Dynamics of the cerebral autoregulatory response to paced hyperventilation assessed using subcomponent and time-varying analyses.

Cerebral blood flow (CBF) can be altered by a change in partial pressure of arterial CO2 (Pco2), being reduced during hyperventilation (HPV). Critical closing pressure (CrCP) and resistance area product (RAP) are parameters that can be studied to understand this change, but their dynamic response has not been investigated during paced HPV (PHPV). Seventy-five participants had recordings at rest and during PHPV. Blood pressure (BP) (Finometer), bilateral CBF velocity (CBFV) (transcranial Doppler), end-tidal CO2 (capnography), and heart rate (HR) were recorded continuously. Subcomponent analysis (SCA) and time-varying CrCP, RAP, and dynamic cerebral autoregulation (autoregulation index, ARI) were estimated by comparing PHPV with poikilocapnia. PHPV caused a change in CBFV (P < 0.01), EtCO2, (P < 0.01), HR (P < 0.001), and RAP (P < 0.01). SCA demonstrated RAP was the main parameter explaining the changes in CBFV due to PHPV. The time-varying step responses for CBFV and RAP during PHPV demonstrated considerable nonstationarity compared with poikilocapnia (P < 0.00001). Although time-varying ARI was temporarily depressed, after 60 s of PHPV it was significantly higher (6.81 ± 1.88) (P < 0.0001) than in poikilocapnia (5.08 ± 1.86). The mean plateau of the RAP step response was -98.3 ± 58.8% 60 s after the onset of PHPV but -71.7 ± 45.0% for poikilocapnia (P = 0.0026), with no corresponding changes in CrCP (P = 0.6). Further work is needed to assess the role of sex and aging in our findings, and the potential for using RAP and CrCP to improve the sensitivity and specificity of CO2 reactivity studies in cerebrovascular conditions.NEW & NOTEWORTHY The dynamic response of critical closing pressure (CrCP) and resistance-area product (RAP) of the cerebral circulation to a step change in mean arterial pressure can shed light on the nonstationary changes induced by paced hyperventilation and the effects of hypocapnia on the autoregulation of cerebral blood flow. Contrary to hypercapnia, where the response is dominated by CrCP, hypocapnia shows an initial depression of cerebral autoregulation, followed by improvements controlled by changes in RAP.

Alterations in arterial CO2 rather than pH affect the kinetics of neurovascular coupling in humans.

KEY POINTS: We investigated the influence of arterial PCO2 ( PaCO2 ) with and without acute experimental metabolic alkalosis on neurovascular coupling (NVC). We assessed stepwise iso-oxic alterations in PaCO2 prior to and following intravenous NaHCO3 to acutely elevate arterial pH and [HCO3- ]. The NVC response was not altered following NaHCO3 between stepwise PaCO2 stages; therefore, NVC is acutely mediated by PaCO2 rather than the prevailing arterial [H+ ]/pH. The NVC response was attenuated by 27-38% with -10 mmHg PaCO2 and the absolute peak change was reduced by -19% with +10 mmHg PaCO2 irrespective of acutely elevated arterial pH/[HCO3- ]. The NVC kinetics (i.e. time to peak) were markedly slower with hypercapnia versus hypocapnia (24 ± 5 vs. 7 ± 5 s, respectively) likely indicating an influence of resting cerebrovascular tone on NVC responsiveness. ABSTRACT: Elevations in cerebral metabolism necessitate appropriate coordinated and localized increases in cerebral blood flow (i.e. neurovascular coupling; NVC). Recent pre-clinical work indicates that arterial PCO2 ( PaCO2 ) mediates NVC independently of arterial/extracellular pH; this has yet to be experimentally tested in humans. The goal of this study was to investigate the hypotheses that: (1) the NVC response would be unaffected by acute experimentally elevated arterial pH; rather, PaCO2 would regulate any changes in NVC; and (2) stepwise respiratory alkalosis and acidosis would each progressively reduce the NVC response. Ten healthy males completed a standardized visual stimulus-evoked NVC test during matched stepwise iso-oxic alterations in PaCO2 (hypocapnia: -5, -10 mmHg; hypercapnia: +5, +10 mmHg) prior to and following intravenous NaHCO3 (8.4%, 50 mEq/50 ml) that elevated arterial pH (7.406 ± 0.019 vs. 7.457 ± 0.029; P < 0.001) and [HCO3- ] (26.2 ± 1.5 vs. 29.3 ± 0.9 mEq/l; P < 0.001). Although the NVC response was collectively attenuated by 27-38% with -10 mmHg PaCO2 (stage post hoc: all P < 0.05), this response was unaltered following NaHCO3 (all P > 0.05) irrespective of the higher pH (P = 0.002) at each matched stage of PaCO2 (P = 0.417). The absolute peak change was reduced by -19 ± 41% with +10 mmHg PaCO2 irrespective of acutely elevated arterial pH/[HCO3- ] (stage post hoc: P = 0.022). The NVC kinetics (i.e. time to peak) were markedly slower with hypercapnia versus hypocapnia (24 ± 5 vs. 7 ± 5 s, respectively; stage effect: P < 0.001). Overall, these findings indicate that temporal patterns in NVC are acutely regulated by PaCO2 rather than arterial pH per se in the setting of acute metabolic alkalosis in humans.

Arterial carbon dioxide and bicarbonate rather than pH regulate cerebral blood flow in the setting of acute experimental metabolic alkalosis.

KEY POINTS: We investigated the influence of arterial PCO2 ( PaCO2 ) with and without acutely elevated arterial pH and bicarbonate ([HCO3- ]) on cerebral blood flow (CBF) regulation in the internal carotid artery and vertebral artery. We assessed stepwise iso-oxic alterations in PaCO2 (i.e. cerebrovascular CO2 reactivity) prior to and following i.v. sodium bicarbonate infusion (NaHCO3- ) to acutely elevate arterial pH and [HCO3- ]. Total CBF was unchanged irrespective of a higher arterial pH at each matched stage of PaCO2 , indicating that CBF is acutely regulated by PaCO2 rather than arterial pH. The cerebrovascular responses to changes in arterial H+ /pH were altered in keeping with the altered relationship between PaCO2 and H+ /pH following NaHCO3- infusion (i.e. changes in buffering capacity). Total CBF was ∼7% higher following NaHCO3- infusion during isocapnic breathing providing initial evidence for a direct vasodilatory influence of HCO3- independent of PaCO2 levels. ABSTRACT: Cerebral blood flow (CBF) regulation is dependent on the integrative relationship between arterial PCO2 ( PaCO2 ), pH and cerebrovascular tone; however, pre-clinical studies indicate that intrinsic sensitivity to pH, independent of changes in PaCO2 or intravascular bicarbonate ([HCO3- ]), principally influences cerebrovascular tone. Eleven healthy males completed a standardized cerebrovascular CO2 reactivity (CVR) test utilizing radial artery catheterization and Duplex ultrasound (CBF); consisting of matched stepwise iso-oxic alterations in PaCO2 (hypocapnia: -5, -10 mmHg; hypercapnia: +5, +10 mmHg) prior to and following i.v. sodium bicarbonate (NaHCO3- ; 8.4%, 50 mEq 50 mL-1 ) to elevate pH (7.408 ± 0.020 vs. 7.461 ± 0.030; P < 0.001) and [HCO3- ] (26.1 ± 1.4 vs. 29.3 ± 0.9 mEq L-1 ; P < 0.001). Absolute CBF was not different at each stage of CO2 reactivity (P = 0.629) following NaHCO3- , irrespective of a higher pH (P < 0.001) at each matched stage of PaCO2 (P = 0.927). Neither hypocapnic (3.44 ± 0.92 vs. 3.44 ± 1.05% per mmHg PaCO2 ; P = 0.499), nor hypercapnic (7.45 ± 1.85 vs. 6.37 ± 2.23% per mmHg PaCO2 ; P = 0.151) reactivity to PaCO2 were altered pre- to post-NaHCO3- . When indexed against arterial [H+ ], the relative hypocapnic CVR was higher (P = 0.019) and hypercapnic CVR was lower (P = 0.025) following NaHCO3- , respectively. These changes in reactivity to [H+ ] were, however, explained by alterations in buffering between PaCO2 and arterial H+ /pH consequent to NaHCO3- . Lastly, CBF was higher (688 ± 105 vs. 732 ± 89 mL min-1 , 7% ± 12%; P = 0.047) following NaHCO3- during isocapnic breathing providing support for a direct influence of HCO3- on cerebrovascular tone independent of PaCO2 . These data indicate that in the setting of acute metabolic alkalosis, CBF is regulated by PaCO2 rather than arterial pH.

Pathophysiological and clinical considerations in the perioperative care of patients with a previous ischaemic stroke: a multidisciplinary narrative review.

With an ageing population and increasing incidence of cerebrovascular disease, an increasing number of patients presenting for routine and emergency surgery have a prior history of stroke. This presents a challenge for pre-, intra-, and postoperative management as the neurological risk is considerably higher. Evidence is lacking around anaesthetic practice for patients with vascular neurological vulnerability. Through understanding the pathophysiological changes that occur after stroke, insight into the susceptibilities of the cerebral vasculature to intrinsic and extrinsic factors can be developed. Increasing understanding of post-stroke systemic and cerebral haemodynamics has provided improved outcomes from stroke and more robust secondary prevention, although this knowledge has yet to be applied to our delivery of anaesthesia in those with prior stroke. This review describes the key pathophysiological and clinical considerations that inform clinicians providing perioperative care for patients with a prior diagnosis of stroke.

Intra-aortic balloon pump does not influence cerebral hemodynamics and neurological outcomes in high-risk cardiac patients undergoing cardiac surgery: an analysis of the IABCS trial.

BACKGROUND: The intra-aortic balloon pump (IABP) is often used in high-risk patients undergoing cardiac surgery to improve coronary perfusion and decrease afterload. The effects of the IABP on cerebral hemodynamics are unknown. We therefore assessed the effect of the IABP on cerebral hemodynamics and on neurological complications in patients undergoing cardiac surgery who were randomized to receive or not receive preoperative IABP in the 'Intra-aortic Balloon Counterpulsation in Patients Undergoing Cardiac Surgery' (IABCS) trial. METHODS: This is a prospectively planned analysis of the previously published IABCS trial. Patients undergoing elective coronary artery bypass surgery with ventricular ejection fraction ≤ 40% or EuroSCORE ≥ 6 received preoperative IABP (n = 90) or no IABP (n = 91). Cerebral blood flow velocity (CBFV) of the middle cerebral artery through transcranial Doppler and blood pressure through Finometer or intra-arterial line were recorded preoperatively (T1) and 24 h (T2) and 7 days after surgery (T3) in patients with preoperative IABP (n = 34) and without IABP (n = 33). Cerebral autoregulation was assessed by the autoregulation index that was estimated from the CBFV response to a step change in blood pressure derived by transfer function analysis. Delirium, stroke and cognitive decline 6 months after surgery were recorded. RESULTS: There were no differences between the IABP and control patients in the autoregulation index (T1: 5.5 ± 1.9 vs. 5.7 ± 1.7; T2: 4.0 ± 1.9 vs. 4.1 ± 1.6; T3: 5.7 ± 2.0 vs. 5.7 ± 1.6, p = 0.97) or CBFV (T1: 57.3 ± 19.4 vs. 59.3 ± 11.8; T2: 74.0 ± 21.6 vs. 74.7 ± 17.5; T3: 71.1 ± 21.3 vs. 68.1 ± 15.1 cm/s; p = 0.952) at all time points. Groups were not different regarding postoperative rates of delirium (26.5% vs. 24.2%, p = 0.83), stroke (3.0% vs. 2.9%, p = 1.00) or cognitive decline through analysis of the Mini-Mental State Examination (16.7% vs. 40.7%; p = 0.07) and Montreal Cognitive Assessment (79.16% vs. 81.5%; p = 1.00). CONCLUSIONS: The preoperative use of the IABP in high-risk patients undergoing cardiac surgery did not affect cerebral hemodynamics and was not associated with a higher incidence of neurological complications. Trial registration http://www.clinicaltrials.gov (NCT02143544).

Dynamic cerebral autoregulation: A marker of post-operative delirium?

OBJECTIVE: We investigated the potential association of cerebral autoregulation (CA) with postoperative delirium (PD), a common complication of cardiac surgery with cardiopulmonary bypass (CPB). METHODS: In patients undergoing coronary artery bypass graft (CABG) surgery with CPB, cerebral blood flow velocity (CBFV) and blood pressure (BP) were continuously recorded during 5-min preoperatively (T1), after 24 h (T2), and 7 days after procedure (T3). Prospective multivariate logistic regression analysis was performed to determine the independent risk factors of PD. Autoregulation index (ARI) was calculated from the CBFV response to a step change in BP derived by transfer function analysis. RESULTS: In 67 patients, mean age 64.3 ±â€¯9.5 years, CA was depressed at T2 as shown by values of ARI (3.9 ±â€¯1.7), compared to T1 (5.6 ±â€¯1.7) and T3 (5.5 ±â€¯1.8) (p < 0.001). Impaired CA was found in 37 (55%) patients at T2 and in 7 patients (20%) at T3. Lower ARI at T1 and T2 were predictors of PD (p = 0.003). CONCLUSION: Dynamic CA was impaired after CABG surgery with CPB and was a significant independent risk factor of PD. SIGNIFICANCE: Assessment of CA before and after surgery could have considerable potential for early identification of patients at risk of PD, thus reducing poor outcomes and length of stay. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT02143544, April 30, 2014).

Cerebral autoregulation in cardiopulmonary bypass surgery: a systematic review.

Cardiopulmonary bypass surgery is associated with a high incidence of neurological complications, including stroke, delirium and cognitive impairment. The development of strategies to reduce the incidence of such neurological events has been hampered by the lack of a clear understanding of their pathophysiology. Cerebral autoregulation (CA), which describes the ability of the brain to maintain a stable cerebral blood flow over a wide range of cerebral perfusion pressures despite changes in blood pressure, is known to be impaired in various neurological disorders. Therefore, we aimed to systematically review studies reporting indices of CA in cardiopulmonary bypass surgery. Databases such as MEDLINE, Web of Science, Cochrane Database of Systematic Reviews and EMBASE were searched for relevant articles. Titles, abstracts and full texts of articles were scrutinized according to predefined selection criteria. Two independent reviewers undertook the methodological quality screening and data extraction of the included studies. Twenty of 2566 identified studies were relevant. Studies showed marked heterogeneity and weaknesses in key methodological criteria (e.g. population size and discussion of limitations). All but 3 of the 20 studies described impairments of CA with cardiac surgery. Eleven studies investigated clinical outcomes, and 9 of these found a significant relationship between these and impaired CA. There is a general agreement that cardiac surgery is associated with changes in CA and that clinical outcomes appear to be significantly related to impaired CA. Further studies are now needed to determine prognostic significance and to inform future therapeutic strategies.

Cerebral hemodynamics: concepts of clinical importance.

Cerebral hemodynamics and metabolism are frequently impaired in a wide range of neurological diseases, including traumatic brain injury and stroke, with several pathophysiological mechanisms of injury. The resultant uncoupling of cerebral blood flow and metabolism can trigger secondary brain lesions, particularly in early phases, consequently worsening the patient's outcome. Cerebral blood flow regulation is influenced by blood gas content, blood viscosity, body temperature, cardiac output, altitude, cerebrovascular autoregulation, and neurovascular coupling, mediated by chemical agents such as nitric oxide (NO), carbon monoxide (CO), eicosanoid products, oxygen-derived free radicals, endothelins, K+, H+, and adenosine. A better understanding of these factors is valuable for the management of neurocritical care patients. The assessment of both cerebral hemodynamics and metabolism in the acute phase of neurocritical care conditions may contribute to a more effective planning of therapeutic strategies for reducing secondary brain lesions. In this review, the authors have discussed concepts of cerebral hemodynamics, considering aspects of clinical importance.

Cerebral hemodynamics: concepts of clinical importance / Hemodinâmica encefálica: conceitos de importância clínica

Cerebral hemodynamics and metabolism are frequently impaired in a wide range of neurological diseases, including traumatic brain injury and stroke, with several pathophysiological mechanisms of injury. The resultant uncoupling of cerebral blood flow and metabolism can trigger secondary brain lesions, particularly in early phases, consequently worsening the patient's outcome. Cerebral blood flow regulation is influenced by blood gas content, blood viscosity, body temperature, cardiac output, altitude, cerebrovascular autoregulation, and neurovascular coupling, mediated by chemical agents such as nitric oxide (NO), carbon monoxide (CO), eicosanoid products, oxygen-derived free radicals, endothelins, K+, H+, and adenosine. A better understanding of these factors is valuable for the management of neurocritical care patients. The assessment of both cerebral hemodynamics and metabolism in the acute phase of neurocritical care conditions may contribute to a more effective planning of therapeutic strategies for reducing secondary brain lesions. In this review, the authors have discussed concepts of cerebral hemodynamics, considering aspects of clinical importance.

Alterações hemodinâmicas e metabólicas do encéfalo ocorrem frequentemente em diversas doenças neurológicas, principalmente em condições de traumatismo cranioencefálico e acidente vascular encefálico, com vários mecanismos patofisiológicos lesionais. O desacoplamento resultante do fluxo sanguíneo e do metabolismo encefálico pode resultar em lesões encefálicas secundárias, principalmente nas primeiras fases, e, consequentemente, no agravamento do desfecho neurológico dos pacientes. Diversos fatores influenciam o fluxo sanguíneo encefálico, entre eles, a concentração sanguínea de gases, viscosidade sanguínea, temperatura corpórea, débito cardíaco, altitude, autorregulação cerebrovascular e acoplamento neurovascular, que é mediado por óxido nítrico (ON), monóxido de carbono (CO), eicosanoides, radicais livres derivados do oxigênio, endotelinas, potássio, íons hidrogênio e adenosinas. Melhor compreensão destes fatores é fundamental para o manejo clínico dos pacientes neurológicos críticos. A avaliação hemodinâmica e metabólica do encéfalo nas lesões encefálicas agudas pode contribuir para o planejamento de estratégias de redução das lesões encefálicas secundárias. Nesta revisão, os autores discutiram princípios da hemodinâmica encefálica, considerando os aspectos de importância clínica.

A pressäo crítica de fechamento na modelagem da hemodinâmica cerebral / Critical pressure of closure critical in cerebral hemodynamic modelling

A dinâmica da relação entre a pressão sanguínea arterial e o fluxo sangüíneo cerebral em pretermos foi modelada como um sistema linear. Os resultados sugerem que este modelo poderia explicar a Pressão Critica de Fechamento, como sendo, pelo menos parcialmente, um efeito da própria dinâmica do sistema.

Estudo preliminar de dados para análise de determinantes de saúde no Brasil / Preliminary analisis of determinants of health in Brazil

A disponibilidade de dados confiáveis sobre o sistema de Saúde é indispensável para o desenvolvimento de trabalhos na área de planejamento em saúde. O presente trabalho descreve a implementaçäo de um banco de dados relativos aos setores Saúde, Social, Econômico e Ambiental. As dificuldades de seleçäo dos dados säo apresentados bem como um método exclusivamente matemático para interpolaçäo de populaçöes. Um estudo do erro quando se utiliza interpolaçäo linear para as variáveis näo demográficas, indica um erro médio de 12% para interpolaçäo de uma amostra em variáveis do setor saúde, mostrando a viabilidade deste procedimento quando necessário. A caracterizaçäo da funçäo de probabilidade das principais variáveis sugere uma distribuiçäo gaussiana na maioria dos casos

Caracterizaçäo dinâmica de séries históricas de determinantes de saúde / Dinamic characterization of health determinants historical series

Uma metodologia foi desenvolvida para a caracterizaçäo da ordem e do Número de Graus de Liberdade de séries temporais de curta duraçäo (número de pontos menor que 30). O problema dessa caracterizaçäo aparece com frequência em Epidemiologia, na modelagem de surtos epidemiológicos ou determintes de saúde com base em indicadores coletados anualmente. Utilizando-se os cinco primeiros coeficientes da funçäo de autocorrelaçäo, a ordem de um grupo de séries fica determinada pela distância mínima entre os coeficientes das séries e os de conjuntos de séries-padröes previamente construidos a partir da simulaçäo de processos com ordem conhecida. Para as séries de mortalidade das 60 maiores cidades brasileiras no período 1960-1983 verificou-se que a ordem é superior ou igual a 5, o que corresponde a no máximo 0,2 graus de liberdade por ponto. O erro desta estimativa é uma funçäo do tamanho e do número de séries empregados. Estes resultados possuem aplicaçäo no desenvolvimento de critérios de interpolaçäo para séries semelhantes com ausência de dados e na escolha da estrutura de modelos matemáticos de determinantes de saúde

Utilizaçäo de tecnologias neonatais / Utilization of neonatal technology

Os Cuidados Intensivos Neonatais (CIN) säo constituidos por um aparato tecnológico complexo, o qual encontra-se em fase de difusäo no país. Para que a alocaçäo de recursos e formulaçäo de políticas tecnológicas para o setor sejam possíveis é necessário desenvolver uma capacitaçäo na avaliaçäo das múltiplas tecnologias, que compöem os CIN incluindo-se as novas metodologias para caracterizaçäo do custo e benefício e interaçöes entre tecnologias individuais. Na UTI neonatal do Instituto Fernandes Figueira, foram estudados a utilizaçäo de 53 tecnologias em 38 casos na faixa de peso de nascimento 1000-1499g e 44 casos entre 1500-1999g. Através de técnicas multivariáveis como a análise de agrupamentos foi possível identificar grupos ou "pacotes" de tecnologias com padröes uniformes de utilizaçäo. Estes resultados têm aplicaçäo no planejamento de novas UTI neonatais e na escolha de opçöes para desenvolvimento tecnológico no país

Desenvolvimento de um cardiógrafo de descolamento (D.C.G.) / Development of a displacement cardiograph

Este trabalho refere-se ao desenvolvimento e testes iniciais de um Cardiógrafo de Deslocamento (D.C.G.) para realizar mediçöes de maneira näo-invasiva da atividade mecânica do coraçäo. O cardioquimógrafo, como também é denominado, é um dispositivo eletrônico que empregando um campo eletromagnético, registra movimentos cardíacos internos ao tórax. A bobina sensora näo necessita estar em contato com o paciente pois o campo penetra dentro do corpo. Distúrbios no campo devido a cinética das paredes do coraçäo säo eletricamente convertidos em sinal analógico, apresentando um padräo de registro característico

Processamento de sinais de impedância elétrica do tórax / Signs of electrical impedance of the thorax

Medidas contínuas da impedância elétrica do tórax refletem o fluxo sangüíneo instantâneo nas grandes artérias intratorácicas constituindo-se em uma técnica promissora para avaliaçäo näo-invasiva da funçäo ventricular e diagnóstico precoce de doença cardiovasculares. Na COPPE/UFRJ foi desenvolvido um instrumento para mediçäo do sinal e os primeiros estudos concentraram-se na determinaçäo dos critérios mais adequados para aquisiçäo e processamento do sinal. Esta fase inclui a investigaçäo dos efeitos introduzidos pela respiraçäo e sua influência sobre o sinal de origem cardiovascular. O mapeamento do sinal de impedância na superfície anterior do tórax mostrou que a atividade cardíaca também pode ser detectada e deu subsidios para auxiliar a interpretaçäo da origem dos sinais detectados. Em pacientes com doença coronariana, a primeira derivada do sinal apresenta um padräo temporal distorcido na fase inicial da sistole, que pode ser detectado em repouso, tornando viável e atraente a aplicaçäo do método na rotina clínica