RESUMO
BACKGROUND: In the POISE-2 (PeriOperative ISchemic Evaluation 2) trial, perioperative aspirin did not reduce cardiovascular events, but increased major bleeding. There remains uncertainty regarding the effect of perioperative aspirin in patients undergoing vascular surgery. The aim of this substudy was to determine whether there is a subgroup effect of initiating or continuing aspirin in patients undergoing vascular surgery. METHODS: POISE-2 was a blinded, randomized trial of patients having non-cardiac surgery. Patients were assigned to perioperative aspirin or placebo. The primary outcome was a composite of death or myocardial infarction at 30 days. Secondary outcomes included: vascular occlusive complications (a composite of amputation and peripheral arterial thrombosis) and major or life-threatening bleeding. RESULTS: Of 10 010 patients in POISE-2, 603 underwent vascular surgery, 319 in the continuation and 284 in the initiation stratum. Some 272 patients had vascular surgery for occlusive disease and 265 had aneurysm surgery. The primary outcome occurred in 13·7 per cent of patients having aneurysm repair allocated to aspirin and 9·0 per cent who had placebo (hazard ratio (HR) 1·48, 95 per cent c.i. 0·71 to 3·09). Among patients who had surgery for occlusive vascular disease, 15·8 per cent allocated to aspirin and 13·6 per cent on placebo had the primary outcome (HR 1·16, 0·62 to 2·17). There was no interaction with the primary outcome for type of surgery (P = 0·294) or aspirin stratum (P = 0·623). There was no interaction for vascular occlusive complications (P = 0·413) or bleeding (P = 0·900) for vascular compared with non-vascular surgery. CONCLUSION: This study suggests that the overall POISE-2 results apply to vascular surgery. Perioperative withdrawal of chronic aspirin therapy did not increase cardiovascular or vascular occlusive complications. Registration number: NCT01082874 ( http://www.clinicaltrials.gov).
Assuntos
Aspirina/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Constrição Patológica/etiologia , Constrição Patológica/mortalidade , Feminino , Humanos , Masculino , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Assistência Perioperatória/métodos , Assistência Perioperatória/mortalidade , Inibidores da Agregação Plaquetária/efeitos adversos , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/prevenção & controle , Hemorragia Pós-Operatória/induzido quimicamente , Resultado do Tratamento , Doenças Vasculares/etiologia , Doenças Vasculares/mortalidade , Procedimentos Cirúrgicos Vasculares/mortalidadeRESUMO
BACKGROUND: Propofol is used to induce deep sedation or general anaesthesia for procedures in children. Adjuvants, such as ketamine, are routinely added to reduce the dose of propofol required and propofol-related adverse events. We conducted a randomised controlled trial to determine the effective bolus dose of propofol in combination with ketamine that induces adequate depth of anaesthesia in 50% of children (ED50) undergoing gastro-duodenoscopy. METHODS: Children were randomised to one of four doses of ketamine: 0 (control), 0.25, 0.5, and 1 mg kg-1, followed by a dose of propofol according to Dixon's up-and-down methodology. Excessive movement, coughing, gagging, or airway obstruction that prevented endoscope insertion was considered a failure. RESULTS: The ED50 of propofol (median, 95% CI) was greater in the ketamine 0, 0.25, and 0.5 mg kg-1 groups compared with the ketamine 1 mg kg-1 group (6.1, 4.1-8.1; 4.5, 2.9-6; 4.7, 3.1-6.2 mg kg-1vs 1.1, 0.5-1.8 mg kg-1, respectively, P<0.008). Total dose of propofol administered during the procedure was reduced with ketamine 1 mg kg-1. The mean arterial pressure was lower in the ketamine 0 mg kg-1 group compared with the 1 mg kg-1 group during and immediately after the procedure. The ketamine 1 mg kg-1 group experienced a higher incidence of nausea and visual disturbances. CONCLUSIONS: Ketamine at 0.5-1 mg kg-1 reduces the dose of propofol required to provide general anaesthesia for gastro-duodenoscopy in children and may reduce the incidence of propofol-related changes in haemodynamics. CLINICAL TRIAL REGISTRATION: NCT 02295553.
Assuntos
Anestésicos Dissociativos/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Endoscopia Gastrointestinal/métodos , Ketamina/administração & dosagem , Propofol/administração & dosagem , Adolescente , Período de Recuperação da Anestesia , Anestésicos Dissociativos/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Pressão Arterial/efeitos dos fármacos , Criança , Relação Dose-Resposta a Droga , Método Duplo-Cego , Duodenoscopia/métodos , Feminino , Gastroscopia/métodos , Humanos , Intubação Intratraqueal , Ketamina/efeitos adversos , Masculino , Náusea/induzido quimicamente , Náusea/epidemiologia , Propofol/efeitos adversos , Transtornos da Visão/induzido quimicamente , Transtornos da Visão/epidemiologiaRESUMO
Previous studies in our laboratory demonstrated a reversal of anesthetic actions on aged neurons by decreasing extracellular [Ca(2+)] in hippocampal slices. Such maneuver indirectly attenuated Ca(2+) influx, hence decreased exogenous intraneuronal Ca(2+) loads during neuronal activity and consequently improved intracellular Ca(2+) concentration homeostasis. Therefore, in the present study we hypothesized that decreasing exogenous Ca(2+) loads by blocking voltage-gated calcium influx in aged neurons would oppose isoflurane actions. Conversely, increasing endogenous Ca(2+) loads by suppressing calcium efflux during forced reversal of Na(+)/Ca(2+) exchanger function would enhance anesthetic effects. Hippocampal slices were prepared from young (2-4 months) and old (24-26 months) Fischer 344 rats. Isoflurane depressed the evoked dendritic field excitatory postsynaptic potentials by approximately 45% in slices taken from old animals. However, application of isoflurane in addition with CoCl(2) or nifedipine opposed the anesthetic actions, which then depressed the evoked dendritic field postsynaptic potentials by only 15%. Selective blockade of the N-type and P/Q-type calcium channels with omega-conotoxin GVIA and omega-conotoxin MVIIC respectively caused rapid but partial depression of synaptic transmission in slices taken from old Fischer 344 rats. However, isoflurane actions in these aged slices were not affected compared with slices perfused only with normal artificial cerebrospinal fluid. Young and aged slices were then exposed to a low sodium perfusate that forces the Na(+)/Ca(2+) exchanger protein into a reverse mode, thus increasing intracellular Ca(2+) concentration. Isoflurane actions under such conditions were profoundly potentiated in aged slices but were not altered in young hippocampi. The current results show that in aged central neurons, selectively blocking L-type calcium channels opposes anesthetic-induced depression of excitatory synaptic transmission. On the contrary, increasing calcium loads in aged neurons potentiates these actions.
Assuntos
Envelhecimento/fisiologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo L/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Isoflurano/farmacologia , Neurônios/efeitos dos fármacos , Análise de Variância , Anestésicos Inalatórios/farmacologia , Animais , Cálcio/metabolismo , Canais de Cálcio Tipo L/metabolismo , Interações Medicamentosas , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Hipocampo/citologia , Hipocampo/metabolismo , Técnicas In Vitro , Neurônios/citologia , Neurônios/metabolismo , Ratos , Ratos Endogâmicos F344RESUMO
1. The effects of general anaesthetics were investigated on neuronal sensitivities to transmitter substances, which were determined by iontophoretic applications of acetylcholine, glutamate, N-methyl-D-aspartate (NMDA) and gamma-aminobutyrate (GABA) during intracellular recording in in vitro slice preparations of neocortex (guinea-pig). 2. In most of the 65 neurones studied, perfusion of isoflurane (0.5-2.5 minimum alveolar concentration (MAC)) or Althesin (25-200 microM) and, in some cases, halothane (0.5-2 MAC), markedly reduced the depolarizing responses and associated membrane conductance changes evoked by dendritic applications of acetylcholine, glutamate, NMDA and GABA. 3. The order of depression was acetylcholine greater than glutamate or NMDA much greater than GABA. This selectivity could also be assessed from the EC50 for the isoflurane-induced depression of the just-maximal responses to acetylcholine, which was 0.9 MAC compared with an EC50 = 1.9 MAC for the suppression of glutamate responses. The selectivity was less pronounced in the case of the actions of Althesin, where the EC50s were 75 microM for the depression of acetylcholine responses and 90 microM for the depression of glutamate responses. 4. The hyperpolarizing responses observed when GABA was applied near the perikaryon in 7 neurones, were slightly reduced (approximately 15%) in 4, and unchanged in 3 neurones during anaesthetic application. 5. The pronounced depression of the responsiveness to the putative arousal transmitters and an observed blockade of acetylcholine-induced potentiation of glutamate actions suggest that anaesthetics produce unconsciousness, at least in part, by interfering with subsynaptic mechanisms of neocortical activation.
Assuntos
Anestésicos/farmacologia , Córtex Cerebral/efeitos dos fármacos , Neurotransmissores/farmacologia , Acetilcolina/antagonistas & inibidores , Acetilcolina/farmacologia , Mistura de Alfaxalona Alfadolona/farmacologia , Animais , Relação Dose-Resposta a Droga , Antagonistas de Aminoácidos Excitatórios , Antagonistas GABAérgicos , Glutamatos/farmacologia , Cobaias , Técnicas In Vitro , Isoflurano/farmacologia , Potenciais da Membrana/efeitos dos fármacos , N-Metilaspartato/antagonistas & inibidores , N-Metilaspartato/farmacologia , Ácido gama-Aminobutírico/farmacologiaRESUMO
1. The effects of hypomagnesia on the neuronal responses induced by iontophorectically applied acetylcholine, glutamate, N-methylaspartate (NMDA) and gamma-aminobutyric acid (GABA) were investigated using intracellular recording techniques in in vitro slices of sensorimotor cortex (guinea-pigs). 2. Perfusion with Mg-free media, with or without tetrodotoxin (TTX), induced a small hyperpolarization (approximately 4 mV) and a small decrease (approximately 10%) in the input resistance of neurones. During TTX-blockade of Na-spike genesis, spontaneous depolarizing waves of low frequencies were observed in neurones of slices under Mg-free conditions. 3. The effects of acetylcholine and to a lesser extent, GABA actions, were depressed in a dose-dependent, reversible manner by decreases in the [Mg2+] of the perfusing media. In neurones of slices that had been incubated in Mg-free artificial cerebrospinal fluid to ensure a maximal depletion, the responses to these transmitters were potentiated by each sequentially administered increase in extracellular [Mg2+]. The actions of NMDA were potentiated during perfusion of Mg-free media. However, the responses to glutamate, which may activate receptors for NMDA, were either depressed or unchanged under these conditions. 4. A regulatory role for external Mg cations in the responses of neocortical neurones to the transmitter substances, acetylcholine and GABA, can be inferred from these investigations which simulate hypomagnesemia. The dose-dependent depression of GABA actions by low extracellular [Mg2+] additionally provides a plausible mechanism that may contribute to the neuronal hyperexcitability that is observed during conditions of hypomagnesemia.
Assuntos
Córtex Cerebral/metabolismo , Deficiência de Magnésio/metabolismo , Neurotransmissores/farmacologia , Acetilcolina/farmacologia , Animais , Córtex Cerebral/efeitos dos fármacos , Glutamatos/farmacologia , Ácido Glutâmico , Cobaias , Técnicas In Vitro , Magnésio/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Neurônios Motores/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/metabolismo , Ácido gama-Aminobutírico/farmacologiaRESUMO
1. The effects of the volatile anaesthetic, isoflurane, were investigated on evoked dendritic field excitatory postsynaptic potentials (f.e.p.s.p.) and antidromic and orthodromic population spikes recorded extracellularly in the CA1 cell layer region in the in vitro hippocampal slice taken from young mature (2-3 months) and old (24-27 months) Fisher 344 rats. 2. Isoflurane depressed the f.e.p.s.ps and the orthodromically-evoked population spikes in both old and young hippocampi. However, the magnitude of the anaesthetic-induced depression was greater in slices taken from old rats compared to those taken from young rats during the application of different isoflurane concentrations (0.5-5%). 3. In the presence of the GABA(A) antagonist, bicuculline methiodide (15 microM), isoflurane suppressed the f.e.p.s.ps to the same extent as was observed in the absence of the GABA(A) antagonist. 4. Orthodromically evoked population spikes were suppressed by isoflurane in a manner quantitatively similar to the suppression of the f.e.p.s.ps. However, antidromic population spikes and presynaptic volleys evoked in young and old slices were resistant to anaesthetic action. In addition, paired pulse facilitation ratio of the evoked dendritic f.e.p.s.ps was not affected in both young and old slices during the application of isoflurane. 5. When slices were exposed to low Ca2+/high Mg2+ solution, isoflurane (1 and 3%) depressed the f.e.p.s.ps in aged slices to the same extent as in young slices. 6. The augmented anaesthetic depression of f.e.p.s.ps in old compared to young hippocampi in the absence and presence of bicuculline, and the lack of anaesthetic effects on antidromic population spikes and presynaptic volleys in old and young slices, suggest that the increased sensitivity of anaesthetic actions in old hippocampi is due to age-induced attenuation of synaptic excitation rather than potentiation of synaptic inhibition. Furthermore, elimination of the increased sensitivity of old slices to anaesthetic actions when the slices were perfused with low Ca2+/high Mg2+ medium, which presumably would decrease intracellular [Ca2+], suggests that the enhanced anaesthetic effects in aged neurones might be related to increased intraneuronal [Ca2+] in the synaptic terminal.
Assuntos
Envelhecimento/fisiologia , Hipocampo/efeitos dos fármacos , Isoflurano/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Animais , Bicuculina/farmacologia , Cálcio/metabolismo , Potenciais Pós-Sinápticos Excitadores , Antagonistas GABAérgicos/farmacologia , Hipocampo/fisiologia , Técnicas In Vitro , Magnésio/metabolismo , Ratos , Ratos Endogâmicos F344RESUMO
The effects of the volatile anaesthetic isoflurane on dendritic field excitatory postsynaptic potentials (fEPSP) were compared in hippocampal slices taken from young mature and old Fisher 344 rats. Application of isoflurane (1% v/v) to young brain slices produced minimal effects on the recorded fEPSPs. On the contrary, the same anaesthetic concentration depressed field responses obtained from old hippocampal slices by 42 +/- 6.8% compared with baseline values. Such increased sensitivity to anaesthetic action in the old slices was consistently observed with administration of higher isoflurane concentrations. The presynaptic afferent volley was unaffected by application of low or high anaesthetic concentration, suggesting that age-induced changes in nerve fibre conduction and probably nerve ending excitability are not involved in the increased vulnerability of old synapses to anaesthetic action. Other synaptic sites are probably involved in the mechanisms of age-dependent potentiation of anaesthetic suppression of synaptic transmission.
Assuntos
Envelhecimento/fisiologia , Anestésicos Inalatórios/toxicidade , Hipocampo/citologia , Isoflurano/toxicidade , Sinapses/efeitos dos fármacos , Animais , Dendritos/efeitos dos fármacos , Dendritos/fisiologia , Depressão Química , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados/fisiologia , Hipocampo/efeitos dos fármacos , Técnicas In Vitro , Células Piramidais/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344RESUMO
Organotypic brain slices cultured on semi-porous membranes is an increasingly popular in vitro preparation for studying mechanisms of ischemic brain damage. To model in vivo hypoxia, cultured brain slices are exposed to anaerobic atmosphere by placing them into a special incubator. This requirement limits the use of in vitro ischemic models to highly specialized laboratories. Here, we describe a simple method that reproduces hypoxic injury, where cultured hippocampal slices are submerged into glucose-free deoxygenated medium for 1 h. The extent and distribution of hippocampal neuronal loss obtained with this treatment resembled that caused by hypoxia in living tissue in situ, i.e. CA1 pyramidal cell layer was most vulnerable and dentate granular cell layer was least susceptible to hypoxia as measured with fluorescence of the viability marker propidium iodide (PI). Electrophysiologic functional impairment determined by field recordings of CA1 pyramidal neurones temporally coincided with the extent of neuronal death. In addition, known neuroprotective treatments, such as hypothermia and phenytoin application ameliorated neuronal damage in a pattern similar to previously published reports. Therefore, the present in vitro model of ischemia is simple, reliable and of low cost. It is well suited for short and long-term studies of the mechanisms of hypoxic brain damage.
Assuntos
Hipóxia Celular , Hipocampo/citologia , Hipocampo/fisiologia , Neurônios/fisiologia , Células Piramidais/fisiologia , Animais , Isquemia Encefálica , Morte Celular , Meios de Cultura , Estimulação Elétrica/métodos , Modelos Neurológicos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Técnicas de Cultura de Órgãos/métodos , Técnicas de Patch-Clamp , Fenitoína/farmacologia , Células Piramidais/citologia , Células Piramidais/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Simultaneous assessment of synaptic activity and glutamate efflux in guinea pig hippocampal brain slices was made before, during and after a 10-min period of hypoxia. Spontaneous glutamate efflux was assessed by determining glutamate concentration in the superfusion medium at discrete times using high performance liquid chromatography (HPLC). Synaptic activity was assessed using extracellular recording of the evoked population spike in the CA1 region following stimulation of the Schaffer collateral pathway. Hypoxia decreased (P < 0.05) the amplitude of the population spike by 3 min and abolished it by 5 min. This was accompanied by an increase (P < 0.05) in glutamate concentration in the superfusate at 10 min. Following re oxygenation, the population spike returned to baseline amplitude by 5 min and was greater (P < 0.05) than baseline at 10 and 20 min of recovery. Glutamate concentration returned to baseline levels by 1 min of recovery. This experimental preparation can be used to explore the temporal relationship between glutamate efflux and synaptic activity during hypoxia. The results of this study indicate that, in the hippocampal CA1 region, post-synaptic elements are more sensitive than their presynaptic counterparts to hypoxia.
Assuntos
Glutamatos/metabolismo , Hipocampo/fisiologia , Tratos Piramidais/fisiologia , Sinapses/fisiologia , Transmissão Sináptica , Animais , Hipóxia Celular , Cromatografia Líquida de Alta Pressão , Potenciais Evocados , Glutamatos/análise , Ácido Glutâmico , Cobaias , Técnicas In Vitro , Cinética , Masculino , Fatores de TempoRESUMO
Perikaryal application of GABA produced a hyperpolarization and increased the input conductance in neurons of layers IV-V of neocortex (guinea pig). This response faded during brief applications and had a long duration when the application period was increased from 4s to greater than 10 s. The sensitivity of the first response to blockade by the selective antagonist, bicuculline, indicated a mediation by gamma-aminobutyric acid-A (GABAA) receptors. The longer duration response was mimicked to some extent by the GABAB agonist, baclofen. Dendritic application of GABA induced a depolarization and a conductance increase - a response which was not particularly sensitive to antagonism by bicuculline. The depolarizing response also did not have a clearly defined reversal potential and may be a consequence of complex changes in membrane conductance, possibly for Cl and Ca or Na. Fading in both types of responses may result from a concomitant postsynaptic activation of a Cl conductance with Na-dependent GABA uptake.
Assuntos
Córtex Cerebral/fisiologia , Neurônios/fisiologia , Ácido gama-Aminobutírico/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Bicuculina/farmacologia , Córtex Cerebral/citologia , Dendritos/efeitos dos fármacos , Condutividade Elétrica , Eletrofisiologia , Cobaias , Técnicas In Vitro , Potenciais da Membrana/efeitos dos fármacos , Tetrodotoxina/farmacologiaRESUMO
OBJECTIVE: To investigate the acute and chronic effects of nitrendipine on plasma catecholamines in hypertensive patients. DESIGN: The variations in level of plasma noradrenaline and adrenaline were measured in the supine and standing positions before and after the initial dose, and after 12 weeks of nitrendipine therapy. Following a washout placebo period, treatment was initiated by a single 20 mg dose of nitrendipine. This was followed by a double-blind randomization into two groups: one receiving 10 mg nitrendipine twice daily, the other receiving 20 mg once daily. SETTING: Clinical investigation unit, University Hospital (University of British Columbia site), Vancouver, British Columbia. PATIENTS: Sixteen patients (seven males and nine females), mean age 51 years (range 27 to 63), with mild to moderate, uncomplicated hypertension. RESULTS: Two hours after administration of the initial 20 mg nitrendipine dose to all patients, there was a significant fall in the supine and standing systolic and diastolic blood pressure - from 164 +/- 3/102 +/- 1 to 139 +/- 2/87 +/- 2 mmHg, and from 153 +/- 4/105 +/- 1 to 139 +/- 3/90 +/- 1 mmHg, respectively. The supine and standing heart rates were unchanged. After 12 weeks of nitrendipine therapy, blood pressure was reduced (2 h after the dose) to a similar extent as that seen after the initial dose. Acute and chronic nitrendipine administration significantly increased supine and standing noradrenaline, but not adrenaline. Two hours after the initial 20 mg dose, supine noradrenaline increased from 3404 +/- 585 to 4005 +/- 644 pmol/L and standing noradrenaline increased from 3769 +/- 609 to 5821 +/- 615 pmol/L. At the end of the 12 weeks of therapy, similar dose-dependent effects were observed 2 h after the dose, but not 12 or 24 h after the dose, in both groups. The percentage increase in noradrenaline produced by nitrendipine in the standing position was consistently greater than in the supine position. CONCLUSIONS: Chronic nitrendipine therapy results in a daily increase in plasma noradrenaline (2 h after the dose), and the effect is greater in the standing position.
Assuntos
Epinefrina/sangue , Hipertensão/tratamento farmacológico , Nitrendipino/uso terapêutico , Norepinefrina/sangue , Sistema Nervoso Simpático/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Nitrendipino/administração & dosagem , Postura/fisiologia , Fatores de TempoAssuntos
Anestésicos/farmacologia , Encéfalo/fisiologia , Cálcio/fisiologia , Sinapses/fisiologia , Transmissão Sináptica/efeitos dos fármacos , Animais , Potenciais Evocados/efeitos dos fármacos , Halotano/farmacologia , Isoflurano/farmacologia , Modelos Neurológicos , Sinapses/efeitos dos fármacosRESUMO
The effects of two general anaesthetics, isoflurane--a volatile agent, and Althesin--a steroid preparation, were studied on the membrane electrical properties and spike activities of 64 neurons in in vitro slice preparations of neocortex excised from anterior cingulate and sensorimotor areas of guinea-pig brain. Spontaneous activity was depressed, and the thresholds for spikes evoked by intracellular injections of current pulses were increased in most neurons during applications of isoflurane in clinical concentrations (0.5-2.5 minimum alveolar concentration or MAC) and Althesin (15-100 microM). The MAC values are equivalent to 1-4% isoflurane in the gaseous phase. Applications in the higher ranges (1.5-2.5 MAC and 300-1500 microM) usually induced a small hyperpolarization (range, 3-8 mV) and an increase (10-30%) in input conductance. The repetitive spike firing evoked by current-pulse injections was inhibited and not uncommonly, abolished completely by an anaesthetic application. A striking feature in the actions of both agents on all neurons was the dose-dependent, reversible depression in amplitude and duration of the postspike afterhyperpolarizations (AHPs). These effects could not be attributed to anaesthetic induced changes in resting potentials, input conductances, or to the reduced number of evoked spikes. Bicuculline (50 microM) was applied concomitantly in 8 neurons with the anaesthetics to block Cl-conductances mediated by GABA-receptors that otherwise may "contaminate" the AHPs. In the presence of bicuculline, both anaesthetics produced a greater reduction in the amplitude and duration of the AHPs which are generated through Ca2+-mediated K+-conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Mistura de Alfaxalona Alfadolona/farmacologia , Anestésicos/farmacologia , Córtex Cerebral/fisiologia , Isoflurano/farmacologia , Inibição Neural/efeitos dos fármacos , Animais , Bicuculina/farmacologia , Córtex Cerebral/efeitos dos fármacos , Potenciais Evocados/efeitos dos fármacos , Cobaias , Técnicas In Vitro , Potenciais da Membrana/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Receptores de GABA-A/fisiologiaRESUMO
A decrease in synaptic excitation as well as an enhancement of neuronal inhibition in the central nervous system have been suggested as possible mechanisms of anaesthesia which we have investigated with intraneuronal recording techniques in neocortex. The effects of a volatile agent--isoflurane and a steroid preparation--Althesin, on excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) evoked by epicortical electrical stimulation were investigated in in vitro slice preparations of anterior cingulate and sensorimotor cortices of guinea pig. Applications of isoflurane (0.5-2.5 minimum alveolar concentration or MAC) and Althesin (10-200 microM) induced a dose-dependent, reversible depression of EPSPs with EC50's of 1 MAC and approximately 50 microM respectively. In order to eliminate the possibilities of a shunting effect on EPSPs by the conductances involved in the concomitant IPSPs, a GABAA-antagonist (bicuculline) was applied together with the anaesthetics. With this IPSP blockade, both anaesthetics depressed the EPSPs and were effective in reducing the epileptiform activities evoked by bicuculline during the subpial stimulation. The IPSPs also were evoked during the blockade of K-conductances by internal Cs-applications in order that the effects of anaesthetics could be studied exclusively on the Cl-mediated GABAergic IPSPs. Both isoflurane (0.5-2.5 MAC) and Althesin (10-100 microM) depressed the IPSPs in a dose dependent manner. These investigations demonstrate that applications of isoflurane and Althesin depressed the excitabilities of neocortical neurons by interfering with synaptic excitation, possibly at pre- and postsynaptic sites, rather than by potentiating neuronal inhibition.
Assuntos
Mistura de Alfaxalona Alfadolona/farmacologia , Anestésicos/farmacologia , Córtex Cerebral/fisiologia , Isoflurano/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Bicuculina/farmacologia , Córtex Cerebral/efeitos dos fármacos , Césio/farmacologia , Estimulação Elétrica , Cobaias , Técnicas In Vitro , Potenciais da Membrana/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacosRESUMO
PURPOSE: To describe the presentation and management of complete upper airway obstruction with life threatening arterial oxygen desaturation that occurred during attempted awake fibreoptic intubation in two patients presenting with unstable C-spine injury. CLINICAL FEATURE: Complete upper airway obstruction occurred during awake fibreoptic intubation of two men (ASA II; 68 & 55 yr old) presenting with unstable C-spine fractures. In both cases, bag and mask ventilation with CPAP failed to relieve the progressive hypoxemia. A surgical airway was established urgently to oxygenate the two patients who were suffering progressive life-threatening oxygen desaturation. One patient had trans-cricothyroid jet ventilation performed through a 16G intravenous cannula prior to an urgent tracheostomy. In the other patient, an emergency tracheostomy was inserted. Interestingly, both patients had been sedated in the Neurosurgical Intensive Care Unit with morphine and benzodiazepines before their scheduled surgeries. The most likely etiology for the complete upper airway obstruction was laryngospasm due to inadequate topicalization of the airway and additional sedation given in the operating room. Neither patients suffered any new neurological deficits following these events. They went on to have uneventful surgeries. CONCLUSION: This case report suggest that prior to awake fibreoptic intubation, oxygenation, adequate topicalization with testing to verify the lack of pharyngeal and laryngeal responses and careful assessment of sedation levels in the operating room are prudent for a safe endoscopic intubation.
Assuntos
Obstrução das Vias Respiratórias/etiologia , Vértebras Cervicais/lesões , Intubação Intratraqueal/efeitos adversos , Fraturas da Coluna Vertebral/complicações , Idoso , Analgésicos Opioides/efeitos adversos , Ansiolíticos/efeitos adversos , Benzodiazepinas , Sedação Consciente/efeitos adversos , Tecnologia de Fibra Óptica/instrumentação , Ventilação em Jatos de Alta Frequência , Humanos , Hipóxia/etiologia , Hipóxia/terapia , Intubação Intratraqueal/instrumentação , Laringismo/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Morfina/efeitos adversos , Oxigênio/sangue , Traqueostomia , VigíliaRESUMO
PURPOSE: Retropharyngeal abscess formation has the potential for acute respiratory compromise from obstruction or secondarily from rupture. The initial attempt to secure the airway is of paramount importance. We describe a patient with an unstable cervical spine secondary to Pott's disease who developed progressively obstructing retropharyngeal cold abscess. CLINICAL FEATURES: A 33-yr-old man with an unstable C-spine in halo traction presented with progressive airway obstruction secondary to retropharyngeal abscess extending from the cervical to the mid-thoracic vertebrae. After review of computerized tomography (CT) and magnetic resonance (MR) studies, preparations were made to secure the airway through fibreoptic assisted intubation. A conservative approach was chosen to secure the airway before surgical airway control as a first line approach. Following local and topical anesthesia, awake endoscopy was performed to assess the extent of obstruction and possibility of intubation without abscess rupture. A narrow tract along the lateral pharynx was identified to continue inferiorly to the epiglottis, from which point the cords were visualized. Extensive edema and abscess formation otherwise distorted the normal anatomy and prevented visualization from other directions. The airway was successfully secured without trauma with a well-lubricated 7.0 mm ID endotracheal tube. CONCLUSION: This report suggests that selected cases of tense obstructing retropharyngeal abscesses can be effectively managed with fibreoptic endoscopy for assessment and subsequent intubation before requiring surgical airway control as a first line strategy.
Assuntos
Obstrução das Vias Respiratórias/complicações , Abscesso Retrofaríngeo/complicações , Doenças da Coluna Vertebral/complicações , Tuberculose da Coluna Vertebral/cirurgia , Adulto , Obstrução das Vias Respiratórias/diagnóstico por imagem , Obstrução das Vias Respiratórias/patologia , Humanos , Intubação Intratraqueal , Imageamento por Ressonância Magnética , Masculino , Radiografia , Abscesso Retrofaríngeo/diagnóstico por imagem , Abscesso Retrofaríngeo/patologia , Doenças da Coluna Vertebral/diagnóstico por imagem , Doenças da Coluna Vertebral/patologia , Tuberculose da Coluna Vertebral/diagnóstico por imagem , Tuberculose da Coluna Vertebral/patologiaRESUMO
Electrophysiological studies were performed on in vitro slice preparations of sympathetic ganglia excised from peripherally perfused, brain-dead human donors. The intracellular recordings in 16 neurons showed resting potentials and input resistances mostly in the ranges reported for sympathetic neurons in other mammals. The high input resistances (approximately 29 M omega) can account for the long membrane time constants measured in three neurons (means = 13.9 ms). Spikes that were part of anodal break responses as well as those evoked by current pulse injections were tetrodotoxin sensitive and were more prolonged in duration by tetraethylammonium than by 4-aminopyridine applications. Administrations of isoflurane (0.5-2 minimum alveolar concentrations) by perfusion did not greatly affect the membrane properties, but produced a marked reduction in repetitive spike firing evoked by current pulse injections as well as in the postspike afterhyperpolarizations, suggesting that a sympathetic neurogenic mechanism may contribute to the hypotension observed clinically during isoflurane anaesthesia. These investigations demonstrate for the first time that human sympathetic ganglion neurons can be studied successfully in in vitro preparations, and hence are valuable for direct relevance to the human condition.
Assuntos
Gânglios Simpáticos/fisiologia , Neurônios/fisiologia , Adolescente , Adulto , Aminopirina/farmacologia , Membrana Celular/fisiologia , Criança , Humanos , Técnicas In Vitro , Potenciais da Membrana , Pessoa de Meia-Idade , Compostos de Tetraetilamônio/farmacologia , Tetrodotoxina/farmacologiaRESUMO
The aim of these investigations was to examine directly with fura-2 microspectrofluorimetry, the effects of general anesthetics on the resting level and glutamate-stimulated increase of intraneuronal free calcium ([Ca++]i) in cultured hippocampal neurons. Media were chosen for the preferential activation by glutamate of either the quisqualate (QUIS media) or N-methyl-D-aspartate (NMDA media) receptor subtypes. Continuous perfusion (20 min) of either media that had been saturated with isoflurane (0.5-4%) or, in some cases halothane (3-4%), produced only small and inconsistent changes in resting [Ca++]i. The rise in [Ca++]i induced by glutamate (or in some cases, NMDA) that was applied in the mainstream of QUIS or NMDA media was attenuated greatly during such applications of isoflurane or halothane for 6 to 20 min. Analysis of concentration-response relationships revealed that the EC50 values for the isoflurane-depressions were 1.7% for the Ca response to glutamate in QUIS media and 1.2% in NMDA media. Application of isoflurane blunted the peak increases in [Ca++]i produced by brief (1 min) applications of 50 mM K. Verapamil (25 microM) did not reduce the resting [Ca++]i and had long-lasting depressant effects on glutamate-stimulated increases in [Ca++]i in NMDA media. The effects of 2% isoflurane and verapamil were approximately additive. These investigations provided evidence that isoflurane reduced the increase in [Ca++]i which resulted from Ca influx linked directly to receptors for glutamate in addition to Ca entry due to activation of voltage-gated Ca channels.
Assuntos
Anestésicos/farmacologia , Cálcio/análise , Glutamatos/farmacologia , Neurônios/química , Aminoácidos/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Fura-2 , Halotano/farmacologia , Hipocampo/citologia , Hipocampo/metabolismo , Líquido Intracelular/metabolismo , Isoflurano/farmacologia , N-Metilaspartato/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ácido Quisquálico/farmacologia , Ratos , Espectrometria de Fluorescência , Verapamil/farmacologiaRESUMO
PURPOSE: To describe loss of the airway during tracheostomy and suggest a method for re-establishment of the airway and providing rescue oxygenation. CLINICAL FEATURES: A 22-yr-old female diagnosed with encephalomyelopathy was admitted to the intensive care unit with a progressively deteriorating level of consciousness and respiratory failure requiring intubation and ventilation. Several weeks later, an elective tracheostomy was performed under anesthesia. The surgeon made an anterior tracheal wall incision and inserted a cuffed #6 Shiley tracheostomy tube. No end-tidal CO(2) was detected and the patient could not be ventilated. After another failed attempt at insertion of a second tracheostomy tube, the diagnosis was made of a false passage within the trachea. The Shiley tracheostomy tube was removed and a #6 regular endotracheal tube was introduced in the trachea through the tracheostomy incision. The patient now could be ventilated with difficulty and low readings of end-tidal CO(2) were noted. Despite all efforts to further ventilate the patient, the arterial oxygen saturation never recovered, resulting in cardiac arrest. CONCLUSION: To restore a lost airway during tracheostomy, we recommend that a jet ventilation airway exchange catheter (JVAE) be inserted in the endotracheal tube through a bronchoscope port attachment prior to surgical entry into the trachea. The JVAE will also ensure continued ability to oxygenate the patient.
Assuntos
Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/terapia , Complicações Intraoperatórias/terapia , Oxigenoterapia , Traqueostomia/efeitos adversos , Adulto , Gasometria , Broncoscopia , Evolução Fatal , Feminino , Escala de Coma de Glasgow , Parada Cardíaca/etiologia , Humanos , Traqueia/anatomia & histologia , Traqueia/cirurgiaRESUMO
The objective of this study was to determine the effectiveness of two prophylactic approaches against the anticipated hypotension induced by propofol during rapid-sequence intubation. Thirty-six male or female nonpremedicated ASA class I-II patients aged 21-60 yr undergoing elective outpatient surgery were included in the study. Patients were randomly allocated to receive pre-induction ephedrine sulphate (70 micrograms x kg(-1)iv), pre-induction volume loading (12 ml x kg(-1) Ringer's lactate) or no treatment. Rapid-sequence intubation with cricoid pressure was then performed with propofol (2.5 mg. x kg(-1)) and succinylcholine (1.5 mg x kg(-1). The lungs were subsequently ventilated with 0.25-0.5% isoflurane in a 2:1 N2O/O2 mixture. Vecuronium was given once neuromuscular function had recovered from the succinylcholine. Heart rate and systemic arterial blood pressure were measured non-invasively before induction, after propofol administration and every minute for ten minutes after intubation. Pre-induction volume loading prevented the hypotension observed before surgical stimulation in control and ephedrine groups. Moreover, pre-induction volume loading was not associated with increases in heart rate after intubation as was ephedrine administration. The intubating conditions were excellent to satisfactory in most patients and the overall incidence of adverse events during intubation was mainly due to pain during injection of propofol. The present study showed that preoperative volume loading is more efficacious than pre-induction administration of ephedrine sulphate in maintaining haemodynamic stability during rapid-sequence induction with propofol and succinylcholine. In addition, propofol in combination with succinylcholine provides excellent conditions for rapid-sequence intubation.