted in an ethical manner. Further information is needed about the experiences and motivations of families and substitute decision makers who provide consent for research on critically ill intensive care unit patients at the end of life.
Assuntos
Pesquisa Biomédica/ética , Estado Terminal/mortalidade , Unidades de Terapia Intensiva , Cuidados para Prolongar a Vida , Assistência Terminal , Obtenção de Tecidos e Órgãos , Suspensão de Tratamento , Atitude do Pessoal de Saúde , Canadá , Cuidados Críticos , Morte , Tomada de Decisões , Comitês de Ética em Pesquisa , Ética em Pesquisa , Humanos , Consentimento Livre e Esclarecido , Estudos Observacionais como Assunto , Estudos Prospectivos , Projetos de PesquisaRESUMO
OBJECTIVE: The process of controlled donation after circulatory death (cDCD) is strongly connected with the process of withdrawal of life-sustaining therapy. In addition to impacting cDCD success, actions comprising withdrawal of life-sustaining therapy have implications for quality of palliative care. We examined pilot study data from Canadian intensive care units to explore current practices of life-sustaining therapy withdrawal in nondonor patients and described variability in standard practice. DESIGN: Secondary analysis of observational data collected for Determination of Death Practices in Intensive Care pilot study. SETTING: Four Canadian adult intensive care units. PATIENTS: Patients ≥18 years in whom a decision to withdraw life-sustaining therapy was made and substitute decision makers consented to study participation. Organ donors were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Prospective observational data on interventions withdrawn, drugs administered, and timing of life-sustaining therapy withdrawal was available for 36 patients who participated in the pilot study. Of the patients, 42% died in ≤1 hour; median length of time to death varied between intensive care units (39-390 minutes). Withdrawal of life-sustaining therapy processes appeared to follow a general pattern of vasoactive drug withdrawal followed by withdrawal of mechanical ventilation and extubation in most sites but specific steps varied. Approaches to extubation and weaning of vasoactive drugs were not consistent. Protocols detailing the process of life-sustaining therapy withdrawal were available for 3 of 4 sites and also exhibited differences across sites. CONCLUSIONS: Standard practice of life-sustaining therapy withdrawal appears to differ between selected Canadian sites. Variability in withdrawal of life-sustaining therapy may have a potential impact both on rates of cDCD success and quality of palliative care.
Assuntos
Cuidados Críticos/métodos , Unidades de Terapia Intensiva/estatística & dados numéricos , Cuidados para Prolongar a Vida/estatística & dados numéricos , Suspensão de Tratamento/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá , Morte , Feminino , Humanos , Cuidados para Prolongar a Vida/métodos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Fatores de TempoRESUMO
OBJECTIVE: The process of withdrawal of life-sustaining therapy remains poorly described in the current literature despite its importance for patient comfort and optimal end-of-life care. We conducted a structured review of the published literature to summarize patterns of withdrawal of life-sustaining therapy processes in adult ICUs. DATA SOURCES: Electronic journal databases were searched from date of first issue until April 2014. STUDY SELECTION: Original research articles describing processes of life-support therapy withdrawal in North American, European, and Australian ICUs were included. DATA EXTRACTION: From each article, we extracted definitions of withdrawal of life-sustaining therapy, descriptions and order of interventions withdrawn, drugs administered, and timing from withdrawal of life-sustaining therapy until death. DATA SYNTHESIS: Fifteen articles met inclusion criteria. Definitions of withdrawal of life-sustaining therapy varied and focused on withdrawal of mechanical ventilation; two studies did not present operational definitions. All studies described different aspects of process of life-support therapy withdrawal and measured different time periods prior to death. Staggered patterns of withdrawal of life-support therapy were reported in all studies describing order of interventions withdrawn, with vasoactive drugs withdrawn first followed by gradual withdrawal of mechanical ventilation. Processes of withdrawal of life-sustaining therapy did not seem to influence time to death. CONCLUSIONS: Further description of the operational processes of life-sustaining therapy withdrawal in a more structured manner with standardized definitions and regular inclusion of measures of patient comfort and family satisfaction with care is needed to identify which patterns and processes are associated with greatest perceived patient comfort and family satisfaction with care.
Assuntos
Assistência Terminal , Suspensão de Tratamento/normas , HumanosRESUMO
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.
Assuntos
Suporte Vital Cardíaco Avançado/métodos , Parada Cardíaca/mortalidade , Parada Cardíaca/terapia , Obtenção de Tecidos e Órgãos/organização & administração , Sinais Vitais/fisiologia , Suspensão de Tratamento , Adulto , Canadá , Reanimação Cardiopulmonar/métodos , Criança , Pré-Escolar , Estudos de Coortes , Morte , Estudos de Viabilidade , Feminino , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva , Masculino , Projetos Piloto , Estudos Prospectivos , Controle de Qualidade , Fatores de TempoRESUMO
OBJECTIVE: To evaluate acute rehabilitation practices in pediatric critical care units across Canada. DESIGN: Retrospective cohort study. SETTING: Six Canadian, tertiary care pediatric critical care units. PATIENTS/SUBJECTS: Six hundred children aged under 17 years admitted to pediatric critical care unit during a winter and summer month of 2011 with a greater than 24-hour length of stay. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome of interest was the nature and timing of pediatric critical care unit rehabilitation practices.Rehabilitation was classified according to mobility and nonmobility interventions. Predictors of mobilization and the time to mobilization were evaluated through regression and time-dependent survival analyses, respectively. The most common form of rehabilitation provided in pediatric critical care unit was physical therapy (45.5% patients) followed by occupational therapy (4.5%) and speech and language therapy (1.5%). Interventions were primarily nonmobility in nature (69.7% of sessions), most frequently in the form of chest physiotherapy (42.7% of sessions). The median time to mobilization was 2 days (interquartile range, 1-6) as compared with 1 day for nonmobility interventions (interquartile range, 1-3). Only 57 patients (9.5%) received early mobilization. Regression analyses revealed that increasing age, admission during winter, neuromuscular blockade, and sedative infusions were associated with an increased likelihood of receiving mobility therapy. Increasing age was a predictor of early mobilization, while neuromuscular blockade was associated with delayed mobilization. No significant differences in adverse events were found between nonmobility and mobility interventions. CONCLUSIONS: Only half of the children receive rehabilitation while in the pediatric critical care unit, and when it occurs, therapy is primarily focused on respiratory function. Mobilization appears to be reserved for at-risk children who were muscle relaxed and sedated; however, its implementation in these patients is delayed. Future pediatric-specific research is essential to identify patients at risk and to understand treatment priorities and rehabilitation strategies to improve functional recovery in critically ill children.
Assuntos
Cuidados Críticos/métodos , Estado Terminal/reabilitação , Deambulação Precoce/estatística & dados numéricos , Fatores Etários , Canadá , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Bloqueio Neuromuscular , Terapia Ocupacional/estatística & dados numéricos , Avaliação de Resultados da Assistência ao Paciente , Modalidades de Fisioterapia/estatística & dados numéricos , Padrões de Prática Médica , Estudos Retrospectivos , Estações do Ano , Fonoterapia/estatística & dados numéricos , Fatores de Tempo , CaminhadaRESUMO
OBJECTIVE: To document the legal guardian-related barriers to consent procurement, and their stated reasons for non-participation in a paediatric critical care research study. STUDY DESIGN: A multicentre, prospective, cohort study. PARTICIPANTS: Legal guardians of children who participated in a multicentre study on adrenal insufficiency in paediatric critical illness. Data were collected on all consent encounters in the main study. METHODS: Screening data, reasons for consent not being obtained, paediatric risk of mortality (illness severity) scores and age were collected on all 1707 patients eligible for participation in the Adrenal Insufficiency Study. RESULTS: The main barriers to approaching legal guardians for consent were lack of availability of the legal guardians (321/1707) and language barriers (84/1707). Legal guardians of 917 patients were approached with an overall consent rate of 42% (range 14-56% across the seven sites). 81% of the 528 legal guardians who declined consent provided an unsolicited reason for refusal. The three most commonly stated reasons were: being overwhelmed (117/429), not wanting anything else done to their child (63/429) and not wanting an additional medication (53/429). In addition, 14.2% cited research-related concerns as the reason for their non-participation. CONCLUSIONS: Barriers to consent procurement in a non-therapeutic paediatric critical care study appear to occur at many levels with lack of availability of legal guardians, and legal guardians feeling overwhelmed, being the most commonly recorded reasons. Further research into the impact of these findings on the validity and generalisability of the results of such studies is necessary prior to the development and study of future consent models.
Assuntos
Insuficiência Adrenal , Cuidados Críticos , Estado Terminal , Consentimento Livre e Esclarecido/ética , Tutores Legais , Experimentação Humana não Terapêutica/ética , Seleção de Pacientes/ética , Adolescente , Adulto , Canadá , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Tutores Legais/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: Limited evidence exists on the use of corticosteroids in pediatric shock. We sought to determine physicians' practices and beliefs with regard to the management of pediatric shock. DESIGN: Cross-sectional, Internet-based survey. SETTING: Canada. SUBJECTS: Physicians identified as practicing pediatric intensive care in any of 15 academic centers. MEASUREMENTS AND MAIN RESULTS: Seventy of 97 physicians (72.2%) responded. Physicians stated that they were more likely to prescribe steroids for septic shock than for shock following cardiac surgery (odds ratio, 1.9 [95% CI, 0.9-4.3]) or trauma (odds ratio, 11.46 [95% CI, 2.5-51.2]), and 91.4% (64/70) would administer steroids to patients who had received 60 cc/kg of fluid and two or more vasoactive medications. Thirty-five percent of respondents (25/70) reported that they rarely or never conducted adrenal axis testing before giving steroids to patients in shock. Eighty-seven percent of respondents (61/70) stated that the role of steroids in the treatment of fluid and/or vasoactive drug-dependent shock needed to be clarified and that 84.3% would be willing to randomize patients into a trial of steroid efficacy who were fluid resuscitated and on one high-dose vasoactive medication. However, 74.3% stated that they would start open-label steroids in patients who required two high-dose vasoactive medications. CONCLUSIONS: This survey provides information on the stated beliefs and practices of pediatric critical care physicians with regard to the use of steroids in fluid and/or vasoactive drug-dependent shock. Clinicians feel that the role of steroids in shock still requires clarification and that they would be willing to randomize patients into a trial. This survey may be useful as an initial framework for the development of a future trial on the use of steroids in pediatric shock.
Assuntos
Corticosteroides/uso terapêutico , Atitude do Pessoal de Saúde , Fármacos Cardiovasculares/efeitos adversos , Hidratação/efeitos adversos , Padrões de Prática Médica/estatística & dados numéricos , Choque Séptico/tratamento farmacológico , Testes de Função do Córtex Suprarrenal/estatística & dados numéricos , Canadá , Criança , Estudos Transversais , Humanos , Unidades de Terapia Intensiva Pediátrica , Ensaios Clínicos Controlados Aleatórios como Assunto , Choque Séptico/etiologia , Inquéritos e QuestionáriosRESUMO
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.
Assuntos
Cuidados Críticos/estatística & dados numéricos , Morte , Parada Cardíaca/mortalidade , Canadá , Cuidados Críticos/normas , Coleta de Dados , Humanos , Médicos/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/estatística & dados numéricosRESUMO
INTRODUCTION: The reemergence of organ donation after circulatory determination of death (DCDD) in Canada demands the establishment of clear, evidence-based guidelines for the determination of death. The primary purpose of this study was to investigate the variability in specific criteria, diagnostic tests, and recommended wait periods for the determination of death after cardiac arrest. METHODS: We used PubMed and Web of Science to perform a structured search of the medical literature for articles published up to January 1, 2010. We also performed an unstructured search of the internet for unrestricted, readily available, nonjournal sources. We limited the search to countries that are most active in DCDD. RESULTS: A total of 26 documents were retrieved; 21 medical professional society/institution statements and 5 national/international guidelines. Specific criteria for the determination of death after cardiac arrest were cited in 24 documents: 14 recommend cardiocirculatory criteria alone; 6 oblige the requirement of a prolonged waiting period after declaration to ensure neurological death; 3 recommend following "accepted medical practice" without specific details; and 1 leaves the definition up to "national authorities." Only 16 of the documents require specific diagnostic procedures with unresponsiveness, absent arterial pulse and apnea cited the most consistently. Specific wait periods after declaration are required for the determination of death after cardiac arrest in 24 documents, cited times range from 2 to 10 minutes, with a 5-minute period the most frequent. CONCLUSIONS: This review is the first to document the variability of guidelines and statements for the determination of death after cardiac arrest, in countries where the practice of DCDD is becoming increasingly common. The scarcity of peer-reviewed published guidelines in the medical literature exemplifies the need for further investigation. We believe these results will inform the ethical discussions surrounding the determination of death after cardiac arrest. Clear and consistent guidelines based on evidence are needed to fulfill medical, ethical, and legal obligation and to ensure public trust.
Assuntos
Morte , Parada Cardíaca/mortalidade , Formulação de Políticas , Guias de Prática Clínica como Assunto , HumanosRESUMO
BACKGROUND: Hypothermia therapy improves survival and the neurologic outcome in animal models of traumatic brain injury. However, the effect of hypothermia therapy on the neurologic outcome and mortality among children who have severe traumatic brain injury is unknown. METHODS: In a multicenter, international trial, we randomly assigned children with severe traumatic brain injury to either hypothermia therapy (32.5 degrees C for 24 hours) initiated within 8 hours after injury or to normothermia (37.0 degrees C). The primary outcome was the proportion of children who had an unfavorable outcome (i.e., severe disability, persistent vegetative state, or death), as assessed on the basis of the Pediatric Cerebral Performance Category score at 6 months. RESULTS: A total of 225 children were randomly assigned to the hypothermia group or the normothermia group; the mean temperatures achieved in the two groups were 33.1+/-1.2 degrees C and 36.9+/-0.5 degrees C, respectively. At 6 months, 31% of the patients in the hypothermia group, as compared with 22% of the patients in the normothermia group, had an unfavorable outcome (relative risk, 1.41; 95% confidence interval [CI], 0.89 to 2.22; P=0.14). There were 23 deaths (21%) in the hypothermia group and 14 deaths (12%) in the normothermia group (relative risk, 1.40; 95% CI, 0.90 to 2.27; P=0.06). There was more hypotension (P=0.047) and more vasoactive agents were administered (P<0.001) in the hypothermia group during the rewarming period than in the normothermia group. Lengths of stay in the intensive care unit and in the hospital and other adverse events were similar in the two groups. CONCLUSIONS: In children with severe traumatic brain injury, hypothermia therapy that is initiated within 8 hours after injury and continued for 24 hours does not improve the neurologic outcome and may increase mortality. (Current Controlled Trials number, ISRCTN77393684 [controlled-trials.com].).
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Lesões Encefálicas/terapia , Hipotermia Induzida , Adolescente , Temperatura Corporal , Lesões Encefálicas/classificação , Lesões Encefálicas/complicações , Lesões Encefálicas/mortalidade , Criança , Pré-Escolar , Crianças com Deficiência , Feminino , Escala de Coma de Glasgow , Humanos , Hipotensão/tratamento farmacológico , Hipotermia Induzida/efeitos adversos , Lactente , Pressão Intracraniana/efeitos dos fármacos , Estimativa de Kaplan-Meier , Tempo de Internação , Masculino , Estado Vegetativo Persistente/etiologia , Reaquecimento , Solução Salina Hipertônica/administração & dosagem , Estatísticas não Paramétricas , Fatores de Tempo , Falha de Tratamento , Vasoconstritores/uso terapêuticoRESUMO
OBJECTIVES: 1) To determine the levels of glial fibrillary acidic protein (GFAP) in both cerebrospinal fluid and serum; 2) to determine whether serum GFAP levels correlate with functional outcome; and 3) to determine whether therapeutic hypothermia, as compared with normothermia, alters serum GFAP levels in children with severe traumatic brain injury (TBI). DESIGN: Laboratory-based analyses; postrandomized, controlled trial. SETTING: Four Canadian pediatric intensive care units and a university-affiliated laboratory. PATIENTS: Twenty-seven children, aged 2-17 yrs, with severe TBI (Glasgow Coma Scale score of ≤ 8). INTERVENTIONS: Hypothermia therapy (32.5°C) for 24 hrs with cooling started within 8 hrs of injury and rewarming at a rate of 0.5°C every 2 hrs or normothermia (37.0°C). MEASUREMENTS AND MAIN RESULTS: GFAP was measured in cerebrospinal fluid and serum, using enzyme-linked immunosorbent assay. Levels of GFAP were maximal on day 1 post-TBI, with cerebrospinal fluid GFAP (15.5 ± 6.1 ng/mL) 25-fold higher than serum GFAP (0.6 ± 0.2 ng/mL). Cerebrospinal fluid GFAP normalized by day 7, whereas serum GFAP decreased gradually to reach a steady state by day 10. Serum GFAP measured on day 1 correlated with Pediatric Cerebral Performance Category scores determined at 6 months post-TBI (ρ = 0.527; p = .008) but failed to correlate with the injury scoring on admission, physiologic variables, or indices of injury measured on computerized tomography imaging. The areas under the receiver operating characteristic curves for pediatric intensive care unit day 1 serum GFAP in determining good outcome were 0.80 (pediatric cerebral performance category, 1-2; normal-mild disability) and 0.91 (pediatric cerebral performance category, 1-3; normal-moderate disability). For a serum GFAP cutoff level of 0.6 ng/mL, sensitivity and specificity were 88% to 90% and 43% to 71%, respectively. Serum GFAP levels were similar among children randomized to either therapeutic hypothermia or normothermia. CONCLUSIONS: GFAP was markedly elevated in cerebrospinal fluid and serum in children after severe TBI and serum GFAP measured on pediatric intensive care unit day 1 correlated with functional outcome at 6 months. Hypothermia therapy did not alter serum GFAP levels compared with normothermia after severe TBI in children. Serum GFAP concentration, together with other biomarkers, may have prognostic value after TBI in children.
Assuntos
Lesões Encefálicas/fisiopatologia , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Adolescente , Lesões Encefálicas/líquido cefalorraquidiano , Lesões Encefálicas/metabolismo , Criança , Pré-Escolar , Escala de Coma de Glasgow , Humanos , Índices de Gravidade do TraumaRESUMO
RATIONALE: Adrenal insufficiency is a clinical condition associated with fluid- and catecholamine-resistant hypotension. OBJECTIVES: The objectives of this study were to determine the prevalence of adrenal insufficiency, risk factors and potential mechanisms for its development, and its association with clinically important outcomes in critically ill children. METHODS: A prospective, cohort study was conducted from 2005 to 2008 in seven tertiary-care, pediatric intensive care units in Canada on patients up to 17 years of age with existing vascular access. Adrenocorticotropic hormone stimulation tests (1 microg) were performed and adrenocorticotropic hormone levels measured in all participants. MEASUREMENTS AND MAIN RESULTS: A total of 381 patients had adrenal testing on admission. The prevalence of adrenal insufficiency was 30.2% (95% confidence interval, 25.9-35.1). Patients with adrenal insufficiency had higher baseline cortisol levels (28.6 microg/dl vs. 16.7 microg/dl, P < 0.001) and were significantly older (11.5 yr vs. 2.3 yr, P < 0.001) than those without adrenal insufficiency. Adrenal insufficiency was associated with an increased need for catecholamines (P < 0.001) and more fluid boluses (P = 0.026). The sensitivity and specificity of the low-dose adrenocorticotropic hormone stimulation test were 100% and 84%, respectively. CONCLUSIONS: Adrenal insufficiency occurs in many disease conditions in critically ill children and is associated with an increased use of catecholamines and fluid boluses. It is likely multifactorial in etiology and is associated with high baseline cortisol levels. Further research is necessary to determine which of these critically ill children are truly cortisol deficient before any treatment recommendations can be made.
Assuntos
Insuficiência Adrenal/epidemiologia , Estado Terminal , Adolescente , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/terapia , Hormônio Adrenocorticotrópico/sangue , Fatores Etários , Canadá , Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Catecolaminas/uso terapêutico , Criança , Pré-Escolar , Feminino , Hidratação , Humanos , Hidrocortisona/sangue , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Prevalência , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Ferimentos e Lesões/epidemiologiaRESUMO
BACKGROUND: Accurate and reliable evaluation of cardiac index (CI) in critically ill pediatric patients can optimize their management. Although validated, noninvasive ultrasound measurement techniques have been previously shown to be unreliable because of observer variability. OBJECTIVE: To confirm intra- and inter-observer reliability when using the noninvasive USCOM(®) in healthy anesthetized children. METHODS: Prospective observational study at the Children's Hospital of Eastern Ontario, Ottawa, included newborns to 12 years of age undergoing elective surgery or magnetic resonance imaging. The USCOM(®) was used to assess CI via aortic flow with a trans-sternal approach. Two trained observers were responsible for taking two measurements of CI each at steady state in randomized succession after stable depth of anesthesia was achieved. RESULTS: Fifty-nine patients were included. Forty-seven (80%) were between 3 and 7 years old, with 57% male. The mean difference ± sd for repeat CI measurements by each of two observers was 0.11 ± 0.47 and 0.05 ± 0.65 l·min(-1) ·m(-2) , respectively. Intra-observer reliability for these repeat measurements by each observer determined by Lin's concordance correlation coefficient was 0.92 and 0.85, respectively. The mean difference ± sd between observers was 0.16 ± 0.59 l·min(-1) ·m(-2) , and Lin's concordance correlation coefficient was 0.87. The two observers subjectively rated measurements as 'Difficult' or 'Very difficult' only 14% (16/118) and 3% (4/118) of the time, respectively. No adverse events were reported. CONCLUSION: This study confirms that the USCOM(®) is relatively easy to use and reliable in healthy children when operated by trained users.
Assuntos
Anestesia , Débito Cardíaco/fisiologia , Ecocardiografia/instrumentação , Ecocardiografia/métodos , Monitorização Intraoperatória/instrumentação , Monitorização Intraoperatória/métodos , Anestesia por Inalação , Anestésicos Inalatórios , Pressão Sanguínea/efeitos dos fármacos , Criança , Pré-Escolar , Competência Clínica , Estudos de Coortes , Ecocardiografia/efeitos adversos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Éteres Metílicos , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes , Sevoflurano , Termodiluição/métodosRESUMO
RATIONALE: Vasopressin has been proposed as a potent vasoactive agent in the treatment of vasodilatory shock in adults and children. The objective of this trial was to evaluate the efficacy and safety of vasopressin as an adjunctive agent in pediatric vasodilatory shock. METHODS: In this multicenter, double-blind trial, children with vasodilatory shock were randomized to receive low-dose vasopressin (0.0005-0.002 U/kg/min) or placebo in addition to open-label vasoactive agents. Vasoactive infusions were titrated to clinical endpoints of adequate perfusion. The primary outcome was time to vasoactive-free hemodynamic stability. Secondary outcomes included mortality, organ-failure-free days, length of critical care unit stay, and adverse events. MEASUREMENTS AND MAIN RESULTS: Sixty-five of 69 children (94%) who were randomized received the study drug (33 vasopressin, 32 placebo) and were included in the analysis. There was no significant difference in the primary outcome between the vasopressin and placebo groups (49.7 vs. 47.1 hours; P = 0.85). There were 10 deaths (30%) in the vasopressin group and five (15.6%) in the placebo group (relative risk, 1.94; 95% confidence interval, 0.75-5.05; P = 0.24). There were no significant differences with respect to organ failure-free days (22 vs. 25.5 days; P = 0.11), ventilator-free days (16.5 23 days; P = 0.15), length of stay (8 vs. 8.5 days; P = 0.93), or adverse event rate ratios (12.0%; 95% confidence interval, -2.6 to 26.7; P = 0.15). CONCLUSIONS: Low-dose vasopressin did not demonstrate any beneficial effects in this pediatric trial. Although not statistically significant, there was a concerning trend toward increased mortality. Clinical trial registered with www.controlled-trials.com (ISRCTN11597444).
Assuntos
Arginina Vasopressina/uso terapêutico , Choque/tratamento farmacológico , Vasoconstritores/uso terapêutico , Adolescente , Arginina Vasopressina/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Insuficiência de Múltiplos Órgãos/prevenção & controle , Análise de Sobrevida , Resultado do Tratamento , Vasoconstritores/efeitos adversosRESUMO
This report is a feasibility study on the utility of gel-free proteomics in identifying peripheral biomarkers of brain injury. The study was performed in six pediatric patients admitted to the intensive care unit for severe traumatic brain injury (TBI). Serum samples collected at admission (less than 8 h after injury) were used for determining the levels of S100beta by enzyme-linked immunosorbent assay (ELISA) and for proteomics analyses. Serum samples were depleted of high abundant albumin and immunoglobulin, and were compared to a pooled reference from several healthy individuals. After labeling and separation on an ionic column, six different serum fractions were analyzed using Isotope-Coded Affinity Tag (ICAT), followed by tandem mass spectrometry (MS/MS) protein sequencing and identification. Ninety-five unique, differentially expressed proteins were identified, including several with a likely brain origin. Several proteins with pattern similarity to S100beta identified by hierarchical clustering could be considered for evaluation in a larger patient sample as potential peripheral markers of TBI.
Assuntos
Lesões Encefálicas/líquido cefalorraquidiano , Proteínas do Líquido Cefalorraquidiano/líquido cefalorraquidiano , Adolescente , Biomarcadores/líquido cefalorraquidiano , Criança , Pré-Escolar , Bases de Dados de Proteínas , Ensaio de Imunoadsorção Enzimática , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Masculino , Orosomucoide/líquido cefalorraquidiano , Proteômica , Radioisótopos/líquido cefalorraquidiano , Proteínas S100/líquido cefalorraquidianoRESUMO
BACKGROUND: Total joint replacement (TJR) procedures have been one of the most rewarding interventions for treating patients suffering from joint disease. However, developing a periprosthetic joint infection (PJI) is a serious complication that is associated with the highest burden of cost and reduction in patients' quality of life compared to other complications following TJRs. One of the main challenges facing clinicians who are treating PJIs is accurately diagnosing infection in a timely fashion. Multiple orthopedic associations have published clinical guidelines for diagnosing PJI which are based solely on consensus approaches, expert opinions, and narrative reviews. We believe that a higher quality of scientific rigor is necessary to establish a diagnostic guideline that represents current evidence more accurately and that identifies important knowledge gaps in PJI diagnosis. Therefore, we will conduct a systematic review on diagnostic performance of blood markers, synovial fluids, and tissue tests for diagnosing PJI. METHODS/DESIGN: Electronic search strategies will be developed and tested by an experienced medical information specialist in consultation with the review team, and gray literature will be searched using the checklist from CADTH's Grey Matters Light. Two reviewers will independently screen the literature for inclusion using the prespecified eligibility criteria. Non-English language and animal-only studies will be excluded. Quality assessment and data extractions by reviewers will be verified, and disagreements will be resolved through consensus or third party adjudication. We will assess the quality of individual studies using the QUADAS-2 tool and use GRADE to summarize the strength of body of evidence. Analyses of evidence will be conducted in accordance with the Cochrane Handbook for Diagnostic Test Accuracy Reviews. DISCUSSION: We will conduct a systemic review of tests (blood markers, synovial fluids, and tissue testing) for diagnosing PJI in patients' knee, hip, and shoulder joint replacements. This will be the first scientifically rigorous and comprehensive systematic review in the field and may feed into an evidence-based clinical practice guideline. We will compare the findings of this review with the consensus-based guides and discuss the differences, similarities, and knowledge gaps. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015023768.
Assuntos
Artroplastia de Substituição/efeitos adversos , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Infecções Relacionadas à Prótese/diagnóstico , Líquido Sinovial/microbiologia , Membrana Sinovial/patologia , Biomarcadores/sangue , Diagnóstico Precoce , Medicina Baseada em Evidências , Humanos , Guias de Prática Clínica como Assunto , Projetos de Pesquisa , Membrana Sinovial/microbiologia , Revisões Sistemáticas como AssuntoRESUMO
PURPOSE: Consent for research is a difficult and unpredictable process in pediatric critical care populations. The objectives of this study were to describe consent rates in pediatric critical care research and their association with patient, legal guardian, consent process, and study design-related factors. METHODS: A prospective, cohort study was conducted from 2009 to 2010 in six tertiary care pediatric intensive care units (PICU) in Canada with legal guardians of patients who were approached for consent for any ongoing PICU research study. Data were recorded on details of the consent process for all consent encounters. RESULTS: We recorded 271 consent encounters. The overall consent rate was 80.1% (217/271). We observed higher consent rates when the research assistant was introduced by a member of the clinical team prior to approaching the family (89.7 vs. 77.7%; P = 0.04). Legal guardians of cardiac surgery patients were less likely to provide consent than those of all other patients (75.3 vs. 86.0%; P = 0.03). There was no difference in consent rates between therapeutic (117/145, 80.7%) versus non-therapeutic studies (100/126, 79.4%; P = 0.88). CONCLUSION: This study provides future researchers with consent data for determination of recruitment rates, sample sizes, budget estimations, and study timelines. Future pediatric critical care studies should consider incorporating the lower consent rates in cardiac surgery patients and routine introduction of the research assistant to the family by a member of the patient's care team into their study designs. The potential influence of parental factors on consent rates in pediatric critical care studies requires further research.